Physical Activity and Gallstone Disease

Аim: to present data of Russian and foreign studies about association between physical activity (PA) and gallstone disease (GSD).Key point. A low PA level is one of the four major risk factors for chronic non-infectiuos diseases. The frequency of low PA in men and women of the Russian Federation (according to the medical examination in 2016) is 19 %. The global prevalence of GSD is up to 20 % among adults. Many systematic reviews and meta-analyses have confirmed an inverse association between GSD and PA in the world, regardless of potential risk factors for GSD, with a clear dose-dependent effect — the relative risk (RR) of GSD was 0.87 (95 % CI 0.83–0.92) per 20 metabolic equivalents (MET) of PA per week. According to our results of an epidemiological survey in the framework of the WHO MONICA program in Novosibirsk (n = 870) among women aged 25–64 with low total PA (less than 800 MET/min/week), as well as with the first class of PA in leisure-time, GSD occurred much more often (class 1 — 33 %, classes 2–4 — 8.7–11.0 %, p < 0.01). PA favorably affects almost all mechanisms of gallstone formation: improves cholesterol metabolism in bile, increases serum HDL cholesterol, bile acid synthesis, stimulates the release of cholecystokinin, reduces mucin hypersecretion, increases the diversity and richness of the intestinal microbiota. Daily PA serves as a preventive measure for GSD: the risk of GSD is reduced by 66 % (95 % CI 0.18–0.86).Conclusion. EASL has recognized PA as a protective agent against gallstone formation

Frequency of hyperglycemia and polymorphism of TNF and TP53 genes in patients with acute pancreatitis, chronic pancreatitis, pancreatic cancer

BACKGROUND: «The vicious circle» of associations of diabetes mellitus (DM) with pancreatic pathology, when pancreatic diseases can initiate DM, and type 2 DM — cause functional and organic pancreatic pathology, determines the search for possible associations. Some studies have established a relationship between TNF or TP53 polymorphisms with DM or with pancreatic diseases.AIMS: to determine and compare fasting plasma glucose and the frequency of hyperglycemia in patients with acute pancreatitis (APp), chronic pancreatitis (CPp), pancreatic cancer (PCp) depending on gender, etiology or stage of the disease, polymorphism -308G/A TNF gene in all patients, and polymorphism 72Arg/Pro gene TP53 in PCp..MATERIALS AND METHODS: At the observational multicenter clinical cross-sectional uncontrolled case-study 44 APp, 97 CPp and 45 PCp were examined; the groups were comparable by sex/age. Informed consent form for participate in the study was obtained from all patients. The main outcome of the study: frequency of hyperglycemia in APp, CPp, PCp, considering the polymorphism TNF and TP53 genes. RESULTS: The lowest age-standardized fasting plasma glucose (FPG) was found in CPp (6,2±0,2 mmol/l) than in APp (6,7±0,2 mmol/l, p=0,041). In PCp (6,6±0,2 mmol/l), the average levels of FPG did not differ substantially when compared with APp (p=0,749) or CPp (p=0,092). In APp, the norm of GP was detected less frequently (31,8%) than in CPp (54,6%, χ2 =6,3, p=0,012), and the frequency of the norm of GP in PCp (48,9%) did not differ with that in APp or CPp. The frequency of FPG≥6,1<7,0 mmol/l did not differ in APp (20,5%), CPp (9,3%) or PCp (17,8%). The frequency of FGP≥7.0 mmol/l did not differ in APp CPp and PCp: 47,7, 36,1, 33,3%. Logistic regression analysis revealed a tendency for an increased chance of having stage 3–4 PC with FPG≥7,0 mmol/l (Exp (B)=3,205 95%CI 0,866–11,855, p=0,081) in PCp, but not in patients with pancreatic necrosis or “definite» СP.The frequencies of G/G (71,4, 74,7, 76,2%), G/A (26,2, 24,1, 23,8%) of TNF genotypes did not differ in APp, CPp or PCp, p>0,05. In PCp genotypes Arg/Arg, Arg/Pro, Pro/Pro polymorphism gene 72Arg/Pro TP53 in 2,4, 35,7, 61,9% of cases. No associations of GP≥7,0 mmol/l with TNF polymorphism in APp, CPp, PCp and with TP53 polymorphism in PCp were obtained.CONCLUSIONS: The frequency of FGP≥7,0 mmol/l did not differ for various pancreatic disease and was not associated with the risk of pancreatic necrosis and “defined” CP. The -308G/A polymorphism TNF gene did not differ in APp, CPp or PCp and was not associated with impaired carbohydrate metabolism. The 72Arg/Pro polymorphism TP53 gene in PCp was not associated with impaired carbohydrate metabolism

Educational Tourism: Tribute to Fashion or New Educational Opportunities?

The relevance of this article lies in the need to study educational tourism as one of the ways to motivate students in educational process.  The article discusses new technologies in the educational process, which must be made more saturated and practically applicable. Visualization and the ability to implement the acquired knowledge can interest students and increase their interest in learning the information included in the curriculum. The purpose of the study is to analyze the importance of educational tourism for students. Research methods: As research methods, the following ones were used: questionnaire survey of participants of educational tours and free-style interviews with teachers and organizers of educational tourism, allowing identifying such characteristics of educational tourism’s value for students as awareness of participants about the project, previous personal experience, interest and satisfaction with the project. Research results: the article considers the importance of educational tourism from the point of view of its participants like students, accompanying teachers, from the point of view of the organizers of the tourist and educational project. The novelty and originality of the research lies in the fact that educational tourism is considered as an alternative to educational activities, which allows not only to make a trip, but also to acquire new knowledge, skills and abilities during it, which will be learned much better than just memorizing the material from the book. It is shown that the value of educational tourism can be assessed if there is knowledge about its components such as interest and personal experience of its participants, satisfaction or dissatisfaction with certain elements of the educational tour, awareness of the project possibilities, features of the organization and implementation of the tour. It is revealed that educational tourism performs not only directly educational, but also socially significant functions for society. The study shows that the project participants perceive the educational component easily and without difficulties and there is a high interest of students in educational tours. It is revealed that the accompanying notes a positive dynamic in the interest in the educational process after participation in the project. Both its participants and its organizers perceive the possibility of expanding the project positively. It is determined that the greatest difficulty in the organization of educational tourism is caused by the lack of support of state structures, which in turn causes difficulty in entering new sites where the project can be implemented. It is shown that the educational component of the project is positively evaluated by both direct consumers and teachers in terms of the correctness in the construction of the narrative and semantic parts. It is shown that to the positive aspects of educational tourism can be attributed the emotional involvement of participants in the educational process during the excursion service, as well as increasing the level of their interest in further study. Practical significance: the data obtained in this work can be used in social psychology, pedagogy, age psychology, pedagogical psychology, as well as for further theoretical development of this issue

Metabolic Risk Factors and Their Impact on Quality of Life in Patients with Pancreatic Cancer, Acute or Exacerbated Chronic Pancreatitis

Аim: to evaluate metabolic risk factors and their impact on quality of life in patients with pancreatic cancer (PC) and in patients with acute or exacerbated chronic pancreatitis.Materials and methods. Forty-five patients with PC (group 1) and 141 patients with acute pancreatitis or exacerbated chronic pancreatitis (group 2) in an observational multicenter clinical cross-sectional uncontrolled study were examined. Clinical, laboratory and instrumental examination of patients and assessment of risk factors (lipid profile, blood plasma glucose, obesity, arterial hypertension) were carried out in accordance with clinical recommendations. Patients completed the SF-36 questionnaire once to assess quality of life at hospital admission before treatment.Results. In group 1, indicators of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) in blood serum (3.7 ± 0.2; 2.2 ± 0.2 and 0.8 ± 0.1 mmol/L) were lower than in group 2 (5.1 ± 0.1; 3.1 ± 0.1 and 1.2 ± 0.1 mmol/L; p < 0.05). Arterial hypertension was more common in group 1 (55.6 %) than in group 2 (34.8 %; p = 0.013). The presence of arterial hypertension increases the chance of having PC by 2.7 times (p < 0.05). Body mass index parameters, including obesity, as well as parameters of triglycerides, and fasting plasma glucose, did not differ between the groups. Logistic regression analysis revealed a direct relationship with PC HDL hypocholesterolemia (Exp B = 4.976; p < 0.001) and arterial hypertension (Exp B = 2.742; p = 0.027) and an inverse relationship — with hypercholesterolemia (Exp B = 0.204; p = 0.002). The chance of having PC was not associated with age, fasting plasma glucose ³ 7.0 mmol/L, obesity. Quality of life indicators were higher in group 1 than in group 2 on four SF-36 scales: bodily pain (68.1 ± 5.1 and 36.8 ± 2.0; p < 0.001), general health (51.1 ± 2.5 and 38.0 ± 1.7 points; p < 0.001), social functioning (74.7 ± 3.0 and 64.5 ± 2.2 points; p = 0.007), role emotional functioning (28.2 ± 5.2 and 12.5 ± 3.1 points; p = 0.007) and in the general domain “physical component of health” (40.2 ± 1.0 and 33.6 ± 0.8 points; p < 0.001). In group 1 with HDL hypocholesterolemia compared with its absence, the indicators of role emotional functioning (22.2 ± 5.1 and 51.9 ± 13.7 points; p = 0.020) were lower, with arterial hypertension compared with its absence — role physical functioning (5.0 ± 4.0 and 25.5 ± 7.5 points; p = 0.036) and role emotional functioning (16.0 ± 5.1 and 43.3 ± 8.8 points; p = 0.007) were lower.Conclusions. In patients with PC arterial hypertension was more common and the levels of total cholesterol, LDL-C and HDL-C were lower than in patients with acute or exacerbated chronic pancreatitis. The chance of having PC is directly associated with HDL hypocholesterolemia, with arterial hypertension, inversely — with hypercholesterolemia, and is not associated with age, fasting plasma glucose ³ 7 mmol/L, or obesity. In patients with PC, quality of life indicators were higher on four SF-36 scales and on the general domain “physical component of health” than in the group with acute or exacerbated chronic pancreatitis. In patients with PC metabolic factors significantly worsened self-assessment of quality of life in terms of role functioning; in patients with acute or exacerbated chronic pancreatitis there was no such association

Results of Modeling Experiments in Designing Immuno-Enzyme Test-System for the Detection of Antibodies to <I>Yersinia pestis</I> F1 (ELISA-Ab-F1 <I>Yersinia pestis</I>)

Designed is immuno-enzyme test-system for the detection of antibodies to Yersinia pestis capsular antigen F1 – “ELISA-Ab-F1 Yersinia pestis”. On the model of laboratory mice it is demonstrated that this test-system is highly specific, its diagnostic titer being 1/320.Diagnostic value of the test-system is 83.3–88.9 % as revealed through investigations of sera and blood suspension samples, swabs of thoracic organs of animals, inoculated with live plague vaccine, strains of plague microbe, containing and deprived of pFra, as well as with heterologous bacteria

Constructing and Medical Trials of a Monoclonal Dot-Immuno-Enzyme Test-System “DIATul-M” for Tularemia Microbe Detection

mc/ml. Additionally, this test-system has been proving for acquisition of sustainable results after 6 months of storing (the observation period). Medical trials of the panel of reagents “Monoclonal dot-immuno-enzyme test-system for tularemia microbe detection” have shown it to be a prospective preparation for implementation into the national healthcare practices both under stationary and field conditions

Проблема раннего восстановления удержания мочи после радикальной простатэктомии

Background. The highest rate of incontinence after radical prostatectomy (RP) is observed in the first 2–6 months after surgery. In order  to decrease the period of incontinence, virous surgical methods aimed at preservation and reconstruction of structures participating  in the mechanism of urine retention has been developed and improved.The study objective is to evaluate effectiveness of an original method of formation of an urethral anastomosis in the early continence recovery.Materials and methods. Data on 126 patients who underwent retropubic RP were analyzed. Depending on the method of urethral anastomosis formation, patients were divided into 2 groups: in the 1st group (n = 52) the patients underwent PR with urethra suspension m. levator ani, in the 2nd (n = 74) – standard RP. In the 1st group, 6 ligatures were applied to the anterior and posterior urethra walls: at the 12 and 6 hour projections through the mucosa, submucosa, and smooth muscle; at the 10, 2, 4, and 8 hour projections – more laterally with capture of the m. levator ani medial margins. Continence recovery was evaluated on days 1, 7, and 14 after urinary catheter removal and then at days 30, 90, 180, and 365 after RP. The criteria of continence were absence of urine leakage at rest and during physical activity and a necessity of using a safety liner.Results. There weren’t any significant differences at day 1 after urinary catheter removal between the two groups (р &gt; 0.05). In the 1st group, continence values at days 30, 90, and 180 after RP were significantly higher (57.7, 69.2, and 71.1 %, respectively) compared to the 2nd group (35.1, 41.9, and 51.3 %, respectively) (р &lt;0.05).Conclusion. Results of this work show significant benefits of RP with urethra suspension m. levator ani compared to standard RP per continence recovery criteria at days 7, 14, 30, 90, and 180 after the surgery. The technique of urethra suspension m. levator ani is easy to perform and ensures early continence recovery after RP.Введение. Часто недержание мочи после выполнения радикальной простатэктомии (РПЭ) регистрируют в первые 2–6 мес после оперативного вмешательства. В целях сокращения периода инконтиненции разработаны и усовершенствованы различные хирургические методы, направленные на сохранение и восстановление структур, участвующих в механизме удержания мочи.Цель работы – оценить эффективность применения оригинального метода формирования уретроцистоанастомоза в раннем восстановлении функции удержания мочи.Материалы и методы. Проанализированы данные 126 пациентов, подвергнутых позадилонной РПЭ. В зависимости от метода формирования уретроцистоанастомоз больные были разделены на 2 группы: пациентам 1-й группы (n = 52) выполнена РПЭ с суспензией уретры m. levator ani, 2-й (n = 74) – стандартная РПЭ. В 1-й группе на переднюю и заднюю стенки уретры накладывали 6 лигатур: в проекции 12 и 6 ч условного циферблата через слизистую, подслизистую оболочки и гладкомышечный слой; на 10, 2, 4 и 8 ч – более латерально с захватом медиальных краев m. levator ani. Восстановление функции удержания мочи оценивали через 1, 7 и 14 сут с момента удаления уретрального катетера и далее через 30, 90, 180 и 365 сут после проведения РПЭ. Критерием удержания мочи служило отсутствие подтекания мочи в покое или при физической нагрузке и необходимости использования страховочной прокладки.Результаты. Достоверных различий в показателях удержания мочи на 1-е сутки после удаления уретрального катетера в обеих группах не выявлено (р &gt;0,05). В 1-й группе показатели континенции через 30, 90 и 180 сут после выполнения РПЭ были достоверно выше (57,7; 69,2 и 71,1 % соответственно) по сравнению со 2-й группой (35,1; 41,9 и 51,3 % соответственно) (р &lt;0,05). Заключение. Результаты настоящей работы демонстрируют значительные преимущества РПЭ с суспензией уретры m. levator ani по сравнению со стандартной РПЭ по показателю восстановления континенции на 7, 14, 30, 90 и 180-е сутки после операции. Техника суспензии уретры m. levator ani проста в выполнении и обеспечивает восстановление функции удержания мочи в более ранние сроки после РПЭ

Идентификация маркеров аденокарциномы желудка на основе биоинформатического поиска и анализа генной экспрессии

Introduction. Searching for specific and sensitive molecular tumor markers is one of the important tasks of modern oncology. These markers can be used for early tumor diagnosis and prognosis as well as for prediction of therapeutic response, estimation of tumor volume or to assess disease recurrence through monitoring. Gene expression data base mining followed by experimental validation of results obtained is one of the promising approaches for searching of that kind.Objective: to identify several membrane proteins which can be used for serum diagnosis of intestinal type of gastric adenocarcinoma.Materials and methods. We used bioinformatic-driven search using Gene Ontology and The Cancer Genome Atlas (TCGA) data to identify mRNA up-regulated in gastric cancer (GC). Then, the expression levels of the mRNAs in 55 pare clinical specimens were investigated using reverse transcription polymerase chain reaction.Results. Comparative analysis of the mRNA levels in normal and tumor tissues using a new bioinformatics algorithm allowed to identify 3 high-copy transcripts (SULF1, PMEPA1 and SPARC), intracellular content of which markedly increased in GC. Expression analysis of these genes in clinical specimens showed significantly higher mRNA levels of PMEPA1 and SPARC in tumor as compared to normal gastric tissue. Interestingly more than twofold increase in expression level of these genes was observed in 75 % of intestinal-type GC. The same results were found only in 25 and 38 % of diffuse-type GC respectively.Conclusions. As a result of original bioinforamtic analysis using TCGA data base two genes (PMEPA1 and SPARC) were shown to be significantly upregulated in intestinal-type gastric adenocarcinoma. The findings show the importance of further investigation to clarify the clinical value of their expression level in stomach tumors as well as their role in carcinogenesis.Введение. Одна из важных задач современной онкологии – поиск ассоциированных с опухолями молекулярных маркеров, которые могут использоваться для диагностики и прогнозирования рака, оценки степени радикальности операции и последующего лечения, а также раннего выявления рецидивов. Одним из продуктивных вариантов подобного поиска является анализ транскриптомных баз данных с применением методов биоинформатики с последующей валидацией полученных результатов на клиническом материале.Цель исследования – поиск мембранных белков, которые могут быть использованы для сывороточной диагностики аденокарциномы желудка интестинального гистологического типа.Материалы и методы. Идентификацию потенциальных маркеров рака желудка (РЖ) проводили с использованием баз данных Gene Ontology и the Cancer Genome Atlas (TCGA). Последующую оценку дифференциальной экспрессии генов выполняли на парных образцах аденокарциномы и нормальной ткани желудка, взятых от 55 пациентов. Экспрессию генов оценивали с помощью полимеразной цепной реакции с обратной транскрипцией в режиме реального времени по методу ΔCq.Результаты. Сравнительный анализ уровней синтеза матричных РНК (мРНК) нормальных и опухолевых тканей с применением нового алгоритма биоинформатического поиска привел к идентификации 3 наиболее высококопийных транскриптов (SULF1, PMEPA1 и SPARC), внутриклеточное содержание которых заметно повышается при РЖ. При анализе уровня мРНК данных генов в клиническом материале наблюдалось более чем двукратное увеличение уровня экспрессии PMEPA1 и SPARC в 75 % образцов РЖ интестинального гистологического типа. В образцах РЖ диффузного гистологического типа этот показатель составил 25 и 38 % соответственно.Выводы. Использование оригинального биоинформатического подхода, основанного на анализе данных TCGA, позволило выявить 2 гена (PMEPA1 и SPARC), преимущественно экспрессирующихся в опухолях желудка интестинального типа. Полученные результаты свидетельствуют об актуальности дальнейшего исследования роли этих генов в патогенезе РЖ и оценки клинической значимости уровня их экспрессии в опухолевой ткани

Экзосомальные протеазы при колоректальном раке

The objective is to evaluate the level of ADAM10 and ADAM17 (a disintegrin and metalloproteinase) proteases, as well as 20S-proteasomes in blood plasma exosomes of patients with colorectal cancer.Materials and methods. The study included 60 patients with colorectal cancer (T2–4N0–2M0–1) and 10 control patients. The material for the study was EDTA blood plasma. Exosomes of blood plasma were isolated by ultrafiltration with ultracentrifugation. The level of tetraspanin-associated (ADAM10 and ADAM17) and tetraspanin-non-associated (20S-proteasome) proteases was evaluated by flow cytometry and Western blotting.Results. A twice negative subpopulation (ADAM10–/ADAM17–) predominated in blood plasma exosomes of colorectal cancer patients and control patients. The level of ADAM10+/ADAM17– exosomes was significantly higher in the exosomes of the plasma of control patients. There were no significant differences between the ADAM10/ADAM17 subpopulations and the 20S-proteasome level, depending on sex, age and tumor grade. A decrease in the ADAM10+/ADAM17– subpopulation was found in patients with metastatic colorectal cancer with hematogenous metastases compared with patients with T2–4N1–2M0 and 20S-proteasome compared to T2–4N0M0. A decrease in ADAM10–/ ADAM17+ exosomes and 20S-proteasomes level was found in exosomes of patients with colorectal cancer with a metabolic syndrome  in comparison with patients without metabolic disorders.Цель исследования – оценить уровень протеаз ADAM10 и ADAM17 (a disintegrin and metalloproteinase), а также 20S-протеасом в экзосомах плазмы крови больных колоректальным раком.Материалы и методы. В исследование были включены 60 больных колоректальным раком (T2–4N0–2M0–1) и 10 пациентов контрольной группы. Материалом для исследования послужила 3-замещенная калиевая соль этилендиаминтетрауксусной кислоты (ЭДТА) плазма крови. Экзосомы плазмы крови выделены методом ультрафильтрации с ультрацентрифугированием. Уровень тетраспанин-ассоциированных (ADAM10 и ADAM17) и тетраспанин-неассоциированных (20S-протеасомы) протеаз оценивали с помощью проточной цитометрии и вестерн-блоттинга.Результаты. Дважды негативная субпопуляция (ADAM10– / ADAM17–) преобладала как в экзосомах плазмы крови больных колоректальным раком, так и в экзосомах пациентов контрольной группы. Обнаружены статистически значимые различия в уровне ADAM10+ / ADAM17– экзосом у пациентов контрольной группы по сравнению с больными колоректальным раком. Не выявлено значимых различий между субпопуляциями ADAM10 / ADAM17 и уровнем 20S-протеасом экзосом в зависимости от пола, возраста и степени дифференцировки опухоли. У пациентов с метастатическим колоректальным раком с гематогенными метастазами выявлено снижение субпопуляции ADAM10+ / ADAM17– экзосом по сравнению с пациентами с местно-распространенным колоректальным раком (T2–4N1–2M0) и 20S-протеасом по сравнению с пациентами с T2–4N0M0. В экзосомах больных колоректальным раком с наличием метаболического синдрома выявлено снижение ADAM10– / ADAM17+ экзосом и уровня 20S-протеасом по сравнению с больными без метаболических нарушений