Binary Proton Therapy of Ehrlich Carcinoma Using Targeted Gold Nanoparticles.

Proton therapy can treat tumors located in radiation-sensitive tissues. This article demonstrates the possibility of enhancing the proton therapy with targeted gold nanoparticles that selectively recognize tumor cells. Au-PEG nanoparticles at concentrations above 25 mg/L and 4 Gy proton dose caused complete death of EMT6/P cells in vitro. Binary proton therapy using targeted Au-PEG-FA nanoparticles caused an 80% tumor growth inhibition effect in vivo. The use of targeted gold nanoparticles is promising for enhancing the proton irradiation effect on tumor cells and requires further research to increase the therapeutic index of the approach.

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.

[The functioning of call-center in conditions of COVID-19 pandemic].

In conditions of persisting high morbidity of COVID-19, issues related to prompt and timely medical care of population remains actual ones. The purpose of the study to analyze activities of the call-center of the Ministry of Health Care of the Udmurt Republic related to organization of medical care of COVID-19 patients in the Udmurt Republic. MATERIALS AND METHODS: The statistical (descriptive statistics) and descriptive methods were applied. The indicators of functioning of the call-center of the Ministry of Health Care of the Udmurt Republic in 2020-2022 were analyzed. The psychological characteristics of telephone counseling were studied. The satisfaction of medical organizations and citizens with services of call-center operators was assessed. THE RESULTS: The main principles of telephone counseling are confidentiality, maintenance of framework of working conversation, respect to personality of addressee. In 2020 the call center phone line received 34160 calls, in 2021 - 128339 calls, in 2022 - 65618 calls. In 25 months of operation the call-center operators received 228,117 calls from citizens related to issues of new coronavirus infection. The number of patient calls to the hot-line increases significantly when incidence of new coronavirus infection increases (r=0.885; p<0.05). Most frequently (25.1%) citizens contacted the call-center of the Ministry of Health Care of the Udmurt Republic due to inability to reach the polyclinic and on issues related to primary before-doctor care. The second place in terms of frequency (18.5%) took issues related to PCR-test results. The third place (14.1%) took issues related to duration of quarantine for patients and persons residing with them, possibility for children to attend preschool and educational institutions. The number of outgoing calling in 2020 was 16146, in 2021 - 89269 and in 2022 9936 calls. During 25 months of operation, call-center operators made 204,782 calls to citizens to monitor their health status and invite them to vaccinations and health screenings. More than half of outgoing calls (58.3%) were related to audio-monitoring of patients undergoing outpatient treatment with making-up of electronic protocol. CONCLUSIONS: During the period of increasing of COVID-19 morbidity, the call-center becomes an independent structural unit of organizing patient care. The medical organizations and citizens are satisfied with functioning of the call-center of the Ministry of Health Care of the Udmurt Republic organized in order of improving the organization of medical care of patients with COVID-19.

[Living related liver transplantation in the Republic of Uzbekistan: current status and development prospects]. / Rodstvennaya transplantatsiya pecheni v Respublike Uzbekistan: nyneshnee sostoyanie i perspektivy razvitiya.

OBJECTIVE: To analyze primary results of living related liver transplantation in the Republic of Uzbekistan. MATERIAL AND METHODS: There were 44 living related transplantations of the right liver lobe in patients with decompensated liver failure between February 2018 and February 2023. RESULTS: Uneventful postoperative period was observed in 17 (38.6%) recipients. Other 27 patients (61.4%) developed 47 various postoperative complications (1-3 events per a patient). Of these, 8 (18.2%) patients required early postoperative re-laparotomy. Among 44 patients, 9 (20.5%) ones died in early postoperative period, and one patient died in long-term period (3 years after transplantation) from chronic rejection under refusal to take immunosuppressive drugs. Early satisfactory results were obtained in 79.5% of patients, long-term favorable outcomes - in 77.3% of cases. CONCLUSION: Engraftment rates and survival of recipients to a large extent depend on surgical strategy, baseline disease and clinical severity. The so-called "center effect" is essential at initial stages of implementation of the program.

[Influence of early surgery and endoscopic interventions on the risk of infection in patients with pancreatic necrosis]. / Vliyanie rannikh operativnykh i endoskopicheskikh vmeshatel'stv na risk infitsirovaniya u patsientov s pankreonekrozom.

OBJECTIVE: To prevent purulent-septic complications in patients with destructive pancreatitis. MATERIAL AND METHODS: A cohort study included 488 patients with pancreatic necrosis: group 1 (n=331) - active surgical strategy, group 2 (n=157) - follow-up and therapy. We used binary logistic regression to predict purulent-septic complications. RESULTS: Original model of independent variables significantly (p<0.001) revealed 5.3 times higher risk of infectious complications after laparotomy within the first week after hospitalization. Incidence of these events increased by 2.8 times in patients biliary pancreatitis compared to alcohol-alimentary pancreatitis. Complication rate was higher in older patients (by 2.1% for each year). Risk of purulent-septic complications decreased by 57.4% in women compared to men. There was no significant correlation between risk of infectious complications and endoscopic procedures. Specificity and sensitivity of the model was 74.2 and 72.6%, respectively. CONCLUSION: Original model significantly predicts the risk of purulent-septic complications within the first week after hospitalization. Refusal of early active surgical strategy in these patients will significantly reduce the likelihood of purulent-septic complications.

[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.

Hard Magnetic Properties and the Features of Nanostructure of High-Temperature Sm-Co-Fe-Cu-Zr Magnet with Abnormal Temperature Dependence of Coercivity.

This paper presents methods and approaches that can be used for production of Sm-Co-Fe-Cu-Zr permanent magnets with working temperatures of up to 550 °C. It is shown that the content of Sm, Cu, and Fe significantly affects the coercivity (Hc) value at high operating temperatures. A decrease in the content of Fe, which replaces Co, and an increase in the content of Sm in Sm-Co-Fe-Cu-Zr alloys lead to a decrease in Hc value at room temperature, but significantly increase Hc at temperatures of about 500 °C. Increasing the Cu concentration enhances the Hc values at all operating temperatures. From analysis of the dependence of temperature coefficients of the coercivity on the concentrations of various constituent elements in this alloy, the optimum chemical composition that qualifies for high-temperature permanent magnet (HTPM) application were determined. 3D atom probe tomography analysis shows that the nanostructure of the HTPM is characterized by the formation of Sm2(Co,Fe)17 (2:17) cells relatively smaller in size along with the slightly thickened Sm(Co,Cu)5 (1:5) boundary phase compared to those of the high-energy permanent magnet compositions. An inhomogeneous distribution of Cu was also noticed in the 1:5 phase. At the boundary between 1:5 and 2:17 phases, an interface with lowered anisotropy constants has developed, which could be the reason for the observed high coercivity values.

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.

[Advanced endoscopic vacuum therapy for anastomotic leakage in the upper gastrointestinal tract]. / Usovershenstvovannaya endoskopicheskaya vakuumnaya terapiya pri nesostoyatel'nosti anastomozov verkhnikh otdelov zheludochno-kishechnogo trakta.

OBJECTIVE: To evaluate the effectiveness and clinical aspects of advanced endoscopic vacuum therapy for esophagogastric, esophagointestinal and gastrointestinal anastomotic leakage, to identify disadvantages and further possibilities for its improvement. MATERIAL AND METHODS: The study included 69 people. Esophagodudodenal anastomotic leakage was detected in 34 patients (49.27%), gastroduodenal anastomotic leakage - in 30 patients (43.48%), esophagogastric anastomotic leakage - in 4 (7.25%) patients. Advanced endoscopic vacuum therapy was used for these complications. RESULTS: Vacuum therapy in patients with esophagodudodenal anastomotic leakage led to complete healing of defect in 31 (91.18%) cases. In 4 (14.8%) cases, minor bleeding was noted during replacement of vacuum dressing. There were no other complications. Three (8.82%) patients died from secondary complications. Treatment of gastroduodenal anastomotic failure resulted complete healing of defect in 24 (80%) patients. Six (20%) patients died including 4 (66.67%) cases associated with secondary complications. Vacuum therapy for esophagogastric anastomotic leakage resulted complete healing of defect in 4 (100%) patients. CONCLUSION: Advanced endoscopic vacuum therapy is a simple, effective and safe method of therapy for esophagogastric, esophagoduodenal and gastrointestinal anastomotic leakage.

[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.

[Damage control strategy in surgical treatment of patients with severe gastroduodenal bleeding]. / Primenenie strategii Damage control pri khirurgicheskom lechenii patsientov s tyazhelymi gastroduodenal'nymi krovotecheniyami.

OBJECTIVE/: To objectify patient condition and improve treatment outcomes in patients with benign severe gastroduodenal bleeding. MATERIAL AND METHODS: We analyzed the immediate results of staged surgical treatment of patients with benign severe gastroduodenal bleeding according to the accepted concept of «Damage Control Surgery¼. The Rockall risk scoring system and the Glasgow-Blatchford score (GBS) were used. We preferred two-stage intervention in patients with Rockall score ≥5 and Glasgow-Blatchford score ≥11. RESULTS: Staged approach according to the concept of «Damage Control Surgery¼ in patients with benign severe gastroduodenal bleeding ensures positive results by minimizing surgical trauma and perioperative bleeding, early stabilization of hemostasis and subsequent successful restoration of digestive function. CONCLUSION: The concept of «Damage Control Surgery¼ in patients with benign severe gastroduodenal bleeding can reduce mortality and incidence of postoperative complications.

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.

Three-dimensional modeling of intense unipolar THz pulses formation during their amplification in nonequilibrium extended Xe plasma channel.

We develop a three-dimensional (3D) fully self-consistent model for analysis of an ultrashort THz pulse propagation and amplification in a nonequilibrium plasma channel formed in xenon by a femtosecond UV laser pulse. The model is based on the self-consistent solution of a second order wave equation in the cylindrical geometry and the kinetic Boltzmann equation for the electron velocity distribution function (EVDF) at different points of the spatially inhomogeneous nonequilibrium plasma channel. We analyze the wide range of plasma and seed pulse parameters and reveal the optimal regimes for producing high intensity outgoing THz fields as well as highly unipolar THz pulses within the proposed mechanism. It is demonstrated that the process of EVDF relaxation in plasma limits the amplification of THz pulses at the level of ∼10^{7}W/cm^{2}. Both focusing features of nonequilibrium plasma and the possibility of producing THz pulses with a high degree of unipolarity are confirmed for the case of 3D geometry.

Low-Threshold Induced-Side-Scattering Instability at the Tokamak Edge Transport Barrier Predicted in O-Mode Electron Cyclotron Resonance Heating Experiments.

The trapping of a lower hybrid wave in the tokamak edge transport barrier is predicted, reducing by 3 orders of magnitude the excitation threshold for the absolute parametric decay instability that leads to side scattering of the ordinary microwave pump in electron cyclotron resonance heating (ECRH) experiments. This process is similar to the stimulated Raman scattering instability in laser physics and can result in substantial anomalous scattering of the pump wave, like in laser fusion experiments. The corresponding broadening of the ECRH power deposition profile can reduce the ability of this method to control the neoclassical tearing modes both in present day machines, as ASDEX-Upgrade, where the theory can be checked, and in fusion reactors such as ITER and DEMO.

Amorphous and crystalline cerium(IV) phosphates: biocompatible ROS-scavenging sunscreens.

This paper reports on a comprehensive study of the UV-shielding properties (namely, the sun protection factor and the factor of protection against UV-A radiation) and cytotoxicity (including photocytotoxicity) of amorphous and crystalline cerium(IV) phosphates. It has been shown that cerium(IV) phosphate NH4Ce2(PO4)3 is characterised by UV-shielding properties that are comparable to those of nanocrystalline TiO2 and CeO2. Moreover, cerium(IV) phosphates did not show toxicity towards cell cultures of NCTC L929 line mouse fibroblasts and human mesenchymal stem cells, in a wide range of concentrations, and even enhanced the proliferative activity of the latter. In a model study of the photoprotective properties of cerium(IV) phosphates on human mesenchymal stem cells, the pronounced protective effect of NH4Ce2(PO4)3 was observed, which was comparable to the shielding action of nanocrystalline CeO2. The results have shown that tetravalent cerium phosphates can be considered as promising UV-filters for sunscreen applications.

Biological Activity and Probable Mechanisms of Action of Derivatives of Tryptanthrin and Mostotrin Alkaloids.

The alkaloid tryptanthrin and its water-soluble derivative mostotrin exhibit high antimicrobial and antitumor activity. To develop more active and less toxic preparations, syntheses and testing of the biological activities of a number of new and/or little-studied analogs were performed. Some of them have been shown to have higher cytotoxicity against tumor and microbial cells than tryptanthrin and mostotrin. Thus, 8-fluorotryptanthrin effectively inhibits the proliferation of various tumor cell lines, namely: K-562/4, HCT-116 and HCT-116p53ko at lower concentrations than tryptanthrin, and 2,8-difluorostotrin exhibits a stronger antimicrobial effect against pathogenic bacteria S. aureus ATCC 29213 than mostotrin. It has been established that the antiproliferative properties of 8-fluorotryptanthrin and 8-fluoromostotrin are associated with their ability in nanomolar concentrations to inhibit the cell cycle of tumor cells at the stage of transition from the G1 phase to the S phase. The data obtained indicate the prospects for further in-depth studies of their antitumor properties.

Clinical and diagnostic manifestations of tickborne mixed infection in combination with COVID-19.

The coexistence of various pathogens inside the patient's body is one of the poorly studied and current issues. The aim of the study is to identify the relationship between the indicators of complex laboratory diagnostics and the clinical manifestations of a mixed disease during subsequent infection with the SARS-CoV-2 virus using the example of a case of chronic encephalitis-borreliosis infection. Seven blood serum samples were collected from the patient over the course of a year. For the etiological verification of the causative agents of TBE, Lyme disease and COVID-19, the methods of ELISA and PCR diagnostics were used. The patient was diagnosed with Lyme disease on the basis of the detection of IgG antibodies to Borrelia 5 months after the onset of the disease, since she denied the tick bite. In the clinical picture, there was an articular syndrome and erythema migrans. Later, IgG antibodies to the TBEV were found in the blood. Throughout the study, IgM antibodies to Borrelia were not detected. The exacerbation of Lyme disease could be judged by the clinical manifestations of this disease and by the growth of specific IgG antibodies. A feature of this case was that during an exacerbation of the Lyme disease, an infection with the SARS-CoV-2 virus occurred. Treatment (umifenovir, hydroxychloroquine, azithromycin, ceftriaxone) was prescribed, which improved the condition of the underlying disease, decreased joint pain, decreased IgG levels to borrelia. However, during this period, serological markers of TBEV appear: antigen, IgM antibodies, and the titer of IgG antibodies increases. Most likely, this was facilitated by the switching of the immune system to the SARS-CoV-2 virus, with the simultaneous suppression of borrelia with antibiotics and the appointment of hydroxychloroquine, which has an immunosuppressive effect. Despite the activation of the virus, clinical manifestations of TBE were not observed in the patient, which is most likely associated with infection with a weakly virulent TBEV strain. The further course of tick-borne infections revealed the dominant influence of B. burgdorferi in relation to TBEV. Laboratory studies have shown that suppression of the activity of the borreliosis process by etiotropic treatment subsequently led to the activation of the persistent TBEV.

Evidence for the formation of two types of oxygen interstitials in neutron-irradiated α-Al2O3 single crystals.

Due to unique optical/mechanical properties and significant resistance to harsh radiation environments, corundum (α-Al2O3) is considered as a promising candidate material for windows and diagnostics in forthcoming fusion reactors. However, its properties are affected by radiation-induced (predominantly, by fast neutrons) structural defects. In this paper, we analyze thermal stability and recombination kinetics of primary Frenkel defects in anion sublattice - the F-type electronic centers and complementary oxygen interstitials in fast-neutron-irradiated corundum single crystals. Combining precisely measured thermal annealing kinetics for four types of primary radiation defects (neutral and charged Frenkel pairs) and the advanced model of chemical reactions, we have demonstrated for the first time a co-existence of the two types of interstitial defects - neutral O atoms and negatively charged O- ions (with attributed optical absorption bands peaked at energies of 6.5 eV and 5.6 eV, respectively). From detailed analysis of interrelated kinetics of four oxygen-related defects, we extracted their diffusion parameters (interstitials serve as mobile recombination partners) required for the future prediction of secondary defect-induced reactions and, eventually, material radiation tolerance.