Bismuth Nanoparticles Increase Effectiveness of Proton Therapy of Ehrlich Carcinoma.

We studied the antitumor activity of the combined use of local proton irradiation in two modes (10 and 31 Gy) with preliminary intra-tumoral injection of two types of bismuth nanoparticles differing in surface coating: coated with the amphiphilic molecule Pluronic-F127 or Silane-PEG (5 kDa)-COOH polymer. Nanoparticles were used in doses of 0.75 and 1.5 mg/mouse. In two independent series on experimental tumor model (solid Ehrlich carcinoma), bismuth nanoparticles of both modifications injected directly into the tumor enhanced the antitumor effects of proton therapy. Moreover, the radiosensitizing effect of bismuth nanoparticles administered via this route increased with the increasing the doses of nanoparticles and the doses of radiation exposure. In our opinion, these promising data obtained for the first time extend the possibilities of treating malignant neoplasms.

Cytotoxicity of Laser-Synthesized Nanoparticles of Elemental Bismuth.

High X-ray absorption combined with photothermal properties make bismuth nanoparticles (Bi NP) a promising agent for multimodal cancer theranostics. However, the synthesis of Bi NP by the "classical" chemical methods has numerous limitations, including potential toxicity of the produced nanomaterials. Here we studied in vitro toxicity of laser-synthesized Bi NP coated with Pluronic F-127 on mouse fibroblast cell line L929. The survival of L929 cells decreased linearly with increasing the concentration of Bi NP in a concentration range of 3-500 µg/ml; the LC50 value was 57 µg/ml. The unique combination of functional properties and moderate toxicity of the laser-synthesized Bi NP makes them a new promising platform for sensitization of multimodal cancer theranostics.

[ICG technologies in surgical treatment of benign diseases in gynecology]. / ICG-tekhnologii v khirurgicheskom lechenii dobrokachestvennykh zabolevanii v ginekologii.

ICG (indocyanine green) angiography is a method of visualizing blood flow and tissue perfusion based on intravenous administration of ICG and assessment of vascular distribution through an infrared fluorescence camera. Since the advent of ICG as a near-infrared fluorophore, fluorescence imaging has become an important tool in many areas of surgery. Several options for ICG angiography have been recently proposed in surgical gynecology. The authors describe application of ICG including assessment of myometrial and endometrial perfusion in myomectomy or resection of adenomyosis, tissue perfusion in surgical treatment of endometriosis, blood flow in hard-to-reach places in laparoscopic procedures and reconstructive surgery. ICG was useful in laparoscopic management of some benign gynecological diseases. In particular, this technology can improve treatment of endometriosis, especially deep infiltrative endometriosis, benign neoplasms.

Effect of Drug Encapsulation and Hydrothermal Exposure on the Structure and Molecular Dynamics of the Binary System Poly(3-hydroxybutyrate)-chitosan.

In this work, film materials based on binary compositions of poly-(3-hydroxybutyrate) (PHB) and chitosan with different ratios of polymer components in the range from 0/100 to 100/0 wt. % were studied. Using a combination of thermal (DSC) and relaxation (EPR) measurements, the influence of the encapsulation temperature of the drug substance (DS) of dipyridamole (DPD) and moderately hot water (at 70 °C) on the characteristics of the PHB crystal structure and the diffusion rotational mobility of the stable TEMPO radical in the amorphous regions of the PHB/chitosan compositions is shown. The low-temperature extended maximum on the DSC endotherms made it possible to obtain additional information about the state of the chitosan hydrogen bond network. This allowed us to determine the enthalpies of thermal destruction of these bonds. In addition, it is shown that when PHB and chitosan are mixed, significant changes are observed in the degree of crystallinity of PHB, degree of destruction of hydrogen bonds in chitosan, segmental mobility, sorption capacity of the radical, and the activation energy of rotational diffusion in the amorphous regions of the PHB/chitosan composition. The characteristic point of polymer compositions was found to correspond to the ratio of the components of the mixture 50/50%, for which the inversion transition of PHB from dispersed material to dispersion medium is assumed. Encapsulation of DPD in the composition leads to higher crystallinity and to a decrease in the enthalpy of hydrogen bond breaking, and it also slows down segmental mobility. Exposure to an aqueous medium at 70 °C is also accompanied by sharp changes in the concentration of hydrogen bonds in chitosan, the degree of PHB crystallinity, and molecular dynamics. The conducted research made it possible for the first time to conduct a comprehensive analysis of the mechanism of action of a number of aggressive external factors (such as temperature, water, and the introduced additive in the form of a drug) on the structural and dynamic characteristics of the PHB/chitosan film material at the molecular level. These film materials have the potential to serve as a therapeutic system for controlled drug delivery.

[Questionnaire of the Ryzhikh National Medical Research Centre for Coloproctology is a new tool for assessing chronic pelvic pain and pelvic organ dysfunction]. / Oprosnik NMITs koloproktologii imeni A.N. Ryzhikh ­ novyi instrument otsenki khronicheskoi tazovoi boli i narusheniya funktsii tazovykh organov.

The article presents the work of a multidisciplinary team of experts from various fields of medicine to optimize the «Questionnaire for assessing chronic pelvic pain and pelvic organ dysfunction (QCPPD) of the Ryzhikh National Medical Research Centre for Coloproctology¼ for use in clinical practice. The survey of respondents was conducted from June 28 to September 28, 2021. As a result of this survey, by repeatedly making edits and clarifications during communication with respondents, the final version was obtained, which allows assessing the patient's subjective sensations by the nature and localization of pelvic pain, sensitivity disorders and pelvic organ function. The main objective of this Questionnaire is to differentiate patients with neurogenic pain from a huge number of patients with chronic pelvic pain. This aspect will allow a more targeted approach to the diagnosis and pathogenetically justified treatment of patients, including after appropriate instrumental examinations. The work of a multidisciplinary team implies a higher degree of objectification and terminological accuracy of the Questionnaire under discussion. The presented version of the «Questionnaire for assessing chronic pelvic pain and pelvic organ dysfunction (QCPPD) of the Ryzhikh National Medical Research Centre for Coloproctology¼ will be primarily used in coloproctological patients with pelvic pain problems and anal incontinence and obstructive defecation. Further studies will be directed to the clinical evaluation of the results of the work carried out.

Polymer-coated BiOCl nanosheets for safe and regioselective gastrointestinal X-ray imaging.

Bismuth-based compounds are considered to be the best candidates for computed tomography (CT) imaging of gastrointestinal (GI) tract due to high X-ray absorption. Here, we report the introduction of polymer-coated bismuth oxychloride (BiOCl) nanosheets for highly efficient CT imaging in healthy mice and animal with colitis. We demonstrate simple, low cost and fast aqueous synthesis protocol which provides gram-quantity yield of chemically stable BiOCl nanosheets. The developed contrast gives 2.55-fold better CT enhancement compared to conventional contrast with negligible in vivo toxicity. As a major finding we report a regioselective CT imaging of GI tract by using nanoparticles coated with differentially charged polymers. Coating of nanoparticles with a positively charged polymer leads to their fast accumulation in small intestine, while the coating with negatively charged polymers stimulates prolonged stomach retention. We propose that this effect may be explained by a pH-controlled aggregation of nanoparticles in stomach. This feature may become the basis for advancement in clinical diagnosis of entire GI tract.

Investigation of the Distribution of Magnetic Nanoparticles in Tumor Tissues by the Method of Scanning Magnetic Force Nanotomography.

The development of effective biomedical technologies using magnetic nanoparticles (MNPs) for the tasks of oncotherapy and nanodiagnostics requires the development and implementation of new methods for the analysis of micro- and nanoscale distributions of MNPs in the volume of cells and tissues. The paper presents a new approach to three-dimensional analysis of MNP distributions - scanning magnetic force nanotomography as applied to the study of tumor tissues. Correlative reconstruction of MNP distributions and nanostructure features of the studied tissues made it possible to quantitatively estimate the parameters of three-dimensional distributions of composite nanoparticles based on silicon and iron oxide obtained by femtosecond laser ablation and injected intravenously and intratumorally into tumor tissue samples of B16/F1 mouse melanoma. The developed technology based on the principles of scanning probe nanotomography is applicable for studying the features of three-dimensional micro- and nanoscale distributions of magnetic nanoparticles in biomaterials, cells and tissues of various types.

A Method for Assessing the Efficiency of the Nucleotide Excision Repair System Ex Vivo.

The nucleotide excision repair (NER) is one of the main repair systems present in the cells of living organisms. It is responsible for the removal of a wide range of bulky DNA lesions. We succeeded in developing a method for assessing the efficiency of NER in the cell (ex vivo), which is a method based on the recovery of TagRFP fluorescent protein production through repair of the damage that blocks the expression of the appropriate gene. Our constructed plasmids containing bulky nFlu or nAnt lesions near the tagrfp gene promoter were shown to undergo repair in eukaryotic cells (HEK 293T) and that they can be used to analyze the efficiency of NER ex vivo. A comparative analysis of the time dependence of fluorescent cells accumulation after transfection with nFlu- and nAnt-DNA revealed that there are differences in how efficient their repair by the NER system of HEK 293T cells can be. The method can be used to assess the cell repair status and the repair efficiency of different structural damages.

[Uterine adenosarcoma. Report of 5 cases and review of literature]. / Adenosarkoma matki. Opisanie pyati nablyudenii i obzor literatury.

Uterine adenosarcoma is an uncommon biphasic tumor with benign epithelial and malignant mesenchymal components, often presenting difficulties for morphological diagnosis. We describe 5 cases of adenosarcoma of the uterine corpus and cervix, and vaginal stump in patients aged 46-76 years. Clinical data, ultrasound results, morphological data, including immunohistochemical studies with antibodies to CD10, estrogen and progesterone receptors, desmin, smooth muscle actin, and Ki-67 are presented. Large polypoid mass of the epithelial-mesenchymal structure within the uterine cavity in women of peri - and postmenopausal age require the exclusion of malignancy of the mesenchymal component with searchig for diagnostic criteria - periglandular cuffing of the stromal cells and mitoses.

Biocompatibility and Bioresorption of 3D-Printed Polylactide and Polyglycolide Tissue Membranes.

We studied biocompatibility and bioresorption of 3D-printed polylactide and polyglycolide tissue membranes. Ultrasound microscopy and histological examination showed that membranes fabricated of a copolymer of lactic and glycolic acids in a mass ratio of 1:9 are bioresorbed and have good biocompatibility with soft tissues (connective tissue, adipose tissue, and epithelium). An important feature of the copolymer membranes, which differs them from pure polylactide membranes, is the formation of a thin fibrous capsule that did not interfere its destruction by the mechanism of hydrolytic resorption.

[Optimization of treatment of acute poisoning with severe psychodisleptics]. / Optimizatsiya lecheniya ostrykh otravlenii psikhodisleptikami tyazheloi stepeni.

OBJECTIVE: To increase the efficacy of acute poisoning with severe psychodisleptics. MATERIAL AND METHODS: Fifty-two patients with acute psychoactive substance poisoning were studied. Patients of the main group (n=27) received cytoflavin infusion in combination with inhaled sedation with sevoflurane in addition to conventional therapy. The comparison group consisted of 25 patients who received conventional therapy. RESULTS AND CONCLUSION: Augmentation of conventional therapy with cytoflavin in combination with inhaled sedation with sevoflurane, affecting various links in the pathogenesis of acute severe poisoning with psychodisleptics, made it possible to cope in a shorter time.

[Takayusu Arteritis on the background of congenital vascular anomaly?]

The article described a female patient with high-grade arterial hypertension diagnosed at her young age. Congenital abdominal aortic hyperplasia and conformity with criteria for Takayasu arteritis were diagnosed at 10 years following the clinical manifestation.

Geminate recombination in organic photovoltaic blend PCDTBT/PC71BM studied by out-of-phase electron spin echo spectroscopy.

The key process in organic solar cell operation is charge separation under light illumination. Due to the low dielectric constant of organic materials, the Coulomb attraction energy within the interfacial charge-transfer state (CTS) is larger than the thermal energy. Understanding the mechanism of charge separation at the organic donor/acceptor interface still remains a challenge and requires knowledge of the CTS temporal evolution. To address this problem, the CTS in the benchmark photovoltaic blend PCDTBT/PC71BM was studied by the out-of-phase Electron Spin Echo (ESE). The protocol for determining the CTS geminate recombination rate for certain electron-hole distances was developed. Simulating the out-of-phase ESE trace for the CTS in the PCDTBT/PC71BM blend allows precise determination of the electron-hole distance distribution function and its evolution with the increase in the delay after the laser flash. Distances of charge separation up to 6 nm were detected upon thermalization at a temperature of 20 K. Assuming the exponential decay of the recombination rate, the attenuation factor ß = 0.08 Å-1 is estimated for the PCDTBT/PC71BM blend. Such a low attenuation factor is probably caused by a high degree of hole delocalization along the PCDTBT chain.

The Adhesion of Human Dermal Fibroblasts on Anodized Nanotube-layered Titanium, Modified for Implantology Application.

Anodization of titanium implants is accompanied by the formation of titanium oxide nanotubes improving osseointegration. An excessive fibroblast adhesion on the surface might lead to the formation of fibrous capsule resulting in implant rejection. In our research, we demonstrated that the adhesion activity of human dermal fibroblasts on anodized surface was not elevated, which is promising for the use of titanium with nanotube-layered surface for implantology.

Mixed dysprosium-lanthanide nitride clusterfullerenes DyM2N@C80-Ih and Dy2MN@C80-Ih (M = Gd, Er, Tm, and Lu): synthesis, molecular structure, and quantum motion of the endohedral nitrogen atom.

Systematic exploration of the synthesis of mixed-metal Dy-M nitride clusterfullerenes (NCFs, M = Gd, Er, Tm, Lu) is performed, and the impact of the second metal on the relative yield is evaluated. We demonstrate that the ionic radius of the metal appears to be the main factor allowing explanation of the relative yields in Dy-M mixed-metal systems with M = Sc, Lu, Er, and Gd. At the same time, Dy-Tm NCFs show anomalously low yields, which is not consistent with the relatively small ionic radius of Tm3+ but can be explained by the high third ionization potential of Tm. Complete separation of Dy-Gd and Dy-Er, as well as partial separation of Dy-Lu M3N@C80 nitride clusterfullerenes, is accomplished by recycling HPLC. The molecular structures of DyGd2N@C80 and DyEr2N@C80 are analyzed by means of single-crystal X-ray diffraction. A remarkable ordering of mixed-metal nitride clusters is found despite similar size and electronic properties of the metals. Possible pyramidalization of the nitride clusters in these and other nitride clusterfullerenes is critically analyzed with the help of DFT calculations and reconstruction of the nitrogen inversion barrier in M3N@C80 molecules is performed. Although a double-well potential with a pyramidal cluster structure is found to be common for most of them, the small size of the inversion barrier often leads to an apparent planar structure of the cluster. This situation is found for those M3N@C80 molecules in which the energy of the lowest vibrational level exceeds that of the inversion barrier, including Dy3N@C80 and DyEr2N@C80. The genuine pyramidal structure can be observed by X-ray diffraction only when the lowest vibrational level is below the inversion barrier, such as those found in Gd3N@C80 and DyGd2N@C80. The quantum nature of molecular vibrations becomes especially apparent when the size of the inversion barrier is comparable to the energy of the lowest vibrational levels.

Nuclear nanomedicine using Si nanoparticles as safe and effective carriers of 188Re radionuclide for cancer therapy.

Nuclear nanomedicine, with its targeting ability and heavily loading capacity, along with its enhanced retention to avoid rapid clearance as faced with molecular radiopharmaceuticals, provides unique opportunities to treat tumors and metastasis. Despite these promises, this field has seen limited activities, primarily because of a lack of suitable nanocarriers, which are safe, excretable and have favorable pharmacokinetics to efficiently deliver and retain radionuclides in a tumor. Here, we introduce biodegradable laser-synthesized Si nanoparticles having round shape, controllable low-dispersion size, and being free of any toxic impurities, as highly suitable carriers of therapeutic 188Re radionuclide. The conjugation of the polyethylene glycol-coated Si nanoparticles with radioactive 188Re takes merely 1 hour, compared to its half-life of 17 hours. When intravenously administered in a Wistar rat model, the conjugates demonstrate free circulation in the blood stream to reach all organs and target tumors, which is radically in contrast with that of the 188Re salt that mostly accumulates in the thyroid gland. We also show that the nanoparticles ensure excellent retention of 188Re in tumor, not possible with the salt, which enables one to maximize the therapeutic effect, as well as exhibit a complete time-delayed conjugate bioelimination. Finally, our tests on rat survival demonstrate excellent therapeutic effect (72% survival compared to 0% of the control group). Combined with a series of imaging and therapeutic functionalities based on unique intrinsic properties of Si nanoparticles, the proposed biodegradable complex promises a major advancement in nuclear nanomedicine.

New functional material: spark plasma sintered Si/SiO2 nanoparticles - fabrication and properties.

A bulk nanostructured material based on oxidized silicon nanopowder was fabricated using a spark plasma sintering technique. Structural investigations revealed that this material has the composition of ∼14 nm core Si granules inside an SiO2 shell. Photoluminescence measurements have shown that the emission spectra lie in the energy range of 0.6-1.1 eV, which is not typical of the emissions of the Si/SiO2 nanostructures reported in numerous papers. This result can be explained by the formation of energy states in the bandgap and the participation of these states in both electronic transport and photoluminescence emission. Annealing of the sample leads to a decrease in defect density, which in turn leads to quenching of the 0.6-1.1 eV photoluminescence. In this case ∼1.13 eV inter-band transitions in the Si core start to play a dominant role in radiative recombination. Thus, the possibility of controlling the photoluminescence emission over a broad wavelength range was demonstrated.

[Efficacy and safety of anticoagulant treatment for non-valvular atrial fibrillation in multimorbid patients].

OBJECTIVE: Assessment of the safety and efficacy of anticoagulant treatment in patients with nonvalvular atrial fibrillation (AF) in a multimorbidity setting. MATERIALS AND METHODS: The cross-sectional study included 104 patients diagnosed with nonvalvular AF and followed in the medical facilities of Yekaterinburg. The subjects were interviewed, anthropometric measurements were made, and the risk of thromboembolic complications was evaluated using the CHA2DS2-VASc score. The Charlson multimorbidity index was calculated, and patients were divided into two groups: Group 1 with a low level of multimorbidity (not more than 5 points) and Group 2 with a high level of multimorbidity (6 points or more). The data are presented as a median and interquartile range (25%; 75%). RESULTS: The study population included 40 males and 64 females. The median age was 71 (62.5; 80) years. The level of multimorbidity was estimated as 5 (3; 6) points. Group 1 included 64 patients, and Group 2 included 40 patients. Thirty-nine percent of the sample patients had a paroxysmal form of AF, 10% had a persistent form, and 51% had permanent AF. The group of patients with a high level of multimorbidity included more patients with permanent AF and fewer patients with paroxysmal AF as compared with a moderate level of multimorbidity (p<0.01). Anticoagulant treatment was indicated for 92 (88.5%) patients. It was administered to 70.7% of patients; 29.3% did not receive it. Among patients receiving anticoagulants, warfarin was administered to 18.5%, and new oral anticoagulants (NOACs) were administered to 81.5%. Complications were reported in 15.2% of anticoagulant treatment cases. Bleeding was reported in 21.7% of cases of warfarin administration and 12.5% of cases of NOAC treatment (p=0.32). The median number of risk factors for bleeding per patient was 5 (4; 5.5). The Charlson index and the total number of risk factors are significantly correlated (R=0.37, p<0.05). CONCLUSION: In real-world clinical practice in Ekaterinburg, Russia, 7 of 10 patients with AF for whom anticoagulant treatment was indicated actually received it; NOACs are prescribed four times more often than warfarin. With a higher level of multimorbidity, the risk of bleeding under the pressure of anticoagulant treatment increases; thus, NOACs should be preferred over warfarin for treatment of multimorbid patients.

Electrostatic Interaction across a Single-Layer Carbon Shell.

Ions inside of fullerene molecules are model systems for the study of the electrostatic interaction across a single layer of carbon. For TbSc2N@C80 on h-BN/Ni(111), we observe with high-resolution X-ray photoelectron spectroscopy a splitting of the C 1s core level. The data may be explained quantitatively with density functional theory. The correlation of the C 1s eigenvalues and the Coulomb potential of the inside ions at the corresponding carbon sites indicates incomplete screening of the electric field due to the endohedral ions. The screening comprises anisotropic charge transfer to the carbon atoms and their polarization. This behavior is essential for the ordering of endohedral single-molecule magnets and is expected to occur in any single-layer material.

Magnetic hysteresis in self-assembled monolayers of Dy-fullerene single molecule magnets on gold.

Fullerene single molecule magnets (SMMs) DySc2N@C80 and Dy2ScN@C80 are functionalized via a 1,3-dipolar cycloaddition with surface-anchoring thioether groups. The SMM properties of Dy-fullerenes are substantially affected by the cycloaddition. Submonolayers of the physisorbed derivatives exhibit magnetic hysteresis on an Au(111) surface at 2 K as revealed by X-ray magnetic circular dichroism.