Cognitive impairment in patients with type 2 diabetes mellitus: prevalence, pathogenetic mechanisms, the effect of antidiabetic drugs

In recent years, a large amount of data has been accumulated on the relationship between cognitive impairment, dementia and diabetes mellitus. This article presents an overview of modern literature, including the definition of cognitive functions, the modern classification of cognitive impairment, pathogenetic mechanisms of diabetes mellitus influence on the development of cognitive impairment and dementia (neurogenesis, integrity of the blood-brain barrier, systemic inflammatory reactions, hyper- and hypoglycemia, insulin resistance, vascular dysfunction of the microvasculature and increase in glucocorticosteroids). The influence of anti-diabetic medications on cognitive functions has been examined in detail: insulin preparations, oral hypoglycemic agents of the biguanide group (metformin), thiazolidinediones (rosiglitazone and pioglitazone), sulfonylurea derivatives (glycazide, glipizide), a-glucosidase (acarbose) inhibitors, incretin-directed therapy (receptor agonists glucan-like peptide (exenatide and liraglutide) and inhibitors of dipeptidylpeptidase type 4 (sitagliptin, vildagliptin and alogliptin)), sodium glucose inhibitors cotransporter type 2. The data demonstrating a multidirectional effect on the cognitive functions of various antidiabetic drugs is presented, the possible influence on the rate of progression of cognitive impairment and the risk of dementia of intensive control of plasma glucose level in comparison with the standard decrease in patients with type 2 diabetes is analyzed

Molecular Diagnostics of Histoplasmosis

Histoplasmosis is a systemic fungal disease that occurs worldwide. The highest incidence of the disease is reported on the American continent. It also occurs in China, India, South-Eastern Asia, Africa, Australia and Europe. Clinical syndromes of histoplasmosis are not specific and in most cases immunocompetent individuals are asymptomatic or present mild influenza-like disease. Immunocompromised patients especially individuals with AIDS, can develop a severe and fatal disease due to fungal dissemination to many organs. Etiological agent of histoplasmosis is the dimorphic fungus Histoplasma capsulatum, which inhabits the soils contaminated with bird or bat droppings. Three biological varieties are considered for this fungus: H. capsulatum var. capsulatum, H. capsulatum var. duboissii and H. capsulatum var. farciminosum. Genetic differences are observed among H. capsulatum strains from diverse regions of the world. The main molecular methodologies for genetic typing of fungi are based on DNA fingerprinting. They have been an important instrument to identify possible sources of infection in outbreaks of histoplasmosis. Genetic profiles of H. capsulatum, isolated from bats and humans, helped to understand the distribution of the disease in certain endemic regions. The con-ventional diagnosis of histoplasmosis is performed by means of cultural and microscopic examination of samples from the respiratory tract and biologic fluids. However, these techniques yield positive results in only 50 % of cases. In the last two decades, approaches for the detecting of H. capsulatum in clinical samples, using different molecular targets, based on PCR assay have been developed. Their use can shorten the time span of analysis for diagnosis confirmation. Molecular methods have high specificity and sensitivity and reduce the risk of infection for the laboratory personnel. In this study we reviewed the recently published data on the use of main molecular methods for diagnosis of histoplasmosis

Psychosocial aspects of the usage of modern technologies in diabetes mellitus

This article represents a review of trials on the relationship between the use of modern technologies in the treatment of diabetes, such as continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM), and the psychological characteristics of patients. The review includes Russian studies and foreign publications. The analysis showed that the psychological aspects of using CSII are considered more often than CGM. Most Russian authors agree that the use of technology is associated with an increased psychological well-being of patients. Foreign researchers generally agree with the same point of view but also report a weaker correlation. One of the most significant conclusions of this analysis is that the use of modern technologies itself does not guarantee an improved quality of life (QOL) and psychological well-being, but technologies such as CSII and CGM provide patients with opportunities to achieve greater effectiveness in treating diabetes, improving clinical and metabolic parameters and therefore improving QOL. However, the use of these devices, as well as many other technological tools, is associated with certain psychological problems, both in terms of their acquisition and influence on patients’ subjective well-being. Early diagnosis and prevention of such problems should be one of the tasks in preparing patients for the use of modern technologies. A positive effect on both clinical and metabolic indicators as well as on the mental sphere and social life of patients can be achieved only by combining complete training (optimally—according to specialised programmes) with medical support

Маркеры активности экзогенных интерстициальных заболеваний легких

The aim of this study was to investigate values of pulmonary fibrosis markers alveomucin and KL-16 and the airway damage marker CC-16 for evaluating activity and progressing of extrinsic interstitial lung diseases (ILD) in dependence on etiology. Methods. Levels of Krebs von den Lungen-6 glycoprotein (KL-6), alveomucin and Clara cell protein (CC16) were measured using the ELISA method. The study involved 13 patients with pneumoconiosis, 26 patients with extrinsic allergic alveolitis (EAA) and 20 patients with extrinsic toxic alveolitis (ETA) both in active and stable status. Results. KL-6 and alveomucin were found to be more valuable markers for assessing activity of extrinsic fibrosing alveolitis compared to CC16. Alveomucin had higher specificity but lower sensitivity compared to KL-6. Conclusion. Alveomucin could be used as a screening test in cases with clinical susceptibility for extrinsic alveolitis. On contrary, KL-6 and alveomucin could be used for assessing therapeutic efficacy of EAA and ETA.Уровень гликопротеина Krebs von den Lungen-6 (KL-6), альвеоломуцина и белка булавчатых клеток (club cells) – СС16 при экзогенных интерстициальных заболеваниях легких был исследован методом иммуноферментного анализа. Обследованы больные пневмокониозом (n = 13), экзогенным аллергическим (n = 26) и экзогенным токсическим (n = 20) альвеолитом в период активности и ремиссии заболевания. Установлено, что KL-6 и альвеоломуцин являются более информативными маркерами для оценки активности экзогенных фиброзирующих альвеолитов по сравнению с СС16. Альвеоломуцин обладает более высокой специфичностью, но меньшей чувствительностью, чем KL-6, и может применяться для скринингового исследования при подозрении на экзогенные альвеолиты. Для оценки эффективности терапии экзогенных аллергических и токсических альвеолитов целесообразно мониторировать уровень KL-6 и альвеоломуцина сыворотки крови

CHARACTERISTICS OF AUTOIMMUNE INFLAMMATION IN THE PATIENTS WITH LUNG TUBERCULOSIS

Tuberculosis is a granulomatous disease caused by Mycobacterium tuberculosis, being characterized by the development of caseous granulomas in various organs, mainly in lungs. M. tuberculosis is known to be a trigger for autoimmune inflammation, due to the possible mimicry of bacterial proteins as autoantigens. Recently, a significance of mesenchymal vimentin as an autoantigen in mycobacterial infections has been actively discussed. The aim of the present study was to determine autoantibodies for various vimentin modifications in the patients with tuberculosis.The study was performed in 2014-2017 and included 28 patients with pulmonary tuberculosis (group I), 30 patients with nonspecific lung diseases (group II): 15 with granulomatous polyangiitis, and 15 with different alveolites. Control group consisted of healthy subjects (n = 40). Concentration of antibodies to mutated citrullinated vimentin (anti-MCV) was measured using ELISA (ORGENTEC, Germany). The patients with elevated anti-MCV levels were tested for antibodies to cyclic citrullinated peptide (anti-CCP) using ELISA technique (EUROIMMUN, Germany). Statistical analysis was carried out using GraphPad Prism 6 (GraphPad Software, USA), Statistica 10 (Statsoft, USA) using nonparametric analysis of samples with Mann-Whitney and Chi-square criteria, and Spearman method for correlation analysis. The differences were considered statistically significant at p < 0.05.The anti-MCV concentrations were significantly higher in patients with tuberculosis (group I, 60.7% of cases, 17/28) than in group II, and control group (23.6 and 25.0% of cases, respectively). No statistically significant differences were revealed between the results of anti-MVC and anti-CCP levels in comparison group with the control group (p = 0.18).High levels of anti-MCV antibodies in the patients with pulmonary tuberculosis reflect an opportunity of developing autoimmune process in the disease pathogenesis. Measurement of plasma anti-MCV antibody concentrations may be important for correction of the therapy, especially upon administration of immunosuppressive and hormonal corticosteroid drugs. It has been shown that anti-CCP are not characteristic to the lung diseases

Balloon Dilatation of Esophageal Strictures in Children With Bullous Epidermolysis: Description of Case Series

Esophageal strictures are the most common complications of bullous epidermolysis in children. Strictures cause the development of dysphagia that prevents oral alimentation and receipt of an adequate amount of nutrients that is accompanied by a violation of nutritional status, weight loss, and delayed physical development of a child. Disturbed swallowing can also cause aspiration syndrome, pneumonia, and airway obstruction. To eliminate dysphagia and reduce the risk of complications, it is necessary to restore esophageal patency. The article describes the results of X-ray with assisted balloon dilatation in 19 children with bullous epidermolysis and dysphagia. It is shown that this method of esophagus recanalization allows to effectively and safely restore oral alimentation of children already in the first day after intervention with a gradual expansion of the diet

ВОЗМОЖНОСТИ ЛЕКАРСТВЕННОЙ ТЕРАПИИ АНДРОГЕН-ПОЗИТИВНОГО РАКА МОЛОЧНОЙ ЖЕЛЕЗЫ

There are some types of breast cancer (BC) that depend on their molecular characteristics. However, lately researchers provide date regarding the presence of additional receptors of triple negative breast cancer (TNBC). One of them is LA R-subtype that has androgen receptors (AR) on breast cancer cells. The role of AR in the development of this pathology is still controversial. According to some authors, stimulation of AR leads to the proliferation suppression, in the opinion of others – to the activation and potentiation of tumor invasion. There is also a version of the dichotomous effect of androgens that depends on the concentration of this hormone. The various effects of LA R-subtype therapy of BC are also explained by the presence of many other regulator proteins that interact with AR. The first attempts to treat BC with androgen have begun since the 40s of the last century, but in those years it did not have the desired effect and was not used until recently. Currently, the basic mechanisms of the effect of androgens on BC cells on the molecular level are known, and researches try to use androgen therapy, also in combination with aromatase inhibitors to increase the concentration of endogenous testosterone. The effects of selective androgen receptor modulators and anabolic steroids are being studied. However, in the last decade, the largest number of studies focused on the study of anti-androgen therapy. Patients receive AR antagonists, such as enzalutamide, bicalutamide, that are prescribed for prostate cancer. Enzalutamide blocks both androgen- and estrogen-mediated tumor growth, and therefore can be used regardless of the presence of estrogen receptors (ER), in contrast to bicalutamide. The results showed a significant increase in disease free survival up to 16.5 months in patients with hormone positive BC.Существует несколько типов рака молочной железы (РМЖ) в зависимости от их молекулярных характеристик. В последних публикациях мировой литературы приводятся данные о наличии дополнительных подтипов тройного негативного РМЖ. Одним из них является laR-подтип, который характеризуется наличием андрогеновых рецепторов (АР). Роль АР в развитии РМЖ до сих пор остается спорной. По мнению одних авторов, стимуляция АР приводит к подавлению пролиферации, по мнению  других, – к ее активации и потенцированию инвазии опухоли. Существует версия о дихотомическом эффекте андрогенов в зависимости от концентрации гормона. Также направление эффекта терапии laRподтипа зависит от множества других белков- регуляторов, взаимодействующих с АР. В 1940-х гг. прошлого века были предприняты первые попытки лечения РМЖ препаратами андрогенового ряда, однако без значительного эффекта, в связи с чем они больше не применялись до начала XXi века. В настоящее время известны основные механизмы действия андрогенов на клетки РМЖ. В рамках научных исследований предпринимаются попытки андрогеновой терапии, в том числе в сочетании с ингибиторами ароматазы с целью увеличения концентрации эндогенного тестостерона. Изучаются эффекты селективных модуляторов рецепторов андрогенов и анаболических стероидов. Однако в последнее десятилетие  наибольшее количество исследований направлено на изучение антиандрогеновой терапии антагонистами АР, такими как энзалутамид и бикалутамид. При этом энзалутамид блокирует как андроген-, так и эстроген-опосредованный рост опухоли, в связи с чем может применяться вне зависимости от наличия эстрогеновых  рецепторов (РЭ) в отличие от бикалутамида. Результаты одного из крупнейших исследований энзалутамида в сочетании с экземестаном показывают значительное увеличение выживаемости без прогрессирования у пациенток с гормон-позитивным РМЖ – до 16,5 мес (по сравнению с 4,3 мес в контрольной группе)

Комплексная оценка речевого развития детей, зачатых с помощью экстракорпорального оплодотворения

Introduction. The high frequency of the use of assisted reproductive technologies and the inconsistency of information about the parameters of the cognitive development of IVF children determined the formulation of the research problem.The purpose of the work is to assess the originality of the speech development of children and adolescents conceived using the IVF procedure. The age of the children at the time of the survey was from 5 to 15 years.Methods and materials. A sample of 51 children (29 boys), mean age (7.9±2.8) years, 14 children had psychiatric diagnoses (ASD, mental retardation, etc.). Research methods: speech therapy assessment of speech development, neuropsychological diagnostics according to L.S. Tsvetkova, WICS, descriptive statistics, correlation analysis.Results. 41% of children had mild variants of speech development delay under 3 years old, 59 % of children had normal speech development. With age, the frequency of detected deviations in speech development decreases, so that in older age group (from 11 to 15 years old), 85 % have normotypical development of speech. Correlation analysis showed the originality of the correlations of the parameters of speech development, neuropsychological assessment, and scores on Wechsler subtests.Conclusions. An unambiguous conclusion about the violation of speech development in children conceived by IVF cannot be drawn, however, in the presence of mental pathology and taking into account the age of the mother and the number of ART procedures, attention should be paid to the provision of speech therapy and neuropsychological correction from an early age.Введение. Высокая частота использования вспомогательных репродуктивных технологий (ВРТ) и противоречивость информации о параметрах когнитивного развития детей, зачатых с помощью экстракорпорального оплодотворения (ЭКО) определила постановку проблемы исследования.Цель работы — оценка своеобразия речевого развития детей и подростков, зачатых с помощью процедуры ЭКО и находящихся в возрастном интервале от 5 до 15 лет.Методы и материалы. Выборка из 51 ребенка (29 мальчиков), средний возраст — (7,9±2,8) года, 14 детей имели психиатрические диагнозы (расстройства аутистического спектра(РАС), шизотипическое расстройство (ШТР) и др.). Применяли логопедическую оценку развития речи, нейропсихологическую диагностику по Л.С. Цветковой, диагностику IQ по Векслеру, описательную статистику, корреляционный анализ.Результаты. У 41 % детей имелись легкие варианты задержки речевого развития в возрасте до 3 лет, нормативно развивалась речь у 59 % детей. С возрастом частота выявляемых отклонений в речевом развитии падает, в старшей возрастной группе (от 11 до 15 лет) норма развития речи встречалась у 85 % испытуемых. Корреляционный анализ показал своеобразие корреляционных плеяд у детей, зачатых с помощью ЭКО, при сопоставлении параметров речевого развития, нейропсихологической оценки, баллов по субтестам Векслера.Заключение. Однозначного вывода о нарушении речевого развития у детей, рожденных с помощью ЭКО, сделать нельзя, однако при наличии психической патологии и с учетом возраста матери и числа применения процедур ВРТ следует обратить внимание на оказание логопедической и нейропсихологической коррекции с раннего возраста

Частичная и полная спонтанная регрессия семиномы яичка: клинические наблюдения

Spontaneous tumour regression is a rare phenomenon in which there is a complete or partial regression of the primary tumour, clinically manifested by metastatic lesions. We report a case of a 34-year-old male with partial spontaneous regression of testicular seminoma detected by a supraclavicular lymph node biopsy. He underwent inguinal orchifunicolectomy. Based on the results of histological examination, against the background of multiple complexes of intratubular germ cell neoplasia in situ, foci of invasive growth and involution were identified, indicating a spontaneously regressing testicular tumour. We report the second case of a 52-year-old male with total spontaneous regression of testicular seminoma detected by a spermatic cord biopsy. Based on the results of histological examination, against fibrosis and proliferation of Leydig cells, there are atrophy of seminiferous tubules and complexes of intratubular germ cell neoplasia in situ in part of them.Спонтанная регрессия опухоли – редкое явление, при котором происходит полная или частичная регрессия первичной опухоли, клинически проявляющееся метастатическими поражениями. В статье описаны 2 клинических случая. В 1-м наблюдении частичная спонтанная регрессия семиномы яичка выявлена при биопсии надключичного лимфатического узла. У 34-летнего мужчины была проведена паховая орхифуникулэктомия. По результатам гистологического исследования на фоне множественных комплексов внутриканальцевой герминогенно-клеточной неоплазии  in situ выявлены небольшие очаги инвазивного роста и инволюции, указывающие на спонтанно регрессировавшую опухоль яичка. Во 2-м клиническом случае полная спонтанная регрессия семиномы яичка выявлена при биопсии образования пахового канатика у пациента 52 лет. По результатам гистологического исследования операционного материала, полученного при паховой орхифуникулэктомии, в ткани яичка на фоне выраженного фиброза стромы с пролиферацией клеток Лейдига отмечались атрофичные семенные канальцы, в части которых имелись комплексы внутриканальцевой герминогенно-клеточной неоплазии in situ

Mechanisms of gap gene expression canalization in the Drosophila blastoderm

<p>Abstract</p> <p>Background</p> <p>Extensive variation in early gap gene expression in the <it>Drosophila </it>blastoderm is reduced over time because of gap gene cross regulation. This phenomenon is a manifestation of canalization, the ability of an organism to produce a consistent phenotype despite variations in genotype or environment. The canalization of gap gene expression can be understood as arising from the actions of attractors in the gap gene dynamical system.</p> <p>Results</p> <p>In order to better understand the processes of developmental robustness and canalization in the early <it>Drosophila </it>embryo, we investigated the dynamical effects of varying spatial profiles of Bicoid protein concentration on the formation of the expression border of the gap gene <it>hunchback</it>. At several positions on the anterior-posterior axis of the embryo, we analyzed attractors and their basins of attraction in a dynamical model describing expression of four gap genes with the Bicoid concentration profile accounted as a given input in the model equations. This model was tested against a family of Bicoid gradients obtained from individual embryos. These gradients were normalized by two independent methods, which are based on distinct biological hypotheses and provide different magnitudes for Bicoid spatial variability. We showed how the border formation is dictated by the biological initial conditions (the concentration gradient of maternal Hunchback protein) being attracted to specific attracting sets in a local vicinity of the border. Different types of these attracting sets (point attractors or one dimensional attracting manifolds) define several possible mechanisms of border formation. The <it>hunchback </it>border formation is associated with intersection of the spatial gradient of the maternal Hunchback protein and a boundary between the attraction basins of two different point attractors. We demonstrated how the positional variability for <it>hunchback </it>is related to the corresponding variability of the basin boundaries. The observed reduction in variability of the <it>hunchback </it>gene expression can be accounted for by specific geometrical properties of the basin boundaries.</p> <p>Conclusion</p> <p>We clarified the mechanisms of gap gene expression canalization in early <it>Drosophila </it>embryos. These mechanisms were specified in the case of <it>hunchback </it>in well defined terms of the dynamical system theory.</p