Temperature-Induced Restructuring of Mycolic Acid Bilayers Modeling the Outer Membrane: A Molecular Dynamics Study.

The emergence of new drug-resistant strains of the tuberculosis pathogen (Mtb) is a new challenge for modern medicine. Its resistance capacity is closely related to the properties of the outer membrane of the Mtb cell wall, which is a bilayer membrane formed by mycolic acids (MAs) and their derivatives. To date, the molecular mechanisms of the response of the Mtb outer membrane to external factors and, in particular, elevated temperatures have not been sufficiently studied.

Free Energy Barriers for Passive Drug Transport through the Outer Membrane: A Molecular Dynamics Study.

The emergence of multi-drug-resistant tuberculosis strains poses a significant challenge to modern medicine. The development of new antituberculosis drugs is hindered by the low permeability of many active compounds through the extremely strong bacterial cell wall of mycobacteria. In order to estimate the ability of potential antimycobacterial agents to diffuse through the outer mycolate membrane, the free energy profiles, the corresponding activation barriers, and possible permeability modes of passive transport for a series of known antibiotics, modern antituberculosis drugs, and prospective active drug-like molecules were determined using molecular dynamics simulations with the all-atom force field and potential of mean-force calculations.

Conformational Dynamics and Stability of Bilayers Formed by Mycolic Acids from the Outer Membrane.

Bilayers of mycolic acids (MAs) form the outer membrane of that has high strength and extremely low permeability for external molecules (including antibiotics). For the first time, we were able to study them using the all-atom long-term molecular dynamic simulations (from 300 ns up to 1.2 μs) in order to investigate the conformational changes and most favorable structures of the mycobacterial membranes.

Effect of Polyvinylidene Fluoride Membrane Production Conditions on Its Structure and Performance Characteristics.

Poly (vinylidene fluoride) membranes were prepared by freeze-casting. The effects of PVDF concentration, and freezing temperature on the morphology, crystallization, and performance of prepared membranes were examined. Polymer concentration was varied from 10 to 25 wt%.

Effect of probiotics on hemodynamic changes and complications associated with cirrhosis: A pilot randomized controlled trial.

Background: Bacterial translocation exacerbates the hyperdynamic circulation observed in cirrhosis and contributes to a more severe disease course. Probiotics may reduce bacterial translocation and may therefore be useful to redress the circulatory imbalance.

Aim: To investigate the effect of probiotics on hemodynamic parameters, systemic inflammation, and complications of cirrhosis in this randomized placebo-controlled trial.

Neuropsychological evaluation of cognitive disorders in children after COVID-19.

The article presents the results of neuropsychological remote and face-to-face testing of 25 children aged 12 to 17 years in the nearest (during and 1-2 weeks after the treatment) and later period (2-12 months) after COVID-19 infection with predominant respiratory tract infection, organized in Ekaterinburg in the State Autonomous Institution "Children's Hospital № 8". Indication of family contact with patients with a new coronavirus infection was found in all patients, a positive nasopharyngeal swab for SARS-CoV-2 RNA by PCR was found in 58%, non-focal neurological complaints were found in 54% of children. The control group consisted of 25 pupils of Moscow comprehensive schools (14 girls and 11 boys) aged between 12 and 16 years who were examined before the pandemic.

A Recent Ten-Year Perspective: Bile Acid Metabolism and Signaling.

Bile acids are important physiological agents required for the absorption, distribution, metabolism, and excretion of nutrients. In addition, bile acids act as sensors of intestinal contents, which are determined by the change in the spectrum of bile acids during microbial transformation, as well as by gradual intestinal absorption. Entering the liver through the portal vein, bile acids regulate the activity of nuclear receptors, modify metabolic processes and the rate of formation of new bile acids from cholesterol, and also, in all likelihood, can significantly affect the detoxification of xenobiotics.

Gut-liver axis in cirrhosis: Are hemodynamic changes a missing link?

Recent evidence suggests that the condition of the gut and its microbiota greatly influence the course of liver disease, especially cirrhosis. This introduces the concept of the gut-liver axis, which can be imagined as a chain connected by several links. Gut dysbiosis, small intestinal bacterial overgrowth, and intestinal barrier alteration lead to bacterial translocation, resulting in systemic inflammation.

Probiotics in hepatology: An update.

The gut-liver axis plays an important role in the pathogenesis of various liver diseases. Probiotics are living bacteria that may be used to correct disorders of this axis. Notable progress has been made in the study of probiotic drugs for the treatment of various liver diseases in the last decade.

Gut dysbiosis is associated with poorer long-term prognosis in cirrhosis.

Background: Gut dysbiosis is common in cirrhosis.

Aim: To study the influence of gut dysbiosis on prognosis in cirrhosis.

Methods: The case-control study included 48 in-patients with cirrhosis and 21 healthy controls.

Correlation of Objective Endpoints and Subjective Patient-Reported Outcomes in NAFLD Treatment with Essential Phospholipids: Real-World Data Based on Pooled Analysis of Observational Studies.

Background: While no "gold-standard" pharmacotherapy for nonalcoholic fatty liver disease (NAFLD) is yet established, essential phospholipids (EPLs) are reported to decrease steatosis and improve laboratory parameters.

Objective: This analysis evaluated adherence and satisfaction with EPL treatment as patient-reported outcomes and their relationship with changes in laboratory and ultrasound parameters among Russian patients with NAFLD.

Methods: Data were pooled from three observational Russian studies-MANPOWER (2015-2016), LIDER 1 (2012-2013), and LIDER 2 (2013)-in which EPLs were used for at least 12 weeks in the treatment of liver diseases and which measured both subjective and objective endpoints.

Effectiveness of phosphatidylcholine as adjunctive therapy in improving liver function tests in patients with non-alcoholic fatty liver disease and metabolic comorbidities: real-life observational study from Russia.

Objective: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of abnormal results of liver function tests. Earlier research showed that polyenylphosphatidylcholine (PPC) has hepatoprotective effects and thus can be used for the treatment of NAFLD and the prevention of its progression. Accordingly, the aim of this observational study was to evaluate if PPC administered as adjunctive therapy in routine clinical practice can effectively improve liver function tests of NAFLD in Russian patients with associated metabolic comorbidities.

Effectiveness of phosphatidylcholine in alleviating steatosis in patients with non-alcoholic fatty liver disease and cardiometabolic comorbidities (MANPOWER study).

Objective: The concept of using naturally occurring compounds such as polyenylphosphatidylcholine (PPC) as an adjunctive therapy to treat non-alcoholic fatty liver disease (NAFLD) and alleviate or reverse hepatic steatosis appears a very attractive option for liver protection. We aim to evaluate if PPC adjunctive therapy can effectively improve the ultrasonographic features of NAFLD in routine clinical practice in Russian patients with cardiometabolic comorbidities.

Design: This 24-week, observational, prospective study was carried out in 174 medical sites across 6 federal districts of Russia.

Real-world comorbidities and treatment patterns among patients with non-alcoholic fatty liver disease receiving phosphatidylcholine as adjunctive therapy in Russia.

Objective: Previous research conducted in Russia showed that the number of patients with non-alcoholic fatty liver disease (NAFLD) and associated metabolic comorbidities is large. We conducted an observational study to describe the management of NAFLD in patients with metabolic syndrome in Russia.

Design: A total of 2843 adult patients from 174 medical sites across 6 federal districts of Russia with newly diagnosed NAFLD, who had at least one of four comorbidities, namely overweight/obesity, hypertension, type 2 diabetes mellitus, and hypercholesterolaemia, and who received phosphatidylcholine (PPC) as an adjunctive treatment to standard care, were enrolled during 2015-2016.

[Myocardial Contractile Function in Patients with Liver Cirrhosis and Syndrome of Bacterial Overgrowth Syndrome].

Objective: to study myocardial contractile function in patients with liver cirrhosis and ascites in the presence of bacterial overgrowth syndrome (BOS) and pathological bacterial translocation.

Materials And Methods: We included in this study 59 patients with Child-Pugh class B and C liver cirrhosis (LC) of various etiology and ascites. Control group comprised 12 patients with ischemic heart disease complicated by chronic heart failure (CHF).

Platelet count to spleen diameter ratio non-invasively identifies severe fibrosis and cirrhosis in patients with autoimmune hepatitis.

Background And Aim: Non-invasive markers are essential to assess the progression of chronic liver diseases to fibrosis/ cirrhosis and the effectiveness of therapeutic strategies. The aim of this study was to evaluate the ability of non-invasive markers to identify significant fibrosis, severe fibrosis, and cirrhosis in patients with autoimmune hepatitis (AIH).

Methods: Seventy-six patients with AIH were enrolled in the study and analyzed for the following parameters of liver fibrosis: Fibrosis 4 score (FIB-4), aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AAR), AST to platelet count ratio (APRI), and platelet count to spleen diameter (PC/SD) ratio.

[Structure and dynamics of occupational lung diseases in workers of Moscow region under longstanding 50 years of observation].

The article covers data on occupational morbidity in Moscow region over last 50 years. Stable number of newly diagnosed occupational diseases was seen up to first half of 1990s. Afterwards, steady decrease in occupational morbidity is seen with closure of major industrial enterprises.

AZT 5'-Phosphonates: Achievements and Trends in the Treatment and Prevention of HIV Infection.

Despite the numerous drawbacks, 3'-azido-3'-deoxythymidine (AZT, Zidovudine, Retrovir) remains one of the key drugs used in the treatment and prevention of HIV infection in both monotherapy and HAART. A strategy in searching for new effective and safe AZT agents among latent (depot) forms of AZT has yielded its first positive results. In particular, the sodium salt of AZT 5'-H-phosphonate (Nikavir, phosphazide) has demonstrated clinical advantages over parent AZT: first and foremost, lower toxicity and better tolerability.

[Risk factors of arterial hypertension in patients with vibrational disease in Moscow region].

The article covers results of study that involved 204 male patients of occupational pathology department over recent 6 years, with diagnosed vibration disease. 103 of the examinees (50,5%) had vibration disease combined with arterial hypertension. Parameters of the study were age, occupation, length of exposure to vibration, level of the vibration, endogenous risk factors according to literature data (body build index, heart rate, functional changes index, glomerular filtration rate, creatinine level, cholesterol level, HDL and LDL levels, triglycerids levels, WBC and RBC counts).

Anti-HIV therapy with AZT prodrugs: AZT phosphonate derivatives, current state and prospects.

Importance Of The Field: AIDS, a disease caused by human immunodeficiency virus, was called 'plague of the twentieth century'. 3'-Azido-3'-deoxythymidine (AZT), the first compound approved for the treatment of HIV, is still a mandatory component of treatment schemes. However, its toxicity stimulated a search for new agents.

5'-aminocarbonyl phosphonates as new zidovudine depot forms: antiviral properties, intracellular transformations, and pharmacokinetic parameters.

The main disadvantages of 3'-azido-3'-deoxythymidine (zidovudine, AZT), the most common anti-HIV drug, are toxicity and a short half-life in the organism. The introduction of an H-phosphonate group into the AZT 5' position resulted in significant improvement of its therapeutic properties and allowed a new anti-HIV drug, Nikavir (AZT H-phosphonate). In this work, we described a new group of AZT derivatives, namely, AZT 5'-aminocarbonylphosphonates.

[Ventilatory and gas exchange functions of the lungs in occupational and other pulmonary diseases].

Aim: To study lung ventilation and gas exchange in interstitional and obstructive diseases of dust-induced and non-occupational origin for correction of pulmonary diseases.

Material And Methods: Diffuse lung capacity (Erich Jaeger unit) and biomechanical properties of the ventilation system (total plethysmography on the bodyplethysmograph made by Erich Jaeger) were investigated in 132 patients including 87 with occupational dust-induced pulmonary diseases (pneumoconiosis, dust bronchitis, exogenic allergic alveolitis, bronchial asthma) and 45 patients with non-occupational diseases: sarcoidosis (n = 28), exogenic allergic alveolitis (n = 10) and bronchial asthma (n = 7).

Results: The changes were of the same type but different severity.

The human vomeronasal type-1 receptor family--detection of volatiles and cAMP signaling in HeLa/Olf cells.

The human genome harbors 5 remnant genes coding for vomeronasal type-1 receptors, compared with 187 of such receptors in mice. In rodents, vomeronasal type-1 receptors are typically expressed in the vomeronasal organ. They are believed to be highly selective and sensitive pheromone detectors, as may be inferred from one receptor, V1rb2, responding to picomolar concentrations of the mouse pheromone 2-heptanone.