Biotech Ltd Research Articles

DETERMINATION OF IL-1β mRNA GENE EXPRESSION AND HMGB-1 mRNA GENE EXPRESSION IN WOMEN WITH GENITAL ENDOMETRIOSIS ASSOCIATED WITH INFERTILITY AT THE STAGE OF PREPARATION FOR ASSISTED REPRODUCTIVE TECHNOLOGIES

Despite the large number of studies on the identification and search for noninvasive early diagnostic markers of genital endometriosis, this problem remains relevant today. It is important to introduce early diagnosis of genital endometriosis for the purpose of timely prevention and treatment.Objective: to study the expression levels of IL-1β and HMGB-1 mRNA genes in women with genital endometriosis associated with infertility, and to evaluate the effect of our proposed preparation for assisted reproductive technologies on the level of IL-1β and HMGB-1 mRNA gene expression.Material and methods. To analyze gene expression IL-1β and HMGB-1 and determine relative normalized mRNA expression IL-1β and HMGB-1, the polymerase chain reaction method was used with real-time reverse transcription(RT-PCR. The object of molecular genetic studies using the RT-PCR method was the fraction of mononuclear cells isolated from the whole blood of patients with endometriosis. In this study, we performed a retrospective analysis of the medical records of 30 women with infertility undergoing an assisted reproductive technology program. The main group consisted of 20 women diagnosed with external genital endometriosis who underwent assisted reproductive technologies. Women in the main group, in addition to standard training for assisted reproductive technologies, received a probiotic containing Lactobacilli 1010 manufactured by Unic Biotech Ltd, India. They took one pill twice a day for one month as part of a general treatment before undergoing assisted reproductive technologies. We determined the expression level of IL-1β and HMGB-1 before and after this preparation stage. The control group consisted of 10 women who had tubal infertility due to a previous inflammatory disease, but according to the results of a comprehensive clinical and laboratory examination, they were compared to healthy women. These women, aged 21 to 42 years, with a mean age of 29,75 years, did not receive our proposed preparation with the inclusion of a probiotic. This study was conducted at the Bukovyna State Medical University and the clinic "Yuzko medical center".Results. In the main group, the IL-1β mRNA gene expression level before training was (26,7877±0,01), which was significantly higher than the level after training (0,1610±0,01*). Consequently, the use of the probiotic led to a dramatic reduction in elevated mesothelin levels, underscoring its efficacy and potential application in assisted reproductive technology training programs. Also, a high level of expression of mRNA genes can be noted HMGB-1in whole blood of women of the main group before preparation for assisted reproductive technologies (table 2). Expression level of mRNA genes HMGB-1in whole blood of women of the main group before preparation for assisted reproductive technologies was (11,9198±0,01). After our proposed preparation for assisted reproductive technologies with the inclusion of a probiotic, the mRNA gene expression level HMGB-1in the whole blood of women of the main group was (0,2821±0,01*). Therefore, our proposed preparation for assisted reproductive technologies with the inclusion of a probiotic is quite effective, since the expression levels of IL-1β mRNA genes and HMGB-1sharply decreased.Conclusions. Extremely high expression of mRNA genes IL-1β and HMGB-1 indicates a close connection between the pathogenesis of endometriosis and inflammation. The inclusion of probiotics in the complex scheme of preparation for assisted reproductive technologies leads to a noticeable improvement in the well-being of the patient and a significant decrease in the expression of IL-1β and HMGB-1 mRNA genes. Therefore, we recommend our proposed preparation for assisted reproductive technologies with the inclusion of a probiotic.

Probiotics and NLRP3 mRNA inflammasome levels in women with endometriosis-related infertility undergoing assisted reproductive technologies.

This research was conducted at Bukovinian State Medical University and the Centre of Reproductive Medicine and included a total of 30 infertile women. The control group consisted of 10 women with tubal infertility resulting from a prior history of inflammation, who, following a comprehensive clinical and laboratory assessment, exhibited no other underlying health conditions and could be regarded as essentially healthy individuals. Participants in the control group ranged from 21 to 42 years, with an average age of 29.75 years. The control group did not receive the probiotic Femina Probiz. The main group, on the other hand, included 20 women diagnosed with external genital endometriosis who were undergoing assisted reproductive technologies. These patients were administered the probiotic Femina Probiz manufactured by Unic Biotech Ltd in India. They were instructed to take one tablet containing 10×10^9 Lactobacillus organisms twice daily for one month as part of their preparatory treatment before proceeding with assisted reproductive technologies. The levels of NLRP3 inflammasome were measured before and after this preparatory phase. The incidence of primary infertility was significantly higher in patients belonging to the main group.

INFLUENCE OF PROBIOTICS ON THE MESOTHELIN LEVEL IN WOMEN WITH ENDOMETRIOSIS ASSOCIATED WITH INFERTILITY IN COMPLEX PREPARATION FOR ASSISTED REPRODUCTIVE TECHNOLOGIES.

The aim: To study the determination of Mesothelin level in women with endometriosis associated with infertility and estimate influence of probiotic on endometriosis according of Mesothelin level in complex preparation before assisted reproductive technologies. Materials and methods: In this study, we conducted a retrospective analysis of the medical records of 40 infertile women who underwent assisted reproductive technologies while also using the probiotic "Femina Probiz." We divided the participants into two groups. The control group comprised 11 women who had tubal infertility due to a previous inflammatory condition but were otherwise found to be in good health through comprehensive clinical and laboratory assessments. These women, aged between 21 and 42 with an average age of 29.75 years, did not use the probiotic "Femina Probiz." The main group consisted of 29 women diagnosed with external genital endometriosis who were undergoing assisted reproductive technologies. Women in the main group received the probiotic "Femina Probiz" from Unic Biotech Ltd, India. They took one tablet twice a day for one month as part of their overall treatment before undergoing assisted reproductive technologies. We measured the Mesothelin levels before and after this preparation phase. This study was conducted at Bukovinian State Medical University and Centre of Reproductive Medicine. It's worth noting that the primary infertility incidence was significantly higher in the main group of patients. Results: In the main group, we observed that the Mesothelin level was 0.73±0.01, which was significantly higher than the post-preparation level (0.59±0.01). In contrast, the control group had a Mesothelin level of 0.49±0.01. Interestingly, we noted that the Mesothelin level in patients increased approximately twofold before preparation compared to those who had undergone preparation. This suggests that the use of the probiotic led to a sharp reduction in the elevated Mesothelin levels. Consequently, the significant decrease in Mesothelin levels after using the probiotic indicates its effectiveness and potential utility in the preparation phase of assisted reproductive technologies programs. Conclusions: The elevated Mesothelin levels indicate a strong association between the pathogenesis of endometriosis and inflammation, as well as damage to the peritoneum. The incorporation of a probiotic as part of a comprehensive preparation regimen prior to assisted reproductive technologies notably enhances the overall health of patients and leads to a reduction in Mesothelin levels. Based on our findings, we highly recommend the inclusion of this probiotic preparation in clinical practice.

A NEW APPROACH TO ASSISTED REPRODUCTIVE TECHNOLOGIES PREPARATION IN WOMEN WITH ENDOMETRIOSIS ASSOCIATED INFERTILITY USING PROBIOTICS.

Aim: To examine the expression Nlrp3-inflammasome in the blood of women with endometriosis-associated infertility using assisted reproductive technologies with included probiotic and estimate a new approach with included probiotic for preparation to assisted reproductive technologies. Materials and methods: For the purpose of the research we examined 30 infertile women. Control group consisted of 10 women with tubal infertility due to an inflammatory process in the anamnesis, in whom, as a result of a complex clinical and laboratory examination, no other diseases were detected and in terms of their health they could be equated with practically healthy women (age from 21 to 42 years, the average age was 29.75 years) and who did not take probiotic. The main group consists from 20 women with external genital endometriosis were included in assisted reproductive technologies. Patients from main group took probiotic produced by Unic Biotech Ltd, India. 1 tablet twice a day with 10×109 Lactobacillus during 1 month in complex preparation (treatment) before assisted reproductive technologies. The indices of Nlrp3 - Inflammasome determined before and after preparation. The study was performer in Bukovinian State Medical University and Centre of Reproductive Medicine. To analyze the expression of the NLPP3-inflammasome gene and determine the relative normalized expression of NLPP3 mRNA, we used the polymerase chain reaction with reverse transcription in real time (RT-PCR). The object for molecular genetic studies by the RT-PCR method was the fraction of mononuclear cells isolated from the whole blood of patients with endometriosis. The value of p (authenticity difference) was determined by Student's table-Fischer. Differences between contrasting averages were considered significant at p <0.05. Results: Analized the results of our research stated that in main group expression of Nlrp-3 inflammasome was 24,43, which is significantly higher than after preparation (0,70 accordingly). In control group expression of Nlrp3-inflammasome was 0,54. Expression of Nlrp-3 inflammasome increased in patients before preparation more than 34 times compare with patients after preparation accordingly. Conclusions: consequently, after using probiotic, the increased level of Nlrp3-inflammasome sharply decreases, indicating the effectiveness and the possibility of use in the programme for assisted reproductive technologies preparation.

CONTENT OF MOBILE PHOSPHORUS COMPOUNDS UNDER DIFFERENT METHODS AND RATES OF FERTILIZER APPLICATION DURING THE PERIOD OF THEIR ACTIVE CONSUMPTION BY POTATO PLANTS

The article highlights the results of research on the influence of spread and local fertilization methods on the duration of localization, availability and migration of phosphorus compounds in the subsoil zone during the cultivation of seed potatoes. The research was conducted in a field experiment of the Department of Agrochemistry and Quality of Crop Production in the National University of Life and Environmental Sciences of Ukraine on the land use territory of Biotech LTD (Boryspil district, Kyiv region) during 2019-2022. FPK 8-24 was used as a pre-sowing fertilizer in the variant with a spreading method using a self-propelled sprayer Tecnoma Lazer 3000, and potassium chloride was applied using a John Deere 6195M unit and a spreader MVD 1000, followed by their incorporation with a Vaderstad Carrier CR 400 disk to a depth of 10 cm. Localized application was carried out by a unit consisting of a John Deere 8300 and a Peliper RV 3000 cultivator: phosphorus fertilizers (RKD 8-24) were applied with a tape (15 cm depth), and potash fertilizers were applied in a strip (10-12 cm width, 18-20 cm depth) (Bykin &amp; Panchuk, 2021). Nitrogen fertilizers, as a background in all variants, were applied to the pre-sowing soil in the form of UAN-25 + S4, considering the nitrogen applied with FFR 8-24. The use of local fertilization allows to better optimize the nutrition of potato plants. During the period of active phosphorus consumption, a higher content of phosphorus compounds was observed in the variants where fertilizers were applied locally than in the variant where fertilizers were applied in a scattered manner. In particular, even with the application of a reduced rate of fertilizers (P40K90) locally on the background of N150, a higher content of phosphorus and potassium in the soil during the growing season was observed compared to the variant where the full rate of fertilizers (P80K180) was applied on the background of N150 by the scatter method. It was found that fertilizer localization provided a longer period of phosphorus availability in high concentrations. Also, the formation of concentration zones in deeper soil layers was noted, which were less affected by the negative effects of weather conditions and provided potato plants with this element even when the upper soil layers dried out.

National Blood Foundation 2021 Research and Development summit: Discovery, innovation, and challenges in advancing blood and biotherapies.

National Blood Foundation 2021 Research and Development summit: Discovery, innovation, and challenges in advancing blood and biotherapies.

Epidemiological Evaluation of Associated Risk Factors of Helicobacter pylori Infection Using Noninvasive Methods: A Case Study of Peptic Ulcer Patients in Lafia, Nigeria.

Background: Due to its persistent nature, ulcers brought on by Helicobacter pylori have been a significant public health concern. This study looked at how specific risk factors affected the prevalence of Helicobacter pylori infection among peptic ulcer patients visiting medical institutions in Lafia, Nigeria. Methods: The blood and stool samples of 180 individuals (71 men and 109 women) were collected randomly, checked for H. pylori using test strips for H. pylori antibodies and antigens (Azure Biotech Inc.), and the feces also were grown on Columbia blood agar base (TITAN Biotech Ltd). Using a standardized questionnaire, some participant risk data was also gathered.Results: A positive culture method (CM) test result was obtained from 14/71 (19.72%) of the 71 male patients and 37/109 (33.94%) of the 109 female subjects out of a total of 210 subjects. For CM alone, it was discovered that female participants had a considerably greater incidence of Helicobacter pylori infection than their male counterparts (p=0.038). Nevertheless, all analytical techniques discovered no evidence of a significant difference between age groups (p>0.05). Only the blood antibody (BAB) approach showed a substantially greater prevalence (p=0.021) in married patients, with 79/116 (68.10%) reactive instances. The presence of drinking water source (p < 0.001, 0.001, 0.002 using CM, BAB, and SAG, respectively) and number of occupants per room (p < 0.001, 0.001, 0.002 using CM, BAB, and SAG, respectively) as potential risk factors for H. pylori infection was also demonstrated.Conclusion: The majority of risk factors that were taken into consideration for this study demonstrated a strong correlation with Helicobacter pylori infection in Lafia, Nigeria.

Early Humoral Responses of Hemodialysis Patients After Inactivated SARS-CoV-2 Vaccination.

PurposeTo detect antibody responses to inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in patients undergoing hemodialysis and to investigate vaccine-related adverse events.Patients and MethodsA total of 120 hemodialysis (HD) patients and 24 healthy controls (HCs) who had not been previously infected with SARS-CoV-2 and had received their first dose of the inactivated vaccine (CoronaVac; Sinovac Biotech Ltd) were recruited for this study. All participants were scheduled to receive a second dose of inactivated SARS-CoV-2 vaccine. Serum-specific immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies against the SARS-CoV-2 were detected at least 14 days after the second dose of vaccine using a commercial kit. Positive and negative results were defined as a sample/cutoff (S/CO) ratio≥1.00 and <1.00, respectively. Vaccination-related adverse events were assessed using a standardized questionnaire.ResultsThere were no significant differences regarding the seroprevalences of IgG and IgM antibodies against SARS-CoV-2 and the self-reported vaccination-related adverse events between HD patients and HCs. The analysis results for HD patients suggest that 82 (68.3%) and 27 (22.5%) tested positive for IgG and IgM, respectively. The levels of IgG were higher than IgM levels (P<0.0001). In addition, the IgG-positive group had significantly higher serum albumin levels than the IgG-negative group (P<0.05). Only mild vaccine-related adverse events were observed in two patients (1.66%) and in one healthy individual (4.2%).ConclusionThe seroprevalences of IgG and IgM antibodies against SARS-CoV-2 and vaccination-related adverse effects are similar between HD and HCs. The inactivated SARS-CoV-2 vaccine is effective and safe in inducing near-term immunity in hemodialysis patients.

Effectiveness of COVID-19 vaccine (Covaxin) against breakthrough SARS-CoV-2 infection in India

ABSTRACT India approved COVID-19 vaccine called Covaxin, developed by the Indian Council of Medical Research and Bharat Biotech Ltd. The primary objective of the study was to estimate the effectiveness of Covaxin in preventing breakthrough SARS-CoV-2 infection in healthcare workers (HCWs). A test-negative matched case-control study was conducted among HCWs of tertiary care hospital in Eastern India. Any HCW who tested positive for COVID-19 using RT-PCR during April and May 2021 was taken as the case. The HCWs who tested negative for COVID-19 by RT-PCR were considered as controls after matching with the date of testing and profession of the cases. Vaccination data were collected from the institution’s vaccine database and recall. In case of discrepancy, it was confirmed from the CoWIN portal (cowin.gov.in). The sample size was 670 participants (335 pairs). Conditional logistic regression models were used to calculate the adjusted odds ratio for breakthrough SARS-CoV-2 infection. Vaccine effectiveness was calculated using the following formula: VE = (1-aOR) × 100%. Sensitivity analysis was done for effectiveness of Covaxin, excluding Covishield vaccination. The mean age of participants was 29.1 years (SD = 7.1), and the majority were males (55.2%). Among the study participants, 60% were completely vaccinated, 18.51% were partially vaccinated, and 21.49% were unvaccinated. After adjusting for age, gender, type of household and past history of COVID-19 disease in conditional logistic models, the vaccine effectiveness was 22% (aOR 0.78, 95% CI: 0.52–1.17; p = .233). Sensitivity analysis with Covaxin showed an effectiveness of 29% (aOR 0.71, 95% CI: 0.47–1.08; p = .114) for preventing breakthrough SARS-CoV-2 infection.

COMPARISON OF A RAPID TEST WITH bPAG ELISA IN PREGNANCY DIAGNOSIS IN COWS

Early pregnancy detection is vital for properly managing livestock farms by re-inseminating nonpregnant females and minimizing the calving intervals. The present investigation was executed to compare a rapid test (Dairy Cow Pregnancy Test from Span Biotech Ltd. Shenzhen, China) with a commercial bPAG ELISA test (IDEXX®) for pregnancy diagnosis in non-descriptive cows. The study also aimed to elucidate if the rapid test could be an alternative method to ELISA in the field. Blood and urine samples were collected from 43 cows to measure the concentrations of bovine pregnancy-associated glycoproteins (bPAGs) in the blood samples and detect progesterone via the rapid test in the urine samples. Examining the genital tracts was achieved after slaughtering the cows to determine the uterus’ state, used as the reference standard for both tests. The results showed that the bPAG ELISA test was more accurate in pregnancy detection than the rapid test. However, there were no statistically significant differences (P &gt; 0.05) between both methods’ results. We conclude that the rapid test can be a suitable alternative method to the bPAG ELISA test for diagnosing pregnancy in cows in field conditions.

Short-Term Immunogenicity Profiles and Predictors for Suboptimal Immune Responses in Patients with End-Stage Kidney Disease Immunized with Inactivated SARS-CoV-2 Vaccine

IntroductionPatients with end-stage kidney disease (ESKD) are at risk of severe coronavirus disease and mortality. Immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inactivated whole-virus vaccine in patients with ESKD has never been explored.MethodsWe conducted a prospective cohort study of 60 patients with ESKD and 30 healthy controls. All participants received two doses of an inactivated whole-virus SARS-CoV-2 vaccine (Sinovac Biotech Ltd) 4 weeks apart. SARS-CoV-2-specific humoral and cell-mediated immune responses were investigated and referenced with healthy controls.ResultsAfter two doses, an anti-receptor-binding domain immunoglobulin G of 50 AU/ml or greater was present in 53 of 60 patients (88%) in the ESKD group and all participants (100%) in the control group (P = 0.05). The percentage of patients with ESKD and controls with neutralizing antibodies of 35% threshold or greater was 58% and 88%, respectively (P = 0.01). Furthermore, the proportion of patients with ESKD and S1-specific T cell response was comparable with controls (82% vs. 77%, P = 0.45). Old age, high ferritin level, and low absolute lymphocyte count were independently associated with poor humoral immune responses.ConclusionsPatients with ESKD could develop similar SARS-CoV-2-specific cell-mediated immune responses compared to healthy controls, although suboptimal humoral immune responses were observed following two doses of SARS-CoV-2 vaccination. Therefore, patients with ESKD and the abovementioned factors are at risk of generating inadequate humoral immune responses, and a vaccine strategy to elicit greater immunogenicity among these relatively immunocompromised patients is warranted. (Thai Clinical Trials Registry, TCTR20210226002).

Продуктивність насіннєвої картоплі за локального внесення фосфорних і калійних добрив

Ukraine is a leader in potato production, among the top three producer countries and ranks second in the world in terms of per capita potato consumption, second only to Belarus. It produces 139 kg per year per capita, with a world average of about 33 kg/person/year. According to UCAB, in recent years the area under potatoes has increased by 2.7% to 1325 thousand hectares. However, the average yield for the last three years was 15.8 t/ha. In some advanced farms of Ukraine the yield reaches 30–40 t/ha due to the introduction of scientific developments in production. However, in general, the potential for economic productivity of potatoes in Ukraine now remains completely untapped. Potato plants are demanding to the presence of nutrients in the soil. Soil nutrients must be available for plants and in sufficient quantity. It causes by the biological characteristics of potatoes. The effectiveness of mineral fertilizers depends on the methods and quality of their application. The traditional method of fertilization involves fertilizers broadcasting on the soil surface with their tillage. As a result of uneven placement of fertilizer granules in the soil layer, the transition of nutrients into unavailable form to plants, which causes the uneven plants development and maturation of tubers. Therefore, one of the ways to improve the potatoes nutrition and reduce nutrient losses and obtain high stable crop yields is the local application of mineral fertilizers in the area of the root system location. Local application of phosphorus determines it better availability throughout the growing season, which provides accelerated growth and development of roots and shoots, as well as the formation of the optimal number of tubers. Local placement of potassium improves its availability and provides enhanced synthesis and transport of carbohydrates in plants, increases the absorption of moisture and nutrients by the roots, strengthens their resistance to disease and improves the quality of tubers. The aim of our researching was to investigate the effectiveness of the phosphorus and potassium application in different methods and phosphorus and potassium rates and to establish it impact in the productivity of seed potatoes. The research was located in the field experiment of the Department of Agrochemistry and Quality of Crop Products named by O.I. Dushechkina NULES of Ukraine on the territory of LLC "Biotech LTD" (Boryspil district, Kyiv region) during 2019–2020. Early-maturing variety Tiras was selected for research. The planting area was 495m2 of the accounting area was 312m2. The experiment was repeated 4 times. The placement of options was systematic. As a result of research it was established that local application of phosphorus and potassium fertilizers provided such a level of yield of Tiras potatoes, which was not inferior to the variant with the fertilizers broadcasting. Yield growth in variants with local application ranged from 0.6 t/ha to 2.9 t/ha, depending on the rates. The application of local fertilizer with the rate of P60K135 caused the highest yield of seed potatoes among the options (33.4 t/ha), as well as the highest yield of seed fraction. It was 31.6 t/ha.

Projecting the Transition of COVID-19 Burden Towards the Young Population While Vaccines are Rolled Out: A Modelling Study

Background: SARS-CoV-2 infection causes most cases of severe illness and fatality in older age groups. In China, over 85% of individuals aged ≥12 years have been vaccinated against COVID-19 (albeit with vaccines developed against historical lineages), while children aged 0–11 years are currently not eligible for vaccination (as of September 2021). Here, we aimed to assess whether the importation of Delta variant infections will shift the COVID-19 burden from adults to children.Methods: We developed an age-structured SARS-CoV-2 transmission model to simulate epidemics triggered by the importation of Delta variant infections. We then used the model to quantify the age-specific incidence of SARS-CoV-2 infections, cases, hospitalisations, intensive care unit (ICU) admissions, and deaths.Findings: Under a vaccination program targeting 12+ years old individuals, symptomatic SARS-CoV-2 infections and hospitalisation are projected to shift towards children and young adolescents, with 13% of symptomatic infections and 30% of hospitalisations occurring in those aged 0–11 years. Extending the vaccination roll-out to include children aged 3–11 years is estimated to dramatically decrease the burden of symptomatic infections and hospitalisations within this age group (54% and 81%, respectively), but would have a low impact on protecting infants (aged 0–2 years).Interpretation: In the absence of non-pharmaceutical interventions, the importation of Delta variant infections could lead to widespread transmission and substantial disease burden in mainland China, even with vaccination coverage as high as 97% of the population aged ≥12 years. Our findings highlight the need to strengthen vaccination efforts by simultaneously extending the target population and elevating vaccine effectiveness.Funding: Funding was provided by the Key Program of the National Natural Science Foundation of China and the National Institute for Health Research (NIHR) Declaration of Interest: H.Y. received research funding from Sanofi Pasteur, GlaxoSmithKline, Yichang HEC Changjiang Pharmaceutical Company, Shanghai Roche Pharmaceutical Company, and SINOVAC Biotech Ltd. M.A. received research funding from Seqirus. Except for research funding from SINOVAC Biotech Ltd, which is related to the data analysis of clinical trials of immunogenicity and safety of CoronaVac, the others are not related to COVID-19. All the other authors have no competing interests.

Safety, Tolerability and Immunogenicity of an Inactivated SARS-CoV-2 Vaccine (CoronaVac) in Healthy Children and Adolescents: A Randomised, Double-Blind, and Placebo-Controlled, Phase 1/2 Clinical Trial

Background: The COVID-19 vaccine for children and adolescents, who are indispensable populations to curb the pandemic, would protect this population against rare severe COVID-19 and infectious conditions. Here we aimed to assess the safety, tolerability and immunogenicity of a candidate COVID-19 vaccine, CoronaVac, containing inactivated SARS-CoV-2, in children and adolescents aged 3-17 years old. Methods: We did a randomised, double-blind, placebo-controlled phase 1/2 clinical trial of CoronaVac in healthy children and adolescents aged 3-17 years old in Zanhuang (Hebei, China). Vaccine (in 0 ·5ml aluminum hydroxide adjuvant) or placebo (adjuvant only) was given by intramuscular injection in two doses (day 0 and day 28). We conducted phase 1 trial in 71 participants with an age de-escalation in tree groups and dose-escalation in two blocks (1.5ug or 3ug per injection). Within each block, participants were randomly assigned (3:1) using block randomisation to receive CoronaVac or placebo. In phase 2, participants were randomly assigned (2:2:1) using block randomisation to receive either CoronaVac at 1.5ug or 3ug per dose, or placebo. The primary safety endpoint was adverse reactions within 28 days after each injection in all participants who received at least one dose. The primary immunogenicity endpoint was seroconversion rate at 28 days after the second injection and its GMT as the secondary endpoint. This study is ongoing and is registered with ClinicalTrials.gov (NCT04551547).Findings: Between October 31 and December 2, 2020, 72 participants were enrolled in phase 1, and between December 12 and December 30, 2020, 480 participants were enrolled in phase 2. 500 participants received at least one dose of vaccine or placebo (n=71 for phase 1 and n=479 for phase 2; safety population). In the combined safety profile of phase 1 and phase 2, any adverse reactions within 28 days after injection occurred in 56 (26%) of 219 participants in the 1·5ug group, 63 (29%) of 217 in the 3ug group and 27 (24%) of 114 in the placebo group, without significant difference. Most adverse reactions were mild and moderate in severity and injection site pain (73[13%]) of 550 participants was the most frequently reported event. As of March 12, 2021, only one serious adverse event has been reported, which was considered unrelated to vaccination. In phase 1, seroconversion after the second dose was observed in 27 of 27 participants (100·0% [95%CI 87·3-100·0]) in the 1·5ug groups and 26 of 26 participants (100·0% [86·8-100·0]) in the 3ug group, with the geometric mean titers of 55·0 (95%CI 38·9-77·9) and 117·4 (87·8-157·0). In phase 2, seroconversion was seen in 180 of 186 participants (96·8% [93·1-98·8]) in the 1·5ug group and 180 of 180 participants (100·0% [98·0-100·0]) in the 3ug group, with the geometric mean titers of 86·4 (73·9-101·0) and 142·2 (124·7-162·1). There were no detectable antibody responses in the placebo groups. Interpretation: CoronaVac was well tolerated and induced strong neutralising antibody responses in children and adolescents aged 3-17 years. The study has provided solid safety and immunogenicity data to support the further study and use of CoronaVac in children and adolescents.Trial Registration: NCT04551547Funding Statement: Chinese National Key Research and Development Program and Beijing Science and Technology Program.Declaration of Interests: QG and XL are employees of Sinovac Life Sciences Co., Ltd. YS, WY and LW are employees of Sinovac Biotech Ltd. All other authors declare no competing interests.Ethics Approval Statement: The clinical trial protocol and informed consent form were approved by the Ethics Committee of Hebei CDC (IRB2020-005).

Економічна ефективність збалансованих схем удобрення картоплі столової макро- і мезоелементами на темно-сірому опідзоленому ґрунті за використання рідких фосфоровмісних добрив

Економічна ефективність збалансованих схем удобрення картоплі столової макро- і мезоелементами на темно-сірому опідзоленому ґрунті за використання рідких фосфоровмісних добрив

The UK IBD Registry COVID-19 Risk Tool; Patient Generated Data Can Improve the Hospital Record

Background: The COVID-19 pandemic has necessitated identifying individuals at higher risk of severe outcomes who should be shielded and provided with government support. We describe the initial results and validation of a web-based tool targeted at patients in the UK with inflammatory bowel disease (IBD) to self-stratify their risk according to a risk grid developed by an expert consensus body within gastroenterology.Methods: We designed a secure web-based survey, compliant with information governance, which was targeted directly at patients in the UK with IBD and promoted via social media. Patient-entered data were directly compared to data held by their local IBD specialist teams.Findings: Between 1st April and 3rd August 2020, we received responses from 34,078 participants with IBD from 176 UK trusts or health boards. Overall, based on these data, 25·9% of participants met the consensus criteria defined for shielding and a further 46·5% were in a moderate risk category. We assessed intra-rater reliability in 1,442 participants using the tool twice or more; most items had almost perfect agreement (kappa >0·80).We validated the patient-entered data against hospital-entered data and medical records for 2,862 patient datasets from ten hospitals. Weighted kappa was 0·59 (95% confidence interval 0·56 - 0·62). After manual resolution of discrepancies, kappa was 0·89 (95% CI 0·87 - 0·91). Of 966 patients identified as requiring shielding in the final dataset for these ten centres, 51·0% had been missed by the hospital-entered data, largely because of incomplete or discrepant information on comorbidity and current disease activity.Interpretation: We have demonstrated that patient-generated data can facilitate rapid risk stratification with respect to COVID-19 and compensate for deficiencies in hospital data. We have validated these data across repeat entry and have demonstrated their reliability compared to pre-existing secondary care data. These findings have important implications for public health and chronic disease management.Funding Statement: Galapagos Biotech Ltd; Biogen GmbH; Tillotts Pharma UK Ltd; Amgen LtdDeclaration of Interests: Author Vida Cairnes has received honoraria for speaking from Falk, Pharmacosmos, Abbvie and Tillots. I have received support to attend conferences fromPharmacosmos, Ferring, Takeda, Falk and Abbvie. I am in receipt of education funding from Crohn’s & Colitis UK. All other authors have nothing to declare. Ethics Approval Statement: The IBD Registry was the Data Controller for the COVID-19 UK IBD Risk Tool. Information Governance (IG) included the DPIA, Privacy Notices, approved information/content development for patients plus Information Sharing Agreements for hospital teams in order to allow the data to be shared. The lawful basis for data collection was under the COPI Notice issued for COVID-19.10 Information was freely provided by participants.

In vitro assay of biological activity of a national preparation of macrophage activating factor (GcMAF-RF)

В статье сообщается о разработанном оригинальном способе получения витамин D3-связывающего белка (DBP) и его конвертации в макрофаг-активирующий фактор GcMAF-RF. Согласно разработанному регламенту, DBP получали из плазмы крови человека, применяя аффинную колоночную хроматографию, очи- щали и модифицировали до GcMAF-RF с использованием цитоиммобилизованных гликозидаз (бета-галакто- зидаза и нейраминидаза). Принадлежность полученного полипептида к Gc-группе глобулинов плазмы крови подтверждали вестерн-блотом с использованием специфических антител. Полученный полипептид по своим молекулярным свойствам соответствует описанному в литературе белку GсMAF, находящемуся на стадии кли- нических испытаний в США, Британии, Израиле и Японии (Saisei Mirai, Reno Integrative Medical Center, Immuno Biotech Ltd, Efranat, Catalytic Longevity). Биологическую активность препарата GcMAF-RF определяли по индук- ции у перитонеальных макрофагов мыши фагоцитарной активности и способности продуцировать моноок- сид азота (NO) in vitro. Фагоцитарную активность макрофагов оценивали по эффективности захвата магнитных шариков. Степень активации макрофагов рассчитывали по отношению числа захваченных шариков к общему числу макрофагов. Уровень продукции NO оценивали по накоплению монооксида азота в культуральных су- пернатантах перитонеальных макрофагов колориметрическим методом с использованием реактива Грисса. Показано, что GcMAF-RF кратно увеличивает фагоцитарную активность макрофагов и достоверно увеличивает продукцию ими монооксида азота. Выделенный оригинальным способом активатор макрофагов GcMAF-RF по своим характеристикам (согласно материалам, опубликованным в печати) соответствует препаратам GcMAF, представляемым на рынке зарубежными компаниями, и может рассматриваться как новый отечественный био- логически активный препарат с широким спектром действия. Наибольший интерес вызывает его способность через активацию макрофагов усиливать адаптивный иммунитет организма. В этой связи предполагаются два направления терапевтического применения препарата GcMAF-RF. Препарат может быть востребован в области лечения онкологических заболеваний и, кроме того, может быть использован при лечении ряда нейродегене- ративных патологий и иммунодефицитных состояний.

MicroRNA Modification of Coxsackievirus B3 Decreases Its Cardiotoxicity, While Retaining Oncolytic Potency Against Lung Cancer

Background: We recently discovered that coxsackievirus B3 (CVB3) is a potent oncolytic virus against KRAS-mutant (KRASmut) lung adenocarcinoma. Nevertheless, the evident cardiotoxicity restricts the use of wild-type (WT)-CVB3 for lung cancer therapy. The current study aims to genetically engineer the CVB3 genome to decrease its toxicity towards normal tissues and to extend our previous research to determine the safety and oncolytic efficacy of the modified CVB3 in treating TP53-and/or RB1-mutant small cell lung cancer (TP53mut/RB1mut SCLC). Methods: A microRNA-modified CVB3 (miR-CVB3) was generated via inserting multiple copies of tumor-suppressive miR-145 and miR-143 target sequences into the 5' untranslated region of the viral genome. The safety and effectiveness of the miR-CVB3 were then examined in cultured cells and using a TP53mut/RB1mut SCLC cell-derived xenograft model. Findings: In vitro experiments revealed that miR-CVB3 retained the ability to infect and lyse KRASmut lung adenocarcinoma and TP53mut/RB1mut SCLC cells, but with a markedly reduced cytotoxicity towards cardiomyocytes. In vivo study demonstrated that a single dose of miR-CVB3 via systemic administration resulted in a significant tumor regression. Most strikingly, mice treated with miR-CVB3 all survived the time-course of the experiment with greatly attenuated cardiotoxicities and decreased viral titers as compared to WT-CVB3-treated mice. Interpretation: We generated a recombinant CVB3 that was powerful in destroying both KRASmut lung adenocarcinoma and TP53mut/RB1mut SCLC, with a negligible toxicity towards normal tissues. Fundings: This work was supported by the BC Lung Association, Providence Health Care Research Institute and Vancouver Coastal Health Research Institute Innovation and Translational Research Award. Declaration of Interest: WWGJ is the Chief Scientific Officer at Virogin Biotech Ltd. HL (H Liu) and CSN are partially sponsored by Virogin Biotech Ltd. through MITACS Accelerate Program. No conflicts of interest were disclosed by others. Ethical Approval: The protocol was approved by the University Animal Care Committee (A18-0275).

Grain sorghum yield as affected by row spacing and fertilization practice

Purpose. To establish varietal characteristics of yield formation in grain sorghum as affected by row spacing and fertilization system.Methods. The field experiment was carried out during the 2015–2017 period in a multifactorial stationary experiment in LLC Biotech LTD located in the central part of Boryspil district (Kyiv region) of the Left-Bank Forest-Steppe of Ukraine. Experiment design: factor A – hybrid: ‘Lan 59’, ‘Burgo F1’, ‘Briggo F1’; factor B – dose of nitrogen fertilizers: N60P60K60 (control), N60P60K60 + N20, N60P60K60 + N40, N60P60K60 + N60; factor C – row spacing: 35 cm, 50 cm, 70 cm.Results. The average yield of grain sorghum for years of research ranged from 3.98 to 9.14 t/ha, depending on hybrid, row spacing and fertilization practice. It was also found that average grain yield in 2015 amounted to 7.29 t/ha; 2016 was critical with regard to weather conditions – the realization of the biological potential of sorghum plants was significantly lower – at the level 6.33 t/ha; in 2017, the average yield was 7.15 t/ha of grain. Among the hybrids, the least productive was ‘Lan 59’ (5.14 t/ha), and an average yield of ‘Burgo F1’ and ‘Briggo F1’ were 7.57 and 8.06 t/ha, respectively. The maximum yield for all hybrids was formed at the 50-cm row spacing, namely ‘Lan 59’ – 5.40,” ‘Briggo F1’ – 8.48 t/ha and ‘Burgo F1’ – 7.86 t/ha, respectively. With the pre-sowing application of N60 compared to N20, the yield of hybrid ‘Lan 59’ grew by 0.41–0.51 t/ha, ‘Briggo F1’ by 0.27–0.40, ‘Burgo F1’ by 0.22–0.29 t/ha.Conclusions. The biggest share in sorghum yield formation had the ‘hybrid’ factor (43%). ‘Conditions of year’ factor (21%) and ‘dose of nitrogen’ (20%) had an equivalent effect, and ‘inter-row spacing’ factor amounted to 10%. Studies have shown that there is a positive moderate correlation between yield and dose of pre-sowing nitrogen (r = 0.49). Grain sorghum plants react positively to additional nitrogen, what is manifested in increased yields. This dependence can be explained not only by moderate nitrogen application rates but also by the low level of hydrolyzed nitrogen stock in the soil of the experimental plot.

Chronic Myeloid Leukemia in Adolescents and Young Adults Treated with Generic Form of Imatinib in Resource Limited Setting: A Single Center Experience from Myanmar

Chronic myeloid leukemia (CML) is an acquired myelo-proliferative disorder characterized by the presence of BCR-ABL1 fusion transcript with deregulated tyrosine kinase activity. Leukemias are one of the leading causes of cancer related deaths in adolescents and young adults (AYA) particularly in resource limited countries. Recent democratic government in Myanmar holds supportive policies for treatment of cancers in younger population and subsidizes some therapies including imatinib mesylate, a selective BCR-ABL 1 tyrosine kinase inhibitor, although there is still limitation for cytogenetic and molecular monitoring of therapy. This study on response to imatinib in newly diagnosed chronic phase CML was carried out during January 2016 to February 2018 at the North Okkalapa General and Teaching Hospital of Yangon, Myanmar where molecularly confirmed new CML in chronic phase were treated with generic form of imatinib bought by hospital tender system, Unitinib (United Biotech (P) ltd. India) followed by cytogenetic analysis of bone marrow and molecular detection of BCR-ABL1 transcript from peripheral blood by in house real time PCR machine at one year. They are divided into AYA (aged 15-39 years) and adult age groups (40 years and older) and clinical parameters and response to treatment with imatinib 400mg per day were compared. Among 56 cases (median age of 39.5 years, male to female ratio of 1.5:1), half were AYA (28 of 56) with median age of 28.5 years compared to 50 years in adult group with higher male to female ratio of 3.6:1 in AYA group. Patients in AYA had larger spleen size (11 vs 5.5 cm) and higher median white cell count compared to adults (366 x 109/l vs 224 x 109/l) although initial platelet count, peripheral blood eosinophil, basophil and blast percent and Sokal score were comparable. Additional chromosomal abnormalities were detected in 2 AYA and 3 adults with CML. There was no difference in complete haematologic response at 3 and 12 months between AYA and adults (96.4% vs 96.4% and 92.9% vs 89.3% respectively). At 12 months, complete cytogenetic response of AYA at 67.9% was less than 75.0% of adults, it was statistically not significant. Using in house molecular method although not standardized, 14.3% of AYA and 32.1% of adults were molecularly undetectable at one year. The response of AYA to imatinib in this study was comparable to adults despite having adverse prognostic features and receiving only generic forms of treatment in resource limited setting and it would further help support from authorities for leukemia in younger population. DisclosuresNo relevant conflicts of interest to declare.