ORIGINAL ARTICLES
Introduction. Vitamin D3 possesses antioxidant, anti-inflammatory, immunomodulatory, and other properties, has been shown to be effective in some autoimmune diseases, which is a prerequisite for studying its effect, when applied locally, on the clinical status and morphology of the site of injury in ulcerative colitis (UC).
The aims was to study the effect of vitamin D3 in the composition of original rectal suppositories on the clinical status and morphology of the lesion of colon in experimental UC.
Materials and methods. UC was modeled by two-stage administration of oxazolone. Rectal suppositories were prepared on the basis of a 10% aqueous solution of vitamin D3. The clinical status was assessed using the Disease activity index (DAI) scale. In the area of colon damage, the number of neutrophils, lymphocytes, eosinophils, histiocytes, plasmocytes and fibroblasts was examined per mm² d the tissue damage index (TDI) was calculated.
Results and Discussion. In experimental UC, DAI increase an ulcerative defect is recorded in the colon, the number of neutrophils, lymphocytes, eosinophils, plasma cells, histiocytes, fibroblasts, TDI increases. The use of original rectal suppositories with vitamin D3 in experimental UC leads to a decrease in DAI, the size of the ulcer and TDI, a decrease in the infiltration of the intestinal wall by neutrophils, lymphocytes, eosinophils and plasma cells, an increase in the infiltration of histiocytes, fibroblasts.
Conclusions. In experimental oxazolone-induced colitis, the clinical picture and morphology of the injury site characteristic of UC are recorded. The use of original rectal suppositories with vitamin D3 a total dose of 18,000 IU leads to a decrease in the severity of clinical signs and a decrease in the representation in the colon wall of cells involved in tissue destruction, an increase in the representation of cells mediating repair, which was reflected in a decrease in the area of the ulcer and tissue damage index , the severity of clinical signs according to DAI weakens as lymphocytes and plasma cells decrease in the area of damage to the colon, decrease in the size of the ulcer and decrease in TDI, increase in histiocytes and fibroblasts.
The aim of the study was to study the changes in the morphofunctional state of the liver after the combined transplantation of multipotent mesenchymal stromal (MMSC) and stellate liver cells (ZCP) in animals with partial hepatectomy.
Materials and methods. The MMSC culture was isolated from the placental chorion of 5 laboratory animals f female mice aged 3-4 months, weighing 22-23 g, gestation period of 18 days. The mononuclear fraction of the cells was obtained by sequential mechanical and enzymatic treatment of the placental tissue. The cultivation of MMSCs was carried out in a CO2 incubator at a temperature of 37 0C with a carbon dioxide content of 5% and a humidity of 90%. ZCP was isolated by collagenase-pronase perfusion of the liver, followed by cell separation in the histodense density gradient. MMSCs of the 3rd passage were introduced, and ZKP was introduced immediately after isolation. MMSCs at a dose of 4 million cells/kg and ZCP at a dose of 9 million cells/ kg were used for transplantation to labotory animals. The cells were injected 1 hour after partial hepatectomy. The biochemical parameters of peripheral blood and morphometric parameters of the liver were evaluated on the 3rd, 7th day after the administration of MMSC.
Results. As a result of the study, it was found that the combined transplantation of MMSC and ZCP after partial hepatectomy leads to the restoration of the level of enzymes that characterize cytolysis and cholestasis, normalization of the protein-synthetic function of the liver, normalization morphometric parameters of the liver. A significant mechanism for restoring the morphofunctional state of the liver can be considered the influence of transplanted MMSCs and ZCP on the cell repair system, which leads to a decrease in the severity of programmed cell death of hepatocytes and the level of pathological mitoses.
Discussion. Combined transplantation of MMSCs and HCP after partial hepatectomy leads to an increase in the level of hepatocyte growth factor (HGF), thus contributing to an se in the mitotic activity of hepatocytes and the restoration of liver mass. The transplanted cells also, by increasing the activity of DNA repair enzymes of the PARP family, lead to a decrease in the level of pathological mitoses, inhibition of their programmed cell death.
Conclusions. The conducted studies demonstrate the ability of combined MMSC and PCR transplantation to restore the morphofunctional state of the liver after partial hepatectomy and provide the basis for conducting pilot clinical studies
Introduction. The formation of isthmic-cervical insufficiency (ICI) in 80% is associated with intraamnial inflammation, this is the subject of discussion of new mechanisms of the pathogenesis of premature cervical remodeling. In this regard, it is of interest to study the relationship of ICS with intrauterine and cervicovaginal infections during pregnancy and their impact on the course and outcomes of pregnancy, which was the purpose of our study.
Methods. A prospective cohort study included 100 pregnant women with ICI, taken by a continuous sample. All patients at the time of ICI manifestation underwent a comprehensive clinical and laboratory examination aimed at diagnosing cervicovaginal infections, according to e results of which the pregnant women were divided into 2 groups: the first group consisted of 72 women with ICI and cervicovaginal infections, the second group — 28 women with ICI and normocenosis of the vagina.
Results. There were no significant differences between the compared groups in terms of the history of miscarriage, extragenital pathology and the frequency of complications of this pregnancy. Intrauterine infection during pregnancy in patients of group 1 was observed 4 times more often, being 55.6% (40) versus 14.3% (4) in group 2 (RR = 3.9, 95% CI = 1.5-9.9, p <0.001). Preterm birth was significantly more frequent in women of group 1, accounting for 62.5% (45), in group 2 — 28.6% (8). Perinatal mortality cases were observed only in group 1, amounting to 97‰ (7). In children from women in group 1, complications of the early neonatal period were more common, primarily due to prematurity. In addition, IUI in newborns was diagnosed 10 times more often in group 1, reaching 38.8% (26) of cases, compared with group 2 — 3.6% (1) (RR = 10.87, 95% CI = 1.55–76.22, p <0.001).
Discussion. Perinatal outcomes in ICI associated with cervicovaginal infections are characterized by the presence of perinatal mortality, a higher incidence of preterm birth and IUI of the newborn than in women with ICI without cervicovaginal infection.
Introduction. Since 2011, a technology such as a non-invasive prenatal test (NIPT) has been used in the world i order o identify pregnant women at a high risk of giving birth to a child with chromosomal aneuploidy (CA). An important indicator of the test's effectiveness is the fetal fraction (FF), since its low level does not allow to give a reliable result to a patient.
Aims: to determine the factors that can affect the level of FF during NIPT.
Materials and methods. A retrospective comparative covenant study was carried out. The study included 288 patients who underwent NIPT in 2015-2018 after the standard complex of prenatal diagnosis (t 12-18 weeks of pregnancy). We assessed the correlation of the FF level with various clinical and anamnestic parameters and with indicators of biochemical screening for the first trimester (PAPP-A and β-ХГЧ). A comparison was made in terms of the FF level during pregnancy with a favorable and unfavorable outcome.
Results. The average FF level in patient where CA was detected in the fetus was 9.01 (5.4-11)%, in the absence of CA — 9.7 (6.5-11.95)%, the difference are not statistically significant (p = 0.37). In patients with a physiological course of pregnancy, this indicator was 10.07 (6.6-12.57)%, and in patients with a complicated course of pregnancy, it was significantly lower — 8.11 (5.35-11.29)% (p = 0.02). We also analyzed the presence of a correlation between the level of FF and fetal weight at term, but no statistically significant correlation was found (r=0.13). There is a statistically significant inverse relationship between the FF level d the age of the pregnant woman, the patient's weight and body mass index, the number of pregnancies in the anamnesis, as well as a direct relationship between the FF and the β-hCG level (in MoM).
Conclusions. FF is an important parameter of NIPT. A sufficient level of FF not only indicates a high reliability of the result obtained during NIPT, but also increases the chances of a favorable pregnancy outcome. The level of FF can be influenced by a number of clinical and anamnestic characteristics of the patient (weight body mass index, age, obstetric history). Studies aimed at determining the level of FF in various physiological and pathological conditions during pregnancy seem promising and thanks to them, it is possible that new models for predicting pregnancy complications will subsequently be proposed.
Relevanc. Surgical Site Infection (SSI) after open heart surgery is a significant problem in clinical, social, and economic aspect which causes the need to identification of the preferred procedures for successful prevention of the SSI.
Objectives. To determine risk of the SSI in cardiac surgery depending on complexity of intervention, using of cardiopulmonary bypass (CBP) and use of both internal mammary arteries (IMA).
Methods. Prospective observations study from 2010 to 2019 in cardiac surgery department of the Ural Institute of Cardiology, where in total 4993 open heart surgery procedures were consecutively performed. All SSI cases were recorded up to 90 days after surgery. The analysis was performed to identify risk of cardiopulmonary bypass (CPB), bilateral IMA grafting and combined procedures on the risk of the postoperative wound infection.
Results. During the investigation period, total 220 cases of the SSI (4,5%) have been registered of the 4993 patients undergoing open heart surgery. It included 42 cases of deep sternal infection (0,9%) and 178 cases of superficial infection (3,6%). The main pathogen identified was Staphylococcus epidermidis (56,4%). During the hospital period, 151 cases (66,5%) of SSI have been detected, with the median time to detection of the complication 6 days. The relative mortality risk in deep sternal infection group was 4,4 times higher than in the group without SSI (HR 4,6, 95 % CI 1,5-13,9, p=0,003624). CABG increases the relative risk of SSI in compare with non-CABG procedures (OR 3,086169; 95%CI 1,281 – 7,437), while the complexity of the operation (combined versus isolated interventions) does not significantly increase the risk (OR 0.972283; 95% CI: 0.696 - 1.359). The incidence of SSI in the group of in situ BIMA grafting was 8.8%, significantly increasing the likelihood of the SSI in compare to those with SIMA (OR 2.167983, 95% CI 1.463 - 3.212; p =0,000057). CBP significantly increases the risk of postoperative wound infections (OR 1.523890, 95% CI 1.149 - 2.022, p = 0.001742).
Conclusions. Refusal of cardiopulmonary bypass, simultaneous procedures and bilateral coronary artery bypass does not allow completely to avoid postoperative wound infections. Nevertheless, the technical features of the preparations and use of grafts, including skeletonization, prevention of coagulation and the preference for sequential composite CABG, can reduce the risk associated with the type of the open heart surgery.
Introduction. The leading reason for the growth of oncological morbidity and mortality is the untimely detection and treatment of oncological diseases, restrictions on the availability of specialized oncological medical care formed by the lack of oncologists. For the implementation of the national project to combat oncological diseases, he search for ways to provide medical organizations with personnel is highly relevant. The purpose of the study is to propose ways of providing oncologists to St. Petersburg healthcare institutions at all levels based on an analysis of the staffing level of medical personnel in this profile.
Materials and methods. The indicators of provision of all levels of medical organizations in St. Petersburg with oncologists were analyzed using a continuous method of observation over 5 years in the period from 2014 to 2018. The data obtained were statistically processed and used to calculate the need (surplus) in specialists of this profile, as well as to calculate indicators for long-term planning, taking into account the available staffing of medical institutions of city and federal subordination.
Results and Discussion. The positive dynamics of staffing of doctors-oncologists, especially individuals, was noted. The growth of the indicator in the analyzed period was 13.6%, which did not allow achieving satisfactory indicators: the staffing rate of oncologists was 88.8%, individuals – 86.1%. Differences in the staffing of medical organizations of various types were noted in 2018: the staffing rate in outpatient medical organizations was 81.7%, and in individuals – 66.7%; in hospitals staffing was 95.6%, and in individuals – 91.6%. Calculations of e deficit (surplus) in the staff of oncologists for medical organizations of all types made it possible to establish that there is no pronounced deficit in specialists, but there is a disproportion in their provision, at a loss for outpatient medical organizations. The calculated prospective need for targeted training of oncologists for medical institutions in St. Petersburg amounted to 18 specialists annually.
Conclusion. The actual indicators of staffing of the St. Petersburg oncological service at all levels have been established, approaches have been proposed to meet the needs of medical organizations for oncologists. The implementation of the national project to combat oncological diseases will contribute to the early detection of oncological diseases, increasing the availability of medical care provided for them.
Introduction. The main goal of the state policy in the field of healthcare is to form a system that ensures the availability of medical care and increases the efficiency of medical services. The volume, type and quality of medical care must correspond to the level of morbidity, the needs of the population and the advanced achievements of medical science. Primary health care is the backbone of the health care delivery system. The problem of it improvement, including in rural areas, is a priority and has national significance. The development of measures to increase the availability of primary health care according to the territorial principle is an urgent scientific and practical problem.
The purpose of the study — based on the analysis, methodologically substantiate and develop measures to increase the availability and improve the system of organizing the provision of primary health re to the rural population on a territorial basis.
Materials and methods. Mathematical-statistical and analytical (quantitative, structural, comparative) research methods were used.
Results and Discussion. In the Chelyabinsk Region, there are disproportions in the provision of the population with medical personnel: the provision of the urban population with doctors and l personnel is significantly higher than that of the rural population. The indicator of staffing with paramedical personnel in full-time positions of feldsher-obstetric stations is 20.1% lower than in the Russian Federation. The index of "combination rate" among doctors working in outpatient departments is 1.2 times higher than the target indicator of the National Health Project, and in rural areas it is 1.1 times. In order to unify the organizational and methodological approaches, the authors proposed a classification of medical stations and their organizational and functional structure.
Conclusions. The organization of the provision of primary health care to the rural population according to the territorial-district principle with the formation of an organizational model of the rural medical district will increase the availability of primary medical health care to the rural population.
Introduction. The article is devoted to the analysis of the state of cardiovascular morbidity (CVD), mortality of the population and the demographic situation, as well as determining the prevalence of CVD as a medical and social problem at the federal and regional levels. The analysis of the implementation of the policy of providing medical care to patients with CVD, modern scientific publications on the indicated problem, and the search for ways to solve the medical and social problem of high morbidity and mortality from CVD are carried out.
Materials and methods. The data of official statistical information on the morbidity and mortality of the adult population of the Russian Federation and the Voronezh region for 2010–2019 were used, the works of modern domestic and foreign scientists dealing with the solution of this problem were studied.
Results. It has been established that high CVD and mortality are an acute medical and social problem. Mortality from CVD in Russia in 2019 amount to 46.8% of the total number of deaths. The mortality rate from CVD in Russia exceeds that in the developed countries of the European Union. Despite the presence of positive trends in the fight against this disease, the mortality rate from CVD in the Voronezh region is higher than the average for the Russian Federation (601.8 and 573.2 per 100 thousand population, respectively). The deterioration of the demographic situation, the presence of active targeted projects in this area are the basis for conducting scientific research to find ways to duce CVD and mortality in the adult population.
Conclusion. The high morbidity and mortality from CVD requires a search for new ways to solve the problem, since the existing approaches to its solution are not holistic and universal. It is urgent to develop an integrated approach that takes into account the medical and social characteristics of the adult population of the region.
CASE REPORTS
Introduction. A significant increase in the quality and increase in the life expectancy of HIV patients during treatment with antiretroviral drugs necessitates the implementation of the reproductive function in these patients. The participation of a surrogate mother in the treatment of infertility in HIV-infected potential parents, vided by the Russian legislation, requires additional solutions to a number of clinical and organizational problems. The aim was to substantiate a surrogacy program as a method of choice for the treatment of infertility in patients with HIV-positive status and comorbid cancer and also a multidisciplinary approach to organizing it on the example of a specific clinical situation and based on the analysis literature data.
Materials. We report a case of using a surrogacy program for a married couple with a positive HIV status in the 4th stage of the disease using the husband's sperm and donor oocytes. The use of donor oocytes in this situation is due to the onset of menopause against the background of a comorbid severe cancer that required multiple courses of chemotherapy.
Conclusion. Potential biological parents with a positive HIV status in stage 4 of the disease may have a comorbid oncological pathology, which in itself, as well as its treatment, contributes to a decrease in fertility, and for the future biological mother, it is an obstacle to independently carrying a pregnancy. In this regard, the surrogacy program is the method of choice for the treatment of infertility in this clinical situation. It is advisable for obstetricians-gynecologists (reproductologists) to inform the surrogate mother about the potential risks of infection with the participation of genetic parents with HIV-positive status at various stages of IVF and about preventive measures during gestation in conjunction with the infectious disease specialist of the regional centers for the prevention and control of AIDS.
LITERATURE REVIEWS
Introduction. Preeclampsia is a hypertensive disorder of pregnancy that remains one of e leading causes of maternal and perinatal morbidity and mortality. The preventive strategy of prophylaxis with acetylsalicylic acid gives only a relative reduction in risk, and in a significant part of cases is ineffective. At the same time, the issue of preeclampsia prophylaxis is extremely relevant, since there are no effective methods for treating this condition, with the exception of the completion of gestation.
Purpose of the study. Based on the scientific literature, to evaluate the effectiveness of aspirin in the prevention of preeclampsia and to determine the possible reasons for the lack of effectiveness of such prevention.
Materials and methods. We conducted a search for scientific literature, as a result of which 39 sources were selected for the final scientific review (2010-2020). The PubMed, ResearchGate and Elibrary databases were used to search for scientific literature.
Results and discussion. The article presents a literature review of the analysis of the effectiveness of aspirin for the prevention of preeclampsia over the past 5 years, describes the mechanism of action of aspirin, presents studies that confirm or refute the effectiveness of aspirin depending on the dosage and gestational age. Potential alternative agents for the prevention of preeclampsia in cases of aspirin ineffectiveness have been reviewed.
Conclusion. Literature review data show that the effectiveness of aspirin for the prevention of preeclampsia depends on the chronobiological effect, compliance, gestational duration and dosage. It is necessary to continue research on the effectiveness of aspirin, and studies carried out on the Russian population will be of particular value for the Russian Federation.
Introduction. Despite the notable and rapid progress in the development of medical 3D printing in recent years, not much is known about the use of this technology in obstetrics and gynecology.
The purpose of our review of scientific literature was to determine the current level of 3D printing development, discuss the closest and long term prospects for using this technology in obstetrics and gynecology, and analyze its potential advantages and disadvantages.
Materials and methods. We searched for scientific literature. 378 papers passed a three-step screening, as a result of which 42 sources were selected for the final scientific review.
Results and discussion. The main areas in which dimensional printing can be used in this area of medicine is the creation of simulation models and training for students, the creation of anatomical models for preoperative preparation, the surgical instruments, the creation of new dosage drug forms (including transvaginal ones), and bioprinting of organs and tissues.
Conclusion. The presented literary review allows us to conclude that 3D printing the obstetrics and gynecology is a current rapidly developing direction. The organization of 3D modeling and printing laboratories can significantly increase the efficiency of teaching students and residents. In addition, obstetricians-gynecologists and surgeons should be informed about the possibility of 3D printing surgical instruments according to an individual design. It can inspire them to implement their own ideas and develop domestic innovative developments. Three-dimensional printing of dosage forms and bioprostheses requires more complex technological solutions, and is not yet used in clinical practice. However, given the enormous prospects for these areas, various grants should be envisaged for their development in Russia
Introduction. The article presents an overview of the results of modern evidence-based scientific research on the mechanisms of formation of genital prolapse as one of the fundamental causes of pelvic floor muscle insufficiency in women. A systematic analysis of the current literature data on the involvement of clinical, anamnestic and pathogenetic motives in the development of pelvic organ prolapse in women was carried out.
Objective: to expand the understanding of the role of anamnestic and biological factors in the pathogenesis of genital prolapse in women.
Material and method. The review includes the scale of publications of domestic and foreign authors included in the PubMed database on this topic with a search depth of 20 years. The criteria for inclusion of articles for the system analysis were articles corresponding to the topic chosen for the study of the problem of gynecology, namely, the pathogenesis of genital prolapse in women with a search depth of twenty years. The criteria for exclusion from the study are the age of published scientific works, exceeding a twenty-year period, and inconsistency with the chosen top.
Results. The conducted analysis demonstrates the fundamental role of epigenetic factors and molecular genetic predisposition in patients in the progression of genital prolapse which makes it possible to develop personalized prediction and prevention of pelvic floor dysfunction in women, prevention of social burnout.
Conclusion. Further study of the mechanisms of formation, determination of the most significant molecular and genetic polymorphisms that increase the risk of pelvic organ prolapse in women, is a promising vector of scientific research. These studies will help to form a pathophysiological basis that allow for a thorough examination to identify a predisposition to the development of a severe disease long before its occurrence.
Introduction. The peptide hormone relaxin, which is produced by cells of the corpus luteum during and outside pregnancy, has a huge number of clinically significant effects, mediating many biological mechanisms, including antifibrotic, vasodilatory, angiogenic, anti-inflammatory and antiapoptotic effects.
Purpose of the study: based on the study of modern literature data, to analyze the results of scientific research, representing the current system of views on the physiological and pathophysilogical effects of relaxin.
Materials and methods. A study f scientific publications for the period from 2005 to 2020 in e PubMed and Elibrary databases was carried out using the keywords: relaxin, pregnancy, relaxin signaling pathway, reproductive system, extracellular matrix.
Results and Discussion. The study of modern views on the physiology of relaxin has shown that this hormone mediates its effects by binding to the specific receptor RXFP1, which is localized in a large number of reproductive nonproductive tissues. Relaxin performs many functions related to the remodeling of the extracellular matrix and vasculature. The main uterotropic effects of this peptide include stimulation of growth and vascularization of the uterus, remodeling of extracellular matrix components, and regulation of vascular endothelial growth factor in preparation for implantation.
Conclusion. The progress of the last decade in understanding the biochemistry of the hormone relaxin has formed the basis for a deeper penetration into all the variety of its physiological roles. The participation of relaxin in the mechanisms of relaxation of the myometrium during pregnancy, remodeling of the connective tissue of target organs in the antenatal period creases its potential clinical significance. The prospect of a possible therapeutic use of relaxin preparations in stimulating antenatal transformation of the cervix, in vitro fertilization, therapy of preeclampsia, acute heart failure and myocardial ischemia turns it into a potential therapeutic agent for these pathological conditions.
The purpose of the review: to analyze the evolution of the views of clinicians and researchers on the relationship between gastroesophageal reflux and is extraesophageal bronchial manifestations, and the stages of the formation of the diagnosis of microaspiration of the lower respiratory tract in children.
Materials and methods. Sarch in electronic databases: Elibrary, Federal Electronic Medical Library of the Ministry of Health of the Russian Federation, bibliographic database of articles on medical sciences, created by the US National Library of Medicine MEDLINE.
Main statements. Diagnostics and treatment of gastroesophageal reflux and its extraesophageal manifestations both in the 20th century and at the beginning of the 21-st century present certain difficulties for pediatricians and pulmonologists. Currently, there are numerous domestic and foreign clinical guidelines created with the aim f improving diagnostics and approaches to the treatment of gastroesophageal reflux and "silent" microaspiration of the lower respiratory tract of the respiratory tract. However, the evidence base for the problem under discussion is rather limited, due to the lack of specificity of the symptoms of the disease and the absence of a "gold standard" diagnostics.
Conclusion. The presented review gives information about non-invasive diagnosis of microaspiration in children with bronchial asthma and chronic cough what will help us decide on treatment, taking into account the concomitant gastroesophageal reflux. A non-invasive method for detecting lactose in the induced sputum of the respiratory tract and also an additional determination of the average cytochemical coefficient of macrophages can serve as an effective alternative to the verification of "silent" microaspiration in children with bronchial asthma and chronic cough.
EDUCATION AT A MEDICAL UNIVERSITY
Introduction. To prevent the spread of the COVID-19 pandemic, medical educational institutions have moved o quarantine with distance learning. It was implemented suddenly and imperatively, which can have long-term consequences not only in the form of a decrease in the quality of education, but also in the form of certain psychological problems for both students and faculty.
Aims: to assess the impact of the forced transition to distance learning during the pandemic of a new coronavirus infection on the lifestyle and the degree of satisfaction with education of medical students.
Materials and methods. A one-stage descriptive study was carried out in which 165 students of the 4th-5th year of the Faculty of Medicine and Prevention, who studied remotely at the Department of Obstetrics and Gynecology, took part in it. Among them, an anonymous survey was conducted, which included questions of lifestyle, degree of satisfaction and their opinion on the quality of education.
Results. According to the results of the questioning, distance education influenced the lifestyle of the majority of the students surveyed — 32% began to get better sleep, 26% noted the appearance of sleep disorders. With regard to the nutrition of students, a similar picture is observed — 55% began to eat more regularly and balanced, 21% - ate excessively. Only 7.3% students are most actively involved in the distance learning process, most are periodically distracted (88.5%) or are engaged in other activities (4.2%). The theoretical component of distance learning was assessed by students quite high — 7.7 ± 2.4 points. However, the practical skills caused a lot of dissatisfaction were rated low 4.1 ± 2.4 points. Among the advantages of distance education — 92.7% singled out time and financial savings. Of the shortcomings — 86.1% indicated the lack of work with patients.
Conclusions. The transfer of medical students to distance education entails not only a possible decrease in the quality of education and student motivation to study, but also a significant change in lifestyle.
ISSN 2949-4389 (Online)