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Pregnancy rate is the main factor influencing the productivity and economic efficiency of animal farming. Transfer of bovine cattle embryos is currently one of the most promising methods of overcoming the problem in the reproduction sphere. That is why the objective of our research was to identify progesterone concentration in blood serum and size of the corpus luteum in the cows on the day of embryo transfer in order to improve the strategy of selecting recipient animals, and, as a result, increase the conception rate. All animals admitted to the experiment were divided into three groups based on concentration of progesterone in the blood serum, being 5 ng/cm3 in the third group. Progesterone concentrations in the blood serum and sizes of corpora lutea were determined on the day of embryo transfer (7th day after estrus). The animal was considered pregnant according to a positive result of ultrasound examination. Based on the study results, we concluded that measuring the progesterone content in the blood serum and the size of the corpus luteum are not interchangeable. We found that sizes of corpora lutea did not correlate with concentrations of progesterone in the blood serum of the experimental recipient cows. However, the size of the corpus luteum was of significant predictive value for pregnancy rate. We saw that decrease in its diameter below 15 mm, even against the background of high progesterone concentration, was a negative criterion for selection of the recipient animals. Optimal progesterone concentration in blood serum of the experimental animals was within 2.5–5.0 ng/cm3, leading to the highest pregnancy rate in the groups – 46.7. The hormone parameter outside the indicated range led to a significant decline in the pregnancy rate in the recipient animals. Therefore, when selecting recipient cows prior to transfer, both progesterone concentration in the blood serum and the diameter of the corpus luteum should be taken into account, which should not be beyond the proposed ranges. The data presented and analyzed in the article can help improve the efficiency of transfer of bovine cattle embryos for scientific and industrial purposes.

Mastitis is considered the most common and problematic disease, resulting in significant economic losses due to reduced milk yields, reduced quantity and quality of milk, treatment costs, and premature culling of animals. One of the traditional methods of treating mastitis in cows is using antibiotics, which leads to the emergence of polyresistant strains of microorganisms, the so-called Superbugs. The emergence of Superbugs, which are not sensitive to most existing antibiotics, is a major concern in veterinary and humane medicine. This study aimed to identify pathogens isolated from the secretion of the mammary gland of cows with mastitis to determine their spread and sensitivity to antibiotics. The samples of secretion from the udder were examined by bacteriological method. The isolates were identified by conventional methods and by the modern method – mass spectrometry (MALDI-TOF MS). The sensitivity of the bacterial isolates to antibiotics was determined by the disc diffusion method (Kirby-Bauer). The results of studies of cow mammary gland secretion samples indicate that 49.2% of the isolates are contagious, and 50.8% are environmental ones. The most common among the isolates of mastitis-causing pathogens were Streptoccocus аgalactiae – 16.9%, Streptococcus uberis – 10.9%, Staphylococcus aureus – 10.7%, E. Coli – 9.6%, Corynebacterium bovis – 7.3%, Staphylococcus haemolyticus – 4.8%, Staphylococcus chromogenes – 3.6%, Streptococcus dysgalactiae – 3.4%. Mastitis is caused by algae and yeast – 1% of all detected pathogens, respectively. According to the results of the determination of the sensitivity of isolates of mastitis-causing pathogens to antibiotics, it was found that most isolates were sensitive to Amoxicillin, Ceftiofur, and Rifampicin, and least of them – to Neomycin, Tylosin, Tilmicosin, Bacitracin.

In the conditions of war, economic, social, cultural and artistic institutions should promote the Ukrainian strategic narrative through the so-called "soft power", project activities, economic proposals, as this means strengthening the national identification of civil society, which is so important in the context of national liberation struggle. In fact, the demand for the experience economy can activate the cognitive factor that produces patriotic, socially significant values, feelings and emotions. Therefore, the subject of the study is the effective communication proposals of the impression economy in the context of civil society development. The purpose of the research is to analyse a package of economic proposals and strategies for achieving the progress of economic value, i.e., the implementation of the concept of experience economy, which in the context of war becomes a means of effective communication in the context of the request of responsible business of civil society to actualise the value of national economic identification. The research methodology is based on a combination of systemic and value-based approaches, discourse analysis, which help to reveal the drama and strategies of Ukrainian experience economy cases, their correlation with the specifics of civil society's demands at the national level and the identification of proposals in the context of war; synchronous method (focusing on the conditions of the full-scale Russian invasion of Ukraine) and the use of the monitoring software Similarweb, which allowed to track the recognition of certain projects among customers and the phases of "dramatic development" of the economic offer. The article highlights that, according to J. B. Pine II and J. G. Gilmore, impression is the fourth economic proposition, a new economic value that cannot be compared to a service, because it is achieved through the organisation's cognitive space, through the customer's interest in emotional, physical, intellectual and spiritual dimensions, "effective management of impressions", where efficiency is achieved by "hitting" the intersection of four spheres of impressions – cognitive, aesthetic, entertaining and escapist. According to J. B. Pine II and J. G. Gilmore, the leading role in generating the progression of the economic value of business is played by the understanding of business as theatre (dynamic or stable), unfolding through drama (=strategy), script (=processes), theatre (=work techniques), performance (=proposal), which always has a context (within the limits of intelligence – national identification, patriotic), value markers (support for civil society in war conditions) and a field of interpretation. Thus, the conclusion of the research is the thesis about the evolution from the experience economy to the transformation economy, when the transformation of a customer or company is the ultimate economic offer of the initiator: in the case of the Silpo chain, thanks to the effective communication channels involved, there is such a concept of offer as change, which is a transformation that leads to the so-called "economic pyramid". The educational project "Instoryky" is about prominent historical figures, cases of psychological support for clients through the hotline, engaging clients in the practice of donation through hashtag activism and offers to support animals in wartime in exchange for "psychological support from animals" on the hotline, and educational activities for war veterans. The involvement of food entrepreneurs and their subsequent support through the special project "Lavka tradytsii" is also a good example of effective communication channels.

Intracytoplasmic spermatozoid injection (ICSI) is one of the commonest methods used in assisted reproductive technologies in human medicine. However, this procedure has low efficacy for bovines, mainly because of insufficient activation of oocytes after spermatozoid microinjection. One of the most effective methods of activating oocytes is considered to be the use of phosphorus calcium, though the optimal concentration of activator and its effect on pre-implant development of embyo are still open questions. An oocyte-cumulus complex of clinically healthy cows, retrieved from the ovaries during slaughter, matured over 22–24 h in in vitro conditions. Oocytes with visible polar body had been subjected to intracytoplasmic spermatozoid injection (ICSI), and were 15–30 min later activated in the environment with different concentrations of calcium ionophore for 15–20 min and then transferred for further cultivation in a culture medium with sodium pyruvate. The fertilization rate was identified on the second day at the 2–4th stages of cellular embryo, and the quality of obtained embyos was evaluated on day 8. Based on the statistical analysis of the data, we determined that the artificial activation of bovine oocytes using calcium ionphore after intracytoplasmic spermatozoid injection (ICSI) led to statistically significant improvement in conception and ratio of blastocytes obtained to oocytes injected. In the study, we confirmed that addition of 5, 10 and 50 µМ of the agent had the same efficacy on the activation of occytes of bovine cattle. However, it has to be noted that during further cultivation of the obtained zygotes up to the blastocyte stage (day 8), we saw no significant differences in quality of embryos obtained. Therefore, use of calcium ionophore for the activation of bovine oocytes after intracytoplasmic spermatozoid injection is effective, for it promotes increase in fertilization parameters and ratio of blastocytes obtained to oocytes injected, facilitating production of higher numbers of embyos suitable for transplantation or cooling. Our previous conclusions are valuable for increasing the efficacy of methods of intracytoplasmic injection of bovine spermatozoid and its further use for purposes of science and production.

There are many studies on the improvement of the conditions for cultivating bovine embryos in vitro. However, the issue of co-cultivation of platelets and cow embryos is understudied, although platelet activation leads to the release of a considerable amount of biologically active substances into the culture medium and their co-cultivation with embryos can positively affect the growth and development of the latter. Therefore, the purpose of this study was to investigate the effect of different platelet concentrations in the in vitro culture system on the development of cow embryos. Fertilized zygotes (total number 180) were divided into 5 groups: Group 1 – culture medium without platelet addition (control); Group 2 – medium for cultivation with the addition of 10×106 platelets/cm3 ; Group 3 – final concentration in the system is 20×106 platelets/cm3 ; Group 4 – 50×106 platelets/cm3 ; Group 5 – 100×106 platelets/cm3 . According to the results, it was found that co-cultivation of embryos with platelets in the in vitro system is effective. Thus, a correlation was found between improved embryo development indicators and an increase in platelet concentration. The optimal platelet concentration was 50×106 /cm3 , which allowed obtaining a 13.9% higher level of blastulation, 15.7% higher average embryo size, and 2.5% higher average number of cells in the blastocyst compared to the control. At the same time, the platelet concentration of 100×106 /cm3 led to a significant decrease in the indicators under study, compared with the group without platelets. Therefore, co-cultivation of cow embryos with platelets is advisable since it allows improving the development indicators of cow embryos. The data analysed and presented in this paper will increase the efficiency of cultivation of bovine embryos for both scientific and industrial purposes

According to the International Embryo Technology Society, the number of bovine embryos produced by in vitro fertilization technology is increasing every year. However, despite the large volumes of their production, the effectiveness of this method is still low and needs to be improved. Therefore, the purpose of this study was to compare the effectiveness of two commercial media – Origio Sequential Series (Origio, Denmark) and a panel of products manufactured by Minitube (Germany) in terms of oocyte maturation and development of bovine embryos in vitro. At the first stage of the study, a comparative evaluation of oocyte maturation media was performed: based on TCM 199 (Minitube) and Universal (Origio) culture media. At the second stage, the protocols for culturing bovine embryos were compared: Minitube and the two-stage Origio culture protocol with changing media. Therewith, it was found that the use of TCM 199 medium for oocyte maturation is more effective compared to Universal. Thus, at 48 hours of cultivation (the initial stage of embryo development), 64.3 ± 1.0 and 60.3 ± 1.4% of 2-8 cell embryos were obtained, and on Day 8 – 25.3 ± 1.0 and 20.0 ± 0.6% of blastocysts, respectively. The results of a comparison of bovine embryo culture protocols showed that when using both Minitube and Origio media, the percentage of division and the percentage of resulting embryos corresponded to their known values. It was found that the Minitube cultivation protocol is more effective than Origio. At 48 hours, the number of embryos obtained using the Minitube culture protocol was 1.3% higher compared to Origio, on Day 6 – by 7.8%, and on Day 8 – by 3.8%. The results obtained are a necessary component of the development of successful processes to produce bovine embryos in vitro with further implementation in the ruminant reproduction biotechnology

Producing embryos in vitro is an important technology used to improve the genetic potential of cattle and perfect the programs of their breeding. Regardless of the way they are produced, all embryos that had not been used for transplantation to recipients must be conserved. Because of significantly increased interest in the problem of cryoconservation of embryos, both coming from scientists and businesses, there are emerging new commercial environments that allow the facilitation of cryoconservation and the increase in the embryo survival. Oocyte-cumulus complexes obtained from the ovaries of slaughtered clinically healthy cows matured in 22–24 h in in vitro conditions. The oocytes were co-cultured with spermatozoids in Fertilization medium, and the obtained zygotes were cultured in Culture medium with Sodium-Pyruvate for 4 or 7 days up to the stage of morula or blastocyste, respectively. For the vitrification of cow embryos, we used a commercial kit for the vitrification of human embryos, having compared the duration of equilibration. According to the results of the studies, we observed high efficiency of cryoconservation of cow embryos using the commercial kit for vitrification of human embryos. The results revealed the significant effect of equilibration on survival and further development of embryos. In addition, we described the dependence of development stage of cattle embryo on the duration of the contact of embryo with equilibration solution. Therefore, optimal time of contact of cattle embryos at the morula stage with equilibration solution was 12 minutes. On the 24th h after thawing, 46.7 ± 3.3% of the embryos were observed to undergo blastulation, and on 48th h, this parameter increased to 96.7 ± 3.3%, which corresponded to the parameters in the group of embryos that had not been subjected to cryoconservation. In the conditions of further cultivation, the percentage of blastocystes that hatched in the experimental group was no different from that of the control. At the same time, the highest efficiency of vitrification of blastocystes of cows was seen after the contact with the equilibration solution for 15 min, since the percentage of hatched blastocystes was the same as in the control group. Therefore, using the commercial kit for vitrification of human embryos is beneficial, for it promotes the parameters of cow embryos after vitrification/thawing that are similar to such of intact embryos (without freezing). The data we analyzed and presented in the paper could help to increase the efficiency of cryoconservation of cattle embryos for both scientific and commercial purposes.

In a period of crisis – namely, a pandemic and martial law – the economy is transforming into a system where the main driving forces are the exchange of knowledge, its mutual evaluation, where creativity and creative industries play a significant role, which ultimately form the creative economy, which economist and sociologist Richard Florida called "the new economic era of the 21st century". The purpose of the scientific work is to analyze the tools of Ukrainian creative industries that contribute to the production of a new cultural product or service, have a semantic load, are a resource for strategic communications and increase the potential of the creative economy in martial law (on the examples of successful Ukrainian cases of creative industries in the crisis period). The methodology of the study is based on a combination of systemic and value-based approaches, as well as discourse analysis, which together contribute to the disclosure of structural relationships in the ecosystem of the creative economy (in particular, social capital, entrepreneurial culture, state and international support, innovation potential, reputational capital of Ukraine in the world), their correlations with the peculiarities of national political and economic development and global trends, in particular in times of crisis, such as pandemic and wartime. The scientific work traces the genesis of the formation of a conceptual understanding of the creative economy and creative industries in the Ukrainian dimension, which contains legislative (Order of the Cabinet of Ministers of Ukraine No. 265-r "On Approval of Economic Activities Related to Creative Industries", the Law of Ukraine "On Amendments to the Tax Code of Ukraine and Other Laws of Ukraine on State Support of Culture, Small Business and Creative Industries in Connection with the Implementation of Measures Aimed at Preventing the Occurrence and Spread of Coronavirus Disease (COVID-19)", etc.), terminology (the meaning of the concepts of "creative product", "creative industries", "project", "institutional support grant", etc. was clarified), social and institutional (creation of the Public Union "Center for the Development of the Creative Economy", the National Bureau of the EU program "Creative Europe" in Ukraine, the Startup Fund, the Ukrainian Cultural Foundation (UCF), etc. Special attention in the scientific work is paid to the anonymous online survey of the UCF together with the Ministry of Culture and Information Policy of Ukraine of creative entrepreneurs and creative professionals, which was conducted among UCF 2020-2022 applicants on the state of culture and creative industries during the war (June 2022) in order to form a recovery and strengthening plan, which identified the following needs: transparent competition for managerial positions, restructuring of the management vertical of the industry, international educational trainings and exchange programs for artists and managers of the creative sector; co-production and cooperation in international projects; emphasis on cultural factors in the state international policy; strategy of state support, minimization of document circulation. The analysis of successful Ukrainian cases of creative industries allowed to outline the tools for the development of the creative economy in the crisis period: monetization of hobbies, innovative entrepreneurship, business clustering (in particular, the idea of a cluster of creative industries), brand collaboration, craft production, creation of cultural products such as books, grant/fund support and others, on the terms of donation to support the humanitarian and military needs of Ukrainian society. And the recently created podcast "Frontline of Creative Industries" about the success stories of representatives of this industry, who with their projects resist Russian aggression and support the economy and the institution of national identification of Ukraine, opens up prospects for further analysis of such tools as crowdfunding, revitalization, development of creative clusters of Ukrainian business.

Relevance. The production and quality control of any drugs are strictly regulated. In the case of antiviral vaccines, the requirements for their safety and protective activity are getting tougher every year. Vaccine manufacturers face three tasks: ensuring high immunogenicity, safety and availability of the drug. During the development and production of immunobiological drugs, manufacturers must demonstrate sufficient purification from technological impurities to ensure the purity of the drug. Technological impurities directly depend on the technological process and the expression systems used. The Vero cell line has been widely used in the production of various antiviral vaccines for many decades. Thus, the improvement of technological processes for the purification of vaccine preparations from proteins and DNA of Vero cells is still matter of current interest.Aims. Selection of resins and reagents for ion exchange chromatography to reduce the amount of technological impurities in the inactivated polio vaccine production.Materials and Methods. To obtain viral suspensions, producer cultures were infected with poliovirus type 1 (Sabin strain LSc 2ab), type 2 (Sabin strain P712 Ch 2ab), and type 3 (Sabin strain Leon 12a1b). Multiplicity of infection was 0.02 ± 0.01 TCD50/cell. To evaluate the efficiency of ion-exchange chromatography we determined the degree of purification of fractions from ballast proteins, the degree of purification of fractions from residual cellular DNA, and the degree of extraction of the target antigen using specific formulas.Results and discussion. More than 80 experiments have been performed to purify type 1, type 2, and type 3 poliovirus concentrates using various sorbents. In quality control of purified concentrates of type 1, type 2 and type 3 polioviruses, in addition to analysis for total protein, an analysis was performed for the presence of Vero cell proteins.Conclusion. The use of the proposed modifications of purification of concentrates of Sabin strains of poliovirus types 1, 2 and 3 using ion exchange chromatography allows to obtain inactivated viral products that meet the requirements of WHO and the European Pharmacopoeia both in biochemical parameters (the content of host-cell DNA and the content of ballast proteins, including host-cell proteins) and specific activity (D-antigen content). Furthermore, additional purification of vaccines using ion exchange chromatography allows to reduce the content of residual cellular DNA to almost zero, which makes the inactivated polio vaccine the most attractive for its inclusion in various combined vaccines.

On the global scale of the zoonoses problem, leptospirosis is among the five diseases that pose the greatest threat to humankind today. Leptospirosis is a worldwide zoonotic disease caused by pathogenic Leptospira species. In general, leptospirosis has been registered in more than 150 species of mammals. There are about 300 serovars of Leptospira spp. Serovar Hardjo is one of the most common causes of leptospirosis among cattle globally. In cows, the infection can be completely asymptomatic or cause abortions, stillbirths, infertility, and mastitis. The study's relevance is determined by the negative impact on the economy – productivity loss, and high cost of medical-preventive activities. Leptospirosis also affects humans. In this regard, the present study aimed to determine the prevalence of antibodies to Leptospira interrogans serovar Hardjo in tank milk samples from cows selected from farms in different regions of Ukraine. The method of indirect enzyme-multiplied immunoassay was used for this problem to be investigated. We have investigated 114 tank samples from 66 Ukrainian farms, 63.2% positive, and 36.8% negative. It was established that antibodies to the causative agent of leptospirosis were recorded in different regions of Ukraine. It has been established that the largest number of positive samples was from Kyiv and Cherkasy regions. Our study results complement the study results of other authors and indicate the circulation of this causative agent among the cows in Ukraine, as well as being of practical value for diagnosing and controlling leptospirosis among the cattle.

Cell cultures derived from ticks have become a commonly used tool for the isolation and study of tick-borne pathogens and tick biology. The IRE/CTVM19 cell line, originating from embryos of Ixodes ricinus, is one such line. Previously, reovirus-like particles, as well as sequences with similarity to rhabdoviruses and iflaviruses, were detected in the IRE/CTVM19 cell line, suggesting the presence of multiple persisting viruses. Subsequently, the full genome of an IRE/CTVM19-associated rhabdovirus was recovered from a cell culture during the isolation of the Alongshan virus. In the current work, we used high-throughput sequencing to describe a virome of the IRE/CTVM19 cell line. In addition to the previously detected IRE/CTVM19-associated rhabdovirus, two rhabdoviruses were detected: Chimay rhabdovirus and Norway mononegavirus 1. In the follow-up experiments, we were able to detect both positive and negative RNA strands of the IRE/CTVM19-associated rhabdovirus and Norway mononegavirus 1 in the IRE/CTVM19 cells, suggesting their active replication in the cell line. Passaging attempts in cell lines of mammalian origin failed for all three discovered rhabdoviruses.

The use of biotechnological reproduction methods is a relevant issue since the embryo transfer, obtained after stimulating superovulation, can accelerate reproduction and improve the number of cattle. The purpose of the study was to evaluate the effectiveness of various schemes for stimulating superovulation in cows of the Ukrainian black-pock dairy breed. Therewith, the study analysed the ovarian response to the drug “FSH-Super” under different introduction schemes: Step-up (gradual increase in the dose) and Step-down (gradual dose reduction) and recorded the number of embryos suitable for transplantation. Donor cows were administered the drug “Estrofan” to synchronise the sexual cycle. After 7 days, the drug “Ovarelin” was injected, and after another 7 days, the injection of the drug “Estrofan” was repeated in the same dose. Stimulation of superovulation began on the 10th day of the sexual cycle with the drug “FSH-super” in the form of eight gradually increasing (Step-up) and gradually decreasing (Step-down) doses within 4 days. Artificial insemination was performed 12 and 24 hours after the start of oestrus. During the study, it was discovered that in the group of cows with gradual dose reduction of the drug “FSH-Super”, 83.3% reacted with superovulation, and in the group with the gradual increase – only 71.4%. Therewith, the number of yellow bodies on two ovaries in a donor cow averages 15.6 and 9.2, respectively. An average of 12.4 and 7.8 embryos (Step-down and Step-up) were obtained from the donor, of which 7.8 and 4.2 are suitable for transplantation, respectively. However, in the group of cows with gradually decreasing doses, a higher number of embryos unsuitable for transplantation was obtained – 4.6 and unfertilised oocytes – 2.6, compared with the group of donors with gradually increasing doses, where these indicators are 3.6 and 1.0, respectively. Thus, the use of the drug “FSH-super” to donor cows according to the step-down introduction scheme allows getting more embryos suitable for transplantation. This will allow managing the biotechnological aspects of cattle reproduction and effectively and in a controlled manner accelerate the breeding process in farms of various forms of ownership, fixing the desired genotype in the herd

The studies were conducted on 2–3-months-old males of C57BL/6 mice weighing 20–24 g. Obtaining and operating with adipose tissue-derived mesenchymal stem cell (MSC) culture was performed in a sterile laminar box under conditions of asepsis and antiseptics. The adipose tissue-derived MSC of the 2, 4, 7 and 12 passages were analyzed. Morphometric analysis was performed using a light microscopy. Morphometric parameters such as cell and nucleus area or nuclear-cytoplasmic ratio were calculated using the Axiovision light microscope (Carl Zeiss, Germany) and Image J 1.45 software. Trypan blue dye used for investigation of the viability of MSC. The morphological characteristics of adipose tissue-derived MSC during the process of cultivation changes: at the first passages of cultivation, the cells are spindle-shaped with two, at least three, long cytoplasmic processes, which are located bipolar. Near the nucleus, the Golgi complex is clearly visible – a sign of active cells. At later passages, cells have a small cytoplasmic processes and the bipolar arrangement of processes changes by stellar arrangement. Golgi complex is also clearly visualized. The indicator of the nuclearcytoplasmic ratio in MSC from adipose tissue is significantly reduced at the 7th passage to 0.2189 ± 0.0122 (P < 0.01), and at the 12th passage to 0.1111 ± 0.0086 (P < 0.001) compared to the 2nd passage. The coefficient of proliferation of adipose tissue-derived MSC is significantly reduced at 12th passage. The viability of MSC from adipose tissue with an increasing of a number of passages significantly reduces and at the 12th passage of cultivation reaches 84.67 ± 1.36 (P < 0.05). The content of apoptotic cells that exhibited sensitivity to serum-free cultivation significantly increased at the 7th and 12th passages and was 21.33 ± 1.36 (P < 0.05) and 23.67 ± 0.97% (P < 0.05), respectively

We present the results of a randomized, double-blind, placebo-controlled, multi-center clinical trial phase I/II of the tolerability, safety, and immunogenicity of the inactivated whole virion concentrated purified coronavirus vaccine CoviVac in volunteers aged 18–60 and open multi-center comparative phase IIb clinical trial in volunteers aged 60 years and older. The safety of the vaccine was assessed in 400 volunteers in the 18–60 age cohort who received two doses of the vaccine (n = 300) or placebo (n = 100) and in 200 volunteers in 60+ age cohort all of whom received three doses of the vaccine. The studied vaccine has shown good tolerability and safety. No deaths, serious adverse events (AEs), or other significant AEs related to vaccination have been detected. The most common AE in vaccinated participants was pain at the injection site (p < 0.05). Immunogenicity assessment in stage 3 of Phase II was performed on 167 volunteers (122 vaccinated and 45 in Placebo Group) separately for the participants who were anti-SARS-CoV-2 nAB negative (69/122 in Vaccine Group and 28/45 in Placebo Group) or positive (53/122 in Vaccine Group and 17/45 in Placebo Group) at screening. On Day 42 after the 1st vaccination, the seroconversion rate in participants who were seronegative at screening was 86.9%, with the average geometric mean neutralizing antibody (nAB) titer of 1:20. A statistically significant (p < 0.05) increase in IFN-γ production by peptide-stimulated T-cells was observed at Days 14 and 21 after the 1st vaccination. In participants who were seropositive at screening but had nAB titers below 1:256, the rate of fourfold increase in nAB levels was 85.2%, while in the participants with nAB titers > 1:256, the rate of fourfold increase in nAB levels was below 45%; the participants who were seropositive at screening of the 2nd vaccination did not lead to a significant increase in nAB titers. In conclusion, inactivated vaccine CoviVac has shown good tolerability and safety, with over 85% NT seroconversion rates after complete vaccination course in participants who were seronegative at screening in both age groups: 18–60 and 60+. In participants who were seropositive at screening and had nAB titers below 1:256, a single vaccination led to a fourfold increase in nAB levels in 85.2% of cases. These findings indicate that CoviVac can be successfully used both for primary vaccination in a two-dose regimen and for booster vaccination as a single dose in individuals with reduced neutralizing antibody levels.

Mastitis is one of the most common diseases on dairy farms. It causes significant economic damage associated with the cost of treating sick cows, reduced milk yield and quality indicators of dairy products, and the risk of premature culling of animals. Treatment of cows with mastitis on dairy farms is carried out mainly with antimicrobial drugs, which are usually used without a preliminary test to identify the causative agent of the disease and determine its sensitivity to antimicrobial substances, which is an important part of the effectiveness of therapy. Increasing the resistance of bacteria to antimicrobial substances poses a threat not only to the animal but also to humans, as a consumer of dairy products. The availability of data on the sensitivity of mastitis pathogens to antimicrobial drugs makes it possible for veterinary doctors to choose the most effective antibiotic for treating animals with the shortest duration of treatment. The presented results of studies of breast secret samples taken from cows indicate that in 57.5% of cases, contagious pathogens of mastitis were identified. In particular, Streptococcus agalactiae made 24.1%, Staphylococcus aureus – 18.4%, Corynebacterium spp. – 7.2%, Streptococcus dysgalactiae– 5.6%, Streptococcus uberis – 2.2%. Environmental pathogens accounted for 42.5% of the total number of isolated isolates, among which Streptococci represented gram-positive microflora at 11.5 Streptococcuscus spp. (6.2% Streptococcuscus parauberis (4.4% Streptococcuscus Bovis (0.9%) and Staphylococcus spp. – 10.3%. Gram-negative microflora is 20.6%, among which the largest percentage belongs to E. coli – 8.4% and Klebsiella pneumonia – 1.9%. Mastitis caused by yeast accounted for 1.4% of all diagnosed pathogens. Antimicrobial sensitivity was evaluated using the disk diffusion method (Kirby-Bauer). According to the results of determining the sensitivity of mastitis pathogens to antimicrobial substances, it was found that the highest sensitivity of the isolated isolates was to Ceftiofur, Amoxicillin/clavulanic acid, Rifampicin, Amoxicillin, Gentamicin, Ampicillin, Bacitracin, Cephalexin, Cloxacillin, Enrofloxacin, Trimethoprim/sulfamethoxazole, Oxytetracycline, Lincomycin. The least sensitive – to Spiramycin, Tylosin, streptomycin, neomycin, Marbofloxacin, Tilmicosin, and Danofloxacin.

Introduction. Since the development of inactivated polio vaccines, different stages of the production process have been changed and improved. Current production of inactivated polio vaccines based on both wild and attenuated strains includes several technological stages, one of which is the concentration of the virus-containing liquid, which ensures poliovirus concentration, and purification of the virus-containing liquid from a significant part of the ballast components.Research objective is to compare the characteristics of ultrafiltration membranes and select the membranes that provide optimal value of purification and concentration of poliovirus type 1 (Sabin strain).Materials and methods. Laboratory ultrafiltration systems from two manufacturers with 50, 100, and 300 kDa membranes were used for the concentration. Results were evaluated by the content of total protein, which is the main stress for the subsequent purification stages, the value of infectious virus titer in the concentrate, and the content of D-antigen as the target product.Results and discussion. Obtained results demonstrated that the content of the target product (the highest D-antigen content) and purification from impurity proteins (the total protein content in the concentrate) were most optimal when a membrane with a cut-off of 300 kDa was used for concentration. The study also evaluated the real cut-off components by various membranes to determine the composition of the protein load on the target product.Conclusion. In terms of quality of the resulting target product and the manufacturability of the production process, the use of a 300 kDa membrane is the most appropriate when working out the technology for manufacturing inactivated polio vaccine based on Sabin strains of poliovirus and the Vero line as a producing culture.

The studies were conducted on 2–3 months old males of C57BL/6 mice, weighing 20–24 g. Our work aimed at studying the functional state of the organs of the immune system in mice after administration of allogeneic mesenchymal stem cells of adipose tissue origin. Obtaining and cultivating mesenchymal stem cells were carried out in a sterile laminar box with compliance of asepsis and antiseptic conditions. The abdominal adipose tissue from C57BL/6 mice was cultured in a CO2 incubator at 37 °C and 5% CO2 in DMEM with 10–15% of fetal bovine serum, 1% of antibiotic/antimycotic solution (Sigma-Aldrich, USA). The following groups of animals were formed: 1 group – intact (control); 2 group – animals, to whom 0.5 cm3 of 0.9% NaCl solution (placebo) were injected into the caudal vein; 3 group – animals, to whom 104 of allogeneic mesenchymal stem cells from adipose tissue in 0.5 cm3 of phosphate buffer solution were injected into the caudal vein. The weight index, the content of lymphoid cells in the thymus and spleen in C57BL/6 mice were examined on days 7, 18, and 25 after the administration of mesenchymal stem cells. To assess the lymphocyte content in lymphoid organs, they were weighed (whole thymus, 50 mg of spleen), triturated, and filtered through the nylon cloth. After that, the tissue homogenate was applied to Ficoll-Urografin density gradient (d = 1.077) in a ratio of 3:2. The test tubes were centrifuged at 1500 rpm for 30–40 minutes. After centrifugation, plasma and layer of lymphocytes were above the density gradient; lymphocytes were collected by a Pasteur pipette and washed twice with an arbitrary amount of Hank’s solution by centrifugation at 1500 rpm for 10 minutes. After washing, 1 cm3 of Hank’s solution was added to lymphocytes and they were counted in the Goryaev chamber. Calculation of the cellularity of lymphoid organs was performed in 1 mg of tissue. The transplantation of allogeneic adipose-derived mesenchymal stem cells affects the central and peripheral organs of the immune system. Administration of allogeneic adiposederived mesenchymal stem cells causes a significant increase in the content of lymphoid cells in the thymus on days 7, 18, and 25 by 71%, 57, and 53% (P < 0.05), respectively, compared to the control. At the 7 and 18 days of the immune response, lymphoid cell content in the spleen significantly increases by 33% (P < 0.01) and 19% (P < 0.05), respectively, compared to the control under the administration of allogeneic adipose-derived mesenchymal stem cells. On day 25, values of lymphoid cell content and spleen index return to normal. The thymus and spleen weight indices directly correlate with their lymphoid cell content.

BackgroundEffective response to emerging pandemic threats is complicated by the need to develop specific vaccines and other medical products. The availability of broadly specific countermeasures that could be deployed early in the pandemic could significantly alter its course and save countless lives. Live attenuated vaccines (LAVs) were shown to induce non-specific protection against a broad spectrum of off-target pathogens by stimulating innate immune responses. The purpose of this study was to evaluate the effect of immunization with bivalent Oral Poliovirus Vaccine (bOPV) on the incidence of COVID-19 and other acute respiratory infections (ARIs).Methods and FindingsA randomized parallel-group comparative study was conducted in Kirov Medical University. 1115 healthy volunteers aged 18 to 65 were randomized into two equal groups, one of which was immunized orally with a single dose of bOPV “BiVac Polio” and another with placebo. The study participants were monitored for three months for respiratory illnesses including COVID-19. The endpoint was the incidence of acute respiratory infections and laboratory confirmed COVID-19 in both groups during 3 months after immunization. The number of laboratory-confirmed cases of COVID-19 was significantly lower in the vaccinated group than in placebo (25 cases vs. 44, p=0.036). The difference between the overall number of clinically diagnosed respiratory illnesses in the two groups was not statistically significant.ConclusionsImmunization with bOPV reduced the number of laboratory-confirmed COVID-19 cases, consistent with the original hypothesis that LAVs induce non-specific protection against off-target infections. The findings are in line with previous observations of the protective effects of OPV against seasonal influenza and other viral and bacterial pathogens. The absence of a statistically significant effect on the total number of ARIs may be due to the insufficient number of participants and heterogeneous etiology of ARIs. OPV could be used to complement specific coronavirus vaccines, especially in regions of the world where the vaccines are unavailable, and as a stopgap measure for urgent response to future emerging infections. Clinical trial registration number NCT05083039 at clinicaltrals.gov https://clinicaltrials.gov/ct2/show/NCT05083039?term=NCT05083039&draw=2&rank=1

The unprecedented in recent history global COVID-19 pandemic urged the implementation of all existing vaccine platforms to ensure the availability of the vaccines against COVID-19 to every country in the world. Despite the multitude of high-quality papers describing clinical trials of different vaccine products, basic detailed data on general toxicity, reproductive toxicity, immunogenicity, protective efficacy and durability of immune response in animal models are scarce. Here, we developed a β-propiolactone-inactivated whole virion vaccine CoviVac and assessed its safety, protective efficacy, immunogenicity and stability of the immune response in rodents and non-human primates. The vaccine showed no signs of acute/chronic, reproductive, embryo- and fetotoxicity, or teratogenic effects, as well as no allergenic properties in studied animal species. The vaccine induced stable and robust humoral immune response both in form of specific anti-SARS-CoV-2 IgG and NAbs in mice, Syrian hamsters, and common marmosets. The NAb levels did not decrease significantly over the course of one year. The course of two immunizations protected Syrian hamsters from severe pneumonia upon intranasal challenge with the live virus. Robustness of the vaccine manufacturing process was demonstrated as well. These data encouraged further evaluation of CoviVac in clinical trials.

Objectives: The outbreak of coronavirus disease 2019 (COVID-19) started in December 2019 in China and then spread worldwide over the following months, involving 188 countries. The objective of this study was to determine the molecular epidemiology of the COVID-19 outbreak in Russia. Methods: In this study, two severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains were isolated and genetically characterized. A phylogenetic analysis of all available Russian sequences was then performed and these were compared to the epidemiological data on COVID-19 incidence to evaluate the molecular epidemiology and pattern of virus spread in the territory of Russia. Results and conclusions: Whole genome analysis of the isolates obtained in this study and 216 others isolated in Russia revealed a set of seven common mutations when compared to the original Wuhan virus, including amino acid substitutions in spike protein S and nucleoprotein N, possibly affecting their properties. Phylogenetic analysis of all Russian sequences and 8717 sequences from other countries showed multiple importations of the virus into Russia, local circulation, and several patterns of virus spread.

The plants from the Lamiaceae family are traditional remedies of folk and scientific medicine. They are present at the domestic pharmaceutical market as herbal raw material (HRM); dietary supplements; aromatherapy; as well as being included in the composition of drugs for oral use etc. According to the modern direction of international harmonization of conditions for standardizations of herbal drugs, the topical issue is the development of unified methods of HPTLC identification for HRM, including the Lamiaceae family. The aim of the work was the selection of the unified HPTLC chromatographic conditions for identification of chromatographic profiles of flavonoids and hydroxycinnamic acids of HRM of some Lamiaceae species of Ukraine’s flora, presented at domestic pharmaceutical market, such as Sage, Wild Thyme, Thyme, Oregano, Rosemary, Java tea, Peppermint, Lavender, Anise hyssop, Melissa, Hyssop, White horehound, Motherwort; and comparison of their chromatographic fingerprints. As objects of investigation, the HRM of Lamiaceae family presented at the Ukrainian pharmaceutical market were used. The investigation was conducted by HPTLC procedure using an automatic herbal system of CAMAG, Switzerland at the base of CAMAG laboratory, Muttenz, Switzerland and laboratory of ESTCCTI ESIPP, NUPh, Kharkiv, Ukraine. The harmonized chromatographic conditions for determination of flavonoids and hydroxycinnamic acids for HRM of Lamiaceae species were chosen, these were: stationary phase – HPTLC Si 60 F254; mobile phase – ethyl acetate, formic acid anhydrous, water (8:1:1); sample preparation: solvent – methanol; method of extraction – shaking for 10 min; relative humidity: 33%, temperature 22 ± 5 °C; derivatization with Natural product and PEG reagents; detection – 254 nm, 366 nm, white light before derivatization: 366 nm and white light after derivatization. The reproducibility of results in these chromatographic conditions was ∆RF ≤ 0,05. It was established, that for all investigated species of the family the zone corresponding with the position and colour to rosmarinic acid was detected, thus it can be used as standard substance for «Identification», «Limit-test» and for chromatographic system suitability test. For investigated samples of domestic HRM, the specific zones that can be used for setting acceptance criteria of the «Identification» and «Foreign matters» tests were conducted. After validation investigation involving greater numbers of samples of each species from different growing regions of Ukraine, the obtained HPTLC chromatographic fingerprints could be recommended as reference images for quality control of home-grown HRM of Lamiaceae family.

Year 2003 may be considered as the beginning of the study of “stem cells of the adult heart”, when Beltrami A.P. with his colleagues finally confirmed the presence of the latter in the heart. Later, Makkar R.R. and others proved the efficacy of these cells for treatment of myocardial ischemia. However, despite the positive effect of the use of “stem cells of the adult heart” for myocardial ischemia, an obstacle to their global clinical use are the ethical issues and difficulty in obtaining. Given the above, the aim of our work was to determine the optimal method of obtaining stem cells from the myocardium of cat. The experiments on animals were performed in accordance with the requirements of the “General ethical principles for Experiments on Animals” adopted by the first National Congress on bioethics (dated 20.09.04, Kyiv, Ukraine). To obtain heart tissues the frozen fetuses of kittens, that remained after providing the birth assistance, were used (with the consent of the owners). In order to determine the optimal method for obtaining a stem cells culture of the myocardium of cat we compared the explant method and enzymatic treatment methods of tissues using different combinations of enzymes: 2 mg/ml of collagenase (type II); 2 mg/ml of collagenase (type II) supplemented with 5% bovine serum; 1 mg/ml of collagenase (type II), 1 mg/ml of hyaluronidase and 5% BSA; 2.5% of trypsin; 2.5% of trypsin, 0.5 mg/ml of collagenase (type II) and 0.5 mg/ml of hyaluronidase. In order to determine the optimal method for obtaining a cells culture of the myocardium the counting of the number of cells after the formation of monolayer in one of the experimental groups was carried out (day 5 since the beginning of the research). The counting of number of cells was performed in the Gorjaev's chamber under 200 magnification of microscope in all the squares. The most effective method for obtaining the stem cells culture from the myocardium is to use a combination of enzymes 2.5% of trypsin, 0.5 mg/ml of collagenase (type II) and 0.5 mg/ml of hyaluronidase, which allows to obtain 986.0 ± 9.3 thousand cells capable for proliferation with 10 mg of tissue. The least effective was the explant method (without use of enzymes), because the number of cells attached to the cultural plastic of the cells during its use on day 5 of cultivation was amounted 35.7 ± 6.2 thousand. The proposed method is optimal for obtaining the stem cells culture of the myocardium of the cat, which will be used later in our studies in the treatment of diseases of the heart muscle.

Various types of COVID-19 vaccines, including adenovirus, mRNA, and inactivated ones, have been developed and approved for clinical use worldwide. Inactivated vaccines are produced using a proven technology that is widely used for the production of vaccines for the prevention and control of infectious diseases, including influenza and poliomyelitis. The development of inactivated whole-virion vaccines commonly includes several stages: the production of cellular and viral biomass in cell culture; inactivation of the virus; filtration and ultrafiltration; chromatographic purification of the viral antigen; and formulation with stabilizers and adjuvants. In this study, the suitability of four resins for Size-Exclusion Chromatography was investigated for the purification of a viral antigen for the human COVID-19 vaccine.

The research is aimed at developing an algorithm for valuation by credit institution of the credit limit for a natural person-borrower, with regard to his socio-demographic characteristics, using the logistic regression tools. The improvement of the procedure for valuation of the solvency of an individual borrower is to integrate an empirical approach to the definition of solvency (based on the ratio of official income and expenditure of an individual) with the economic and mathematical methods, allowing to consider the available retrospective data of the financial institution about borrowers and to identify statistically significant regularities. The key role in the algorithm of estimation of credit limit is occupied by development of the logit-model for classification of borrowers for classes of «reliable» and «unreliable», the classification force of which will be to a large extent determinative as to the predictive quality of defining the amount of the credit limit. The publication presents an example of application of the logit-model for credit scoring, including quantitative and qualitative variables, with the help of which the socio-demographic characteristics of borrowers are described. The procedure of using the proposed algorithm is illustrated on the basis of such logit-model.

To make future researches of the results of treatment of diabetes possible, it is necessary to create a model of this pathology in experimental animals. It is crucial to trace the correlation between changes in organs when this pathology occurs in clinical cases and when it occurs in experimental cases. Today we have a number of methods used to form alloxan diabetes in animals, but alloxan monohydrate is the most frequently used. Thus, the purpose of our study was to: study microscopic changes in the liver, heart, and kidneys of alloxan diabetes rats. The experimental model of diabetes was reproduced by a 150 mg/kg single-dose subcutaneous administration of alloxan monohydrate in the form of a 5% solution per citrate buffer (pH 4.5). To prove the development of diabetes, blood glucose levels were measured by a Rightest GM500 blood glucose meter on the 20th day after administration of alloxan. There were used animals with medium severity diabetes (fasting glucose test showings 10 to 20 mmol/l). The experimental animals were euthanized by ethereal anesthesia decapitation. Samples of the liver, heart, and kidneys for histological examination were taken on the 20th day after administration of alloxan. Histologic sections were prepared according to the standard method, coloring was made by hematoxylin and eosin and based on Van Gizon method. We have found that on the 20th day after the simulation of alloxan diabetes, the liver showed microscopic signs of hepatitis with dystrophic changes in hepatocytes and intracellular cholestasis. The kidneys showed destruction of all structural components of the glomeruli with subsequent necrosis and dystrophic changes and destruction of the epithelium of the curvy and straight tubules. The heart showed granular degeneration of cardiocytes, in some areas, and distinct swelling between the muscle fibers bundles and inside the muscle fibers bundles, infiltration of the connective tissue stroma by erythrocytes in others. We believe that it is possible to obtain the most optimal spectrum of signs peculiar for type 1 diabetes by administration of alloxan as evidenced by microscopic changes in organs. Further, this model of diabetes will be used to study the influence of cell transplantation upon the development of the disease.

The purpose of the research described in this article is a comparative analysis of the predictive qualities of some models of machine learning and regression. The factors for models are the consumer characteristics of a used car: brand, transmission type, drive type, engine type, mileage, body type, year of manufacture, seller's region in Ukraine, condition of the car, information about accident, average price for analogue in Ukraine, engine volume, quantity of doors, availability of extra equipment, quantity of passenger’s seats, the first registration of a car, car was driven from abroad or not. Qualitative variables has been encoded as binary variables or by mean target encoding. The information about more than 200 thousand cars have been used for modeling. All models have been evaluated in the Python Software using Sklearn, Catboost, StatModels and Keras libraries. The following regression models and machine learning models were considered in the course of the study: linear regression; polynomial regression; decision tree; neural network; models based on "k-nearest neighbors", "random forest", "gradient boosting" algorithms; ensemble of models. The article presents the best in terms of quality (according to the criteria R2, MAE, MAD, MAPE) options from each class of models. It has been found that the best way to predict the price of a passenger car is through non-linear models. The results of the modeling show that the dependence between the price of a car and its characteristics is best described by the ensemble of models, which includes a neural network, models using "random forest" and "gradient boosting" algorithms. The ensemble of models showed an average relative approximation error of 11.2% and an average relative forecast error of 14.34%. All nonlinear models for car price have approximately the same predictive qualities (the difference between the MAPE within 2%) in this research.

Global polio eradication requires both safe and effective vaccines, and safe production processes. Sabin oral poliomyelitis vaccine (OPV) strains can evolve to virulent viruses and result in poliomyelitis outbreaks, and conventional inactivated poliomyelitis vaccine (Salk-IPV) production includes accumulation of large stocks of neurovirulent wild polioviruses. Therefore, IPV based on attenuated OPV strains seems a viable option. To increase the global supply of affordable inactivated vaccine in the still not-polio free world we developed an IPV made from the Sabin strains–PoliovacSin. Clinical trials included participants 18–60 years of age. A phase I single-center, randomized, double-blind placebo-controlled clinical trial included 60 participants, who received one dose of PoliovacSin or Placebo. A phase II multicenter, randomized, double-blind, comparative clinical trial included 200 participants, who received one dose of PoliovacSin or Imovax Polio. All vaccinations were well tolerated, and PoliovacSin had a comparable safety profile to the Placebo or the reference Imovax Polio preparations. A significant increase in neutralizing antibody levels to polioviruses types 1–3 (Sabin and wild) was observed in PoliovacSin and Imovax Polio vaccinated groups. Therefore, clinical trials confirmed good tolerability, low reactogenicity, and high safety profile of the PoliovacSin and its pronounced immunogenic properties. The preparation was approved for clinical trials involving infants.