Theoretical Study of Microgel Functional Groups' Mobility.

Polymer microgels, micrometer-sized cross-linked polymer particles, are considered to be a promising type of advanced materials for a wide range of applications. To enhance the microgels' applicability, it is essential to incorporate various functional groups into a microparticle polymer network. Yet, the availability of functional groups for the interaction with surroundings depends strongly on the properties of the polymer network and has a great impact on further effective usage. In this theoretical study, we address this question and, with the help of coarse-grained molecular dynamics computer simulations, assess the segmental mobility and accessibility of functional groups bound to polymer network depending on microgel architecture and solvent quality. Additionally, we evaluate the minimum number of functional groups needed to facilitate the hopping mechanism between the functional groups (i.e., charge transfer). As an example of practical implementation of the obtained results, we estimate the optimal network topology for redox-active microgels to provide the maximum charge capacity for the dispersion electrolyte in redox-flow batteries.

Smallpox vaccination in a mouse model.

The monkeypox epidemic, which became unusually widespread among humans in 2022, has brought awareness about the necessity of smallpox vaccination of patients in the risk groups. The modern smallpox vaccine variants are introduced either intramuscularly or by skin scarification. Intramuscular vaccination cannot elicit an active immune response, since tissues at the vaccination site are immunologically poor. Skin has evolved into an immunologically important organ in mammals; therefore, intradermal delivery of a vaccine can ensure reliable protective immunity. Historically, vaccine inoculation into scarified skin (the s.s. route) was the first immunization method. However, it does not allow accurate vaccine dosing, and high-dose vaccines need to be used to successfully complete this procedure. Intradermal (i.d.) vaccine injection, especially low-dose one, can be an alternative to the s.s. route. This study aimed to compare the s.s. and i.d. smallpox immunization routes in a mouse model when using prototypic second- and fourth-generation low-dose vaccines (104 pfu). Experiments were conducted using BALB/c mice; the LIVP or LIVP-GFP strains of the vaccinia virus (VACV) were administered into the tail skin via the s.s. or i.d. routes. After vaccination (7, 14, 21, 28, 42, and 56 days post inoculation (dpi)), blood samples were collected from the retro-orbital venous sinus; titers of VACV-specific IgM and IgG in the resulting sera were determined by ELISA. Both VACV strains caused more profound antibody production when injected via the i.d. route compared to s.s. inoculation. In order to assess the level of the elicited protective immunity, mice were intranasally infected with a highly lethal dose of the cowpox virus on 62 dpi. The results demonstrated that i.d. injection ensures a stronger protective immunity in mice compared to s.s. inoculation for both VACV variants.

Effect of the ati Gene Deletion on the Pathogenicity and Immunogenicity of the Vaccinia Virus.

Among the nonvirion proteins of the vaccinia virus (VACV), a 94-kDa long protein is most abundantly present; the protein is a truncated form of the 150-kDa A-type inclusion (ATI) protein of the cowpox virus encoded by the ati gene. This VACV protein does not form intracellular ATIs, being as it is a major immunogen upon infection/immunization of humans or animals with the VACV. Antibodies specific to this protein are not virus-neutralizing. The present study focused on the effect of the production of this nonstructural major immunogenic VACV protein on the manifestation of pathogenicity and immunogenicity of the virus in the BALB/c mouse model of infection. In order to introduce a targeted deletion into the VACV LIVP genome, the recombinant integration/deletion plasmid pΔati was constructed and further used to generate the recombinant virus LIVPΔati. The pathogenicity of the VACV LIVP and LIVPΔati strains was studied in 3-week-old mice. The mice were intranasally infected with the viruses at a dose of 107 pfu; 50% of the animals infected with the parent LIVP strain died, while infection with the LIVPΔati strain led to the death of only 20% of the mice. Intradermal vaccination of mice aged 6- weeks with the LIVPΔati virus statistically significantly increased the production of VACV-specific IgG, compared to that after intradermal vaccination with VACV LIVP. Meanwhile, no differences were noted in the cell-mediated immune response to the vaccination of mice with VACV LIVP or LIVPΔati, which was assessed by ELISpot according to the number of splenocytes producing IFN-γ in response to stimulation with virus-specific peptides. Intranasal infection of mice with lethal doses of the cowpox virus or the ectromelia virus on day 60 post-immunization with the studied VACV variants demonstrated that the mutant LIVPΔati elicits a stronger protective response compared to the parent LIVP.

[Interaction of DNA Methyltransferase Dnmt3a with Phosphorus Analogs of S-Adenosylmethionine and S-Adenosylhomocysteine].

Enzymatic methyltransferase reactions are of crucial importance for cell metabolism. S-Adenosyl-L-methionine (AdoMet) is a main donor of the methyl group. DNA, RNA, proteins, and low-molecular-weight compounds are substrates of methyltransferases. In mammals, DNA methyltransferase Dnmt3a de novo methylates the C5 position of cytosine residues in CpG sequences in DNA. The methylation pattern is one of the factors that determine the epigenetic regulation of gene expression. Here, interactions with the catalytic domain of Dnmt3a was for the first time studied for phosphonous and phosphonic analogs of AdoMet and S-adenosyl-L-homocysteine (AdoHcy), in which the carboxyl group was substituted for respective phosphorus-containing group. These AdoMet analogs were shown to be substrates of Dnmt3a, and the methylation efficiency was only halved as compared with that of natural AdoMet. Both phosphorus-containing analogs of AdoHcy, which is a natural methyltransferase inhibitor, showed similar inhibitory activities toward Dnmt3a and were approximately four times less active than AdoHcy. The finding that the phosphonous and phosphonic analogs are similar in activity was quite unexpected because the geometry and charge of their phosphorus-containing groups differ substantially. The phosphorus-containing analogs of AdoMet and AdoHcy are discussed as promising tools for investigation of methyltransferases.

[Cognitive disorders in burnout syndrome]. / Kognitivnye narusheniya pri sindrome emotsional'nogo vygoraniya.

OBJECTIVE: To study the impairment of cognitive functions in patients with different stages of the burnout syndrome (BS). MATERIAL AND METHODS: 78 patients aged 25-45 years (average age 36.9±9.5 years) were examined, which at the BS stage were divided into two subgroups: Residence (51.3%, n=40) and Exhaustion (48.7%, n=38). The control group consisted of 106 practically healthy (average age 36.3±7.2 years) The following methods were used: Russian-language version of the MBI questionnaire, questionnaire to diagnose the level of emotional burnout by V.V. Boyko, questionnaire CFQ, method «Learning 10 words¼ by A.R. Luria, registration of cognitive evoked potentials (EP) in the psychophysiological visual test VCPT. RESULTS: Subjective symptoms of memory loss were in 47 patients (60.3% of the total number of patients with EBS): 17 patients (42.5%) from the subgroup Resistance and 30 patients (78.9%) from the subgroup Exhaustion. The quantitative evaluation of the subjective symptoms in the CFQ test showed a reliable increase in all patient groups (p<0.05) and especially in the subgroup Exhaustion. There was statistically reliable decrease of the P200 component in subgroup Resistence and control group in the alloys Cz (p<0.001) and Fz (p<0.001), as well as statistically reliable reduction of the P300 component in the indicated leads (Cz (p<0.001) and Pz (p<0.001)) in patients in the subgroup Resistance. Most BS patients had cognitive complaints that were more common at the Exhaustion stage. At the same time, objective cognitive impairments were detected only in patients at the stage of Exhaustion. Only the long-term memory is affected. Psychophysiological research has shown a decrease in the level of attention in both subgroups, which demonstrated an increased impairment of mental processes. CONCLUSION: Cognitive impairment in patients with BS manifests in various forms of attention, memory impairment, and performance degradation in the resistance and exhaustion phases, and can result from high asthenization.

Position statement: Recommendations on the diagnosis and treatment of Malassezia folliculitis.

Malassezia is a lipophilic yeast that is a part of the human mycobiome. Malassezia folliculitis appears when the benign colonization of the hair follicles, by the Malassezia yeasts, becomes symptomatic with pruritic papules and pustules. Although Malassezia folliculitis is common in hospital departments, diagnosing and treating it varies among dermatologists and countries. The European Academy of Dermatology and Venereology Mycology Task Force Malassezia folliculitis working group has, therefore, sought to develop these recommendations for the diagnosis and management of Malassezia folliculitis. Recommendations comprise methods for diagnosing Malassezia folliculitis, required positive findings before starting therapies and specific treatment algorithms for individuals who are immunocompetent, immunocompromised or who have compromised liver function. In conclusion, this study provides a clinical strategy for diagnosing and managing Malassezia folliculitis.

[Clinical and psychological manifestations of emotional burnout in mothers of children with neuropsychiatric diseases (on a model of ADHD)]. / Kliniko-psikhologicheskie proyavleniya emotsional'nogo vygoraniya u materei detei s psikhonevrologicheskimi zabolevaniyami (na modeli SDVG).

OBJECTIVE: To evaluate the therapeutic efficacy of Pantogam aktiv in the treatment of clinical manifestations of burnout in mothers of children with ADHD. MATERIAL AND METHODS: Under observation were 108 mothers of children with attention deficit hyperactivity disorder (ADHD) aged 25 to 50 years, who had symptoms of burnout in the clinical picture during the initial visit. The following research methods were used in the work: clinical history taking, neurological examination, S. Maslach questionnaire for assessing the burnout manifestations, subjective asthenia rating scale (MFI-20) with five subscales, digital fatigue rating scale (10-point variant), quantitative assessment of autonomic changes (questionnaire A.M. Wein), Spielberger-Khanin Scale for assessing emotional disorders, psychophysiological study of cognitive functions: test of attention variables TOVA (the Test of Variables of Attention). For the treatment of patients, the drug Pantogam Active was used in capsules of 300 mg, at a daily dose of 900 mg (2 capsules in the morning and 1 capsule in the afternoon) for 8 weeks. RESULTS: A re-examination after a course of treatment showed improvement in 68.5% of patients. After treatment, there was a significant decrease in the severity of such indicators of burnout as emotional exhaustion and depersonalization, a significant decrease in the average values according to the A.M. Wayne, a decrease in reactive anxiety, a statistically significant improvement in attention and a decrease in impulsivity (p<0.05). CONCLUSION: Thus, the results of the study indicate that the use of Pantogam active in the treatment of clinical manifestations of parental burnout is characterized by high efficiency. After treatment, there is a significant decrease in fatigue, asthenia, anxiety, and total indicators characterizing burnout. The data obtained make it possible to recommend the use of Pantogam aktiv in the treatment of clinical manifestations of parents burnout in children with neurological diseases.

Experimental and Model Study of a Swirling Fluid Flow in a Converging Channel As a Simulation of Blood Flow in the Heart and Aorta.

Study of swirling flows in channels corresponding to the static approximation of flow channels of the heart and major vessels with a longitudinal-radial profile zR2 = const and a concave streamlined surface at the beginning of the longitudinal coordinate has been carried out. A comparative analysis of the flow structure in channel configurations zRN = const, where N = -1, 1, 2, 3, in the absence and presence of a concave surface was carried out. The numerical modeling was compared with the results of hydrodynamic experiments on the flow characteristics and the shape of the flow lines. The numerical model was used to determine the velocity structure, viscous friction losses, and shear stresses. Numerical modeling of steady-state flows for channels without a concave surface showed that in the channel zR2 = const there is a stable vortex flow structure with the lowest viscous friction losses. The presence of a concave surface of sufficient size significantly reduces viscous friction losses and shear stresses in both the steady state and pulsed modes.

Vacuum breakdown in magnetic dipole wave by 10-PW class lasers.

The vacuum breakdown by 10-PW-class lasers is studied in the optimal configuration of laser beams in the form of an m-dipole wave, which maximizes the magnetic field. Using 3D PIC simulations we calculated the threshold of vacuum breakdown, which is about 10 PW. We examined in detail the dynamics of particles and identified particle trajectories which contribute the most to vacuum breakdown in such highly inhomogeneous fields. We analyzed the dynamics of the electron-positron plasma distribution on the avalanche stage. It is shown that the forming plasma structures represent concentric toroidal layers and the interplay between particle ensembles from different spatial regions favors vacuum breakdown. Based on the angular distribution of charged particles and gamma photons a way to experimentally identify the process of vacuum breakdown is proposed.

Particle trajectories, gamma-ray emission, and anomalous radiative trapping effects in magnetic dipole wave.

In studies of interaction of matter with laser fields of extreme intensity there are two limiting cases of a multibeam setup maximizing either the electric field or the magnetic field. In this work attention is paid to the optimal configuration of laser beams in the form of an m-dipole wave, which maximizes the magnetic field. We consider in such highly inhomogeneous fields the advantages and specific features of laser-matter interaction, which stem from individual particle trajectories that are strongly affected by gamma photon emission. It is shown that in this field mode qualitatively different scenarios of particle dynamics take place in comparison with the mode that maximizes the electric field. A detailed map of possible regimes of particle motion (ponderomotive trapping, normal radiative trapping, radial, and axial anomalous radiative trapping), as well as angular and energy distributions of particles and gamma photons, is obtained in a wide range of laser powers up to 300 PW, and it reveals signatures of radiation losses experimentally detectable even with subpetawatt lasers.

Viral Safety Issues in the Production and Manufacturing of Human Immunoglobulin Preparations from Equine Plasma/Serum.

The current Russian and foreign pharmacopoeias either do not provide any information about existing types of viral diseases in horses or do not present it in full. Data of modern domestic and foreign literature was used to prepare the most complete list of viruses that cause equine diseases including 36 infectious agents, 25 of which are pathogenic for humans, 13 of the 25 of which are widespread throughout Russia. Information is provided on the magnitudes of the disease incubation periods (which are most often within one month), the external clinical signs of these diseases (which can also be asymptomatic), and the maximum possible concentrations of viruses in the blood of horses with these diseases (which can reach 8 log conventional units/mL of blood). This information is offered for use in critical production stages of heterologous immunoglobulin drugs for medical use to assure viral safety.

[Etiopathophysiological mechanism of systemic and local allergic sensitization in the development of chronic rhinitis and chronic rhinosinusitis]. / Etiopatofiziologicheskii mekhanizm obshchei i mestnoi allergicheskoi sensibilizatsii v razvitii khronicheskogo rinita i khronicheskogo rinosinusita.

The persistence, development and exacerbation of chronic rhinitis and chronic rhinosinusitis all involve sensitization to respiratory allergens. The allergic response in question is the IgE-mediated mechanism of rhinitis, which often leads to a complex of etiopathophysiological malfunctions in various organs and systems. For clinical classification and further management of patients, it is important not to miss the detection of both systemic allergic sensitization to aeroallergens (which is achieved by conducting skin prick test or detecting the allergen-specific immunoglobulin E in the blood) and local sensitization (which can be confirmed by conducting nasal provocation test or detecting the nasal-specific immunoglobulin E in nasal mucosa). Before a full examination is conducted and both systemic and local sensitization are ruled out, the diagnosis of non-allergic rhinitis and the management of a patient with non-allergic nasal inflammation may be premature.

Entrainment, stopping, and transmission of microwave solitons of self-induced transparency in counter-propagating magnetized electron beam.

Based on numerical simulations of a boundary problem, we study various scenarios of microwave soliton formation in the process of cyclotron resonance interaction of a short electromagnetic pulse with a counter-propagating initially rectilinear electron beam taking into account the relativistic dependence of the cyclotron frequency on the electrons' energy. When a certain threshold in the pulse energy is exceeded, the incident pulse can propagate without damping in the absorbing beam, similar to the effect of self-induced transparency in optics. However, mutual motion of the wave and electrons can lead to some novel effects. For relatively small energy of the incident pulse, the microwave soliton is entrained by the electron beam opposite to the direction of the wave's group velocity. With an increase in the pulse energy, soliton stopping occurs. This regime is characterized by the close-to-zero pulse velocity and can be interpreted as a variety of the "light stopping." High-energy microwave solitons propagate in the direction of the unperturbed group velocity. Their amplitude may exceed the amplitude of the incident pulse, i.e., nonlinear self-compression takes place. A further increase in the incident energy leads to the formation of additional high-order solitons whose behavior is similar to that of the first-order ones. The characteristics of each soliton (its amplitude and duration) correspond to analytical two-parametric soliton solutions that are to be found from consideration of the unbounded problem.

In situ-Synthesized cadmium sulfide quantum dots in pore-forming protein and polysaccharide matrices for optical biosensing applications.

The main limitation for practical implementation of quantum dots-based sensors and biosensors is the possible contamination of sensing media with quantum dots (QDs) moved out from the sensor structure, being critical for living systems measurements. Numerous efforts have addressed the challenge of pre-synthesized QDs incorporation into porous matrix provide, on the one hand, proper fixation of quantum dots in its volume and preserving a free analyte transfer from the sensing media to them - on the other hand. Here, we propose an alternative insight into this problem. Instead of using preliminary synthesized particles for doping a matrix, we have in situ synthesized cadmium sulfide QDs in porous biopolymeric matrices, both in an aqueous solution and on a mica substrate. The proposed technique allows obtaining QDs in a matrix acting simultaneously as a ligand passivating surface defects and preventing QDs aggregation. The conjugates were used as a photoluminescence sensor for the metal ions and glutathione detection in an aqueous media. Different kinds of sensor responses have been found depending on the analyte nature. Zinc ions' presence initiates the intraband QDs emission increases due to the reduction of non-radiative processes. The presence of copper ions, in contrast, leads to a gradual photoluminescence decrease due to the formation of the non-luminescent copper-based alloy in the QDs structure. Finally, the presence of glutathione initiates a ligand exchange process followed by some QDs surface treatment enhancing defect-related photoluminescence. As a result, three different kinds of sensor responses for three analytes allow claiming development of a new selective QD-based sensor suitable for biomedical applications.

[Emotional and behavioral dysregulation in children with attention deficit hyperactivity disorder]. / Narusheniya emotsional'noi i povedencheskoi regulyatsii u detei s sindromom defitsita vnimaniya s giperaktivnost'yu.

OBJECTIVE: To study disorders of emotional regulation in different types of attention deficit hyperactivity disorder (ADHD) in children. MATERIAL AND METHODS: 58 children suffering from ADHD, aged 12 to 15 years were divided into 2 subgroups (38 children with a combined form of ADHD and 20 children with ADHD with a predominance of inattention). The control group consisted of 30 children without manifestations of neuropsychiatric disorders. The following research methods were used in the work: the SNAP-IY scale to assess the severity of the disease; the Strengths and Difficulties Questionnaire (SCT), a form for parents to assess emotional and behavioral impairments; Spielberger's self-assessment test in the processing of Khanin to assess the level of anxiety; spectral analysis of the EEG with the construction of graphical power spectra and registration of evoked potentials (EP) with the performance of an attention test in the Go/No-Go paradigm. RESULTS: The results of the study showed the presence of emotional and behavioral disorders in children with ADHD, more pronounced in the combined form of the disease. Complaints of emotional lability, tearfulness, irritability were noted in 53 children with ADHD in the study group (61.6%). At the same time, these complaints were registered in 39 children from the first group (72.2%) and 14 children from the second group (43.8%). The level of inattention was approximately the same (3.21±0.64 and 3.43±0.56, respectively), while the level of hyperactivity and impulsivity in adolescents from the first group was significantly higher (3.18±0.54, p<0.01). Indicators of the SCT scale, as a total indicator (3.4±1.6, p<0.01), and on the scales of «behavior problems¼ (7.4±1.6, p<0.01), «emotional problems¼ (8.0±1.6, p<0.01), «problems with peers¼ (7.6±1.3, p<0.01), «prosocial behavior¼ (3.4±1.6, p<0.01) were significantly higher in the subgroup of children from the first group. The performed statistical analysis of the test data for attention in the Go/No-Go paradigm revealed significant differences (p<0.01) in the number of omissions of significant pairs of stimuli between healthy children and a subgroup with ADHD with a predominance of inattention, between healthy children and a subgroup with combined form ADHD. When comparing evoked EEG synchronization in the theta range under Go conditions, we found a significant decrease in this parameter in the range of 200-400 ms in the subgroup of children with ADHD with a predominance of inattention and in the subgroup of ADHD with a combined form; under No-Go conditions, a significant decrease in the magnitude of evoked EEG synchronization was revealed in a subgroup of children with combined form ADHD. CONCLUSION: In general, the results of this study allow us to conclude that impaired cognitive control has a large impact on the development of emotional disorders in children with ADHD.

Ensuring Viral Safety of Equine Immunoglobulins during Production.

Equine blood plasma/serum and intermediates must be monitored for the presence of live viruses pathogenic in humans during production of equine immunoglobulins. Information concerning low-cost and simple methods for the detection of live horse viruses pathogenic and non-pathogenic to humans was gained using data of modern domestic and foreign literature. These methods are based on cultivation of these viruses on sensitive biosystems. The presented information can be used to set up blood plasma/serum control of horses at different stages of immunoglobulin production, i.e., when taking blood from horses during their quarantine period, when collecting blood from immunized horses, and before bottling the medicinal intermediate in the primary package.

[A systematic review of radiotherapy for primary renal cell carcinoma].

Renal cell cancer accounts for 2% of all cancers. The gold standard for managing patients with no evidence of distant metastasis renal cell cancer remains is complete surgical resection. The clinical data investigating preoperative radiotherapy failed to reveal benefited from this methods. The role of routine postoperative radiotherapy in the management of renal cell cancer is not established in patients with localized disease after complete surgical resection. Renal cell cancer is radioresistant tumor for conventional radiation therapy. Although renal cell carcinoma is related to radioresistant tumors, in recent years new promising directions in radiation therapy have become apparent. To overcome the radioresistance of renal cell carcinoma, the use of modified radiation therapy regimens with high doses per fraction is justified. new technologies of radiation therapy, which include stereotactic radiation therapy allows to accurately deliver doses of ionizing radiation to a tumor, without the risk of damage to neighboring tissues and organs. Recent data showing that with the use of high-precision methods, such as SBRT, unresectable local renal cell carcinoma can successfully be treated with durable local control and low toxicity. Nonetheless, prospective, randomized trials and omparative effectiveness studies are needed to further evaluate this ablative modality in the treatment of renal cell carcinoma.

Comparison of the Effectiveness of Transepidemal and Intradermal Immunization of Mice with the Vacinia Virus.

The spread of the monkeypox virus infection among humans in many countries outside of Africa, which started in 2022, is now drawing the attention of the medical and scientific communities to the fact that immunization against this infection is sorely needed. According to current guidelines, immunization of people with the first-generation smallpox vaccine based on the vaccinia virus (VACV) LIVP strain, which is licensed in Russia, should be performed via transepidermal inoculation (skin scarification, s.s.). However, the long past experience of using this vaccination technique suggests that it does not ensure virus inoculation into patients' skin with enough reliability. The procedure of intradermal (i.d.) injection of a vaccine can be an alternative to s.s. inoculation. The effectiveness of i.d. vaccination can depend on the virus injection site on the body. Therefore, the aim of this study was to compare the development of the humoral and cellular immune responses in BALB/c mice immunized with the LIVP VACV strain, which was administered either by s.s. inoculation or i.d. injection into the same tail region of the animal. A virus dose of 105 pfu was used in both cases. ELISA of serum samples revealed no significant difference in the dynamics and level of production of VACV-specific IgM and IgG after i.d. or s.s. vaccination. A ELISpot analysis of splenocytes from the vaccinated mice showed that i.d. administration of VACV LIVP to mice induces a significantly greater T-cell immune response compared to s.s. inoculation. In order to assess the protective potency, on day 45 post immunization, mice were intranasally infected with lethal doses of either the cowpox virus (CPXV) or the ectromelia virus (ECTV), which is evolutionarily distant from the VACV and CPXV. Both vaccination techniques ensured complete protection of mice against infection with the CPXV. However, when mice were infected with a highly virulent strain of ECTV, 50% survived in the i.d. immunized group, whereas only 17% survived in the s.s. immunized group. It appears, therefore, that i.d. injection of the VACV can elicit a more potent protective immunity against orthopoxviruses compared to the conventional s.s. technique.

[SCREENING ASSESSMENT OF MATERIALS THROMBOGENICITY BY THE NUMBER OF PLATELETS ADHERED FROM THE FLOWING NATIVE BLOOD].

The materials used in the construction of implants contacting with blood should be resistant to thrombus formation. One of the stages of a thrombogenicity assessment of materials is to determine the number of platelets adhered to its surface during the exposure to flowing blood under ex viAvo conditions. The aim of this study was to develop a modified test for screening assessment of materials for their thrombogenicity in contact with native blood. For the purpose of the study, flow chambers of were developed, allowing to mountain simultaneously 16 material samples. The chamber was connected to the circulatory system of the experimental animal through arterial and venous ports in such a way that blood, passing through the chamber, returned to the animal. The exposure time was 1 min. After perfusion the samples were rinsed and stained. The number of platelets adhered per unit area was calculated automatically that allowed significant error diminution. A total of 9 experiments were carried out on pigs under ex vivo conditions. The method was validated using standard samples of pyrolytic carbon, VT-6 titanium, glass, and polytetrafluorethylene as reference materials. New materials for synthetic vascular prostheses have been investigated. The developed technique makes it possible to study the thrombogenicity of polymeric materials with sufficient reliability.

[Mutations in the A34R gene increase the immunogenicity of vaccinia virus]. / Мутации в гене A34R, приводящие к увеличению иммуногенности вируса осповакцины.

Vaccination is the most simple and reliable approach of protection to virus infections. The most effective agents are live vaccines, usually low-virulence organisms for humans and closely related to pathogenic viruses or attenuated as a result of mutations/deletions in the genome of pathogenic virus. Smallpox vaccination with live vaccinia virus (VACV) closely related to smallpox virus played a key role in the success of the global smallpox eradication program carried out under the World Health Organization auspices. As a result of the WHO decision as of 1980 to stop smallpox vaccination, humankind has lost immunity not only to smallpox, but also to other zoonotic, orthopoxviruscaused human infections. This new situation allows orthopoxviruses to circulate in the human population and, as a consequence, to alter several established concepts of the ecology and range of sensitive hosts for various orthopoxvirus species. Classic VACV-based live vaccine for vaccination against orthopoxvirus infections is out of the question, because it can cause severe side effects. Therefore, the development of new safe vaccines against orthopoxviral infections of humans and animals is an important problem. VACV attenuation by modern approaches carried out by targeted inactivation of certain virus genes and usually leads to a decrease in the effectiveness of VACV in vivo propagation. As a result, it can cause a diminishing of the immune response after administration of attenuated virus to patients at standard doses. The gene for thymidine kinase is frequently used for insertion/inactivation of foreign genes and it causes virus attenuation. In this research, the effect of the introduction of two point mutations into the A34R gene of attenuated strain LIVP-GFP (ТК-), which increase the yield of extracellular enveloped virions (EEV), on the pathogenicity and immunogenicity of VACV LIVP-GFP-A34R administered intranasally to laboratory mice were studied. It was shown that increase in EEV production by recombinant strain VACV LIVP-GFP-A34R does not change the attenuated phenotype characteristic of the parental strain LIVP-GFP, but causes a significantly larger production of VACV-specific antibodies.