Prospects for the use of fecal microbiota transplantation in obese patients with Type 2 Diabetes Mellitus for weight loss and improvement of insulin sensitivity

Concerning the uncontrolled growth in the incidence of obesity and Type 2 Diabetes Mellitus (T2DM), numerous research have been carried out to study the pathogenetic mechanisms of progress of these diseases and development of new methods for their prevention and treatment in recent years. T2DM is known to be a multifactorial disease, in the development of which both lifestyle and various environmental factors, and genetic predisposition are involved. At the same time, in recent years, a theory has been discussed that intestinal dysbiosis, which is caused with quantitative and qualitative changes in the gut microbiota (GM) is one of the mechanisms of obesity and T2DM development. At the moment, various methods have been proposed for restoring the normal composition of GM, including the administration of prebiotics and metabiotics that stimulate the growth of gut flora, as well as probiotics, which directly include the necessary beneficial bacteria (mainly Bifidobacterium and Lactobacillus). Fecal microflora transplantation (FMT), which allows transferring an entire microbial community into the recipient's body, rather than individual bacteria is the newest and least studied method of GM normalization. In this connection, this method of GM influencing is of great interest for the prevention and treatment of metabolic diseases

Cortical plasticity elicited by acoustically cued monetary losses: An ERP study

Both human and animal studies have demonstrated remarkable findings of experience-induced plasticity in the cortex. Here, we investigated whether the widely used monetary incentive delay (MID) task changes the neural processing of incentive cues that code expected monetary outcomes. We used a novel auditory version of the MID task, where participants responded to acoustic cues that coded expected monetary losses. To investigate task-induced brain plasticity, we presented incentive cues as deviants during passive oddball tasks before and after two sessions of the MID task. During the oddball task, we recorded the mismatch-related negativity (MMN) as an index of cortical plasticity. We found that two sessions of the MID task evoked a significant enhancement of MMN for incentive cues that predicted large monetary losses, specifically when monetary cue discrimination was essential for maximising monetary outcomes. The task-induced plasticity correlated with the learning-related neural activity recorded during the MID task. Thus, our results confirm that the processing of (loss)incentive auditory cues is dynamically modulated by previously learned monetary outcomes

Possibilities of Autologous Fecal Microbiota Transplantation in patients with obesity and diabetes mellitus

Obesity and type 2 diabetes mellitus (T2DM) are major problems for public health all over the world. According to retrospective research, the prevalence of obesity has doubled in more than 70 countries since 1980, as well as the prevalence of obesity complications (atherosclerotic cardiovascular diseases, nonalcoholic fatty liver disease and their complications. There are many drug therapies for T2DM, but it is difficult to achieve a stable, clinically relevant effect on a long-term basis. The fact that a patient has both conditions makes it difficult to optimize carbohydrate metabolism and to achieve normal body weight. Many antidiabetic drugs cause weight again, which, in turn, contributes to the growth of insulin resistance (IR) and requires further intensification of therapy.In the last few years, there is a growing evidence of the relationship between the gut microbiota (GM), obesity and T2DM. There has been a steady growth of interest in such medical technology as fecal microbiota transplantation (FMT) in the world. Since there is data on the association of the gut microbiota (GM) with the development of IR and T2DM, the possibility of FMT can potentially be one of the new methods of treatment. This review presents the current state of the problem and discusses the possibility of modifying GM as a therapeutic strategy in obesity and T2DM with an accent on autologous fecal microbiota transplantation

Мутации в генах эстрогенового рецептора α (ESR1) и киназы семейства SRC (LYN), ассоциированные с резистентностью к гормонотерапии рака яичников

Recently multiple data accumulated concerning mutations in the ESR1 gene coding estrogen receptor α (mutESR1) and in the LYN gene coding non receptor tyrosine kinase SRC family member (mutLYN) that are associated with endocrine therapy resistance and that could be considered as markers of endocrine therapy efficiency. In case of gynecologic cancers including ovarian cancer the most frequent mutESR1 are ESR1L536H/P/R/V , ESR1Y537S/N/C/H, ESR1D538G that emerge in the course of hormonotherapy especially using aromatase inhibitors. mutLYN including LYNE159K, LYND189Y, LYNK209N, LYNA370T, LYNG418R, LYNA503D are also identified. mutESR1 and mutLYN increase transcriptional activity of estrogen receptor α (ERα) coded with ESR1 gene and catalytic activity of LYN kinase inducing endocrine therapy resistance. Interdependence of ESR1 and LYN genes is revealed at the level of proteins that they code as the kinases of the SRC family including LYN activate ERα-dependent transcription due to the phosphorylation of ERα at Y537 amino-acid residue that is the most frequently mutated in tumors with endocrine therapy resistance. The aim of the review is revealing the clinical correlations of mutESR1 and mutLYN with the ovarian cancer endocrine therapy resistance that opens perspectives of mutESR1 and mutLYN use as new predictive markers of ovarian cancer and development of more efficient anti-tumor medicaments. In the review the information obtained from PubMed database for the last 20 years using the following key words: ESR1, LYN, mutation(s), estrogen receptor α (ERα), LYN kinase, SRC family kinases, ovarian cancer, gynecologic(al) cancer is discussed.В последнее время появляются многочисленные данные о мутациях в гене ESR1 (mutESR1), кодирующем эстрогеновый рецептор α (ЭРα), и  гене, кодирующем белок из  семейства SRC нерецепторных тирозинкиназ, LYN (mutLYN), ассоциированных с резистентностью опухолей к эндокринной терапии. Такие мутации могут рассматриваться в  качестве маркеров эффективности эндокринной терапии. В  случае гинекологических злокачественных новообразований, включая рак яичников, наиболее часто наблюдаются mutESR1, а именно ESR1L536H/P/R/V , ESR1Y537S/N/C/H, ESR1D538G, возникающие при лечении пациенток с использованием гормонотерапии, в  особенности ингибиторов ароматазы. Идентифицированы также mutLYN: LYNE159K, LYND189Y, LYNK209N, LYNA370T , LYNG418R, LYNA503D. Мутации в генах ESR1 и LYN ассоциированы с резистентностью к эндокринной терапии рака яичников, так как увеличивают транскрипционную активность ЭРα и каталитическую активность киназы LYN соответственно. Кроме того, наблюдается взаимосвязь генов ESR1 и LYN на уровне кодируемых ими белков, так как киназы семейства SRC, к которым относится LYN, активируют транскрипцию генов-мишеней ЭРα, фосфорилируя рецептор по аминокислотному остатку Y537. При этом в опухолях с резистентностью к эндокринной терапии наиболее часто выявляются мутации ЭРα по аминокислоте Y537.Задачей обзорной статьи был анализ клинических корреляций mutESR1 и mutLYN и резистентности рака яичников к  эндокринной терапии, раскрывающий перспективы использования mutESR1 и mutLYN в  качестве новых предиктивных маркеров и поиска более эффективных противоопухолевых средств. Обсуждены данные, представленные в поисковой системе PubMed за последние 20 лет, полученные с использованием следующих ключевых слов: ESR1, LYN, mutation(s), estrogen receptor α (ERα), kinase LYN, SRC family kinases, ovarian cancer, gynecologic(al) cancer

The exact cosmological solution to the dynamical equations for the Bianchi IX model

Quantum geometrodynamics in extended phase space describes phenomenologically the integrated system ``a physical object + observation means (a gravitational vacuum condensate)''. The central place in this version of QGD belongs to the Schrodinger equation for a wave function of the Universe. An exact solution to the ``conditionally-classical'' set of equations in extended phase space for the Bianchi-IX model and the appropriate solution to the Schrodinger equation are considered. The physical adequacy of the obtained solutions to existing concepts about possible cosmological scenarios is demonstrated. The gravitational vacuum condensate is shown to be a cosmological evolution factor.Comment: LaTeX, 14 pages, to be published in Int. J. Mod. Phys.

Effect of triazavirine on the outcome of a lethal influenza infection and secondary bacterial pneumonia following influenza in mice

Pneumonia often occurs as secondary infection post influenza disease and accounts for a large proportion of the morbidity and mortality associated with seasonal and pandemic influenza outbreaks. The antiviral drug triazavirine is licensed in Russia for the treatment and prophylaxis of acute respiratory infections, including influenza A and B viruses. In the present study, we investigated the efficacy of triazavirine in a mouse model of secondary Staphylococcus aureus pneumonia following A/California/04/2009 (H1N1)pdm09 influenza virus infection. We also performed a study of the efficacy of triazavirine against the A/California/04/2009 (H1N1)pdm09 lethal influenza infection in mice. In this model, triazavirine at the dose of 25 mg/kg/day significantly enhanced the survival of animals (60% compared to 20%) and the mean survival time to death, prevented weight loss, and reduced viral titer in the lungs of mice infected with influenza virus. At doses of 50 and 100 mg/kg/day, triazavirine was highly effective in the treatment of the secondary bacterial pneumonia following influenza infection in mice. At these doses, triazavirine protected 67-75% of animals against death, increased the mean survival time to death by twofold, and reduced the virus titer by 2.2-3.0 log10TCID50/ml compared to the mice in the control group. These findings suggest the possible benefit of triazavirine treatment in reducing post influenza pneumonia incidence in humans.Pneumonia often occurs as secondary infection post influenza disease and accounts for a large proportion of the morbidity and mortality associated with seasonal and pandemic influenza outbreaks. The antiviral drug triazavirine is licensed in Russia for the treatment and prophylaxis of acute respiratory infections, including influenza A and B viruses. In the present study, we investigated the efficacy of triazavirine in a mouse model of secondary Staphylococcus aureus pneumonia following A/California/04/2009 (H1N1)pdm09 influenza virus infection. We also performed a study of the efficacy of triazavirine against the A/California/04/2009 (H1N1)pdm09 lethal influenza infection in mice. In this model, triazavirine at the dose of 25 mg/kg/day significantly enhanced the survival of animals (60% compared to 20%) and the mean survival time to death, prevented weight loss, and reduced viral titer in the lungs of mice infected with influenza virus. At doses of 50 and 100 mg/kg/day, triazavirine was highly effective in the treatment of the secondary bacterial pneumonia following influenza infection in mice. At these doses, triazavirine protected 67-75% of animals against death, increased the mean survival time to death by twofold, and reduced the virus titer by 2.2-3.0 log10TCID50/ml compared to the mice in the control group. These findings suggest the possible benefit of triazavirine treatment in reducing post influenza pneumonia incidence in humans

Clinical Analysis of Late Age Somatoform Algic Disorder Case Following with Pain in Maxillofacial Area: Example of Dental Treatment Groundlessness

Case of somatoform algic disorder with pain in maxillofacial region is described on a 58 years old patient. The patient have been observed by different specialists and underwent numerous medical examinations which led as a result to groundless medical manipulations such as several teeth extirpation, removal of previously mounted metalloceramic constructions.Latest observations show that there is a link between age and pain localization rate at mouth area as well as changes in hypochondriac experience to the increase of supervaluable generations. Thus condition described becomes a disorder which is hard to diagnose and a social problem concerning early diagnostics and treatment. With time and increase of life expectancy as well as increase of assortment and affordability of dental procedures problem of somatoform algic disorder diagnostics in late age becomes more urgent. Clinical case illustrates accumulated practical experience of late age somatoform disorders treatment by combinations of antidepressants and small doses of antipsychotics. Ethiopathogenesis of this condition assessed as nociceptive, neuropathologic and then as psychogenic pain is still to be investigated. Late diagnostics in this case points to a necessity of multidisciplinary approach to such patients’ treatment in order to develop criteria to apply in practice for diagnostic mechanisms optimization and pharmacologic effect on early disorder stages

Feasibility and challenges of performing magnetoencephalography experiments in children with arthrogryposis multiplex congenita

Arthrogryposis multiplex congenita (AMC) has recently drawn substantial attention from researchers and clinicians. New effective surgical and physiotherapeutic methods have been developed to improve the quality of life of patients with AMC. While it is clear that all these interventions should strongly rely on the plastic reorganization of the central nervous system, almost no studies have investigated this topic. The present study demonstrates the feasibility of using magnetoencephalography (MEG) to investigate brain activity in young AMC patients. We also outlined the general challenges and limitations of electrophysiological investigations on patients with arthrogryposis. We conducted MEG recordings using a 306-channel Elekta Neuromag VectorView system during a cued motor task performance in four patients with arthrogryposis, five normally developed children, and five control adults. Following the voice command of the experimenter, each subject was asked to bring their hand toward their mouth to imitate the self-feeding process. Two patients had latissimus dorsi transferred to the biceps brachii position, one patient had a pectoralis major transferred to the biceps brachii position, and one patient had no elbow flexion restoration surgery before the MEG investigation. Three patients who had undergone autotransplantation prior to the MEG investigation demonstrated activation in the sensorimotor area contralateral to the elbow flexion movement similar to the healthy controls. One patient who was recorded before the surgery demonstrated subjectively weak distributed bilateral activation during both left and right elbow flexion. Visual inspection of MEG data suggested that neural activity associated with motor performance was less pronounced and more widely distributed across the cortical areas of patients than of healthy control subjects. In general, our results could serve as a proof of principle in terms of the application of MEG in studies on cortical activity in patients with AMC. Reported trends might be consistent with the idea that prolonged motor deficits are associated with more difficult neuronal recruitment and the spatial heterogeneity of neuronal sources, most likely reflecting compensatory neuronal mechanisms. On the practical side, MEG could be a valuable technique for investigating the neurodynamics of patients with AMC as a function of postoperative abilitation

Flexible management in industry as a factor of region’s sustainable development

This article discusses the development of flexible management technologies in industry in current conditions. The main goal of the research is to study the features of functioning and develop a mechanism for the development of flexible technologies for managing industrial enterprises in Russia as one of the factors for the sustainable development of regions. Taking into account the goal set, the main tasks have been defined. It consists of studying the structure, a number of industrial enterprises by sectors, districts and the Russian Federation’s constituent entities; allocation of the varieties of flexible management technologies; development of a conceptual scheme and stages of the process of forming tools for the development mechanism of industrial enterprises based on flexible management technologies. The study used modern methods of collecting and statistical processing of initial information, in particular, the method of analytical groupings, the method of classifications and typologies, methods of economic, situational and system analysis. The paper deals with issues related to the analysis of the industrial production indices dynamics by entities of the Russian Federation. The problems are identified, the mechanism and stages of development of industrial enterprises have been formed on the basis of flexible management technologies. The main provisions and conclusions reflect the significance of the research and can be used by industrial enterprises in activities aimed at their development in the conditions of economic transformation. The authors’ recommendations will help to increase the competitiveness of enterprises, their sustainable functioning and development in the regions