Broadly Reactive Nanobody Targeting the H3 Hemagglutinin of the Influenza A Virus.

Monoclonal antibodies and recombinant antibody fragments are a very promising therapeutic tool to combat infectious diseases. Due to their unique paratope structure, nanobodies (VHHs) hold several advantages over conventional monoclonal antibodies, especially in relation to viral infections. Influenza A viruses (IAVs) remain a major threat to public health. The hemagglutinin (HA) protein is the main protective and immunodominant antigen of IAVs. In this study, three broadly reactive nanobodies (D9.2, E12.2, and D4.2) to H3N2 influenza strains were isolated and Fc-fusion proteins (VHH-Fcs) were obtained and characterized in vitro. This modification improved the nanobodies' binding activity and allowed for their interaction with a wider range of strains. The D9.2-Fc antibody showed a 100% protection rate against mortality in vivo in a mouse lethal model. Furthermore, we demonstrated that the observed protection has to do with Fc-FcγR interactions. These results indicate that D9.2-Fc can serve as an effective antiviral agent against the H3N2 influenza infection.

Retrospective Analysis of Lipid-Lowering and Antiplatelet Therapy Regimen by Clinical Decision Support Service Based on Real-World Data from Electronic Medical Records "Intellect 3 Study".

Aim      To evaluate prescription of lipid-lowering and antithrombotic therapy in clinical practice and to compare differences in recommendations using the clinical decision support service (CDSS).Material and methods  Electronic medical records (EMR) of 300 patients from the Chazov National Medical Research Center of Cardiology, as well as from medical organizations controlled by the Department of Health of the Lipetsk Region and the Ministry of Health of the Voronezh Region, were analyzed for the period of August - December 2022, during the pilot implementation of CDSS. Retrospective information about the prescription of lipid-lowering and antithrombotic therapy from the EMR was compared with the CDSS guidelines under the expert supervision based on digitized clinical and laboratory profiles of patients. The study primary endpoint was a change in the initially prescribed lipid-lowering and / or antithrombotic therapy as per CDSS guidelines.Results Overall 292 patients were included in the final analysis; 46 (15.7 %) were from the primary prevention group and 246 (84.3 %) from the secondary prevention group. In group 1, the lipid-lowering therapy recommended by the CDSS differed by 50 % (p<0.001) from the baseline therapy recorded in the EMR. In the secondary prevention group, 78.9 % (p<0.001) differences were found in the lipid-lowering therapy recommended in the CDSS guidelines compared to the prescriptions in the EMR. In 76.8 % (p<0.001) of patients, antithrombotic therapy was significantly different from the baseline therapy in the EMR.Conclusion      The use of CDSS may improve the practice of choosing lipid-lowering and antithrombotic therapy for prevention of cardiovascular complications.

Clinical Characteristics and Factors Associated with Poor Outcomes in Hospitalized Patients with Novel Coronavirus Infection COVID-19.

Aim      To evaluate the clinical picture and factors associated with unfavorable outcomes in admitted patients with COVID-19.Material and methods This study included all patients admitted to the COVID Center of the National Research Center of Cardiology of the Russian Ministry of Health Care from May 1 through May 31, 2020. Clinical demographic, laboratory, and instrumental indexes and associated factors were studied with one-way and multivariate logistic regression analysis.Results This study included 402 patients aged 18 to 95 years (mean age, 62.9±14.6 years); 43.0 % of them were older than 65 years. COVID-19 was frequently associated with chronic comorbidities, including arterial hypertension (74.4 %), obesity (41.6 %), history of ischemic heart disease (12.9 %), atrial fibrillation (18.9 %), type 2 diabetes mellitus (DM) (13.0 %), and oncological diseases (9.2 %). 13.0 % of patients were smokers; less than 10% had chronic lung diseases. 3.9% of patients had a combination of COVID-19 and acute coronary pathology, including acute myocardial infarction (MI) in 3.2 % (13) and unstable angina in 0.7 % (3). The most frequent clinical manifestation of COVID-19 were four symptoms: cough (81.1 %), weakness (80.3 %), shortness of breath (71.6 %), and fever (62.7 %). 46.5% of patients had shortage of breath and chest pain/compression, 40.3% had headache, 31.1% had myalgia, 28.8% had anosmia, and 25.5% had ageusia. Arterial oxygen saturation was <93.0 % in 55.7 % of cases. According to laboratory blood tests the patients had anemia (58.2 %), lymphopenia (34.8 %), neutropenia (19.2 %), thrombocytopenia (11.9 %), and increased levels of high-sensitivity C-reactive protein (hsCRP, 87.3 %), interleukin-6 (89.3 %), ferritin (62.1 %), and D-dimer (49.2 %). 56.2% of patients required various regimens of oxygen support. 83 (20.6%) patients were admitted to intensive care and resuscitation units; invasive artificial ventilation was performed only for 34 (8.5 %) patients. In-hospital mortality was 7.7 % (31 / 402). One-way regression analysis identified major factors associated with death during the stay in the hospital: age >55 years, NEWS scale score >4.0, oxygen saturation <92.0 %, blood glucose >5.4 mmol/l, hs-CRP >25.7 mg/l, and creatinine clearance <72.0 ml/min. Furthermore, the risk increased with increasing degree of changes in each factor. According to results of the multivariate regression analysis, three most significant predictors of the hard endpoint, all-cause death during the stay in the hospital, were more than 5-fold increases in aspartate aminotransferase and/or alanine aminotransferase compared to normal levels (relative risk (RR) 16.8 at 95 % confidence interval (CI) 5.0-56.3, р<0.001), pronounced changes in the lungs consistent with a CT-4 picture as shown by computed tomography (CT) (RR 13.4; 95 % CI 3.9-45.5, р<0.001), and MI/unstable angina during the stay in the hospital (RR 11.3; 95 % CI 1.4-90.6, р=0.023). The probability of death was also considerably increased by chronic obstructive pulmonary disease, impaired kidney function (creatinine clearance estimated by Cockcroft-Gault <60.0 ml/min), type 2 DM, oncological diseases, and dementia.Conclusion      This study established factors associated with unfavorable outcomes in admitted patients with COVID-19. This will allow identifying in advance patients with a high risk of complications that require increased attention to take more active diagnostic and therapeutic measures at prehospital and hospital stages.

[The Diagnostic Accuracy of Exercise Treadmill Testing and Stress Echocardiography for the Detection of Obstructive Coronary Artery Disease in Patients Aged ≥ 70 Years].

AIM: to compare diagnostic accuracy of exercise treadmill testing and stress echocardiography in the diagnosis of stable coronary artery disease (CAD) in patients aged >70 years. MATERIALS AND METHODS: The study included 390 patients aged >70 years with suspected stable ischemic heart disease, who underwent elective coronary artery angiography (CAG). Exercise treadmill testing (ETT) according to the modified Bruce protocol was carried out in 189 patients (48 %), bicycle stress echocardiography - in 179 patients (46 %). Initially we determined the prevalence of angiographically significant CAD according to the gender and chest pain character, and identified persons in whom stress testing was appropriate. After that diagnostic accuracy of both tests was evaluated in patients with atypical angina and non-anginal chest pain. RESULTS: Among 72 patients with atypical angina and non-anginal pain who underwent ETT and had unequivocal results, 38 (53 %) had obstructive CAD. ETT for detection of obstructive CAD had sensitivity 79 %, specificity 82 %, positive likelihood ratio (LR+) 4.4, and negative likelihood ratio (LR-) 0.3. Positive result increased probability of obstructive CAD from 53 % to 83 %, negative result reduced probability of obstructive CAD to 25 %. Among 111 patients with atypical angina and non-anginal pain who underwent stress echocardiography and had unequivocal results, 69 (62 %) had obstructive CAD. Sensitivity, specificity, LR+, and LR- of stress echocardiography were equal to 89 %, 95 %, 17.8, and 0.1, respectively. Positive result increased probability of obstructive CAD from 62 % to 95 %, negative result reduced probability of obstructive CAD to 16 %. CONCLUSION: bicycle stress echocardiography was found to be more accurate than ETT to rule in or rule out obstructive CAD in patients aged ≥ 70 years with atypical angina and non-anginal pain.

[Effect of minor bioactive food substances ­ rutin and hesperidin in their separate and combined alimentary arrives on the immune system of rats and the activity of nuclear factor NF-kB liver cells].

The effect of rutin and hesperidin in their separate and combined admission to the immune system and the activity of nuclear factor NF-kB of rat liver cells has been investigated. Wistar male rats with an initial body weight of 224­225 g were divided into 4 groups of 6 rats in each. The rats of the 1st group (control) received a complete semi-synthetic diet, rats in group 2 ­ the same diet supplemented with rutine (400 mg/kg b.w.); the rats of group 3 ­ with the addition of hesperidin (400 mg/kg bw); group 4 ­ with the addition of rutin and hesperidin (400 mg/kg b.w. each) for 14 days. Animals received feed in free access mode in an amount of 25­30 g per rat per day, that corresponded to 15 g of dry formula. Animals received water also in free access. It has been found that rutin and hesperidin, included in the diet of rats both alone (groups 2 and 3) and together (group 4), have immunomodulatory impact which is a reduce of lymphocyte relative content [1st gr. ­ 70.55±1.58%, 2nd gr. ­ 63.62±2.85%, 3rd gr. ­ 62.03±3.16% (p1­3<0.05), 4th gr. ­ 65.75±1.08% (p1­4<0.05)] and an increase of percentage of neutrophil leukocytes [1st gr ­ 19.98±0.97%, 2nd gr. ­ 25.35±3.14%, 3rd gr. ­ 28.27±3.30% (p1­3<0.05), 4th gr. ­ 24.15±1.52% (p1­4<0.05)] and NK-cells in the peripheral blood [1st gr. ­ 3.29±0.45%, 2nd gr. ­ 6.91±0.70% (p1­2<0.05), 3rd gr. ­ 5.88±0.79% (p1­3<0.05), 4th gr. ­ 4.64±0.32% (p1­4<0.05)], that can be considered as a shift in the direction of innate immunity factors. In addition, the combined effect of high doses of rutin and hesperidin led to a change in erythrocyte parameters: an increase in the average volume of red blood cells [1st gr. ­ 56.00±1.06 fl, 2nd gr. ­ 56.67±0.42 fl, 3rd gr. ­ 58.50± 0.99 fl, 4th gr. ­ 59.50±0.99 fl (p1­4<0.05)], and the average content of hemoglobin [1st gr. ­ 18.97±0.45 pg, 2nd gr. ­ 19.10±0.19 pg, 3rd gr. ­ 19.73± 0.32 pg, 4th gr. ­ 20.08±0.33 pg (p1­4=0.07)], as well as increase in the level of TGF-ß1 in peripheral blood [1st gr. ­ 15.55±2.13 ng/ml, 2nd gr. ­ 14.81± 2.36 ng/ml, 3rd gr. ­ 17.02±2.53 ng/ml, 4th gr. ­ 22.14±2.29 ng/ml (p1­4<0.05)] and the expression of nuclear factor NF-kB in the liver cells [1st gr. ­ 16.10± 0.60 ng/ml; 2nd gr. ­ 15.14±2.28 ng/ml; 3rd gr. ­ 15.85±2.09 ng/ml; 4th gr. ­ 20.49±1.68 ng/ml (p1­4<0.05)].

[Assessment of consistency of technological process using control cards on the example of analysis of information on immunogenic activity of pertussis component of DTP vaccine].

AIM: To assess the consistency of technological process of manufacture of DTP vaccine's pertussis component on the basis of its immunogenicity using Shewhart's cards. MATERIALS AND METHODS: Published data of domestic plants belonging to public corporation Mechnikov "Biomed" and Ufa branch of scientific-production organization "Immunopreparat" ingressed in "Microgen" enterprise were used. Immunogenicity of DTP vaccine pertussis componentwas studied. RESULTS: It was revealed that technological process of manufacturing of DTP vaccine's pertussis component on production plants was not always in statistically controlled state. CONCLUSION: Obtained data showed that it is reasonable for quality control departments of manufacturing plants to use Shewhart's cards and methods of statistical management of technological processes for assessment of state of the latter.

[To 20-years anniversary of Chernobyl catastrophe: an attempt to study the vitamin, calcium, iron and selenium status of children and adult population in Slavutich and to correct elicited deficiencies].

The article concisely illustrates the vitamin and mineral state of population of town of Slavutich, including personal of Chernobyl Nuclear Power Station, children of pre-school age and pregnancy women, studied in 1992. Vitamins and minerals deficiency in the main of C and B vitamins and selenium was revealed in all the studied groups. Appropriate measures were developed and introduced to eliminate the detected dusturbances; but however some unsolved problems remained. Taking into account the forthcoming 20th anniversary of Chernobyl disarter, the authors of the come back to considering the obtained data in hope to atlract attention of medical scientific and public to the remained unsolved problems of micronutrient deficiency.

[Prophylaxis of pertussis: development and use of acellular pertussis vaccine].

Modern data substantiating the expediency of the use of acellular pertussis vaccine were analyzed. Serious postvaccinal complications caused by the action of the corpuscular pertussis component of adsorbed DPT vaccine served as the basis for the development of acellular pertussis vaccine (APV). During the period of 1990-1996 as many as 8 international field trials of the effectiveness of APV were carried out. The results of these trials and studies were evaluated in accordance with the unified programs and criteria. The vaccines under test differed by the composition of Bordetella pertussis purified antigens they contained, the methods of their purification and the detoxification of pertussis toxin. All tested APV, with the exception SKB-2, possessed pronounced prophylactic activity.

[Evaluation of the reactogenicity and immunogenic potency of combined vaccine "Bubo-Kok" in the immunization of children against diphtheria, tetanus, pertussis and viral hepatitis B]. / Otsenka reaktogennosti i immunogennosti kombinirovannoi vaktsiny "Bubo-Kok" pri immunizatsii detei protiv difterii, stolbniaka, kokliusha i virusnogo gepatita B.

Combined vaccine "Bubo-Kok" is characterized by safety and high immunological activity. The number of postvaccinal reactions in children aged 1 and 2 years, immunized with vaccine "Bubo-Kok", was not statistically different from those in groups of children immunized with adsorbed DPT vaccine, as well with such vaccine in combination with vaccine against hepatitis B. After the completion of the primary course of immunization 100% of children had protective antibody titers against diphtheria, tetanus and hepatitis B. Antibody titers against pertussis, equal to or exceeding protective titers, were found in more than 70% of immunized children. The immunogenic potency of vaccine "Bubo-Kok" with respect to all its components was not inferior to that of adsorbed DPT vaccine and vaccine against hepatitis B, when introduced simultaneously in different areas of the body. Vaccine "Bubo-Kok" successfully passed state trials and was recommended for registration.

[Evaluation of the stability of pertussis vaccine OCO-3 standard]. / Otsenka stabil'nosti standarta kokliushnoi vaktsiny OCO-3.

The evaluation of the immunogenic activity and residual toxicity of the National Standard of pertussis vaccine (OCO-3) was carried out. As shown by observations lasting for a period of 25 years, the preparation possesses stable immunogenicity and its toxicity remained unchanged, which makes it possible to use OCO-3 for the routine control of the pertussis component of commercial lots of adsorbed DPT vaccine.

[Acute phase proteins and recurrence of angina after effective coronary angioplasty]. / Belki ostroi fazy i retsidiv stenokardii posle uspeshnoi koronarnoi angioplastiki.

AIM: Analysis of relationships between clinical characteristics of the patients, high concentration of acute phase proteins--fibrinogen, C-reactive protein (CRP), activity of the inhibitor of type 1 plasminogen activator (PAI-1)--and frequency of angina recurrence after successful coronary angioplasty (CA). MATERIAL AND METHODS: The trial included 53 patients after successful CA for a single hemodynamically significant stenosis. Peripheral blood was examined for plasm fibrinogen, CRP, activity of PAI-1 one day before and 2 days, 3 and 6 months after CA. After 12-month follow-up the patients were divided into two groups: angina-free patients (n = 37) and with recurrent angina (n = 16). RESULTS: Significant differences between the above groups were in PAI-1 activity 3 and 6 months after CA, in CRP initially, on day 2, after 6 months after CA (p < 0.05) but multifactor analysis has found that only CRP level both initial and on day 2 after CA is an independent predictor of recurrent angina pectoris after successful CA. CONCLUSION: An anginal recurrence after successful CA can be predicted by the initial and postoperative day 2 levels of CRP.

[Approaches to assessing the alimentary load of foreign substances]. / Podkhody k otsenke alimentarno nagruzki chuzherodnymi veshchestvami.

The paper presents approaches to estimating alimentary load with foreign substances. At the same time some substances that are strenuously controlled in environmental objects are essential nutrients, this makes it necessary to evaluate a possible adverse effect not only in terms of their toxic significance, but in terms of their physiological requirements. The study has indicated that truly available deficiencies of nutrients may reasonably substantially modify the toxicity of foreign substances, this, if any data on deficiency of essential dietary substances, makes it necessary to specify the storage coefficient of foreign substances by taking into account a possible modifying action on their toxic effects. These data may be also used as an approach to clarifying physiological requirements for essential nutrients.

[Comparison of dinitrate isosorbide retard forms in ischemic heart disease patients with stable effort angina]. / Sravnenie retardnykh form izosorbida dinitrata u bol'nykh IBS so stabil'noi stenokardiei napriazheniia.

AIM: To compare antianginal and anti-ischemic efficiency and tolerance of two forms of isosorbide dinitrate--cardiket-retard 120 mg and cardiket-retard 40 mg in IHD patients with stable effort angina. MATERIAL AND METHODS: The study included 18 IHD patients with stable angina of functional class II (5 patients) and III (13 patients). The trial was open cross-over. The treatment with both the forms lasted 1 month. Frequency of anginal attacks and exercise tolerance by veloergometry data were assessed. RESULTS: A significant decrease in the number of anginal attacks and greater exercise tolerance was recorded in cardiket 120 mg intake once a day. Both forms were well tolerated, serious side effects were absent. CONCLUSION: Comparison of the two isosorbide dinitrate dosage forms--cardiket 120 mg once a day and cardiket 40 mg 3 times a day--showed that the former is superior by clinical efficiency.

[Comparative study of isosorbide dinitrates and mononitrates in patients with ischemic heart disease and stable angina pectoris caused by stenosing coronary atherosclerosis]. / Sravnitel'noe izuchenie izosorbida di- i mononitratov u bol'nykh ishemicheskoi bolezn'iu serdtsa so stabil'noi stenokardiei, obuslovlennoi stenoziruiushim koronarnym aterosklerozom.

In an open clinical trial 19 patients with angina pectoris (functional class II-III) received in turn either non-retard tablets of isosorbide dinitrate (nitrosorbid, cardiket) in a mean dose 80 mg/day or isosorbide 5-mononitrate (mono mac) in a mean dose 51.5 mg/day. Each drug was given for a month. The effect was assessed by changes in frequency of anginal attacks and exercise tolerance. Non-retard isosorbide dinitrate and isosorbide 5-mononitrate demonstrate a good antiischemic effect, are safe and well tolerated. Isosorbide dinitrate and mononitrates do not differ significantly in reduction of the anginal attacks and by an increase in exercise tolerance but the effective dose of mono mac was 1.5-2 times less than that of nitrosorbide or cardiket, thus it is more cost-effective.

[Long-term assessment of clinical parameters in patients with coronary heart disease after balloon angioplasty and stenting balloon angioplasty]. / Otsenka klinicheskikh pokazatelei bol'nykh IBS v otdalennom periode posle ballonnoi angioplastiki i ballonnoi angioplastiki so stentirovaniem.

The aim of this study was to assess clinical parameters in patients with coronary heart disease (CHD) in the late period after balloon coronary angioplasty (BCA) and intracoronary stenting (ICS). The study included 104 patients who underwent repeated coronary angiography (CA) 2-10 months after successful coronary angioplasty. Clinical parameters were analyzed in 2 groups comparable at the moment of its performance in terms of major clinical characteristics. Group 1 comprised 51 patients following BCA and group 2 included 53 patients after ICS. Six months after the first procedure, repeated coronary angioplasty was performed in 19 (37.2%) and 6 (9.4%) patients after BCA and ICS, respectively (p < 0.05). Recurrent angina pectoris was observed in 42 patients from group 1 and in 25 ones from group 2, which was 82.3 and 47.2%, respectively (p < 0.05). Control CA revealed restenosis of the dilated artery in 22 (43.1%) of the 51 patients of group 1 and in 12 (22.6%) of the 53 patients of group 2. There were no differences between the groups in late postoperative bicycle ergometric and 24-hour ECG monitoring findings. The findings have led to the conclusion that implantation of a stent into the coronary artery greatly prolongs the antiischemic effect of coronary angioplasty and reduces a need for repeated endovascular intervention, which appears as lower incidence rates of restenosis and recurrent angina as compared to routine balloon angioplasty.

[Comparative study of retard and non-retard forms of isosorbide-5-mononitrate in coronary patients with stable angina pectoris]. / Sravnitel'noe izuchenie retardnoi i neretardnoi form izosorbid-5-mononitrata u bol'nykh ishemicheskoi bolezn'iu serdtsa so stabil'noi stenokardiei.

An open cross-over trial compared retard and non-retard forms of isosorbide-5-mononitrate (monomac 50D and isomonat, respectively) in 15 patients with stable angina of effort (functional class II-III). Both drugs were found rather effective, they significantly increase exercise tolerance. A single daily dose of monomac 50D reduced the number of anginal attacks. It was well tolerated, caused no serious side effects and had advantages over isomonat taken 2 or 3 times a day.

Urokinase plasminogen activator system in humans with stable coronary artery disease.

1. The present study compares plasma urokinase plasminogen activator (uPA) peptide levels, plasma plasminogen inhibitor (PAI-1) activity and urokinase receptors (uPAR) on peripheral blood monocytes of patients with stable coronary artery disease (SCAD) and healthy volunteers. 2. Urokinase plasminogen activator levels were analysed by ELISA and PAI-1 activity was determined by a plasmin generation method using the chromogenic substrate S2390. Relative uPAR numbers and the adhesion molecules CD11b/CD18 on peripheral blood monocytes were estimated using specific antibodies and flow cytometry. 3. Patients with SCAD were found to have higher plasma uPA peptide levels than age-matched healthy subjects (10.40 +/- 0.99 vs 8.25 +/- 0.53 pmol/L, respectively; P < 0.05). 4. Plasma PAI-1 activity was also higher in patients with SCAD than in healthy subjects (13.6 +/- 2.5 vs 5.2 +/- 1.0 IU/mL, respectively; P < 0.05). 5. Relative uPAR and CD11b/CD18 adhesion molecules were similar on peripheral blood monocytes of patients with SCAD and in healthy subjects. 6. The data indicate a pattern of expression/activity of uPA and PAI-1 in patients with SCAD suggestive of an impaired fibrinolytic ability.

[Model of nutritional iron deficiency anemia in rats]. / Model' alimentarnoi zhelezodefitsitnoi anemii u krys.

Model of alimentary iron deficiency anemia (AIDA) in rats has been created by the use of iron elimination from all diet components as much as possible. It was established that the time of AIDA development depended on iron content in diet. The model can be used for estimation of efficiency of new food products and food supplements enriched with iron.