bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnetic resonance syndromes of myocardial damage in patients after new coronavirus infection (COVID-19) – two typical clinical cases
Authors: Shelkovnikova T. A. , Pushnikova E. Yu. , Baev A. E. , Ryabov V. V. , Ussov W. Yu.
Published: April 2022

Clinical examples for variants of cardiovascular complications of a new coronavirus infection (COVID-19) are presented when they are visualized by means of magnetic resonance imaging (MRI) of the heart and chest organs with paramagnetic contrast enhancement and synchronization with ECG and respiration signal. The syndromes of post-COVID focal infarct injury and diffuse inflammatory lesion are identified. The picture of MRI visualization of coronary atherosclerotic plaque is presented. The results of quantitative processing of cardiac MRI in these two different syndromes of post-COVID cardiological complications are presented. The presented clinical examples indicate the need for cardiac MRI to monitor patients and assess the long-term cardiovascular effects of COVID-19.
A clinical case of transapical aortic valve implantation for low-gradient stenosis in a comorbid patient with COVID-19-associated pneumonia
Authors: Batalova D. N. , Ryabov V. V. , Petlin K. A.
Published: April 2022

Aortic stenosis is the leading entity in the structure of valvular pathology in adult population with the frequency ranging from 2 to 4% in the general population. The distinct features of this defect include slow progression and frequent lack of correlation between the severity of stenosis according to clinical and instrumental data. The article presents the case of successful transcatheter aortic valve implantation by transapical access in a 71-year-old patient with symptomatic low-flow, low-gradient aortic stenosis, heart failure with preserved left ventricular ejection fraction, a history of coronary artery bypass grafting, severe concomitant pathology, and recent moderate COVID-19 coronavirus infection. The complexity of management of elderly patients with combined pathology is updated, and a multidisciplinary approach to clinical decision-making in a high-risk clinical situation is demonstrated.
Successful endovascular treatment of left main bifurcation lesion using the DK-CRUSH technique with intracoronary imaging using optical coherence tomography: A case report
Authors: Sapoznikov S. S. , Bessonov I. S. , Zyrianov I. P.
Published: April 2022

We report the successful endovascular treatment of true left main bifurcation lesion in a patient with chronic coronary syndrome using the DK-CRUSH technique. We describe technical aspects of bifurcation stenting with intracoronary imaging using optical coherence tomography. Here, we review the current state of the problem of choosing the optimal technique for endovascular treatment of patients with true left main true bifurcation lesion.
Associations between MRI signs of kidney parenchymal changes and biomarkers of renal dysfunction in resistant hypertension
Authors: Ryumshina N. I. , Zyubanova I. V. , Sukhareva A. E. , Manukyan M. A. , Anfinogenova N. D. , Gusakova A. M. , Falkovskaya A. Yu. , Ussov W. Yu.
Published: April 2022

Objective. Resistant hypertension (RHT) is often associated with kidney injury and chronic kidney disease, especially in diabetic patients. Early detection of renal changes contributes to avoiding severe cardiovascular complications, but imaging characteristics of renal dysfunction in RHT remain unclear. The aim of the present study was to determine the relationships between the renal parenchyma volumes and biomarkers reflecting kidney function in a cohort of patients with RHT.

Material and Methods. The study comprised 34 patients with RHT meeting the inclusion criteria. Evaluation of renal function was based on the measurements of estimated glomerular filtration rate (eGFR) and serum levels of creatinine and cystatin C. Renal sizes were assessed by MRI based on absolute and normalized parenchymal kidney volumes.

Results. Primary MRI-based changes in renal parenchyma in patients with RHT demonstrated altered cortical surface, attenuated cortical thickness, lower renal volumes, and round shape of the kidneys compared with the reference characteristics. Positive correlation of moderate power was found between eGFR value and all parameters characterizing renal parenchyma. The strongest direct correlation was found between eGFR and bsa-TKV (r = 0.6166, p = 0.000); ht-TKV correlated with eGFR (r = 0.4751, p = 0.007) and creatinine (r = –0.4302, p = 0.016). According to linear regression analysis, ht-T-Cortex-V < 32.4 was a key element of MRI-presentation of renal dysfunction in patients with eGFR below 60 mL/min/1.73 m2 (sensitivity of 83.3%, specificity of 60.7%, p = 0.03).

Conclusion. MRI study allowed to detect early renal parenchymal changes suggesting the presence of association between renal function and renal parenchymal volume in RHT patients. For the first time, the study revealed MRI-pattern of renal dysfunction in RHT.
Approximation by General Family of Summation Baskakov-Type Operators Preserving the Exponential Functions
Authors: Hussein Sara Adel
Published: April 2022

The present paper is defining and studding a modification of the general family sequence of summation Baskakov-type operators. This modification is preserved that the functions and where is fixed. We show that the uniform convergence theorem of this sequence by using the modulus of continuity to the function being approximated. Finally, we introduce the asymptotic formula for the Voronovskaya-type theorem
Molecular interface between food allergy diagnosis and treatment: Value of a multi-omics approach
Authors: Rebecca O. Dotson  , Diane E. Heck  , Hong Duck Kim
Published: April 2022

Due to the ever-increasing prevalence of Food Allergy (FA) in the United States, many studies have been conducted to better understand mechanisms of Food Allergy, diagnosis, and treatment. Traditional diagnosis of FA can be time-consuming, less dependable, and can lead to severe allergic reaction in some patients. In this review, the latest evidence on testing, appropriate biomarkers for diagnosis, and treatment options are presented. The benefits of trained immunity (TRIM), oral immunotherapy (OIT), sublingual immunotherapy (SLIT), and Epicutaneous immunotherapy (EPIT) are discussed in this review as well. Common biomarkers of food allergies are discussed, including 2S albumins, T-cells, and basophil activation markers. The benefits of a multi-omics approach are highlighted by the complex nature of food allergies and the relationship between genes, proteins, metabolites, and the microbiome in response to allergens. Future possibilities of omics studies pertaining to food allergies are also presented to guide future research.
Anti-plasmodial activity of rifampicin/ dihydro-artemisinin/piperaquine combination on Plasmodium berghei infected mice
Authors: Georgewill Udeme Owunari  , Dan-Jumbo Opuada Victor
Published: April 2022

Introduction: The huge cost of de-novo drug development and the problem of multidrug resistance by plasmodium parasites has made research on drugs with potential for repurposing attractive. The study evaluated the antiplasmodial properties of clinical doses of rifampicin in combination with dihydroartemisinic/piperaquine in Plasmodium berghei-infected mice. Materials/Methods: Curative, suppressive, and prophylactic tests were carried out on adult mice (26 – 30g) infected with P.berghei parasite. They were grouped and treated per oral (p.o) with RIF (15mg/kg), DP (2.5/20 mg/kg) and RIF/DP (15/2.5/20 mg/kg) daily. The negative control (NC) and the positive control (PC) were treated daily p.o with normal saline (0.2mL) and chloroquine (CQ) (10 mg/kg). Normal saline and chloroquine were administered to mice in the first and second groups, respectively, for 3 consecutive days. Similarly, the third group of mice were treated with dihydroartemisinin/piperaquine combination for 3 consecutive days, while rifampicin was given to the fourth group for 7 consecutive days. The last group of mice were administered the dihydroartemisinic/piperaquine dose for 3days and the rifampicin dose for 7 consecutive days. Results: There was significant reduction in parasitemia in the prophylactic, suppressive, and curative studies at RIF (15 mg/kg) (p<0.01), DP (2.5/20 mg/kg) (p<0.001) and RIF/DP (p<0.0001) when compared with to negative control. There was an approximately three-fold decrease in percentage parasitemia in the rifampicin/dihydroartemisinin/piperaquine treatment group when compared to the Chloroquine treatment group. Conclusion: The combination of rifampicin with dihydroartemisinin/piperaquine represent potentially viable additions to the antimalarial arsenal currently available. RIF may be repurposed in combination with DP for malaria treatment.
Trend of heavy metal contamination: A case study on the soil of Amassoma community, Bayelsa state of Nigeria
Authors: Ebimobowei Assayomo  , Timothy Gilbert Anthony  , AyakemeTonkiri  , Dautimiebi Gabriel Andrew  , Okes Imoni
Published: April 2022

Presence of heavy metal contamination in agricultural lands, even at low levels is not desirable for human and animal health. Six soil samples were taken from three locations in Amassoma community in Bayelsa state in the months of April from the year 2019 to 2021. These samples were taken from the rhizosphere of pawpaw tree and scent leaf from the depth of 0-30 cm Samples were prepared by wet-ashing in line with the method defined by Smith 1972 and subjected to Atomic Absorption Spectrophotometry (AAS) and readings analysed with SPSS V.23 and IBM Instat GraphPad Prism V.3. Unpaired t test and trend analysis (graph, moving averages and slope)was used to ascertain significant difference between the yearly means and WHO limit at P<0.05, and trends of heavy metal contamination over the study period respectively. Increase in contamination of Lead (Pb), Cadmium (Cd), and Nickel (Ni) from 2019 to 2021 was revealed as 0.050 mg/kg-1 year-1, 0.005 mg/kg-1 year-1, and 0.063 mg/kg-1year-1 respectively. There was no reported increase in Zinc contamination (0.00 mg/kg-1year-1). Yearly analysis revealed statistically significant differences in observed heavy metal concentrations to that of the WHO limit (p<0.05). The 2-tailed p-value between the means of heavy metals studied and that of the WHO limits were all significantly different. Recommendations are that more researches be conducted to determine heavy metal accumulations in soils in Amassoma and other communities in Bayelsa state Nigeria. Government effort is required to initiate concerted remediation processes of the reported heavy metals to curb future health dangers.
Professional Development Strategies: Organization Experience in addressing the call to action, the Future of Nursing, Leading Change, Advancing Health
Authors: Stella Ekeocha Anele  , Dorothy C Nwanonyiri  , Josephine N Ezemobi  , Margaret Okodua  , Grace Ogiehor-Enoma  , Ednah N Madu  , Julia U Ugorji  , Emilia N Iwu  , Ruth O Ifediora  , Teresa N Nwaneri
Published: April 2022

Introduction and Background: Professional development is vital to achieving excellence in clinical practice, education, administration, health policies, research, and management. In 2010, the Institute of Medicine (IOM) made recommendations for an action-oriented blueprint for the future of nursing. Some of the recommendations include ensuring nurses are well-prepared, nursing organizations to institute residency training for nurses, increase the percentage of nurses who attain a bachelor's degree to 80 percent by 2020, and double the number who pursue doctorates. To respond to these recommendations, the National Association of Nigerian Nurses in North America [NANNNA] a not-for-profit organization, implemented various strategies to support its members in achieving the IOM recommendations. Purpose: The purpose of this study was to evaluate the various strategies used by NANNNA to achieve the IOM recommendations for professional development among its members. Method: NANNNA Research subcommittee conducted an online survey of its members. The academic data obtained from 259 members was analyzed descriptively using SPSS and excel. A total of 323 degrees were attained during the 10 years from the 259 participants. Results: Based on the significant value of 0.029 (i.e., p = .029), which is below 0.05, there is a statistically significant difference in the mean of NANNNA members’ degree attainment. The result shows that the strategies implemented, mentorship, preceptorship, leadership, networking, and inter-professional collaboration, were vital to professional development among its members. This finding has important implications for the future of nursing, leading change and provides new insights into not-for-profit organizational influence on nurses’ personal and professional development.
Evaluation of improved white fleshed sweet potato varieties at Gamo zone, Southern Ethiopia
Authors: Kanko Chuntale Chulda  , Melese Lema Tesema
Published: April 2022

Six white fleshed sweet potato varieties were tested in Gamo zone of southern region, Ethiopia in 2019 and 2020 to evaluate their total root yield potential and demonstrate best performing varieties. The experiment was laid out as a Randomized Complete Block Design with four replications. The combined analysis of variance showed highly significant differences among genotypes on growth, root yield and its components. The maximum number of marketable roots per plot was recorded on variety Hawassa -09 (70.25) whereas minimum number of roots per plot was recorded on ADU (11.00). The highest root yield per hectare was obtained from variety Hawassa -09 (62.16 ton ha-1) followed by Tola and Berkume (53.99 and 52.85 ton ha-1), respectively. The lowest root yield per hectare was recorded from variety ADU (5.21 ton ha-1). Based on the result of this study from six evaluated white fleshed sweet potato varieties Hawassa -09 was recommended for pre extension demonstration at the area and similar agro ecological locations.
Magnitude of antibiotic resistant bacterial colonization of women attending HIV clinic in Lagos, Nigeria
Authors: Dauphin Dighitoghi Moro  , Jyostna Chandwani  , Oluchi Mariam Ukhureigbe  , Igbagbo Ehinmore  , Chinedu Emmanuel Usuah
Published: April 2022

Opportunistic infections due microorganisms particularly bacteria have posed a threat and thus an addition burden on the management of human immunodeficiency virus (HIV) infections worldwide. The high prevalence of bacterial pathogens and the emergence of multiple drug resistance among such bacteria call for serious concern. Bacteriological examination of 320 women attending HIV clinics was carried out using standard microbiological techniques. The antimicrobial susceptibility testing was carried out by the disc diffusion technique by Bauer and CLSI. Of the 320 women, 200 (62.5%) had bacteria, 120 women were confirmed as HIV positive. Ninety (75%) of these women had both HIV-1 and HIV-2, twenty (16.7%) had only HIV-1 and 10 (8.3%) had only HIV-2. Staphylococcus aureus and Escherichia coli were the predominant bacteria. Antibiogram of the bacterial isolates determined by using the Kirby Bauer disk diffusion showed that most of them were susceptible to augmentin, gentamicin, peflacin, ciprofloxacin, ofloxacin and amoxicillin but were highly resistant to commonly used, over-the-counter drugs like chloramphenicol, tetracycline and streptomycin. This thus poses additional burden on the healthcare system in its attempt to manage HIV using anti-retroviral drugs among other methods, along with immunity enhancing drugs while the search for HIV vaccines still continues.
Physicochemical properties and metal speciation in gas flare-impacted soils in Ibeno, NigeriaPhysicochemical properties and metal speciation in gas flare-impacted soils in Ibeno, NigeriaPhysicochemical properties and metal speciation in gas flare-impacted
Authors: Godwin Asukwo Ebong  , Peace Ebubechukwu Anyalebechi  , Essien Daniel Udosen
Published: April 2022

The physicochemical properties and metal speciation in gas flare-impacted soils in Ibeno, Nigeria was assessed in this study. During the study, surface soils were collected from five (5) communities impacted by gas flaring within Ibeno namely: Ukpenekang, Mkpanak, Atabrikang, Inua-Eyet Ikot, and Okorutip. Surface soils were also collected from a location outside Ibeno where there is no impact of gas flaring and used as the Control. These samples and Control were treated analytically and analysed for their physicochemical properties and the different fractions of the metals using standard procedures. Results obtained in the studied soils indicated that, the mean values of pH, organic carbon, electrical conductivity, and cation exchange capacity were all within their acceptable limits. The mean total concentrations of lead (Pb), cadmium (Cd), and nickel (Ni) were also within their recommended limits whereas, the mean total concentration of iron (Fe) was higher than the acceptable limit. However, the levels of all the physicochemical properties including the total concentrations of the trace metals in the studied gas flare-impacted soils were much higher than their levels in the control plot. Results of metal speciation in the studied soils revealed that, Pb and Cd existed predominantly in the acid extractable fraction, Ni in the reducible fraction while, Fe existed mainly in the residual fraction. Nevertheless, in the control plot Pb and Cd existed predominantly in the reducible fraction, Ni in the residual fraction while Fe existed in the residual fraction. The Principal component analysis revealed that anthropogenic factor impacted significantly on all the parameters determined except Fe. The Hierarchical cluster analysis confirmed that, all the parameters determined except Fe emanated mainly from the anthropogenic source and also indicated strong relationships among the parameters. The study revealed that, all the metals in the studied gas flare-impacted soils were in the moderate class of contamination factor. The ecological risk factor and potential ecological index of the metals were in the low ecological risk.
Discontinuation of Corruption Investigation and Prosecution: A Comparison of Indonesia, The Netherlands, and Hong Kong
Authors: Ahwan Ahwan , Santoso Topo
Published: April 2022

The discontinuation of the investigation and prosecution of corruption crimes is one of the important substances of the amendment to Law No. 19 of 2019 concerning the Corruption Eradication Commission which then led to debates both among academicians and legal practitioners. The discourse focused on the essence and concerns of transactional practices in the process of law enforcement for corruption crimes in the future. By using the legal comparative method, this paper tries to compare the provisions regarding the discontinuation of the investigation and prosecution of corruption crimes in Indonesia, Hong Kong, and the Netherlands. The results of the study show that the provisions regarding the discontinuation of the investigation and prosecution of corruption crimes in the three countries have differences in their arrangements. Normatively, Indonesia and the Netherlands regulate this matter in several articles, while for Hong Kong, although they do not regulate it in an expressis verbis manner in the law, the provisions concerning the discontinuation of investigations and prosecutions of corruption crimes are known in their law enforcement practices as seen in the case handling scheme published by the Independent Commission Against Corruption (ICAC). However, the use of the mechanism for terminating the investigation and prosecution of corruption crimes can be seen as a balancing mechanism against the legal process. Regulations regarding the discontinuation of investigations in corruption crimes must be maintained as a control mechanism against the possibility of errors in law enforcement procedures or for other technical reasons.
Urgency of The Position of District Election Supervisory Body in The Resolution of Disputes Between Participants in The Regional Head Election in Indonesia
Authors: Syaputra Muhammad Yusrizal Adi
Published: April 2022

The ad hoc position of the District Election supervisory body will have an impact on actions to carry out the functions and duties of the District Election supervisory body during the election of regional heads. This study aims to determine the urgency of the position of the District Election supervisory body in the formation of effective supervision in the Pilkada and to find out the Mechanism of Dispute Resolution between Election Participants by the District Election supervisory body in the election of regional heads. This study uses a normative juridical research method, with secondary data and a conceptual approach. The data were analyzed qualitatively. The result of the first study is that the decision of the Election supervisory body an ad hoc institution is binding but still limited and not final because the aggrieved party can file a lawsuit to the State Administrative High Court. The mechanism for resolving disputes between participants in the Pilkada organizers by the District Election supervisory body is regulated technically through Election supervisory body Number 2 of 2020. Disputes between participants are carried out on the principle of the quick and simple, same-day to achieve legal certainty and benefit in regional head elections.
Restorative Justice in Child Rape Perpetrators: A Case Study on Perpetrators With Intellectual Disability
Authors: Saefudin Wahyu , Putro Rony Aryono , Sriwiyanti Sriwiyanti
Published: April 2022

The main role of probation officers is implementing restorative justice for the juvenile. However, a rape perpetrator with intellectual disability will encourage a different approach. Therefore, this study aims to explain how the application of restorative justice by probation officers on youth offenders with intellectual disabilities. The method used in this study is an empirical normative method. Primary legal materials were obtained through interviews with probation officers tasked with assisting in the investigation, prosecution, and examination in court, to assist in implementing decisions. Another source of legal materials was also obtained through the document of community research. Finally, secondary legal materials were obtained from various sources such as legislation, library books, and scientific journals. The results show three primary points. First, probation officers have realized restorative justice through their role in community research and mentoring. Second, probation officers provide recommendations for the rehabilitation of offenders. Third, probation officers reinforce other law enforcers such as police, prosecutors, and judges to conduct psychological diagnoses to ensure the child’s condition. However, this study also finds that not all law enforcers can understand and handle children with intellectual disabilities.
Analysis of the Medicinal Products for Human Use Authorised in the Russian Federation
Authors: Kosenko V. V. , Yagudina R. I. , Lednev O. A. , Serpik V. G.
Published: April 2022

The available range of medicinal products is growing every year.

The aim of the study was to analyse the range of medicines authorised in the Russian Federation.

Materials and methods: the analysis covered the data presented in the State Register of Medicines (as of June 2021) and the current regulations specifying the range of medicines.

Results: this article presents the results of analysis of medicines authorised in the Russian Federation, in terms of the following parameters: international non-proprietary names, trade names, groups according to the Anatomical Therapeutic Chemical Classification System, dosage forms, routes of administration, primary and secondary packaging, storage conditions, and shelf life. The analysis demonstrated that there are over 19 thousand medicines authorised in the Russian Federation, most of which are produced in Russia. The largest groups of medicines are antimicrobial products for systemic use, medicines for the treatment of nervous system and cardiovascular system disorders. The most common dosage form is tablets, and the most common primary packaging is vials. The most frequent storage temperature requirements are 15–25 and 2–8 °C. About half of all medicines have the shelf life of 3 years.

Conclusions: the data presented in this article can be used for unification of approaches to maintaining the State Register of Medicines, elaboration of reference books, and will be useful for medicine developers and manufacturers when planning and preparing regulatory submissions.
NMR as Used in the Russian and Foreign Pharmacopoeias for Quality Control of Medicinal Products
Authors: Moiseev S. V. , Kuz’mina N. E. , Luttseva A. I.
Published: April 2022

The ongoing development of the Pharmacopoeia of the Eurasian Economic Union and the current trend for harmonisation of the Russian Pharmacopoeia with the world leading pharmacopoeias suggest the necessity of studying how different pharmacopoeias use nuclear magnetic resonance (NMR) for quality control of medicinal products. The aim of the study was to compare the extent of medicine quality characteristics assessed by NMR in the Russian and foreign pharmacopoeias. The review summarises the experience of various national and world pharmacopoeias in using the NMR method for quality control of medicines and certification of pharmacopoeial reference materials. The comparative analysis covered the following quality parameters: active ingredient identification, determination of the composition of non-stoichiometric compounds, determination of the average polymer chain length in polymers and block copolymers, determination of the absolute content of the active ingredient, identification and quantification of impurities, polymorphism, and crystallinity. It was shown that the United States and Japanese Pharmacopoeias are leading the way in introducing the NMR method into pharmacopoeial analysis. There have been some positive trends in the introduction of the NMR method in the State Pharmacopoeia of the Russian Federation as well. It was concluded that changes are needed in the general chapters “Nuclear Magnetic Resonance Spectroscopy” and “Reference Standards” of the State Pharmacopoeia of the Russian Federation, 14th ed. in order to harmonise the texts with those of the Eurasian Pharmacopoeia and the European Pharmacopoeia and to allow for the possibility of direct identification of a substance by complex analysis of NMR spectral data, without comparing the test sample and the reference standard spectra. The NMR method should be included in the list of absolute methods used for determination of purity of primary chemical reference substances during certification.
Standardisation of the method for prekallikrein activator determination in human immunoglobulin and albumin products
Authors: Kornilova O. G. , Krivykh M. A. , Voropaev A. A. , Fadeikina O. V. , Volkova R. A.
Published: April 2022

Assessment of prekallikrein content is essential for safety control of human immunoglobulin and albumin products. The inherent variability of human prekallikrein reagents and chromogenic substrates indicates the need for standardisation of the chromogenic assay, using the components of a reference standard (RS) not only for construction of calibration curves, but also for confirmation of validity, consistency, and reproducibility of results within different established ranges. The aim of the study was to improve the quality control of human plasma products in terms of prekallikrein activator content. Materials and methods: prekallikrein activator content was determined by the chromogenic assay according to the procedure described in General Monograph 1.8.2.0013.18 of the Russian Pharmacopoeia, using various prekallikrein reagents. An RS was developed in a spiking test, using human albumin solution and Hageman factor beta-fragment reagent. Shewhart control charts were prepared based on the results of determination of prekallikrein activator content in the RS control component.

Results: a two-component RS for prekallikrein activator content with an assigned Hageman factor beta fragment content was developed using the spiking test. The authors substantiated the necessity of using a Russian-produced prekallikrein reagent as the RS component. The in-house reference standard IRS 42-28-445 was certified using all available human prekallikrein reagents, and the IRS 42-28-446 was certified using the prekallikrein reagent included in the kit. The certified prekallikrein activator content is: 51 IU in the batches 1 of IRS components intended for prekallikrein determination; 8.3–11.9 IU/mL in the IRS 42-28-445 control component, after reconstitution in 1.0 mL of purified water, and 5.4–6.6 IU/mL after reconstitution in 2.0 mL of purified water; and 9.1–11.1 IU/mL and 5.6–6.4 IU/mL in the IRS 42-28-446 control component after reconstitution in 1.0 mL and 2.0 mL of purified water, respectively. The IRS component intended for prekallikrein determination is designed for calibration curve construction, while the IRS control component is designed for assessing the validity of test results and preparation of control charts. The analysis of the control charts for the control component made it possible to evaluate the consistency of the analytical process. Conclusions: the components of the developed RSs in combination with Shewhart control charts allow for both determination of prekallikrein activator content, and control of the analytical process, as well as assessment of changes related to the replacement of the reagent batch. The RS control component allows for assessment of analytical process consistency and ensures the standardisation of the test procedure.
Challenges in development and authorisation of gene therapy products
Authors: Soldatov A. A. , Avdeeva Zh. I. , Gorenkov D. V. , Khantimirova L. M. , Guseva S. G. , Merkulov V. A.
Published: April 2022

There are a lot of diseases known today, which are caused by genetic abnormalities. Advances in genetics and biotechnology brought about gene editing technologies that can produce almost any gene, which ultimately led to the emergence of a new class of medicines - gene therapy products (GTPs). The aim of the study was to analyse international experience in development and authorisation of GTPs. The review highlights the challenges in GTP development, related to the search for an optimal approach to therapeutic gene delivery to the target cells. Viral vectors were shown to be a promising gene delivery system, with adenovirus (AV) and adeno-associated virus (AAV) based products demonstrating the highest efficacy and safety. The paper reviews current approaches to gene editing that allow modification of AVs and AAVs to improve GTP efficacy and safety. These modifications are carried out with the aim of, e.g., including a large therapeutic gene into a viral vector, decreasing viral protein expression levels, and decreasing viral vector immunogenicity. The review summarises GTP authorisation procedures in the USA and the European Union, including data on FDA and EMA subcommittees and departments entrusted with advisory functions. The paper mentions that there is one Russian-produced GTP authorised in the Russian Federation, and some other GTPs are in the pipeline. Therefore, the Russian regulatory framework and the Eurasian regulations and recommendations should be updated in order to accommodate for GTP development and authorisation.
Validation of a test procedure for determination of specific activity of human recombinant interferon beta (Infibeta®) using various cell/virus combinations
Authors: Lebedeva Yu. N. , Litvinova N. A. , Lobanova T. N. , Shukurov R. R. , Khamitov R. A. , Gaiderova L. A.
Published: April 2022

Interferon beta preparations have demonstrated efficacy in the treatment of multiple sclerosis. One of the most important quality attributes that support efficacy and safety of interferon beta preparations is specific antiviral activity. Interferon beta activity is determined by the biological test method which can lead to an erroneous final result due to the system uncertainties that contribute to the overall uncertainty. Accurate assessment of specific activity plays an important role in adequate determination of the product’s therapeutic dose, therefore the test method standardisation and validation are of particular relevance. The aim of the study was to validate a test procedure for assessing specific activity of human recombinant interferon beta preparations, using various cell/virus combinations, as illustrated by the example of Infibeta®. Materials and methods: WISH, Vero, A-549, and MDBK cells in combination with mouse encephalomyocarditis virus were used in the study. The testing was performed using the biological test method based on the interferon ability to suppress virus-induced cytopathic effects in cell cultures. The results were processed using methods of mathematical statistics and the GraphPadPrism, Statistical 2/0 software package. Results: the paper compares the results of specific activity determination of Infibeta® (interferon beta-1b) using various cell/virus combinations. The dose-response curves were used to compare the test results. It was demonstrated that all the tested cell lines could be used in the biological test procedure for determination of interferon beta specific activity. However, the best results were obtained with A-549, WISH cells in combination with mouse encephalomyocarditis virus. The following validation characteristics were determined in the cell/virus systems: specificity, linearity, precision, and robustness. Conclusions: the study validated the test procedure that enables measurement of interferon beta specific activity in the range of 4.8–11.2 IU/mL at a satisfactory accuracy level, which guarantees reliable test results. The study demonstrated robustness, intermediate precision, and reproducibility of the test procedure.
Синтез и биологическая активность 5-алкокси- и 5-аминозамещенных 3-бром-4-нитро-1-(тиетан-3-ил)-1H-пиразолов
Authors: Халиуллин Феркат Адельзянович , Клен Елена Эдмундовна , Павлов Валентин Николаевич , Самородов Александр Владимирович , Шепилова Светлана Олеговна , Макарова Надежда Николаевна , Нурланова Сабина Нурлановна , Абзалилов Тимер Айратович
Published: April 2022

5-Алкокси- и 5-аминозамещенные 3-бром-4-нитро-1-(тиетан-3-ил)-1H-пиразолы синтезированы реакциями 3,5-дибром-4-нитро-1-(тиетан-3-ил)-1H-пиразола с алкоголятами натрия и первичными аминами. Структура синтезированных соединений подтверждена с помощью ИК-, 1H и 13C ЯМР-спектроскопии. Исследования in vitro антиагрегантной, антикоагулянтной и антиоксидантной активности выявили перспективные соединения: 3-бром-5-метокси-4-нитро-1-(тиетан-3-ил)-1H-пиразол с антиоксидантным действием и 2-((3-бром-4-нитро-1-(тиетан-3-ил)-1H-пиразол-5-ил)амино)этан-1-ол с антиагрегантным действием. По расчетам in silico для них прогнозируется отсутствие токсических рисков (мутагенности, онкогенности, репродуктивной токсичности, местно-раздражающего действия) и приемлемая биодоступность (по величине площади топологической полярной поверхности).
Синтез, анальгетическая и противовоспалительная активности 5-арил-4-ацетил-3-гидрокси-1-карбоксиметил-3-пирролин-2-онов
Authors: Гейн Владимир Леонидович , Пастухова Евгения Валерьевна , Чащина Светлана Викторовна
Published: April 2022

Взаимодействием метилового эфира ацетилпировиноградной кислоты со смесью ароматического альдегида и гликокола в среде ледяной уксусной кислоты и дистиллированной воды получены 5-арил-4-ацил-3-гидрокси-1-карбоксиметил-3-пирролин-2-оны. Исследована анальгетическая активность полученных веществ по методу «горячей пластины» и определена их противовоспалительная активность на модели асептического каррагенинового воспаления. Установлено, что изученные соединения обладают выраженной анальгетической активностью и относятся к мало токсичным соединениям.
Цитотоксическая активность экстрактов, полученных из интактного растения и клеточных культур Podophyllum peltatum, в отношении клеток рака шейки матки
Authors: Китаева М. П. , Аксенов А. А. , Федотчева Татьяна Александровна , Семейкин А. В. , Шимановский Н. Л.
Published: April 2022

В ФБГНУ ВИЛАР получены клеточные культуры из корня, почки и плода Podophyllum peltatum. Цель исследования — изучить цитотоксическую активность экстрактов органов растения и клеточных культур P. peltatum, а также дать первичную характеристику метаболома растения, отвечающего за эту активность. Методом ультра-эффективной жидкостной хроматографии в составе ацетоновых экстрактов клеточных культур P. peltatum были идентифицированы производные эллаговой, кофейной, галловой кислот, флавоноидов и подофиллотоксина. С помощью резазурин-теста было показано, что ацетоновые экстракты органов растения снижают жизнеспособность клеток HeLa на 52 – 62 %, экстракты каллусных культур — на 52 – 76 %, экстракты суспензионных культур — на 12 – 88 %. Наиболее стабильную цитотоксическую активность проявляют экстракты корневищ с корнями (понижают жизнеспособность клеток на 52 – 60 %), а также экстракты каллусных (на 53 – 74 %) и экстракты суспензионных (на 20 – 60 %) культур, полученных из корня растения. Каллусные и суспезионные культуры клеток из корня P. peltatum могут служить недорогим и удобным сырьем для получения противоопухолевых соединений, что соответствует одной из приоритетных задач современной фармпромышленности — рациональному природопользованию.
Антиоксидантные и генопротекторные свойства α-липоевой (тиоктовой) кислоты при рентгеновском облучении
Authors: Карманова Екатерина Евгеньевна , Черников Анатолий Викторович , Иванов Владимир Евгеньевич , Усачева Анна Максимовна , Брусков Вадим Иванович
Published: April 2022

Установлено, что α-липоевая (тиоктовая) кислота (ЛК), используемая для лечения диабетической и алкогольной невропатии и в комплексной терапии ряда заболеваний, эффективно нейтрализует продукты радиолиза воды, индуцируемого рентгеновским излучением. Влияние ЛК на образование и распад долгоживущих активных форм глобулинов и альбуминов сыворотки крови различно. Этот процесс сопровождается генерацией пероксида водорода и продлением окислительного стресса после облучения. ЛК в диапазоне концентраций от 0,05 до 0,4 мМ устраняет окислительные повреждения ДНК in vitro, но с повышением концентрации ее эффективность снижается. ЛК проявляет генопротекторные и радиомитигаторные (терапевтические) свойства in vivo, снижая образование микроядер в полихроматофильных эритроцитах красного костного мозга мышей после облучения. Полученные результаты и литературные данные свидетельствуют, что ЛК, при соблюдении эффективного фармацевтического окна, является перспективным лекарственным препаратом для предотвращения последствий нарушения редокс-гомеостаза, вызванного радиационным окислительным стрессом.
Побочные эффекты нестероидных противовоспалительных средств и пути их профилактики
Authors: Карева Елена Николаевна , Олейникова Ольга Михайловна , Сереброва Светлана Юрьевна , Кононова Ирина Николаевна , Булгакова Виля Ахтямовна , Шипилова Светлана Юрьевна , Бондарчук Наталия Геннадьевна , Борлакова Марина Салеховна , Яровой Сергей Константинович
Published: April 2022

Нестероидные противовоспалительные средства входят в число наиболее часто назначаемых лекарственных средств. Существует тенденция к еще более широкому их применению в клинической практике в связи с увеличением средней продолжительности жизни и обременением населения возраст-ассоциированными заболеваниями, в первую очередь, с болевым синдромом. При этом альтернативных обезболивающих средств, не вызывающих зависимость и имеющих доказанную эффективность, пока нет. Однако данные многочисленных исследований и мета-анализов свидетельствуют о побочных эффектах нестероидных противовоспалительных средств, включающих желудочно-кишечные, сердечно-сосудистые, печеночные, почечные, церебральные и легочные осложнения. В обзоре представлены современные представления о механизмах основных и побочных эффектов нестероидных противовоспалительных средств и последних разработках в отношении снижения их органотоксичности (химическая модификация фармакофоров). Приведенные сведения будут полезны при оценке соотношения риска и пользы в рациональном использовании нестероидных противовоспалительных средств в более безопасной дозе и продолжительности.
O problema de Snell-Pothenot
Authors: Santos Eduardo Gonçalves dos , Santos Leonardo David Marques dos
Published: April 2022

Os problemas de ordem prática na Matemática remontam praticamente ao seu início, mesmo ainda sem esta ser considerada como um corpo de conhecimentos. No caso da Geometria, a partir dos egípcios, com os problemas de medidas, ela tem se configurado como um ramo da Matemática com raízes eminentemente práticas. O termo “Geometria Prática” encontra-se apresentado sob dois aspectos: um relativo à atitude diante de um problema e outro ligado a um contexto educativo. O presente artigo é um recorte da parte histórica do trabalho de Santos (2020), com uma ampliação a respeito da Geometria Prática, sobre a qual visa apresentar um problema, conhecido como Problema de Ressecção ou, como é mais conhecido, Problema de Snell-Pothenot, em homenagem a Willebrord Snell (ca.1580-1626) e Laurent Pothenot (1650-1732). Trata-se de um problema de levantamento planar, em que são dadas as coordenadas dos três pontos  e , e um observador, em um ponto desconhecido P, que observa o segmento  sob um ângulo α e o segmento  sob um ângulo β. Busca-se determinar a posição do ponto P. E ainda, de forma inversa mas inteiramente análoga, determinar a posição do ponto P, a partir de observações feitas dos pontos A, B e C. A apresentação é composta de um histórico sobre Willebrord Snell, pontuando aspectos importantes de sua vida, bem como de situações em que o problema teve origem. Segue-se então uma discussão a respeito do Problema de Ressecção, para depois fazermos um apanhado sobre Laurent Pothenot.  Em seguida são apresentadas duas soluções desse problema, sendo uma delas classificada como moderna e outra como geométrica. O trabalho é finalizado com as considerações finais e referências.
O ensino de matemática através de atividades ludo-pedagógicas e interativas: perspectivas e possibilidades para as competências da educação 4.0
Authors: Oliveira José Fábio Vieira de , Sena Filho Edvalter da Silva
Published: April 2022

O presente trabalho apresenta práticas e abordagens metodológicas no ensino da Matemática que ampliam o engajamento e aquisição do conhecimento de conceitos matemáticos. As atividades foram desenvolvidas com alunos do 2º e 3º anos da escola EEEP Francisca Castro de Mesquita, localizada na cidade de Reriutaba, pertencente a região da Ibiapaba na zona norte do Ceará. Essas atividades visam aproximar os discentes da Matemática através de práticas e metodologias dinâmicas, possibilitando aos alunos uma maior interação com as ferramentas computacionais e objetos de aprendizagem ludo-pedagógicos. Os resultados sinalizaram que essas práticas favorecem a aquisição e o entendimento de conceitos matemáticos através do raciocínio visual, contribuindo para uma aprendizagem significativa. A presente pesquisa, de cunho qualitativo, tem caráter descritivo por considerar essencial o ambiente escolar como fonte de dados. Esperamos com essa investigação discutir a importância da participação ativa dos estudantes no processo de ensino e aprendizagem da Matemática. O objetivo desse estudo é discutir a utilização de atividades ludo-pedagógicas (jogos) no ensino da matemática a partir uma experiência nas séries do Ensino Médio da educação básica. Este artigo é fruto da Especialização em Qualificação do Ensino de Matemática no Estado do Ceará, ofertada pelo Departamento de Matemática da Universidade Federal do Ceará (UFC), em parceria com a Secretaria de Educação do Estado do Ceará (SEDUC), Coordenadoria Estadual de Formação Docente e Educação a Distância (CODED/CED) e com o apoio financeiro da Fundação Cearense de Apoio ao Desenvolvimento Científico (FUNCAP).
Concepção de estudantes acerca do conceito de representação gráfica no plano cartesiano
Authors: Pinheiro Ana Cláudia Mendonça , Cardoso Mikaelle Barboza , Paula Ana Rachel Brito de
Published: April 2022

Pesquisas sobre representações gráficas no plano cartesiano para o ensino de conceitos matemáticos têm contribuído para a melhoria do ensino dos conceitos de funções, estatística, entre outros, ao longo das últimas três décadas, mas situações recorrentes sobre a aquisição e aplicação desses conceitos ainda constituem relatos de dificuldade na resolução de atividades pelos alunos do Ensino Médio. Dessa forma, esse estudo objetivou conhecer as concepções de estudantes de cursos técnicos do Instituto Federal de Educação, Ciência e Tecnologia do Ceará (IFCE) acerca do conceito de representação gráfica no plano cartesiano, a partir de uma análise das respostas de 98 alunos matriculados na disciplina de Matemática, do primeiro período de 2020.2, de seis Cursos Técnicos. Com enfoque qualitativo e abordagem descritiva, foi realizado um levantamento, organização e análise dos dados, com base nos aspectos da Teoria das Representações Semióticas de Raymond Duval. Os resultados sinalizaram que os estudantes formaram o conceito, dividindo-se em quatro categorias: (1) coordenadas, pares ordenados e/ou localização; (2) características do plano cartesiano; (3) exemplos ou contextos do dia a dia em seus conceitos; e (4) a representação, sistema gráfico e/ou visualização. A maioria dos estudantes percebe o conceito ainda de forma incipiente ou não articulada. Na 4ª categoria, os alunos elaboram conceitos aprofundados em língua materna, bem como características importantes das relações entre as representações gráficas e o plano cartesiano. Espera-se que esse trabalho contribua com orientações para as práticas de ensino deste conteúdo, favorecendo a aprendizagem de estudantes, com o intuito de superar dificuldades encontradas, diminuindo, assim, possíveis lacunas conceituais acerca das representações gráficas no plano cartesiano.
Humanistic Literacy: Exploring Education Policies for MBKM (Collegiate Independent Learning) Programs from the Participation of the Academic Community in Indonesia
Authors:   Universitas Muhammadiyah Malang, Indonesia, Eriyanti Ribut Wahyu , Kusumastuti Frida , . Salahudin , Yumitro Gonda , Roziqin Ali , Dintarini Mayang , Arrozy Ahmad , Wicaksono Agung Prasetyo , Muhibah Siti
Published: April 2022

This paper explores 1) why humanistic literacy is important in welcoming the industrial revolution 4.0, especially in the academic community and 2) how the implementation of MBKM (Collegiate Independent Learning) programs can be the main support in responding to industry 4.0. The purpose of this paper is to illustrate “how” the academic community uses knowledge from humanistic literacy. The study used a sample of 1,753 respondents from the academic community of Universitas Muhammadiyah Malang from December 16 to December 19, 2021 using PISA instruments and UNESCO indicators through Likert scale measurements. We show that humanistic literacy is a knowledge capital for the academic community with scores from respondents at the level of identification (4.3), application (4.22), and reasoning (4.24) that support the academic community for the development of social skills such as collaborative efforts and networking development in producing innovative industrial service products.