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

Cytotoxic Activity of Silyl- and Germyl-Substituted 4,4-Dioxo-3a,6a-Dihydrothieno[2,3−d]isoxazolines-2

The [2+3] dipolar cycloaddition of nitrile oxides to the double C = C bonds of thiophene-1, 1-dioxides leads to formation of the fused isoxazolines-2 (1, 2). Tumor growth inhibition of these compounds strongly depends on the nature of group IV A element increasing from slightly active tert-butyl derivatives to silicon and germanium containing analogues. The products of benzonitrile oxide cycloaddition have greater cytotoxic effect than the compounds obtained from the cycloaddition reaction of 2, 5-disubstituted thiophene-1, 1-dioxides with acetonitrile oxide. Fused silyl substituted isoxazolines-2 are stronger NO-inducers than their germyl and tert-butyl analogues

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

Covariance and Time Regained in Canonical General Relativity

Canonical vacuum gravity is expressed in generally-covariant form in order that spacetime diffeomorphisms be represented within its equal-time phase space. In accordance with the principle of general covariance, the time mapping {\T}: {\yman} \to {\rman} and the space mapping {\X}: {\yman} \to {\xman} that define the Dirac-ADM foliation are incorporated into the framework of the Hilbert variational principle. The resulting canonical action encompasses all individual Dirac-ADM actions, corresponding to different choices of foliating vacuum spacetimes by spacelike hypersurfaces. In this framework, spacetime observables, namely, dynamical variables that are invariant under spacetime diffeomorphisms, are not necessarily invariant under the deformations of the mappings \T and \X, nor are they constants of the motion. Dirac observables form only a subset of spacetime observables that are invariant under the transformations of \T and \X and do not evolve in time. The conventional interpretation of the canonical theory, due to Bergmann and Dirac, can be recovered only by postulating that the transformations of the reference system ({\T},{\X}) have no measurable consequences. If this postulate is not deemed necessary, covariant canonical gravity admits no classical problem of time.Comment: 41 pages, no figure

Obesity with and without type 2 diabetes: are there differences in obesity history, lifestyle factors or concomitant pathology?

Background: Obesity is one of the most significant risk factors for type 2 diabetes (T2D), but a large number of patients with morbid obesity maintain normal glycemia for a long time. There are no definite easy-to-measure clinical features that distinguish severely obese people who will or will not develop T2D. These features may be useful in clinical practice to predict T2D development in obese patients.Aims: We aimed to identify clinical features (lifestyle factors, obesity history, concomitant diseases) that may be associated with T2D in obese patients.Materials and methods: The study was conducted at single center during 2002 and 2017 and recruited patients with BMI≥30 kg/m2 who attended bariatric surgeon. Patients weight and height were assessed by the doctor, other features were obtained from the questionnaire: overweight and obesity history (age of onset, duration, family history of obesity), lifestyle factors, T2D and concomitant diseases medical history. Patients were divided into 2 groups with regard to the presence of T2D. Data analysis was performed with Statistica 13.3.Results: The study included 170 patients with known T2D and 528 patients without history of T2D and prediabetes. Both groups had similar gender structure, as well as current and peak BMI. There were no significant differences in overweight/obesity duration, obesity family history, lifestyle factors and smoking status of patients. Obese patients without T2D were younger than T2D patients at the time of T2D onset (median age 40 and 45 years respectively). Patients without T2D started to gain weight earlier than those with T2D (median age 17 and 25 years respectively) and reached their peak BMI during 1 year before study entry, while patients with T2D went through maximum weight previously. The frequencies of concomitant diseases didn’t differ between the groups with the exception of hypertension that started later in patients with T2D (median age 51 and 47 years in patients with and without T2D respectively); also patients with T2D had gastroesophageal reflux disease (GERD) and chronic back pain less often than patients without T2D with regard to age.Conclusions: Clinical features that distinguished obese patients with and without T2D were age at the start of overweight/ obesity and concomitant disease profile (hypertension, GERD, chronic back pain) at corresponding age

Feсal microbiota transplantation in the format of complex therapy in obesive siblings: clinical case

Obesity and associated metabolic diseases are often accompanied by changes in the gut microbiota leading to metagenome gene diversity decrease. Fecal microbiota transplantation (FMT) is one of the most effective methods for correcting the  intestinal microflora. FMT obtained from healthy donors has been proven to be an effective treatment of infections caused by Clostridium difficile. The use of FMT for correction of metabolic disorders is promising, however, data on its application is limited and has contradictory results. In our work, two patients (siblings) presented with obesity grade II and various types of diabetes mellitus (DM): the older brother (44 years old) with diabetes mellitus type 2 (DM 2), a younger brother (39 years old) with diabetes mellitus type 1 (DM 1). Both patients underwent FMT as part of complex antidiabetic therapy. During the course of treatment, a decrease in body weight was noted in both patients (4–5 kg for the first month of observation, then -1–2 kg per month). One year after FMT, a patient with type 2 diabetes showed a decrease in the severity of insulin resistance (IR), measured by the hyperinsulinemic euglycemic clamp test (initial M-index 2.42 mg/kg*min, after 1 year — 3.83 mg/kg* min) as well as the maintenance of satisfactory carbohydrate metabolism compensation against the diminishing the hypoglycemic therapy. In a patient with DM 1, no significant dynamics of carbohydrate exchange indices, including detected glycated hemoglobin (HbA1c), insulin dose and IR were during the observation period. Metagenomic sequencing of stool samples (n = 20) collected from both patients before and within 1 year after FMT showed no significant changes in the taxonomic profile of the microbiota at the level of microbial families. Metabolomic analysis of the composition of feces showed no directed changes in the composition of metabolites after the FMT procedure, the nature of changes within the samples from each patient during the entire study period was random. Thus, FMT had no effect on the course of DM1, but served as a starting point for weight loss and improvement glucose profile in DM2. However, convincing data confirming a causal correlation between FMT and improvement in the course of T2DM have not been obtained

Experience of long-term use of anti-IgE therapy in a patient with chronic spontaneous urticarial

Chronic spontaneous urticaria is an urgent health problem. Recurrent urticarial rashes, angioedema and severe itching reduce the quality of life of patients. The ineffectiveness of standard therapy requires the search for new modern methods of treating this disease. Taking into account the current data on the pathogenesis, the third line of therapy for chronic spontaneous urticaria is the addition of anti-IgE therapy (omalizumab) to antihistamines of the 2nd generation. The presented clinical case is devoted to the experience of long-term use of omalizumab in a patient with chronic spontaneous urticaria. Having a disease duration of about a year, the patient was thoroughly examined, all concomitant diseases were identified and compensated, parasitic invasion was treated, but this did not lead to a regression of symptoms. Antihistamines of the 2nd generation in standard and increased doses (up to 4 times) did not control the disease, systemic glucocorticosteroids stopped the symptoms for a short time, and therefore, in  the future, the  patient began to use them independently and uncontrollably. Almost daily use of  corticosteroids for 6 months caused the development of complications in the form of weight gain and Cushing’s syndrome. Omalizumab completely stopped all the symptoms during the first day, no side effects were detected. The clinical effect lasted from 3 to 4 weeks. Thus, omalizumab therapy allowed the patient to almost completely get rid of the symptoms of CSC, which significantly improved the quality of life and made it possible to cancel systemic glucocorticosteroids. The peculiarity of the presented case is the duration of the use of omalizumab (more than 2 years) with the inability to cancel due to the return of urticarial rashes and itching

The first and only combination of basal and prandial insulin analogs degludec and aspart: the position of Russian endocrinologists

Insulin therapy for diabetes mellitus is the most effective way to control glycemia with the progression of the disease and the ineffectiveness of other sugar-lowering drugs. At the same time, the existing limitations of traditional insulin preparations, along with increasing attention to the individualized treatment of this disease, are pushing developers to create drugs that most closely reproduce the effect of natural human insulin. In this regard, the appearance of a combination of insulin analogs, the action profile of which practically imitates insulin secretion by a healthy pancreas, presents new possibilities in the treatment of diabetes mellitus. Insulin degludec / insulin aspart (IDegAsp, Ryzodeg®, Novo Nordisk, Denmark) is the first and only soluble combination preparation containing 70% of the ultra-long-acting insulin analogue degludec and 30% of the ultra-short-acting insulin analogue aspart in one injection, which meets the need for both basal and prandial insulin. The combined drug has nothing in common with traditional mixed insulin preparations (both human and analog) and provides doctors and patients with significant advantages over the latter. The article presents the position of Russian experts-diabetologists with extensive experience in the use of IDegAsp regarding the role and place of the drug in real clinical practice. Data from real clinical practice confirm that IDegAsp is a reasonable choice for starting and intensifying insulin therapy for type 2 diabetes mellitus when basal and prandial glycemic control is required. The use of the drug is most appropriate in patients who are on basal, biphasic, basal-plus/basal-bolus regimens and who do not achieve the goals of glycemic control during prior therapy. One of the leading reasons for choosing IDegAsp may also be a lower risk of developing hypoglycemia compared to insulin analogues of previous generations — biphasic insulin aspart and basal insulin glargine 100 U/ml. In addition, IDegAsp is a simple, flexible and safe insulin therapy for patients on premix therapy and basal-plus/basis-bolus regimens who require basal and prandial glycemic control. IDegAsp is a simple, flexible and safe insulin therapy. The greatest benefit of this drug use can be obtained by patients for whom adherence to a complex therapy regimen is difficult (the elderly, with cognitive impairment, after a stroke, with dementia), as well as patients who have an active lifestyle, accompanied by irregular food intake. It is important to note that since January 1, 2021, there is no need for a decision by a special medical commission to prescribe (IDegAsp) Ryzodeg®. This fact, as well as a significant price reduction at the end of 2020, opens up broader prospects for using the drug in the routine practice of a Russian endocrinologist

Interactive simulator for working out the skill of writing recipes for medical students

The purpose of the study is to create a convenient interactive tool for studying and practicing the skills of preparing prescription forms.Цель исследования — создание удобного интерактивного инструмента для изучения и отработки навыков оформления рецептурных бланков