Pub Date : 2023-04-03DOI: 10.36604/1998-5029-2023-87-90-98
Introduction. Cytomegalovirus (CMV) infection directly and indirectly can cause placental dysfunction. One of the reasons for its development may be a deficiency of energy supply due to changes in the level of fatty acids (FA) – the main sources of energy in the cell.Aim. Analysis of the fatty acids concentration and causes of its changes in the placenta during exacerbation of CMV infection in the first trimester of pregnancy.Materials and methods. Biosamples (venous blood, epithelium from the inner surface of the cheek, mucous membrane of the cervical canal, villous chorion) of 32 CMV-seropositive women with an exacerbation of CMV infection in the first trimester of pregnancy (main group) and 30 CMV-seronegative women (control group) were studied. Exacerbation of CMV infection was diagnosed by ELISA to detect IgM and IgG with avidity of 65% or more, PCR to detect CMV DNA. The profile and relative concentration of individual FA in villous chorion lipid extracts were studied by gas-liquid chromatography. The activity of pyruvate dehydrogenase, succinate dehydrogenase, NADP-dependent malate dehydrogenase, and glucose-6-phosphate dehydrogenase was determined by a histochemical method on sections of freshly frozen villous chorion tissues.Results. In the main group placentas, the concentration of medium-chain saturated fatty acids was statistically significantly lower: capric by 50%, lauric by 51%, unsaturated myristoleic by 44%; long-chain unsaturated acids: palmitoleic, oleic, linoleic and α-linolenic fatty acids by 52%, 55%, 57% and 64%, respectively; of polyunsaturated fatty acids with a very long chain: eicosapentaenoic and docosahexaenoic by 44% and 41%, respectively. The activity of enzymes: succinate dehydrogenase, pyruvate dehydrogenase, NADP-dependent malate dehydrogenase and glucose-6-phosphate dehydrogenase decreased.Conclusion. Thus, we found a decrease in energy supply in the placenta during exacerbation of chronic CMV infection in the first trimester of pregnancy. Disorders of placental energy metabolism can cause placental insufficiency, which has adverse consequences for fetal development.
{"title":"The role of fatty acids in disturbance of energy processes in the early placenta with cytomegalovirus infection","authors":"","doi":"10.36604/1998-5029-2023-87-90-98","DOIUrl":"https://doi.org/10.36604/1998-5029-2023-87-90-98","url":null,"abstract":"Introduction. Cytomegalovirus (CMV) infection directly and indirectly can cause placental dysfunction. One of the reasons for its development may be a deficiency of energy supply due to changes in the level of fatty acids (FA) – the main sources of energy in the cell.Aim. Analysis of the fatty acids concentration and causes of its changes in the placenta during exacerbation of CMV infection in the first trimester of pregnancy.Materials and methods. Biosamples (venous blood, epithelium from the inner surface of the cheek, mucous membrane of the cervical canal, villous chorion) of 32 CMV-seropositive women with an exacerbation of CMV infection in the first trimester of pregnancy (main group) and 30 CMV-seronegative women (control group) were studied. Exacerbation of CMV infection was diagnosed by ELISA to detect IgM and IgG with avidity of 65% or more, PCR to detect CMV DNA. The profile and relative concentration of individual FA in villous chorion lipid extracts were studied by gas-liquid chromatography. The activity of pyruvate dehydrogenase, succinate dehydrogenase, NADP-dependent malate dehydrogenase, and glucose-6-phosphate dehydrogenase was determined by a histochemical method on sections of freshly frozen villous chorion tissues.Results. In the main group placentas, the concentration of medium-chain saturated fatty acids was statistically significantly lower: capric by 50%, lauric by 51%, unsaturated myristoleic by 44%; long-chain unsaturated acids: palmitoleic, oleic, linoleic and α-linolenic fatty acids by 52%, 55%, 57% and 64%, respectively; of polyunsaturated fatty acids with a very long chain: eicosapentaenoic and docosahexaenoic by 44% and 41%, respectively. The activity of enzymes: succinate dehydrogenase, pyruvate dehydrogenase, NADP-dependent malate dehydrogenase and glucose-6-phosphate dehydrogenase decreased.Conclusion. Thus, we found a decrease in energy supply in the placenta during exacerbation of chronic CMV infection in the first trimester of pregnancy. Disorders of placental energy metabolism can cause placental insufficiency, which has adverse consequences for fetal development.","PeriodicalId":9598,"journal":{"name":"Bulletin Physiology and Pathology of Respiration","volume":"130 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78254086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-03DOI: 10.36604/1998-5029-2023-87-108-114
L. Dudchenko, S. Belyaeva, E. Solovieva, I. G. Ulchenko, N. Zhukova
Introduction. The increase in the number of patients with post-COVID syndrome determines the relevance of their rehabilitation in sanatorium and resort institutions, of both local and climate-therapeutic resorts.Aim. To identify the possibility for the rehabilitation of patients with severe forms of COVID-19 in the conditions of the climatic pulmonological resort of the South Coast of Crimea in the winter season.Materials and methods. Clinical-anamnestic, laboratory, functional and computed-tomographic results of the examination of the thorax of a patient who had a severe form of COVID-19. Rehabilitation was carried out 21 days complexly using climatotherapy, therapeutic exercise, respiratory, medication and physiotherapy. The effectiveness of treatment was assessed using a 6-minute step test, Borg scale, mMRC dyspnea scale, oxygen assessment chart, rating of health status, Hospital Anxiety and Depression Scale (HADS), Fatigue Assessment Scale (FAS), dyspnea assessment index (DDI/TDI), questionnaires of life quality EQ-5D and SF-36.Results. At the end of the rehabilitation course, general well-being improved, shortness of breath decreased, exercise tolerance increased, positive dynamics of spirographic parameters, Borg scale scores and a 6-minute step test were noted. The indicators of depression on the HADS scale normalized, positive dynamics was noted according to the SF-36 questionnaire of the psychological component of health. The severity of pain/discomfort and anxiety/depression according to the EQ-5D questionnaire decreased. The X-ray picture has improved. When determining the diffusion capacity of the lungs (DLCО), an increase of 30% from the initial value was revealed.Conclusion. Rehabilitation of a patient who had a severe form of COVID-19 with bilateral lung damage in the conditions of the climatic pulmonology resort of the South Coast of Crimea in the winter season is effective. To assess the lung function of patients who have undergone COVID-19, the most effective method can be considered the determination of lung diffusion capacity (DLCО). Spirogram indicators do not always objectively reflect the severity of the condition.
{"title":"Rehabilitation experience of a patient with severe form of COVID-19 at the pulmonological climatic resort of the Southern Coast of Crimea","authors":"L. Dudchenko, S. Belyaeva, E. Solovieva, I. G. Ulchenko, N. Zhukova","doi":"10.36604/1998-5029-2023-87-108-114","DOIUrl":"https://doi.org/10.36604/1998-5029-2023-87-108-114","url":null,"abstract":"Introduction. The increase in the number of patients with post-COVID syndrome determines the relevance of their rehabilitation in sanatorium and resort institutions, of both local and climate-therapeutic resorts.Aim. To identify the possibility for the rehabilitation of patients with severe forms of COVID-19 in the conditions of the climatic pulmonological resort of the South Coast of Crimea in the winter season.Materials and methods. Clinical-anamnestic, laboratory, functional and computed-tomographic results of the examination of the thorax of a patient who had a severe form of COVID-19. Rehabilitation was carried out 21 days complexly using climatotherapy, therapeutic exercise, respiratory, medication and physiotherapy. The effectiveness of treatment was assessed using a 6-minute step test, Borg scale, mMRC dyspnea scale, oxygen assessment chart, rating of health status, Hospital Anxiety and Depression Scale (HADS), Fatigue Assessment Scale (FAS), dyspnea assessment index (DDI/TDI), questionnaires of life quality EQ-5D and SF-36.Results. At the end of the rehabilitation course, general well-being improved, shortness of breath decreased, exercise tolerance increased, positive dynamics of spirographic parameters, Borg scale scores and a 6-minute step test were noted. The indicators of depression on the HADS scale normalized, positive dynamics was noted according to the SF-36 questionnaire of the psychological component of health. The severity of pain/discomfort and anxiety/depression according to the EQ-5D questionnaire decreased. The X-ray picture has improved. When determining the diffusion capacity of the lungs (DLCО), an increase of 30% from the initial value was revealed.Conclusion. Rehabilitation of a patient who had a severe form of COVID-19 with bilateral lung damage in the conditions of the climatic pulmonology resort of the South Coast of Crimea in the winter season is effective. To assess the lung function of patients who have undergone COVID-19, the most effective method can be considered the determination of lung diffusion capacity (DLCО). Spirogram indicators do not always objectively reflect the severity of the condition.","PeriodicalId":9598,"journal":{"name":"Bulletin Physiology and Pathology of Respiration","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85756195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-03DOI: 10.36604/1998-5029-2023-87-83-89
N. A. Ishutina, I. A. Аndrievskaya, I. Sinyakin
Aim. To evaluate the phospholipid composition of erythrocyte membranes in parturient women who had COVID-19-associated community-acquired pneumonia (CAP) in the third trimester.Materials and methods. The material for the study was erythrocytes of peripheral blood of 65 parturient women diagnosed with COVID-19, moderate/severe course, CAP of viral etiology (main group). Patients of the main group, depending on the severity of CAP, were divided into two subgroups: subgroup 1 – moderate course of pneumonia (n=33), subgroup 2 – severe course of pneumonia (n=32). The control group consisted of 35 healthy parturient women. The quantitative composition of phospholipids was studied by two-dimensional thin-layer chromatography according to Kirchner.Results. In subgroup 1, the concentration of phosphatidylethanolamine and phosphatidylcholine in erythrocyte membranes was below the standard values by 38% and 29%, respectively (p<0.001), in subgroup 2, these indicators decreased by 32% and 48%, respectively (p<0.001). At the same time, a significant increase in the concentration of lysophosphatidylcholine was found in patients of subgroup 1 by 92% (p<0.001) and in patients of subgroup 2 by 110% (p<0.001), compared with the group of healthy individuals. In addition, structural changes in the lipid bilayer of erythrocyte membranes under conditions of COVID-19associated CAP were characterized by a pronounced increase in the concentration of minor fractions of phospholipids: phosphatidylserine and phosphatidylinositol in subgroup 1 by 63% and 53%, respectively (p<0.001), in subgroup 2 by 79% and 68%, respectively (p<0.001), compared with similar indicators in the control group.Conclusion. With COVID19-associated CAP in maternity women, structural disorganization of the phospholipid components of erythrocyte membranes is determined, manifested by a decrease in the concentration of phosphatidylethanolamine and phosphatidylcholine with a simultaneous increase in the level of lysophosphatidylcholine, phosphatidylserine and phosphatidylinositol. These disorders increase with increasing severity of pulmonary inflammation. The revealed changes in the lipid spectrum of peripheral blood and the composition of erythrocyte membrane phospholipids in COVID-19-associated CAP indicate the need to develop methods for their correction.
{"title":"Peculiarities of phospholipiid changes in erythrocyte membranes in parturient women with COVID-19-associated community-acquired pneumonia","authors":"N. A. Ishutina, I. A. Аndrievskaya, I. Sinyakin","doi":"10.36604/1998-5029-2023-87-83-89","DOIUrl":"https://doi.org/10.36604/1998-5029-2023-87-83-89","url":null,"abstract":"Aim. To evaluate the phospholipid composition of erythrocyte membranes in parturient women who had COVID-19-associated community-acquired pneumonia (CAP) in the third trimester.Materials and methods. The material for the study was erythrocytes of peripheral blood of 65 parturient women diagnosed with COVID-19, moderate/severe course, CAP of viral etiology (main group). Patients of the main group, depending on the severity of CAP, were divided into two subgroups: subgroup 1 – moderate course of pneumonia (n=33), subgroup 2 – severe course of pneumonia (n=32). The control group consisted of 35 healthy parturient women. The quantitative composition of phospholipids was studied by two-dimensional thin-layer chromatography according to Kirchner.Results. In subgroup 1, the concentration of phosphatidylethanolamine and phosphatidylcholine in erythrocyte membranes was below the standard values by 38% and 29%, respectively (p<0.001), in subgroup 2, these indicators decreased by 32% and 48%, respectively (p<0.001). At the same time, a significant increase in the concentration of lysophosphatidylcholine was found in patients of subgroup 1 by 92% (p<0.001) and in patients of subgroup 2 by 110% (p<0.001), compared with the group of healthy individuals. In addition, structural changes in the lipid bilayer of erythrocyte membranes under conditions of COVID-19associated CAP were characterized by a pronounced increase in the concentration of minor fractions of phospholipids: phosphatidylserine and phosphatidylinositol in subgroup 1 by 63% and 53%, respectively (p<0.001), in subgroup 2 by 79% and 68%, respectively (p<0.001), compared with similar indicators in the control group.Conclusion. With COVID19-associated CAP in maternity women, structural disorganization of the phospholipid components of erythrocyte membranes is determined, manifested by a decrease in the concentration of phosphatidylethanolamine and phosphatidylcholine with a simultaneous increase in the level of lysophosphatidylcholine, phosphatidylserine and phosphatidylinositol. These disorders increase with increasing severity of pulmonary inflammation. The revealed changes in the lipid spectrum of peripheral blood and the composition of erythrocyte membrane phospholipids in COVID-19-associated CAP indicate the need to develop methods for their correction.","PeriodicalId":9598,"journal":{"name":"Bulletin Physiology and Pathology of Respiration","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90730707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-03DOI: 10.36604/1998-5029-2023-87-99-107
I. V. Zhukovets, O. Leshchenko
Introduction. The rising incidence of obesity among children and adolescents has become a major public health problem. Problems of female reproductive function associated with obesity include menstrual irregularities, complications of pregnancy and childbirth, and infertility.Aim. To conduct a prospective analysis of carbohydrate, lipid metabolism, neuroendocrine regulation in women with primary infertility and hypothalamic syndrome of puberty.Materials and methods. Prospective, longitudinal study of adolescent girls (n=170) with hypothalamic dysfunction for 14.2±1.6 years, mean age was 14.41±0.26 years. The second stage of the study included an assessment of the hormonal status and metabolic changes in 86 women, of which 46 were fertile, 26 had primary infertility and 14 had secondary infertility, mean age was 21.89±1.15 years. Clinical and laboratory methods were used to study the indicators of lipid and carbohydrate metabolism, pituitary-ovarian and adrenal hormonal regulation systems, instrumental and functional research methods, as well as statistical analysis methods were carried out.Results. Among adolescent girls with hypothalamic dysfunction a high proportion of secondary amenorrhea − 31% (p=0.042) and metabolic syndrome − 86% was revealed, as well as a significant increase in follicle-stimulating hormone, testosterone, cortisol and a decrease in the concentration of progesterone, inhibin B, an increase in cholesterol, low density lipoproteins, triglycerides, the HOMA index, insulin and a decrease in high density lipoprotein cholesterol. We found a high proportion of polycystic ovary syndrome − 19.8%, polymenorrhea − 18.6%, oligomenorrhea − 19.8%, primary infertility − 30.2%, (p=0.001) in women with a history of hypothalamic obesity in the pubertal period. We determined a set of primary infertility predictors: the presence of triglyceridemia and hyperlipidemia in the puberty period (OR 9.5; 95%CI [1.7–51.9]) and hormone-dependent diseases in the reproductive period (OR 5.6; 95%CI [2.5–18.2]).Conclusion. In our opinion, timely prevention and correction of lipid metabolism disorders in adolescents, as well as early detection of hormone-dependent diseases in the reproductive period are promising for the prevention of reproductive disorders.
{"title":"Hormono-metabolic disorders in women with hypothalamic syndrome in the ontogenetic aspect","authors":"I. V. Zhukovets, O. Leshchenko","doi":"10.36604/1998-5029-2023-87-99-107","DOIUrl":"https://doi.org/10.36604/1998-5029-2023-87-99-107","url":null,"abstract":"Introduction. The rising incidence of obesity among children and adolescents has become a major public health problem. Problems of female reproductive function associated with obesity include menstrual irregularities, complications of pregnancy and childbirth, and infertility.Aim. To conduct a prospective analysis of carbohydrate, lipid metabolism, neuroendocrine regulation in women with primary infertility and hypothalamic syndrome of puberty.Materials and methods. Prospective, longitudinal study of adolescent girls (n=170) with hypothalamic dysfunction for 14.2±1.6 years, mean age was 14.41±0.26 years. The second stage of the study included an assessment of the hormonal status and metabolic changes in 86 women, of which 46 were fertile, 26 had primary infertility and 14 had secondary infertility, mean age was 21.89±1.15 years. Clinical and laboratory methods were used to study the indicators of lipid and carbohydrate metabolism, pituitary-ovarian and adrenal hormonal regulation systems, instrumental and functional research methods, as well as statistical analysis methods were carried out.Results. Among adolescent girls with hypothalamic dysfunction a high proportion of secondary amenorrhea − 31% (p=0.042) and metabolic syndrome − 86% was revealed, as well as a significant increase in follicle-stimulating hormone, testosterone, cortisol and a decrease in the concentration of progesterone, inhibin B, an increase in cholesterol, low density lipoproteins, triglycerides, the HOMA index, insulin and a decrease in high density lipoprotein cholesterol. We found a high proportion of polycystic ovary syndrome − 19.8%, polymenorrhea − 18.6%, oligomenorrhea − 19.8%, primary infertility − 30.2%, (p=0.001) in women with a history of hypothalamic obesity in the pubertal period. We determined a set of primary infertility predictors: the presence of triglyceridemia and hyperlipidemia in the puberty period (OR 9.5; 95%CI [1.7–51.9]) and hormone-dependent diseases in the reproductive period (OR 5.6; 95%CI [2.5–18.2]).Conclusion. In our opinion, timely prevention and correction of lipid metabolism disorders in adolescents, as well as early detection of hormone-dependent diseases in the reproductive period are promising for the prevention of reproductive disorders.","PeriodicalId":9598,"journal":{"name":"Bulletin Physiology and Pathology of Respiration","volume":"74 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76035523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-03DOI: 10.36604/1998-5029-2023-87-8-17
I. Tseimakh, D. E. Bogachev, G. I. Kostuchenko, A. Mamaev, T. A. Kornilova, I. S. Shemyakina, A. Tseimakh, Y. Shoikhet
Aim. To assess the effect of serum homocysteine levels on treatment outcomes in patients with COVID19-associated lung damage, depending on the use of folic acid in complex treatment.Materials and methods. An open, prospective comparative study included 71 hospitalized adult patients with COVID-19-associated lung disease who did not require mechanical ventilation. The main group included 51 patients who received folic acid 15 mg per day in a complex treatment in a fixed combination with pyridoxine hydrochloride and cyanocobalamin. The comparison group included 20 patients in whose therapy folic acid was not used.Results. The use of folic acid was accompanied by a decrease in serum homocysteine concentration by 2.120 (-0.230; 3.680) µmol/L (p=0.004). When constructing a logistic regression model, the effect of a decrease in serum homocysteine (OR 1.289; 95% CI 1.026‒1.620; p=0.029), methylenetetrahydrofolate reductase MTHFR C677T genotype (OR 10.897; 95% CI 1.240‒95.772; p=0.031) on the achievement of 7th day of hospitalization, the cessation of isolation of SARS-CoV-2 virus RNA from the respiratory tract. Multiple linear regression analysis showed an association between the duration of hypoxemic respiratory failure, determined with SaO2≤93%, with the degree of change in serum homocysteine concentration after treatment, single nucleotide polymorphisms of methylenetetrahydrofolate reductase MTHFR C677T, methionine synthase MTR A2756G and methionine synthase reductase MTRR A66G, initial volume of lung damage ≥50% according to CT data, indicators of D-dimers, C-reactive protein, hemoglobin, platelets, concomitant hypertension, diabetes mellitus (R=0.699; R2=0.489; p=0.005).Conclusion. The dynamics of the decrease in serum homocysteine after treatment is an important predictor of the cessation of isolation from the respiratory tract of the SARS-CoV-2 virus RNA on the 7th day of treatment, reducing the duration of hypoxemic respiratory failure in patients with lung damage associated with COVID-19 infection.
的目标。评估血清同型半胱氨酸水平对复合治疗中叶酸使用情况下covid - 19相关肺损伤患者治疗结果的影响。材料和方法。一项开放的前瞻性比较研究纳入了71名住院的成人covid -19相关肺部疾病患者,这些患者不需要机械通气。主要组包括51例患者,每天服用叶酸15毫克,与盐酸吡哆醇和氰钴胺固定联合治疗。对照组包括20例未使用叶酸治疗的患者。服用叶酸可使血清同型半胱氨酸浓度降低2.120 (-0.230;3.680)µmol/L (p=0.004)。在构建logistic回归模型时,血清同型半胱氨酸降低(OR 1.289;95% ci 1.026-1.620;p=0.029),亚甲基四氢叶酸还原酶MTHFR C677T基因型(OR 10.897;95% ci 1.240-95.772;p=0.031)达到住院第7天,停止从呼吸道分离SARS-CoV-2病毒RNA。多元线性回归分析显示,低氧性呼吸衰竭持续时间(以SaO2≤93%测定)与治疗后血清同型半胱氨酸浓度变化程度、亚甲基四氢叶酸还原酶MTHFR C677T、蛋氨酸合成酶MTR A2756G、蛋氨酸合成酶MTRR A66G单核苷酸多态性、CT数据肺损伤初始体积≥50%、d -二聚体、c反应蛋白、血红蛋白、血小板、合并高血压、糖尿病(R=0.699;R2 = 0.489;.Conclusion p = 0.005)。治疗后血清同型半胱氨酸下降的动态是在治疗第7天停止从呼吸道分离SARS-CoV-2病毒RNA的重要预测指标,减少了COVID-19感染相关肺损伤患者低氧性呼吸衰竭的持续时间。
{"title":"Impact of correction of homocisteinemia on clinical outcomes of lung damage associated with COVID-19 coronavirus infection","authors":"I. Tseimakh, D. E. Bogachev, G. I. Kostuchenko, A. Mamaev, T. A. Kornilova, I. S. Shemyakina, A. Tseimakh, Y. Shoikhet","doi":"10.36604/1998-5029-2023-87-8-17","DOIUrl":"https://doi.org/10.36604/1998-5029-2023-87-8-17","url":null,"abstract":"Aim. To assess the effect of serum homocysteine levels on treatment outcomes in patients with COVID19-associated lung damage, depending on the use of folic acid in complex treatment.Materials and methods. An open, prospective comparative study included 71 hospitalized adult patients with COVID-19-associated lung disease who did not require mechanical ventilation. The main group included 51 patients who received folic acid 15 mg per day in a complex treatment in a fixed combination with pyridoxine hydrochloride and cyanocobalamin. The comparison group included 20 patients in whose therapy folic acid was not used.Results. The use of folic acid was accompanied by a decrease in serum homocysteine concentration by 2.120 (-0.230; 3.680) µmol/L (p=0.004). When constructing a logistic regression model, the effect of a decrease in serum homocysteine (OR 1.289; 95% CI 1.026‒1.620; p=0.029), methylenetetrahydrofolate reductase MTHFR C677T genotype (OR 10.897; 95% CI 1.240‒95.772; p=0.031) on the achievement of 7th day of hospitalization, the cessation of isolation of SARS-CoV-2 virus RNA from the respiratory tract. Multiple linear regression analysis showed an association between the duration of hypoxemic respiratory failure, determined with SaO2≤93%, with the degree of change in serum homocysteine concentration after treatment, single nucleotide polymorphisms of methylenetetrahydrofolate reductase MTHFR C677T, methionine synthase MTR A2756G and methionine synthase reductase MTRR A66G, initial volume of lung damage ≥50% according to CT data, indicators of D-dimers, C-reactive protein, hemoglobin, platelets, concomitant hypertension, diabetes mellitus (R=0.699; R2=0.489; p=0.005).Conclusion. The dynamics of the decrease in serum homocysteine after treatment is an important predictor of the cessation of isolation from the respiratory tract of the SARS-CoV-2 virus RNA on the 7th day of treatment, reducing the duration of hypoxemic respiratory failure in patients with lung damage associated with COVID-19 infection.","PeriodicalId":9598,"journal":{"name":"Bulletin Physiology and Pathology of Respiration","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90614936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-03DOI: 10.36604/1998-5029-2023-87-52-61
D. Naumov
Introduction. Cold airway hyperresponsiveness (CAH) is a common condition in patients with asthma, which worsens the clinical course of the disease and the patients’ quality of life. MUC5AC and MUC5B are the main secreted mucins in the respiratory tract, which are involved in normal mucociliary clearance, but also capable of provoking the development of pathological changes in case of dysregulation of their balanced production.Aim. The aim of this study was to determine the dynamics of MUC5AC and MUC5B expression during experimental cooling in patients with asthma depending on the status of CAH.Materials and methods. The study enrolled 98 subjects including 26 patients with chronic non-obstructive bronchitis without exacerbation (control group) and 72 patients with asthma. The expression of MUC5AC, MUC5B and TRPM8 was determined in the upper respiratory tract by quantitative reverse transcription PCR. The production of MUC5AC and MUC5B was also measured in sputum by ELISA. All patients underwent a bronchoprovocation test with isocapnic cold air hyperventilation to detect CAH, and a similar nasal challenge was performed to assess the effect of cooling on the expression of the studied genes.Results. Patients with asthma had 4.22-fold increase in the expression of MUC5AC (p=0.02) in the nasal epithelium as compared with the control group. CAH was associated with an initial 7.33-fold upregulation of MUC5AC (p=0.008) as well as with further increase in MUC5AC expression but a decrease in MUC5B in response to cooling, which was not observed in asthma patients without CAH. Basal TRPM8 expression was associated with baseline level of MUC5AC (ρ=0.41, p=0.04), MUC5B (ρ=0.55, p<0.001) and amount of sputum produced after the cold bronchoprovocation.Conclusion. Asthma patients with CAH demonstrate a more pronounced imbalance in the production of mucins, which is aggravated by cold exposure. This, in turn, can lead to a number of pathological disorders associated with a more severe course of the disease.
{"title":"Profile of MUC5AC and MUC5B mucins expression in asthma patients under cold exposure","authors":"D. Naumov","doi":"10.36604/1998-5029-2023-87-52-61","DOIUrl":"https://doi.org/10.36604/1998-5029-2023-87-52-61","url":null,"abstract":"Introduction. Cold airway hyperresponsiveness (CAH) is a common condition in patients with asthma, which worsens the clinical course of the disease and the patients’ quality of life. MUC5AC and MUC5B are the main secreted mucins in the respiratory tract, which are involved in normal mucociliary clearance, but also capable of provoking the development of pathological changes in case of dysregulation of their balanced production.Aim. The aim of this study was to determine the dynamics of MUC5AC and MUC5B expression during experimental cooling in patients with asthma depending on the status of CAH.Materials and methods. The study enrolled 98 subjects including 26 patients with chronic non-obstructive bronchitis without exacerbation (control group) and 72 patients with asthma. The expression of MUC5AC, MUC5B and TRPM8 was determined in the upper respiratory tract by quantitative reverse transcription PCR. The production of MUC5AC and MUC5B was also measured in sputum by ELISA. All patients underwent a bronchoprovocation test with isocapnic cold air hyperventilation to detect CAH, and a similar nasal challenge was performed to assess the effect of cooling on the expression of the studied genes.Results. Patients with asthma had 4.22-fold increase in the expression of MUC5AC (p=0.02) in the nasal epithelium as compared with the control group. CAH was associated with an initial 7.33-fold upregulation of MUC5AC (p=0.008) as well as with further increase in MUC5AC expression but a decrease in MUC5B in response to cooling, which was not observed in asthma patients without CAH. Basal TRPM8 expression was associated with baseline level of MUC5AC (ρ=0.41, p=0.04), MUC5B (ρ=0.55, p<0.001) and amount of sputum produced after the cold bronchoprovocation.Conclusion. Asthma patients with CAH demonstrate a more pronounced imbalance in the production of mucins, which is aggravated by cold exposure. This, in turn, can lead to a number of pathological disorders associated with a more severe course of the disease.","PeriodicalId":9598,"journal":{"name":"Bulletin Physiology and Pathology of Respiration","volume":"52 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82044514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-23DOI: 10.36604/1998-5029-2022-86-120-128
I. Dovzhikova, I. Andrievskaya, K. S. Lyazgiyan
Introduction. Sex differences in the course and outcomes of the disease were found during the COVID- 19 pandemic.Aim. To summarize the knowledge about the mechanisms underlying sex differences in COVID-19, with a focus on the role of estrogen.Materials and methods. We conducted a study using various databases until September 2022 for the keywords “estrogen” and “COVID-19”. All articles were published in English.Results. The review discusses the involvement of estrogen in the implementation of the immune response in viral infection. Individual paragraphs of the article are devoted to the effect of female sex hormones on coagulation, inflammation, and the renin-angiotensin system.Conclusion. At the end of the paper, it is concluded that there is great potential for future work deciphering hormonal effects on human physiology to explain the heterogeneity in pathogenic responses and may facilitate the development of more effective and personalized interventions.
{"title":"COVID-19 and sex differences: role of estrogen","authors":"I. Dovzhikova, I. Andrievskaya, K. S. Lyazgiyan","doi":"10.36604/1998-5029-2022-86-120-128","DOIUrl":"https://doi.org/10.36604/1998-5029-2022-86-120-128","url":null,"abstract":"Introduction. Sex differences in the course and outcomes of the disease were found during the COVID- 19 pandemic.Aim. To summarize the knowledge about the mechanisms underlying sex differences in COVID-19, with a focus on the role of estrogen.Materials and methods. We conducted a study using various databases until September 2022 for the keywords “estrogen” and “COVID-19”. All articles were published in English.Results. The review discusses the involvement of estrogen in the implementation of the immune response in viral infection. Individual paragraphs of the article are devoted to the effect of female sex hormones on coagulation, inflammation, and the renin-angiotensin system.Conclusion. At the end of the paper, it is concluded that there is great potential for future work deciphering hormonal effects on human physiology to explain the heterogeneity in pathogenic responses and may facilitate the development of more effective and personalized interventions.","PeriodicalId":9598,"journal":{"name":"Bulletin Physiology and Pathology of Respiration","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83669995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-23DOI: 10.36604/1998-5029-2022-86-73-79
L. Nakhamchen, I. Gorikov, V. Kolosov, A. Odireev, I. A. Andrievskay, N. A. Ishutina, A. V. Bushmanov, I. Dovzhikova
Aim. To give immune-hormonal and dopplerometric characteristics of placental insufficiency in pregnant women with exacerbation of chronic bronchitis associated with reactivation of cytomegalovirus infection (CMVI).Materials and methods. The concentration of IL-ie, IL-2 and progesterone was studied in the blood serum, and the pulsation index (PI) in the right uterine artery (RUA) was determined in 80 patients at 21-24 weeks of gestation, uncomplicated and complicated by exacerbation of chronic simple bronchitis due to reactivation of CMVI. In a retrospective analysis, 3 groups were formed. The first group - 30 women with CMV-seronegative physiological pregnancy; the second - 25 patients with chronic bronchitis in the acute stage, initiated by the acute phase of CMVI, leading to chronic compensated placental insufficiency (CCPI); the third - 25 women with exacerbation of chronic bronchitis CMVI etiology, causing the development of chronic subcompensated placental insufficiency (CSPI) in the third trimester of gestation.Results. In the first group, the concentration of IL-ie was 22.8±0.02 pg/mL, IL-2 - 30.6±2.34 pg/mL, progesterone - 130.8±8.19 nmol/L, and the value of PI in RUA - 0.83±0.04 rel. units. In patients of the second group, compared with the first, the level of IL-ie increased by 3.82 times (p<0.00i), IL-2 - by 2.55 times (p<0.00i) and PI in the RUA - by i.40 times (p<0.00i) against the background of a decrease in the progesterone concentration by i.47 times (p<0.00i). The third group compared with the first was characterized by an increase in the concentration of IL-ie by 6.87 times (p<0.001), IL-2 - by 3.19 times (p<0.001) and PI in RUA by i.66 times (p<0.00i) with lower levels of progesterone (i.93 times, p<0.00i). In the third group, in contrast to the second one, an increase in IL-ie was observed by 1.79 times (p<0.001), IL-2 - by 1.24 times (p<0.05) and PI in RUA - by i.i7 times (p<0.05), as well as a decrease in progesterone levels by i.3i times (p<0.0i). There was an increase in the relationship of PI in RUA with the concentration of IL-ie (r=0.69; p<0.001), IL-2 (r=0.75; p<0.001) and progesterone (r=-0.55; p<0.01).Conclusion. A more pronounced systemic inflammatory reaction, leading to inhibition of progesterone synthesis and increased resistance to blood flow at RUA develops in exacerbation of chronic bronchitis in the second trimester of gestation against the background of reactivation of CMVI, which initiates the development of CCPI, in comparison with the exacerbation of bronchopulmonary pathology of a similar etiology, which determines the formation of subsequent CCPI.
{"title":"Immuno-hormonal and dopplerometric characteristics of placental insufficiency in pregnant women with exacerbation of chronic bronchitis associated with reactivation of cytomegalovirus infection","authors":"L. Nakhamchen, I. Gorikov, V. Kolosov, A. Odireev, I. A. Andrievskay, N. A. Ishutina, A. V. Bushmanov, I. Dovzhikova","doi":"10.36604/1998-5029-2022-86-73-79","DOIUrl":"https://doi.org/10.36604/1998-5029-2022-86-73-79","url":null,"abstract":"Aim. To give immune-hormonal and dopplerometric characteristics of placental insufficiency in pregnant women with exacerbation of chronic bronchitis associated with reactivation of cytomegalovirus infection (CMVI).Materials and methods. The concentration of IL-ie, IL-2 and progesterone was studied in the blood serum, and the pulsation index (PI) in the right uterine artery (RUA) was determined in 80 patients at 21-24 weeks of gestation, uncomplicated and complicated by exacerbation of chronic simple bronchitis due to reactivation of CMVI. In a retrospective analysis, 3 groups were formed. The first group - 30 women with CMV-seronegative physiological pregnancy; the second - 25 patients with chronic bronchitis in the acute stage, initiated by the acute phase of CMVI, leading to chronic compensated placental insufficiency (CCPI); the third - 25 women with exacerbation of chronic bronchitis CMVI etiology, causing the development of chronic subcompensated placental insufficiency (CSPI) in the third trimester of gestation.Results. In the first group, the concentration of IL-ie was 22.8±0.02 pg/mL, IL-2 - 30.6±2.34 pg/mL, progesterone - 130.8±8.19 nmol/L, and the value of PI in RUA - 0.83±0.04 rel. units. In patients of the second group, compared with the first, the level of IL-ie increased by 3.82 times (p<0.00i), IL-2 - by 2.55 times (p<0.00i) and PI in the RUA - by i.40 times (p<0.00i) against the background of a decrease in the progesterone concentration by i.47 times (p<0.00i). The third group compared with the first was characterized by an increase in the concentration of IL-ie by 6.87 times (p<0.001), IL-2 - by 3.19 times (p<0.001) and PI in RUA by i.66 times (p<0.00i) with lower levels of progesterone (i.93 times, p<0.00i). In the third group, in contrast to the second one, an increase in IL-ie was observed by 1.79 times (p<0.001), IL-2 - by 1.24 times (p<0.05) and PI in RUA - by i.i7 times (p<0.05), as well as a decrease in progesterone levels by i.3i times (p<0.0i). There was an increase in the relationship of PI in RUA with the concentration of IL-ie (r=0.69; p<0.001), IL-2 (r=0.75; p<0.001) and progesterone (r=-0.55; p<0.01).Conclusion. A more pronounced systemic inflammatory reaction, leading to inhibition of progesterone synthesis and increased resistance to blood flow at RUA develops in exacerbation of chronic bronchitis in the second trimester of gestation against the background of reactivation of CMVI, which initiates the development of CCPI, in comparison with the exacerbation of bronchopulmonary pathology of a similar etiology, which determines the formation of subsequent CCPI.","PeriodicalId":9598,"journal":{"name":"Bulletin Physiology and Pathology of Respiration","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77651062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-23DOI: 10.36604/1998-5029-2022-86-91-101
E. Nekrasov, D. Naumov
Introduction. Human peripheral blood mononuclear cells (PBMCs) are a pool of immune cells and they are also a convenient model system for studying immune pathologies.Aim. Testing for bioactivity of glycerolipid preparations from fern and horsetail species containing long chain polyunsaturated fatty acids (LCPUFAs) towards PBMCs without exogenous stimulation and after phorbol-12-myristate-13-acetate (PMA) plus ionomycin stimulation.Materials and methods. Glycerolipid preparations were produced by fractionation of total lipids, isolated from young fronds of the fern Matteuccia struthiopteris and shoots of the horsetail Equisetum arvense, on silica. Egg phosphatidylcholine was used for comparison. Fatty acids were analyzed by gas chromatography. Mononuclear cells were isolated from blood of patients with asthma. Parameters of cell viability and activation were estimated by flow cytometry.Results. The glycerolipid preparations from the fern and horsetail were found to have a cytotoxic effect while egg phosphatidylcholine was not. The most active was the fraction of fern lipids eluted with methanol which reduced cell viability by 64.6 (51.1-79.0)% in the concentration 2 pg/ml and caused complete cell death in 20 pg/ml. After cell stimulation with PMA/ionomycin, the cytotoxic effect of the preparation increased although the level of PBMCs expressing the marker CD69 did not change. The cytotoxic effect of other glycerolipid preparations was observed in the higher concentrations (20 and/or 80 pg/ml) and it was less pronounced: the cell viability reduced by 7.1 (6.7-9.4)% for the fraction of fern lipids eluted by the mixture chloroform - methanol - water (3:5:2), by 39.8 (26.4-41.6)% and 12.0 (10.0-15.5)% for the fractions of the horsetail lipids eluted with methanol and the chloroform-methanol-water mixture, respectively, in the concentration 80 pg/ml.Conclusion. Comparison of fatty acid composition of the glycerolipid preparations did not confirm a contribution of LCPUFAs to the observed effects. Identification of an active component may allow development of a drug for the local application in a hyperimmune response or for model experiments.
{"title":"Effect of glycerolipid preparations from fern and horsetail on human peripheral blood mononuclear cells under ex vivo conditions","authors":"E. Nekrasov, D. Naumov","doi":"10.36604/1998-5029-2022-86-91-101","DOIUrl":"https://doi.org/10.36604/1998-5029-2022-86-91-101","url":null,"abstract":"Introduction. Human peripheral blood mononuclear cells (PBMCs) are a pool of immune cells and they are also a convenient model system for studying immune pathologies.Aim. Testing for bioactivity of glycerolipid preparations from fern and horsetail species containing long chain polyunsaturated fatty acids (LCPUFAs) towards PBMCs without exogenous stimulation and after phorbol-12-myristate-13-acetate (PMA) plus ionomycin stimulation.Materials and methods. Glycerolipid preparations were produced by fractionation of total lipids, isolated from young fronds of the fern Matteuccia struthiopteris and shoots of the horsetail Equisetum arvense, on silica. Egg phosphatidylcholine was used for comparison. Fatty acids were analyzed by gas chromatography. Mononuclear cells were isolated from blood of patients with asthma. Parameters of cell viability and activation were estimated by flow cytometry.Results. The glycerolipid preparations from the fern and horsetail were found to have a cytotoxic effect while egg phosphatidylcholine was not. The most active was the fraction of fern lipids eluted with methanol which reduced cell viability by 64.6 (51.1-79.0)% in the concentration 2 pg/ml and caused complete cell death in 20 pg/ml. After cell stimulation with PMA/ionomycin, the cytotoxic effect of the preparation increased although the level of PBMCs expressing the marker CD69 did not change. The cytotoxic effect of other glycerolipid preparations was observed in the higher concentrations (20 and/or 80 pg/ml) and it was less pronounced: the cell viability reduced by 7.1 (6.7-9.4)% for the fraction of fern lipids eluted by the mixture chloroform - methanol - water (3:5:2), by 39.8 (26.4-41.6)% and 12.0 (10.0-15.5)% for the fractions of the horsetail lipids eluted with methanol and the chloroform-methanol-water mixture, respectively, in the concentration 80 pg/ml.Conclusion. Comparison of fatty acid composition of the glycerolipid preparations did not confirm a contribution of LCPUFAs to the observed effects. Identification of an active component may allow development of a drug for the local application in a hyperimmune response or for model experiments.","PeriodicalId":9598,"journal":{"name":"Bulletin Physiology and Pathology of Respiration","volume":"10 6 Suppl 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88837831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-23DOI: 10.36604/1998-5029-2022-86-102-119
A. Lenshin, J. Perelman, A. V. Il’in, A. Poberezhskiy, E. A. Ignat’eva, S. A. Kraynov
. Mediastinal cystic formations are well-shaped, often round formations that contain fluid and are lined with epithelium. The main cystic formations include congenital benign cysts (bronchogenic, duplicating the esophagus, neuroenteric, pericardial and thymic cysts), meningocele, mature cystic teratomas and lymphangiomas. Many tumors (e.g., thymomas, Hodgkin's disease, germ cell tumors, mediastinal carcinomas, lymph node metastases, nerve root tumors) may undergo cystic degeneration, especially after radiation or chemotherapy, and show mixed solid and cystic elements on computed tomography (CT) or magnetic resonance imaging (MRI), as well as acquire the structure of cavity formations during the tumor destruction. If the degeneration is extensive, such tumors may be virtually indistinguishable from congenital cysts. However, the history of the disease, visualization of the anatomical location of the formation, some details visible on CT or MRI, allow in many cases to make the correct diagnosis. Familiarity with the radiographic features of mediastinal cystic lesions facilitates accurate diagnosis, differentiation from other cystic lesions, and thus ensures optimal treatment of a patienta.
{"title":"Cysts and cyst-like formations of the mediastum: clinical and radiological manifestations","authors":"A. Lenshin, J. Perelman, A. V. Il’in, A. Poberezhskiy, E. A. Ignat’eva, S. A. Kraynov","doi":"10.36604/1998-5029-2022-86-102-119","DOIUrl":"https://doi.org/10.36604/1998-5029-2022-86-102-119","url":null,"abstract":". Mediastinal cystic formations are well-shaped, often round formations that contain fluid and are lined with epithelium. The main cystic formations include congenital benign cysts (bronchogenic, duplicating the esophagus, neuroenteric, pericardial and thymic cysts), meningocele, mature cystic teratomas and lymphangiomas. Many tumors (e.g., thymomas, Hodgkin's disease, germ cell tumors, mediastinal carcinomas, lymph node metastases, nerve root tumors) may undergo cystic degeneration, especially after radiation or chemotherapy, and show mixed solid and cystic elements on computed tomography (CT) or magnetic resonance imaging (MRI), as well as acquire the structure of cavity formations during the tumor destruction. If the degeneration is extensive, such tumors may be virtually indistinguishable from congenital cysts. However, the history of the disease, visualization of the anatomical location of the formation, some details visible on CT or MRI, allow in many cases to make the correct diagnosis. Familiarity with the radiographic features of mediastinal cystic lesions facilitates accurate diagnosis, differentiation from other cystic lesions, and thus ensures optimal treatment of a patienta.","PeriodicalId":9598,"journal":{"name":"Bulletin Physiology and Pathology of Respiration","volume":"112 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79619607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}