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AIM: To determine the coverage of smoking or/and overweight residents of Russian cities with preventive counseling (PC) on smoking cessation and weight loss and identify the associations of obtaining these types of PC with demographic, socioeconomic, and behavioral characteristics. MATERIAL AND METHODS: The study was conducted based on data from the Know Your Heart study (Arkhangelsk and Novosibirsk, 20152018, n=3234). The coverage of individual groups of the PC population was compared using the Pearson 2 test. The factors associated with the receipt of PC were identified by using binary logistic regression. The quality of the obtained predictive models was assessed by analyzing the ROC curves. RESULTS: Less than half of the participants with increased BMI received PC for weight loss. Sixty-six percent of smokers were counseled to quit smoking. Factors such as gender, age, self-reported health, and number of visits to medical specialists within 12 months were significant for obtaining PC. Socioeconomic characteristics, dispanserization, and the presence of other RF did not show statistically significant differences. CONCLUSIONS: PC is an effective element of preventive medical care. The activity of the health care system in counseling the population from risk groups, especially on the normalization of body weight, needs to be increased. Particular attention should be paid to contingents of persons for whom the coverage was significantly lower.

Dietary pattern usually changes with age; however, certain dietary habits may remain constant.

Introduction: The high prevalence of behavioral risk factors in Russia has a significant impact on the health of the population being a serious threat for both current and future generations. There is substantial evidence on heath differences between and within countries. Aim: To estimate the 7-year survival rate and the association between risk factors and all-cause and cardiovascular mortality among rural residents of the Samara region of Russia. Methods: This is a prospective cohort study conducted in the framework of the "Interepid» international project. The analysis included the data from a representative sample of the 20-64 years old rural residents of the Volzhsky district of the Samara region of the Russian Federation (n=1050). A cross-sectional survey was carried out in 2011-2012. Vital status and deaths from all causes and from cardiovascular diseases were analyzed twice, after 4 years and after 7 years of the follow-up. Results: Smoking, hypertension, excess intake of meat offal, whole milk and yogurt were significantly associated with all-cause mortality among men while hypertension and obesity were the main contributors to all-cause mortality among women. CVD mortality was associated with smoking, hypertension, excess salt intake, excess intake of meat offal among men while hypertension, low physical activity and excess salt were the main risk factors among women. Conclusions: We observed significant contribution of many risk factors to all-cause and CVD mortality over a 7-year follow-up period. The importance of the risk factors significantly varied across genders. The results of the study can be used in planning, implementation and evaluation of the effectiveness of public health interventions.

To continue progress in the treatment of cardiovascular disease, there is a need to improve the overall understanding of the processes that contribute to the pathogenesis of cardiovascular disease (CVD). Exploring the role of gut microbiota in various heart diseases is a topic of great interest since it is not so easy to find such reliable connections despite the fact that microbiota undoubtedly affect all body systems. The present study was conducted to investigate the composition of gut microbiota in patients with atherosclerotic cardiovascular disease (ASCVD) and heart failure syndromes with reduced ejection fraction (HFrEF) and HF with preserved EF (HFpEF), and to compare these results with the microbiota of individuals without those diseases (control group). Fecal microbiota were evaluated by three methods: living organisms were determined using bacterial cultures, total DNA taxonomic composition was estimated by next generation sequencing (NGS) of 16S rRNA gene (V3–V4) and quantitative assessment of several taxa was performed using qPCR (quantitative polymerase chain reaction). Regarding the bacterial culture method, all disease groups demonstrated a decrease in abundance of Enterococcus faecium and Enterococcus faecalis in comparison to the control group. The HFrEF group was characterized by an increased abundance of Streptococcus sanguinus and Streptococcus parasanguinis. NGS analysis was conducted at the family level. No significant differences between patient’s groups were observed in alpha-diversity indices (Shannon, Faith, Pielou, Chao1, Simpson, and Strong) with the exception of the Faith index for the HFrEF and control groups. Erysipelotrichaceae were significantly increased in all three groups; Streptococcaceae and Lactobacillaceae were significantly increased in ASCVD and HFrEF groups. These observations were indirectly confirmed with the culture method: two species of Streptococcus were significantly increased in the HFrEF group and Lactobacillus plantarum was significantly increased in the ASCVD group. The latter observation was also confirmed with qPCR of Lactobacillus sp. Acidaminococcaceae and Odoribacteraceae were significantly decreased in the ASCVD and HFrEF groups. Participants from the HFpEF group showed the least difference compared to the control group in all three study methods. The patterns found expand the knowledge base on possible correlations of gut microbiota with cardiovascular diseases. The similarities and differences in conclusions obtained by the three methods of this study demonstrate the need for a comprehensive approach to the analysis of microbiota.

The present case–control study aimed to assess associations of routine and experimental biomarkers with risk for cardiovascular death and acute myocardial infarction (AMI) in a cohort recruited from the multicenter study “Cardiovascular Epidemiology in Russian Federation” (ESSE-RF) to identify experimental biomarkers potentially suitable for expanded evaluation. A total of 222 subjects included cardiovascular death (N = 48) and AMI cases (N = 63) during 6.5-year follow up and matched healthy controls. Seven routine and eight experimental biomarkers were assayed to analyze associations with outcomes using logistic and Cox proportional hazard regressions. Elevated levels of cardiac troponin I (cTnI), C-reactive protein (CRP), and nitric oxide metabolites (NOx) were independently associated (P

Health literacy is recognized as one of the most important determinants of health on the global level. International comparative population-based surveys on measuring health literacy using unified methodological approaches contribute to decisive national instruments on measurement, monitoring and improvement of health literacy in a population. These studies also contribute to the adaptation of the measures, taking into account the level of health literacy of vulnerable groups in particular. Until today, there was no instrument in the Russian Federation for measuring health literacy at the population level providing internationally comparable data. We attempted to adapt the HLS19 questionnaire developed within the international Health Literacy Survey in 2019 for use in Russia. The adaptation of the questionnaire was based on the European methodology which was tested in several countries of Europe and Asia and included 5 stages: translation from English into Russian, back translation from Russian into English, focus group, expert assessment and field testing. In spite of the fact that the instrument has already been translated into the Russian language and tested in some countries for the Russian-speaking population, a substantial adaptation of the questionnaire was needed taking into account the cultural and linguistic characteristics of the Russian population.

Study Objective: To improve efficiency of cardiovascular disease (CVD) prevention in patients with health category IIIa in Krasnodar Territorial Outpatient Clinic using a factorial analysis (dominant component analysis) of stage 1 health assessment results for 2015 and 2018. Materials and Methods. The study includes subjects who underwent stage 1 health assessment: 2015 — 2,461 people, 2018 — 2,772 people. Patients with health category IIIa were assessed for modifiable risk factors (RF) of CVDs using the dominant component analysis. Study Results. In 2015, health category IIIа was assigned to 29.9% of patients; female patients accounted for 68.5% (median age: 62 years), males accounted for 31.5% (median age: 60 years). In 2018, health category IIIа was recorded for 41.5% of patients; female patients accounted for 64.3% (median age: 63 years), males accounted for 35.7% (median age: 62 years). Factorial analysis demonstrated that male patients have the following composition of modifiable CVD RFs: factor 1 — improper diet (ID) and physical inactivity (PIA); factor 2 — hypercholesterolemia (HCS), tobacco smoking and alcohol abuse (TSAA); factor 3 — arterial hypertension (AH) and ID; factor 4 — AH. Women demonstrated different compositions of CVD RFs: factor 1 — ID and PIA; factor 2 — AH and HCS; factor 3 — BMI > 25 kg/m2 and hyperglycemia; factor 4 — TSAA. Conclusion. Gender differences together with modifiable CVD RFs in patients with risk category IIIa revealed with the help of the dominant component analysis allow correcting RFs taking into account combinations, most contributing to unfavourable cardiovascular events. Keywords: health assessment, risk factor, circulatory diseases, prevention, outpatient clinic, factorial analysis.

Chronic obstructive pulmonary disease (COPD) is one of the main causes of increasing morbidity and mortality worldwide, and therefore is becoming a major public health problem.

Transgenic animals are an important tool in biotechnology, including the production of recombinant proteins in the milk. Traditionally, expression constructs are based on hybrid vectors bearing mammary gland specific regulatory elements from the α-casein (Csn1s1), β-casein (Csn2), whey acidic protein (WAP), or β-lactoglobulin (BLG) genes. Overexpression from the randomly integrated vectors typically provides high levels of expression, but has drawbacks due to unpredictable genome localization. CRISPR-Cas9 targeted transgene integration into the endogenous casein locus could alleviate the need for extensive animal screening to achieve high and reproducible expression levels. We decided to evaluate such a “precise” integration approach, placing the human granulocyte–macrophage colony-stimulating factor (hGMCSF) gene under control of the mouse endogenous alpha-S1-casein (Csn1s1) promoter. We designed two types of transgene integrations: a knock-in in the second exon of the Csn1s1 (INS-GM) and a full-size Csn1s1 replacement with hGMCSF (REP-GM) which was never tested before. The INS-GM approach demonstrated low transgene expression and milk protein levels (0.4% of Csn2 transcripts; 2–11 µg/ml hGMCSF). This was probably caused by the absence of the 3’-polyadenylation signal in the hGMCSF transgene. REP-GM animals displayed high transgene expression, reaching and slightly exceeding the level of the endogenous Csn1s1 (30–40% of Csn2 transcripts), but yielded less hGMCSF protein than expected (0.2–0.5 mg/ml vs 25 mg/ml of Csn1s1), indicating that translation of the protein is not optimal. Homozygous inserts leading to the Csn1s1 knock-out did not have any long standing effects on the animals’ health. Thus, in our experimental design, site-specific transgene integration into the casein locus did not provide any significant advantage over the overexpression approach.

The life-history theory suggests that parental experience of the environment is passed to offspring, which allows them to adapt to prevailing conditions. This idea is supported from the mother’s side, but to a much less extent from the father’s side. Here, we investigated the effect of immunising fathers on pre- and neonatal development and on immune and neuroendocrine phenotypes of their offspring in C57BL/6J mice. Nine days before mating, fathers were intraperitoneally injected with the immunogenic protein keyhole limpet hemocyanin (KLH). Females mated with immunised males had less pre-weaning mortality of newborns compared to those mated with control males. Although the antibody response to KLH was similar for the male offspring of control and immunised fathers, the mass indexes of their main immune organs and their androgen response differed significantly. The mass indexes of the thymus and spleen in adult male offspring of immunised fathers were higher compared with the control offspring. The plasma testosterone levels were significantly decreased after KLH administration in the male offspring of control but not of immunised fathers. This was correlated with changes in sperm average path and straight-line velocities. Finally, excitatory neurotransmitters prevailed over inhibitory ones in the amygdala of the progeny of immunised fathers, while in control offspring, the opposite occurred. This is indicative of complex behavioural changes in the offspring of immunised fathers, including sexual ones. Therefore, the paternal experience of foreign antigens modulates the immune and neuroendocrine systems of their progeny, suggesting possible survival and reproductive adaptations to parasitic pressure.

Aims. The goal of the present case-control study was to assess associations of a panel of routine and experimental biomarkers with the risk for cardiovascular death and acute myocardial infarction (AMI) in a cohort recruited from the multicenter study “Cardiovascular Epidemiology in Russian Federation” (ESSE-RF).Methods and Results. A total of 222 subjects included cardiovascular death (N=48) and AMI cases (N=63) detected during 6.5-year follow up with corresponding numbers of matched healthy controls. The levels of 15 routine and experimental biochemical markers were assayed to analyze associations with the outcomes using logistic and Cox proportional hazard regressions validated by comparison between various groups to assess the estimated hazard ratio (eHR). Elevated levels of cardiac troponin I (cTnI), C-reactive protein (CRP), and metabolites of nitric oxide (NOx) were independently associated (P

Aim. To assess the potential need for expanding medicine assistance programs for patients with coronary artery disease (CAD) and comorbidities, as well as to model its health and social effectiveness in the Russian Federation.Material and methods. To assess the scope and cost of medicine assistance for the healthcare system, the number of patients with CAD and comorbidities was determined based on data from 5 registers of cardiovascular patients organized by the National Medical Research Center for Therapy and Preventive Medicine. We took into account the frequency of drug provision according to standard therapy regimens for stable CAD in combination with comorbidities and (or) conditions that increase the risk of adverse events. To determine the cost of medicine assistance, we used data from the state register for maximum ex-works prices for the medicinal products included in the list of vital and essential drugs. To assess the impact of medicine assistance for patients with CAD and the highest cardiovascular risk on survival prognosis in the period 2023-2025, the number of deaths prevented was calculated. A one-year forecast and a cumulative forecast were performed, taking into account annual increase in the patient population.Results. Patients with CAD and the highest cardiovascular risk (myocardial infarction, stroke, diabetes, chronic obstructive pulmonary disease in history), including in combination with hypertension, heart failure, atrial fibrillation, are priority groups where the prophylaxis of cardiovascular events and death, the expansion of medicine assistance programs will save a greater number of lives. With a one-year forecast, the potential number of deaths prevented by 2025 will be 33582 cases per year, with a cumulative total of 90500 cases over three years, with the costs of 114,8 billion rubles for three years (40 billion rubles per year).Conclusion. Considering the potential of modern therapy in patients with CAD, comorbidities and high cardiovascular risk, the expansion of current of medicine assistance programs for such patients, along with medical follow- up programs, seems to be an important component in health improvement, mortality reduction and life expectancy increase in the population.

Chronic heart failure (CHF) is a pathology that affects more than 37 million people worldwide. Despite the introduction of new drugs into practice, that have proven their effectiveness in the treatment of patients with CHF, the life expectancy of these patients is growing at a slow pace. At the same time, the insufficient effect of neurohormonal blockers for the treatment of patients with CHF with preserved ejection fraction (CHFpEF), which prevails in the general structure of CHF, indicates a significant role of unidentified pathological processes in the development of this form of the disease. In recent years, the role of cardiac fibrosis has been actively studied within the framework of the investigation of the pathogenesis of CHFpEF, the probable biomarkers of which are interleukin (IL) 33 and suppression of tumorigenicity 2 (ST2). This literature review examines the influence of the IL-33/ ST2 interaction as a biomarker of cardiac fibrosis on the course of CHF and the possibilities of its practical application.

The latest vaccination campaign has actualized the potential impact of antigenic stimuli on reproductive functions. To address this, we mimicked vaccination’s effects by administering keyhole limpet hemocyanin (KLH ) to CD1 male mice and used their sperm for in vitro fertilization (IVF). Two-cell embryos after IVF with spermatozoa from control (C) or KLH-treated (Im) male mice were transferred to surrogate mothers mated with vasectomized control (C) or KLH-treated (Im) male mice, resulting in four experimental groups: C–C, Im–C, C–Im, and Im–Im. The pre-implantation losses were significantly lower in the Im–C group than in the C–Im group. At the same time, the resorption rates reduced markedly in the C–Im compared to the Im–C group. Embryo and placenta weights were significantly higher in the Im–Im group. Although the GM-CSF levels were lower in the amniotic fluid of the gestating surrogate mothers in the Im–Im group, they were strongly correlated with embryo mass. The number–size trade-off was only significant in the Im–Im group. This suggests a positive, cooperative effect of spermatozoa and seminal fluid from immune-primed males on embryo growth and the optimal distribution of surrogate mother maternal resources despite the negative impact of males’ antigenic challenge on the IVF success rate.

Aim.In this work, we undertook a study of age/sex-specific mortality rates from circulatory system diseases and certain nosological forms in 2015 and 2018 among outpatients of Research Institute — Ochapovsky Regional Clinical Hospital No. 1 delivering primary healthcare services.Materials and methods.We studied age/sex-specific mortality rates from circulatory system diseases among adult population using the data from the medical records of deceased outpatients (Form 025/u), extracts from autopsy reports, as well as medical certificates of death for 2015 and 2018. Non-standardised and standardised mortality rates were calculated.Results.In 2015, all-cause mortality rate by the medical organisation reached 6.2 per 1,000 population, with the total number of deaths from circulatory system diseases amounting to 49.6%. The non-standardised mortality rates from the circulatory system diseases totalled 307.81 per 100,000 population, including the non-standardised mortality rates from cerebrovascular diseases (44.68), ischemic heart disease (129.08) and myocardial infarction (4.96). Standardised mortality rates from circulatory system diseases amounted to 201.96 (men — 70.58, women — 131.38). In 2015, chronic ischemic heart disease (41.94%) ranked first as the cause of mortality among circulatory system diseases followed by diagnoses requiring additional interpretation and examination of primary medical documentation (35.48%), i.e. not clearly defined causes of death; and cerebrovascular diseases (14.52%). In 2018, chronic ischemic heart disease also ranked first (47.54%) followed by cerebrovascular (36.21%) and other diseases (16.39%) (ICD codes I26, I71.1, R00.8).Conclusion.It is shown that more attention from the cardiological and therapeutic services of primary health care is required in coding death-causing circulatory system diseases.

The state research center of preventive medicine, Moscow, 101990, Russian Federation The arterial hypertension is a leading risk factor of cardio-vascular morbidity and mortality of population in the Russian Federation. The application of modern informational technologies at population level can be on of modes of improvement of arterial hypertension control. The purpose of study. To apply modeling technique for evaluating at the regional level the economic expediency of implementation of remote monitoring of arterial pressure using GPS-tonometer. Materials and methods. The mathematical model of social economic efficiency of remote monitoring of arterial pressure was developed to be applied in the region with 1 million ofpopulation given 90, 70,50 and 30% of monitoring coverage with calculation of number of prevented cases of myocardium infarction, stroke, deaths and averted economic loss during five years. Results. The remote monitoring of arterial hypertension in the region with 1 million ofpopulation would permit preventing 1940 deaths during five years under 90% coverage with remote monitoring of patients with arterial hypertension and at 30% coverage 645 lives would be saved. The mass implementation of remote monitoring permits decreasing load on health care system at the expense of prevention of myocardium infarction (95 cases at 90% coverage during five years), stroke (630 at 90% coverage during five years) and calls of emergency medical care. The remote monitoring is economically expedient since expenses of its implementation are lesser than expected economic effect t the expense of decreasing of visits for medical care and maintenance of manpower resources in economics. Conclusion. The remote monitoring of arterial pressure using various information technologies is a modern and efficient approach to amelioration of arterial hypertension control at the regional level.

There is a canonical life-history trade-off between quantity and quality of offspring, but molecular determinants for this are unknown. Here, we show that knockout of tumor necrosis factor (TNF-KO) in mice switched a relation between the number and size of developing embryos from expectedly negative to unexpectedly positive. Depletion of TNFα imbalanced humoral and trophic maintenance of embryo growth during gestation with respect to the litter size. The levels of embryotrophic GM-CSF cytokine and placental efficiency attained positive correlations with the number and size of embryos in TNF-KO females. Thus, TNFα oversees mother’s resource allocations to balance embryo growth with the number of offspring. Consequently, this suggests an intricate link between the number-size trade-off and immunity given a pivotal role of TNFα in immune homeostasis.

Despite the advances in medicine, about 4 million children under the age of 6 months die annually around the world due to infection, which is 450 deaths per hour (UNISEF, 2009). The degree of development of the immune system of children born in time is determined by many factors, including the immunogenetic similarity or difference of mother and fetus organisms, which, in turn, is due to the genotypes of mating pairs, as well as the selection of surrogate mothers duringin vitrofertilization. From our review of the literature, it follows that immunogenetic interactions of mother and fetus organisms, which occur at all stages of pre- and postnatal development, have a signifcant effect on the resistance of offspring to infections and allergens. Before implantation, the mother’s immune responses are formed under the influence of semen fluid antigens, leukocytes and cytokines, as well as under the influence of the genes of the major histocompatibility complex, which are expressed in embryos at the stage of two cells. After implantation, transplacental transfer of immunoglobulins and immunocompetent cells becomes of immunomodulating importance. It is important to emphasize that, although substances with a high molecular weight usually do not pass through the placenta, this rule does not apply to immunoglobulin G (IgG), which, with a molecular weight of about 160 kDa, overcomes the transplacental barrier due to binding to the fetal Fc receptor. The level of IgG in newborns usually correlates with the level of maternal antibodies. During the period of natural feeding, the immune protection of newborns is provided by the mechanisms of innate immunity and the factors of humoral immunity of mothers. It has been shown that immunoglobulins from the milk of many animal species are transferred through the neonatal intestinal epithelium to the blood. Since breast milk contains large amounts of various immunoactive components, including proteins, cytokines, hormones, immunoglobulins, exosomes containing micro-RNA, and viable immune cells, the immunomodulating effects of breast milk persist even after elimination of maternal immunoglobulins from the blood of the offspring, up to maturation. Analysis of a large body of experimental data shows that the study of mechanisms of “motherfetus” and “mother-newborn” interactions are the basis of a knowledge base needed to fnd means of life-long directed modulation of the descendants’ immune status.

Vavilovskii Zhurnal Genetiki i Selektsii = Vavilov Journal of Genetics and Breeding. 2019;23(5):582-587 (in Russian) Page 587, in Acknowledgements instead of The animals and behavioral testing are supported by the budget project (No. 0324-2019-0041). The MRI study is supported by the budget project (No. 0259-2019-0004). All studies are implemented using the equipment of Center for Genetic Resources of Laboratory Animals at ICG SB RAS, supported by the Ministry of Education and Science of Russia (Unique ID# of the project: RFMEFI62117X0015). should read The animals and behavioral testing are supported by the budget project (No. 0324-2019-0041). The MRI study is supported by the budget project (No. 0259-2019-0004). All studies are implemented using the equipment of Center for Genetic Resources of Laboratory Animals at ICG SB RAS, supported by the Ministry of Education and Science of Russia (Unique ID# of the project: RFMEFI62117X0015). The study was conducted within the basic part of the state task of the Ministry of Science and Higher Education of the Russian Federation (No. 17.7255.2017/8.9). The original article can be found under DOI 10.18699/VJ19.528.Вавиловский журнал генетики и селекции. 2019;23(5):582-587На странице 587 в разделе Благодарности вместо «Работа с животными и поведенческое тестирование выполнены в рамках бюджетного проекта № 0324-2019-0041. Томографические данные получены на средства бюджетного проекта № 0259-2019-0004. Исследование проведено с использованием оборудования ЦКП «Центр генетических ресурсов лабораторных животных» ФИЦ ИЦиГ СО РАН, поддержанного Минобрнауки России (уникальный идентификатор проекта RFMEFI62117X0015)».следует читать: «Работа с животными и поведенческое тестирование выполнены в рамках бюджетного проекта № 0324-2019-0041. Томографические данные получены на средства бюджетного проекта № 0259-2019-0004. Исследование проведено с использованием оборудования ЦКП «Центр генетических ресурсов лабораторных животных» ФИЦ ИЦиГ СО РАН, поддержанного Минобрнауки России (уникальный идентификатор проекта RFMEFI62117X0015). Исследование выполнено в рамках базовой части государственного задания Минобрнауки России (№ 17.7255.2017/8.9)».Оригинальная статья может быть найдена по DOI 10.18699/VJ19.528.

The reproducibility of results obtained with rodent models depends on the genetic purity of the strain and the stability of the environment. However, another potential factor is changes in the gut microbiota due to the transmission of mother’s bacteria during embryo transfer. In this study, we demonstrate the transmission of the microbiota and immune cell blood phenotype to the offspring of 2 strains, C57BL/6JNskrc and BALB/cJNskrc, from surrogate dams of different genotypes. Interstrain embryo transfer resulted in a change in the number of Enterococcus spp. organisms, as shown by quantitative PCR analysis. The number of blood leukocytes was also affected, as estimated by flow cytometry. The number of blood leukocytes, including B cells and helper T cells, and the number of Enterococcus spp. organisms in male C57BL/6JNskrc offspring bornto BALB/cJNskrc surrogate dams became similar to those of male BALB/cJNskrc mice born to BALB/cJNskrc dams. Likewise, the same parameters of male BALB/cJNskrc mice born to C57BL/6JNskrc dams became similar to those of male C57BL/6JNskrc offspring. Researchers should be aware of the possible transmission of the dam’s microbiota and immune cell phenotypes to the experimental strains when planning embryo transfer experiments, because these factors could affect the experimental outcomes or the reproducibility of experimental results.

STUDY QUESTION Does the genotype of the surrogate mother modulate the body composition and immunity of her offspring? SUMMARY ANSWER C57BL/6J (B6) progenies carried by immunodeficient NOD SCID (NS) mothers had increased adaptive but decreased innate, immune responsiveness in comparison with the same genotype offspring carried by immunocompetent mothers, B6 and BALB/c (C); the B6 progenies carried by the same genotype mothers also showed higher body fat than the others. WHAT IS KNOWN ALREADY Differences in the major histocompatibility complex (MHC) genes between mother and foetus is considered as an important factor in prenatal embryo development, whereas the impact of such dissimilarity on the phenotype of the mature progeny is unclear. STUDY DESIGN, SIZE, DURATION Transplantation of two-cell mouse embryos into recipient females of the different MHC (H2) genotypes was used as an approach to simulate three variants of the immunogenic mother-foetus interaction: (i) bidirectional immunogenic dialogue between B6 (H2b haplotype) embryos and C (H2d haplotype) surrogate mother; (ii) one-way immunogenic interaction between B6 embryos and immunodeficient NS (H2g7 haplotype) surrogate mother and (iii) reduced immunogenetic dialogue between embryos and surrogate mother of the same H2b haplotype resulting in only a maternal response to HY antigens of male foetuses. Delivered by Caesarean section, pups were fostered by lactating B6 females and weighed after weaning (n = 171). Body mass and composition and innate and adaptive immunity were assessed in selected progeny groups at 9-11 weeks of age. PARTICIPANTS/MATERIALS, SETTING, METHODS The study was performed on the specific pathogen-free mouse, inbred strains C57BL/6J, NOD SCID and BALB/c. Plasma progesterone in pregnant females was measured by enzyme-linked immunosorbent assay (ELISA). Body composition was determined by magnetic resonance spectroscopy using a low-field NMR spectrometer (EchoMRI, USA). To assess peritoneal macrophage responses (innate immunity) to anthrax, lactate dehydrogenase (LDH) and interleukin-1 (IL-1β) were measured in a culture medium 24 h after the addition of both anthrax-lethal factor and anthrax-protective antigen. To assess adaptive immunity, 9-10 males in experimental groups were infected with Helicobacter hepaticus. Faeces collected 2 and 4 weeks after infection was used for quantitative assessment of the H. hepaticus DNA by real-time polymerase chain reaction. IgA, interferon (IFN-γ), tumour necrosis factor (TNFα), interleukin-17 (IL-17) and interleukin-10 (IL-10) in colon tissue and IgG in serum were determined in samples collected 4 weeks after gavage with H. hepaticus using ELISA. For statistical analyses, ANCOVA, post hoc least significant difference (LSD) test, Student's t-test, Spearman rank correlations and χ2 test were performed. P-value

Smoking influences nutrition type and food-related behavior of the smokers.Aim. To evaluate the specifics of adult population of Russian Federation nutrition type according to smoking status.Material and methods. Analysis was done on the representative selection of nonorganized male and female population, age 25-64 y. o. (n=22258, of those males 8519, females 13698) from 13 regions of Russia. Response about 80%. Nutrition character was assessed by the rates of food items consumption with quantitative assessment in several units. Smoking status was assessed with questionnaire with selection to the groups: non-smokers, past smokers, current smokers.Results. Most prominent differences were found on the intake of fresh vegetables and fruits, of curd, cheese, red meat, sausages, pastry and behavior of adding salt to cooked meals. In comparison with the smokers, non-smokers do more often take curd — by 38%, vegetables and fruits — by 30%, and rarer — red meat, by 25%, and sausages, by 21%; they add salt rarer — by 26%. However, pastry and sweets they eat more commonly, by 19%. With the quittance from smoking, there is increase of curd in the meals by 20%, fresh fruits and vegetables by 19%, and decrease of adding salt behavior by 26%, as by 17% — consumption of sausages and by 11% — high fat dairy (sour cream and cream). Sweets and pastry are consumed only 8% more, that distinguishes the model as healthier and more protective against NCD.Conclusion. Smoking influences negatively food related behavior, shaping the character of nutrition with higher intake of meat and sausages, saltings and adding salt behavior, lower consumption of vegetables and fruits, that should be considered in prevention events.

An increase in the prevalence of chronic noncommunicable diseases is a significant problem for both patients and the health system. According to the World Health Organization "Promoting effective responsible self-care ... is essential to reduce the financial burden on health systems". The term "responsible self-care" means "self-help" and "self-care". The concept of responsible self-care is to create conditions and prerequisites for forming a responsible attitude to own health, children's and family's health by maintaining a healthy lifestyle, wider and more competent use of over-the-counter medication for the prevention or self-care of the trifling ailment and chronic non-communicable diseases, continuing the therapy prescribed by the doctor. Changes in the legislative framework, coordinated activity of medical workers of various levels and specialties, as well as improvement of medical literacy of the population are necessary for the implementation of the practice of responsible self-care in Russia. Promotion of healthy lifestyles and the personal responsibility of people for their health in the media and Internet resources, self-monitoring of the status and basic health indicators, increasing adherence of patients to prescribed medicines for the treatment of chronic diseases based on gained medical know-ledge, skills and habits are the most applicable measures for Russia to date.

Contactins (Cntn1-6) are a family of neuronal membrane proteins expressed in the brain. They are required for establishing cell-to-cell contacts between neurons and for the growth and maturation of the axons. In humans, structural genomic variations in the Contactin genes are implicated in neurodevelopmental disorders. In addition, population genetic studies associate Contactins loci with obesity and hypertension. Cntn5 knockout mice were first described in 2003, but showed no gross physiological or behavioral abnormalities (just minor auditory defects). We report a novel Cntn5 knockout mouse line generated by a random transgene integration as an outcome of pronuclear microinjection. Investigation of the transgene integration site revealed that the 6Kbp transgene construct coding for the human granulocyte-macrophage colony-stimulating factor (hGMCSF) replaced 170 Kbp of the Cntn5 gene, including four exons. Reverse transcription PCR analysis of the Cntn5 transcripts in the wild-type and transgenic mouse lines showed that splicing of the transgene leads to a set of chimeric hGMCSF-Cntn5 transcript variants, none of which encode functional Cntn5 protein due to introduction of stop codons. Although Cntn5 knockout animals displayed no abnormalities in behavior, we noted that they were leaner, with less body mass and fat percentage than wild-type animals. Their cardiovascular parameters (heart rate, blood pressure and blood flow speed) were elevated compared to controls. These findings link Cntn5 deficiency to obesity and hypertension.

The transgenesis technologies are actively used in different fields of biological studies. The most actively used method to obtain transgenic animals by DNA injection in the zygote pronucleus can be accompanied by the violation of the genes’ function instead of integrating the transgenic construction. In this work, the morphophysiological effects of integrating the transgenic construction providing the production of the human granulocyte–macrophage colony-stimulating factor in the milk of the mouse line (GM9) (the insertion of the construction in the intron of the contactin 5 (Cntn5) gene) were described. It was demonstrated that the insertion of the construction did not result in the Cntn5 knockout. However, the gene transcription in the heart and kidneys of transgenic animals changes compared with wild-type animals, and the spectrum of transcripts also changes, indicating a violation in the Cntn5 gene splicing regulation. It is known from the published data that the Cntn5 polymorphisms are associated with an addiction to obesity and a predisposition to arterial hypertension. We studied the main parameters of the fat metabolism and cardiovascular activity in mice homozygous for the transgene insertion in the Cntn5 gene, heterozygous animals, and wild-type animals. The phenotyping carried out demonstrates that homozygous mice have a smaller body weight than wild-type individuals. And the weight difference between genotypes is determined more by significantly lower fat accumulation than by the lag of mutants in the development of the skeleton and muscles constituting the lean mass. Statistically significant differences in the parameters characterizing the intensity of the blood circulation were found in the studied lines. Homozygous mice exceed wild-type individuals by their arterial pressure values, heart rate, and blood flow rate in the tail vessels. It should be noted that heterozygous individuals have intermediate values between mutants and wild-type according to all the measured morphofunctional parameters.

The immune response to immunogenic stimuli depends on various factors such as the cytokine context, way of entry, and immune status of the organism. In mice, the entry of the female’s chemosignals into the male organism via the respiratory system activates the mucosal immune response, which leads to the development of enhanced resistance to infections and is of adaptive value. However, the activation of mucosal immunity depends on the genetic predispositions of the immune response. BALB/c and C57BL/6 are prototypically Th2-and Th1-type mouse strains, respectively; therefore, they can serve as the perfect model organisms for studying the activation mechanism of the lungs’ mucosal immune activation in response to the female’s chemosignals. The respiratory tract’s mucosal immune response to intranasal application of LPS, urea solution, saline solution, and female urine used as a chemosignal was investigated in the BALB/c and C57BL/6 male mice. Application of both female urine and LPS increased the total white blood cell count and protein concentration in the bronchoalveolar lavage fluid (BLF) in BALB/c male mice but not in C57BL/6 male mice, suggesting an important role of the Th2 pathway in the lungs’ mucosal immune response. At the same time, urine application provoked a significantly lower plasma corticosterone elevation than LPS. Thus, the sexual signals associated with infection risks provide genotype-dependent mobilization of the innate immunity without significant activation of physiological stress mechanisms.

The possibility of forecasting indicators of the real estate market. An approach based on the use of lag variables, where the lag time is determined by analyzing the dynamics of relative error. The result is a leading indicator. Forecasted assessment of the near future the price per square meter in Moscow.

Aim. To analyze costs of health care in Russia associated with smoking in 2009. Material and methods. Cardiovascular diseases, cancers and chronic obstructive pulmonary diseases (COPD) were included in the analysis. Calculation was performed on the basis of the relative risks of diseases associated with smoking, and obtained from foreign surveys, official statistics on morbidity and health system resources expenditure, and costs of health-seeking in line with state program of guaranteed free medical care. Results. In 2009 total costs of the health care system associated with smoking exceeded RUR 35.8 bln. It corresponded to 0.1% of gross domestic product in Russia in 2009. The costs structure was the following: hospitalization – RUR 26.2 bln, emergency calls – RUR 1.4 bln, and outpatient health-seeking – RUR 8.2 bln. Costs of outpatient pharmacotherapy were not included into analysis because of lack of baseline data needed for calculations. Cardiovascular diseases caused 62% of the health care costs associated with smoking, cancers – 20.2%, and COPD – 17.8%. Conclusion. The smoking in Russia is associated with significant health care costs. It makes needed resources investment in preventive programs to reduce smoking prevalence.

Embryonic stem cells are commonly used for generating transgenic mice. Embryonic stem cells could participate in the development of chimeric animals after being injected into a blastocyst. Injection of genetically modified embryonic stem cells could lead to the transmission of the germ lines of a transgene or genomic modification in chimeric mice. Such founders are used to produce transgenic lines of mice. There are several projects dedicated to producing knock-out mouse lines (KOMP Repository, EUCOMM, Lexicon Genetics). Nevertheless, there is a need for complex genome modifications, such as large deletions, reporter genes’ insertion into the 3' gene regulatory sequence, or site-specific modifications of the genome. To do this, researchers need an embryonic stem cell line that is able to participate in the formation of chimeric animals even after prolonged cultivation in vitro. Several lines of embryonic stem cells of mice were produced in the Laboratory of Developmental Genetics of the Institute of Cytology and Genetics (ICG), Siberian Branch, Russian Academy of Sciences (SB RAS). We tested the DGES1 cell line (2n = 40, XY) (of the 129S2/SvPasCrl genetic background) for chimeric mice production at the Center for Genetic Resources of Laboratory Animals at ICG SB RAS. Embryonic stem cells were injected into 136 blastocysts (of the B6D2F1 genetic background), which were transplanted into CD-1 mice. Among 66 progeny, 15 were chimeric, 4 of which were more than 80% chimeric judged by the coat color. All chimeras were males without developmental abnormalities. 10 of 15 males were fertile. Microsatellite analysis of the progeny of chimeric mice revealed the contribution of the embryonic stem cell line DGES1 to the gamete formation. Thus, a novel DGES1 embryonic stem cell line could be efficiently used for transgenic mouse production using the B6D2F1 blastocysts and CD-1 recipients.

The paper presents a systematic approach to the selection of methods and algorithms suitable for modeling the dynamics of market indicators. The directions and stages of modeling and forecasting market dynamics in the study of short time series based on the use of fictitious and lag variables, as well as adaptive methods, are formulated. It is shown how the specificity of the data and the size of the series of observations affect the choice of suitable mathematical methods. A range of models suitable for approximating short time series has been determined. Studying the example of labor market research, the choice of the Holt-Winters multiplicative model as the best is substantiated. The model makes it possible to adequately approximate the damping of the oscillation amplitude synchronously with the initial process. When studying the dynamics of real estate market prices, the possibilities of using lag variables as a leading indicator for the purpose of short-term forecasting are shown.

Arterial hypertension is a disease which leads to severe negative social and economic consequences. Pharmacoepidemiologic studies allow assessment of present situation on high blood pressure (BP) treatment and search of ways of its efficacy improvement.Aim. To study treatment of hypertensive patients who had visited the cardiology referral clinic for the first time and to assess treatment dynamics over the following 6 months with the estimation of its efficacy.Material and methods. The study included two steps. At the first step a primary sample of the study participants was formed out of hypertensive patients who had visited for the first time a cardiologist in one of the Moscow district cardiologic dispensary in 2010 with the further completion of expert cards in accordance with the primary medical documentation (n=1766). At the second step the phone survey was conducted 6 months after the first visit with the completion of special questionnaires (n=1419).Results. Recommendations for antihypertensive treatment given to the cardiologic dispensary patients are in line with the current guidelines, and 6 months after the first visit 91% of the patients had continued antihypertensive treatment. However, the efficacy of BP control turned out to be low: target BP level was only detected in 28.8% of the patients, and 36.7% of the respondents developed hypertensive crises during the 6 months.Conclusion. Despite the follow-up in the referral clinic and the intake of the prescribed drugs the patients revealed low efficacy of BP control. The reasons for this fact require further investigation. Probably, the improvement of BP control requires implementation of special education and motivational techniques as short-term contact with specialists does not lead to high efficacy of antihypertensive treatment.

High adherence to blood pressure (BP) medical correction determines clinical and socioeconomic efficacy of antihypertensive treatment. Separate components of adherence are to be studied, including regularity of drugs intake and reasons for non-compliance with medical recommendations in different categories of patients.Aim. Evaluation of antihypertensive drugs (AHD) intake regularity (as a component of treatment adherence) and factors it is influenced by in hypertensive patients who had for the first time visited a specialized cardiology center during the 6-month follow-up after the primary consultation.Material and methods. First, a number of hypertensive patients who had visited a cardiologist of one of Moscow’s district cardiology clinics for the first time in 2010 (n=1766) had formed a sample of the study participants. The expert cards were filled out in accordance with the primary medical documentation data. The second step was conducted 6 months after the first visit by a phone survey with the completion of questionnaires (n=1419).Results. Majority of respondents (74.9%) had been taking AHD regularly 6 months after the primary consultation and 16.2% of the patients had been using them occasionally. 8.9% of the respondents completely refused to control hypertension with drugs. Respondents of male sex (OR=1.4), with poor BP self-control in home settings (OR=2.5), unable to get drugs under the medicine assistance scheme (OR=1.8), those without coronary heart disease (OR=1.9), with hypertension duration less than 5 years (OR=1.9), with changes in antihypertensive therapy regimen as compared to the one recommended by a cardiologist (OR=1.5), those who had 1-2 drugs in the treatment regimen at the moment of the survey (OR=2.4) and patients who had no fixed drug combinations in the treatment scheme (OR=1.4) were shown to have significantly higher probability of irregular AHD intake or complete treatment refusal.Conclusion. Outpatients of the specialized cardiology center are characterized by rather high treatment adherence by AHD intake regularity. We have revealed a number of factors that significantly correlate with reduced antihypertensive treatment adherence. These factors must be taken into account at treatment regimen selection and patients’ follow-up.

Background The medications produced from natural products are widely used as prophylactics for sickness induced by alcohol consumption. One such prophylactic is produced from the Reishi mushroom, Ganoderma lucidum. Because of the antioxidant properties of these preparations, we expect neuroprotective prophylactic effects of Reishi-based medications in alcohol-treated animals. Methods The Reishi (R) suspension was produced as water extract from Altaian mushrooms. Sprague-Dawley male rats were separated into the following 3 experimental groups: Group A + R received R (6 days per week) starting 1 week before alcohol exposure, and during the next 3 weeks, they received both R and alcohol; group A received alcohol; and group C received water. At the end of experiment, we determined the metabolic profile using proton magnetic resonance spectroscopy ((1) H MRS) of the brain cortex and phosphorus magnetic resonance spectroscopy of the liver. Additionally, the blood cells were collected, and the serum biochemistry and liver histology were performed after euthanasia. Results Partial least squares discriminant analysis processing of the brain (1) H MRS gave 2 axes, the Y1 axis positively correlated with the level of taurine and negatively correlated with the level of lactate, and the Y2 axis positively correlated with the content of GABA and glycine and negatively correlated with the sum of the excitatory neurotransmitters, glutamate and glutamine. The Y1 values reflecting the brain energetics for the A + R group exceeded the corresponding values for groups C and A. The maximal level of Y2 reflecting the prevalence of inhibitory metabolites in the brain was observed in the rats exposed to alcohol. Moderate alcohol consumption did not cause significant pathological changes in the livers of the experimental animals. However, 20 days of alcohol consumption significantly increased the number of binuclear hepatocytes compared to the control. This effect was mitigated in the rats that received the Reishi extract. Conclusions Regular administration of the Reishi suspension improved the energy supply to the brain cortex and decreased the prevalence of inhibitory neurotransmitters that are characteristic of alcohol consumption. The alcohol-induced increase in liver proliferation was significantly suppressed by regular administration of the G. lucidum water suspension.

Modeling is the common approach for predicting not only the population health, but also the social and economic burden of disease, which is an important argument while making decisions in health care and prevention.To develop the model for predicting cardiovascular risk, applicable for the assessment of clinical and socio-economic effects of preventive and therapeutic actions at the level of the whole population or part (region, city, group of patients).An analytical model for making decision was performed by using a Markov model consisting of Markov states and probabilities of transition from one state to another within a certain time interval. The model included risk factors and cardiovascular diseases (blood pressure, cholesterol, smoking) and probabilities of transition between them. Data was standardized by age for both males and females. Multivariate sensitivity analysis was performed. The literature search conducted using eLIBRARY.RU (http://elibrary.ru) and CyberLeninka (http://cyberleninka.ru). Consultations with experts in the field of coronary heart disease, stroke, heart failure were carried out.The model, allowing to compare the outcomes of two scenarios (absence/presence of intervention). The model included risk factors: arterial hypertension, smoking, hypercholesterolemia, and important CVD: coronary artery disease, myocardial infarction, unstable angina, heart failure, chronic heart failure after myocardial infarction, transient ischemic attack, stroke, atrial fibrillation. There was absorbent state - death. At the output from the model the patient state was defined as the sum of the Markov states characteristics during the model time horizon. Each result had the cost and outcome, which values could be calculated by simulation modeling ("cohort simulation"). The data analysis from prospective study had shown that mortality increases with age, as expected, but in different age groups impact of cardiovascular causes was different and declined with age. In the case of the blood pressure there was the expected increase of the death risk with the growth of pressure levels, both for males and females, except for males 60-64 years old who had a minimal risk of death at the blood pressure 140-149/90-99 mmHg, and among males with normal blood pressure the risk was higher. Smoking was associated with an expected increase of the death risk among all age groups in both sexes. In males, aged 40-64 years, the death risk was higher at the normal levels of cholesterol (2-5 mmol/l), than at the cholesterol levels equal 5-7 mmol/l. There were no data sources to assess probability of occurrence of the risk factors (hypertension, smoking, hypercholesterolemia) in patients who did not have these factors previously in our studies, and available literature. This requires the prospective studies on at least two slices of surveys (not just with the endpoint analysis). Analysis of the literature on search of prospective Russian studies that would evaluate the probability of transition from one state to another, and consultations with experts have identified that currently conducted studies do not provide all the necessary probability of transition on the basis of national data. In the absence of local data for the model is acceptable to use the results of meta-analyzes of international studies.Markov model will allow for prediction the effectiveness of different interventions, including their socio-economic consequences. The created model will allow in the future to make changes with the appearance of the results of new studies or new data in order to improve modeling accuracy.

In article the minimization problem of the residual for Euler-MacLaurin formula are solved. The solution is used for determination of parameters of a window of sliding summation in smoothing of time series. Results of numerical experiments are given.

The effect of silicon dioxide nanoparticles on the expression of key genes of the brain serotonergic (5-HT) system has been studied in specific pathogen-free mice chronically exposed to Tarkosil nanoaerosol (25-nm particles). Males of the Balb/c and C57Bl/6 strains are used to reveal genetic differences in the response to the nanomaterial. The animals are exposed to aerosol with a mean particle size of 107 nm for 10 days. After exposure, their midbrains, hippocampi, and frontal cortices are examined. The expression rates of genes for 5-HT1A and 5-HT2A receptors; tryptophan hydroxylase (TPH2), the key enzyme in 5-HT production; serotonin transporter (5-HTT); and interleukin 6 (IL6) as a marker of inflammation in the brain are assayed by quantitative reverse transcription PCR. The expression of 5-HT1A is notably elevated in the hippocampus of Balb/c mice, but it tends to decrease in C57Bl/6. No changes in the expression of the genes for 5-HT2A, TPH2, 5-HTT, or IL6 are noted in any brain divisions. Thus, the chronic inhalation of silicon dioxide nanoparticles does not activate nonspecific immunity in the brain, but it exerts contrasting genotype-specific effects on the expression of the 5-HT1A receptor in the hippocampus.

Aim. To estimate incidence rate of first myocardial infarction (MI) with different outcomes and factors, it is influenced by, depending on the intensity of preventive measures in a population of middle-aged men during 15-year follow-up; to evaluate economic efficiency of primary medical prevention.Material and methods. Two populations of middle-aged men with a total of 6656 males (3488 men the group of active prevention and 3168 the group of comparison) were followed up over 15 years.Results. The group of active prevention revealed 22.1% reduced MI incidence rate during 5-year follow-up as compared to the second group, fatal MI incidence rate was 42.4% lower, p0.05), while patients with clinical signs of ischemic heart disease (IHD) and no history of previous MI kept significant distinctions in first MI incidence rate (41% less in the first group, pSuch indices as “life years saved” (LYS) and “quality-adjusted life years saved” (QALYS) for 1000 persons in the active prevention group were 53 and 51 years, respectively during the 5-year follow-up, 147 and 143 years – during the 10-year follow-up. In the long-term actual expenses for 1 LYS were 3.4-fold less than annual gross domestic product (GDP) value, at that charges for primary prevention – 4-fold less, which has been for the first time demonstrated using factual data and not mathematic modeling usually used in scientific literature.Conclusion. The long-term prospective follow-up has demonstrated that the risk of first MI can be reduced by means of active and systematic prevention. Cost-effectiveness of primary prevention, including the one of MI, has been conclusively showed. The results allowed to validate the reasonability of active multifactorial prevention in the settings of primary healthcare, which makes it possible to define scientific-based recommendations for real practice.

Infections with Helicobacter spp. are known to have serious effects on rodent health, especially in immunocompromised animals. In this study three approaches were used to eradicate Helicobacter spp. infection in mice with a deficiency in intestinal proteoglycan (mucin2), namely triple oral antibiotic therapy (amoxicillin, clarithromycin and metronidazole), cross-fostering of neonatal pups by surrogate mothers negative for Helicobacter spp., and in vitro fertilization (IVF) with embryo transfer into Helicobacter-free mothers. However, triple antibiotic therapy in mice with mucin2 deficiency was not effective and had negative effects on reproductive performance, and high susceptibility of mucin2-deficient mice to Helicobacter spp. during the first 12 h after birth rendered cross-fostering impossible. Only IVF with embryo transfer was effective in eradicating Helicobacter infection from transgenic mice with mucin2 deficiency.

Diversity of viruses, bacteria, microscopic fungi, and endo- and ectoparasites is an inevitable environmental factor that influences the host reproduction and that is determined not only by negative effects of infectious diseases but also by activation of protective mechanisms, which provide a confrontation to the pressure of parasites. In the present work, hemocyanin was injected into males of the ICR outbred line in order to study reproductive consequences of antigenic stimulation of males. Intact females were added to control and antigen-stimulated males at the initial stage of antibody formation. During 6 days of combined keeping, a significantly greater amount of ovulated egg cells and living embryos were registered in the females added to males that were injected with hemocyanin compared with that theoretically expected for equal reproductive yield. Females covered by antigen-stimulated males bred larger embryos compared with those in the control. Indices of female fertility depended on prevalence of cellular (Th1) or humoral (Th2) immune responses in antigen-stimulated males. Shift of Th1/Th2 balance resulted in higher preimplantation embryonic losses in females covered by males with a prevalence of cellular immune response; however, they bred larger embryos. Thus, it was established that activation of the immune system in males does not influence their reproductive abilities. This allows us, on the one hand, to explain the contribution of protective reactions of the organism in the increase in fertility of the mammals that inhabit territories with high specific abundance of parasites; on the other hand, it demonstrates new ways of the management of the reproduction of animals bred under human control.

The effect of intranasal applications of suspensions containing Tarkosil 25 nano- and microparticles (nanoT and microT, respectively) on the mucosal immunity and content of leukocytes in blood and seminal fluid have been investigated in SPF mice. Early development of mucosal immune inflammatory reaction have been observed only after the administration of nanoT and only in BALB/c mice, which are characterized by a predominance of humoral immune response (Th2). In turn, the leukocytic reaction of the blood to Tarkosil 25 took place only in C57Bl/6 mice, in which the cellular immune response (Th1) predominates. The application of nanoT also caused an increase in the number of leukocytes in the seminal fluid of mice of both strains. Thus, upon first contact with nanoaerosol, the individual characteristics of the immune response were formed; the study of these characteristics can be used as the basis for methodological approaches to predicting the individual risk of pathologies in persons engaged in the manufacture of Tarkosil 25.

The modification of pre- and postnatal development conferred by immunogenic stimulation of mothers provides a population-level adaptation mechanism for non-genetic transfer of maternal experiences to progeny. However little is known about the transmission of paternal immune experiences to offspring. Here, we show that immune priming of males 3–9 days before mating affects the growth and humoral environment of developing embryos of outbred (ICR) and inbred (C57BL and BALB/c) mice. Antigenic stimulation of fathers caused a significant increase in embryonic bodyweight as measured on Day 16 of pregnancy and altered other gestation parameters, such as feto–placental ratio. Pregnant females mated with immunised males were also characterised by changes in humoral conditions as shown by measurements of blood and amniotic progesterone, testosterone and granulocyte–macrophage colony-stimulating factor (GM-CSF) cytokine concentrations. These results emphasise the role of paternal effects of immune priming on the in utero environment and fetal growth.

In previous studies, we showed that long-term perception of female odor increases flu virus resistance in male mice. To expand on this finding, we examined the ability of female chemical cues to rapidly induce leukocyte mobilization into male lung tissue as a critical condition of signal-derived respiratory infection risk reduction, which is usually associated with sniffing scent marks. Here, we compared the immune and endocrine effects of female chemical cues and lipopolysaccharide (LPS) as common triggers of innate immunity. The number of leukocytes in the lung tissue, concentrations of IL-1β in lung and hypothalamus, and plasma corticosterone and testosterone levels were assessed in ICR male mice 2 h after the intranasal application of female urine, LPS or urine and LPS. Both stimuli induced leukocyte mobilization but, in contrast to LPS, female urine alone did not stimulate increased IL-1β levels in lung and hypothalamus. Plasma corticosterone increased and plasma testosterone decreased in response to LPS, whereas the concentrations of these hormones did not change in response to female chemical cues. Thus, the present study gives additional evidence for an anticipatory adaptation of male mice to potential breeding risks. Appreciable mobilization of leukocytes to the lungs requires less than 2 h and develops through an IL-1β-independent pathway.