Chondroitin sulfate and glucosamine combination in patients with knee and hip osteoarthritis:A long-term observational study in Russia

BACKGROUND Oral treatment of glucosamine(GA) combined with chondroitin sulfate(CS) was reportedly effective for pain relief and function improvement in osteoarthritis patients with moderate to severe knee pain in clinical trials. While the effectiveness of GA and CS on both clinical and radiological findings has been demonstrated, only a few high-quality trials exist. Therefore, controversy regarding their effectiveness in real-world clinical practice remains.AIM To investigate the impact of GA + CS on clinical outcomes of patients with knee and hip osteoarthritis in routine clinical practice.METHODS A multicenter prospective observational cohort study included 1102 patients of both genders with knee or hip osteoarthritis(Kellgren & Lawrence grades Ⅰ-Ⅲ) in 51 clinical centers in the Russian Federation from November 20, 2017, to March 20,2020, who had started to receive oral capsules of glucosamine hydrochloride 500 mg and CS 400mg according to the approved patient information leaflet starting from 3 capsules daily for 3 wk,followed by a reduced dosage of 2 capsules daily before study inclusion(minimal recommended treatment duration is 3-6 mo). Changes in subscale scores [Pain, Symptoms, Function, and Quality of Life(QOL)] of the Knee Injury and Osteoarthritis Outcome Score(KOOS)/Hip Disability and Osteoarthritis Outcome Score(HOOS) questionnaires during the observational period(up to 54-64wk with a total of 4 visits). Patients’ treatment satisfaction, data on the combined oral use of glucosamine hydrochloride and CS, concomitant use of non-steroidal anti-inflammatory drugs(NSAIDs), and adverse events(AEs) were also evaluated.RESULTS A total of 1102 patients with knee and hip osteoarthritis were included in the study. The mean patient age was 60.4 years, most patients were women(87.8%), and their average body mass index was 29.49 kg/m2. All subscale scores(Pain, Symptoms, Function, and QOL) of the KOOS and HOOS demonstrated clinically and statistically significant improvements. In patients with knee osteoarthritis, the mean score increases from baseline to the end of Week 64 were 22.87, 20.78,16.60, and 24.87 on Pain, Symptoms, Physical Function(KOOS-PS), and QOL subscales(P < 0.001for all), respectively. In patients with hip osteoarthritis, the mean score increases were 22.81, 19.93,18.77, and 22.71 on Pain, Symptoms, Physical Function(HOOS-PS), and QOL subscales(P < 0.001for all), respectively. The number of patients using any NSAIDs decreased from 43.1% to 13.5%(P < 0.001) at the end of the observation period. Treatment-related AEs occurred in 2.8% of the patients and mainly included gastrointestinal disorders [25 AEs in 24(2.2%) patients]. Most patients(78.1%) were satisfied with the treatment.CONCLUSION Long-term oral GA + CS was associated with decreased pain, reduced concomitant NSAID therapy, improved joint function and QOL in patients with knee and hip osteoarthritis in routine clinical practice.

On the Possible Cometary Nature of the Uchur Cosmic Body(Fall 3.08.1993)

An expeditionary study of the area of the alleged impact event that occurred on 3.08.1993 in the area of the Lower Konkuli River(southeast of the Aldan Highlands,Lurikan Range,Russia)was carried out.According to the materials of remote sensing,the places of collision with the earth of a cosmic body are determined.In the area of the impact of the shock wave on the Earth’s surface,peat samples were selected,the micro probe analysis of which showed the pres­ence of a cosmogenic substance in concentrations 6-8 times higher than the background.Silicate and magnetite micro spheres,native iron,moissanite,and carbon micro tubes coated with a film consisting of pure nickel were found.Of particular interest were the findings of specific Ni film micro structures that allow us to make an assumption about the cometary nature of the Uchur cosmic body.Most researchers associate the observed flights of fireballs with the sub­sequent fall of meteorites.Researchers are trying to find the massive body of the fallen space body.However,often,even after many years of searching,a massive cosmic body cannot be found.This happened when studying the site of the fall of the Tunguska cosmic body.In this case,it remains to be assumed that the cosmic body contained micro­scopic dust particles.The structure and composition of such particles can only be studied using microscopic research methods.When studying the Uchur cosmic body,the authors concluded that it could be of a cometary nature due to the findings of specific particles-thin films of pure nickel on the surface of plant remains of terrestrial origin.This hy­pothesis arose from the recent discovery of atomic nickel vapors in comets.

当代英国童话中的“胡话”——以罗尔德·达尔的《好心眼儿巨人》为例

胡话既是体裁,也是修辞,是英国童话的重要特征之一。文章从文学和语言学的角度(音系学、形态学以及词汇、句法、语义和视觉效果的层面)分析了罗尔德·达尔的童话作品《好心眼儿巨人》。这部童话并非“纯胡话”作品,但是具有胡话体裁的多种特征,并且运用胡话修辞达到了贴近读者的目的。

当代北美文学中的二重身现象研究——以斯蒂芬·金的《睡眠医师》与彼得·沃茨的《盲视》为例

二重身不仅是人类文明的原型意象,也是重要的文学母题。文章以美国作家斯蒂芬·金的《睡眠医师》与加拿大作家彼得·沃茨的《盲视》为批评文本,着重分析当代北美文学中的二重身现象。参照学界关于二重身的类型划分,文章提出“对抗人物”“狂欢化组合”与“双胞兄弟/姐妹”新的二重身现象分类,并以此为依据,结合文本细读,总结后现代北美文学中二重身现象的重要特征:二重身不是单一的主体人格分裂的幽灵式形象,而是具有更为复杂的纠葛与设定;无意识的释放是二重身现象的重要诱因;二重身人物交互影响复杂多变,既会帮助彼此成长,也会摧毁对方;二重身现象的产生会带给个人、社会以及整个世界不同程度的影响。

The Effect of Quartz Window on Bistability of the Silicon Wafer in Lamp-Based Reactor

The effect of a quartz plate (window) on the silicon wafer temperature is studied in the conditions of the combined thermal transfer in a lamp-based chamber for the rapid thermal treatment (RTP) set up. The chamber for RTP is simulated by a radiative-closed thermal system including the influence of quartz window as a spectral filter of lamp emission and a source of emitted thermal radiation. Energy equations for thermal fluxes involved in the heat input and output from the working wafer and quartz window are solved in spectral approximation. The transfer characteristics that are defined by the temperature dependencies of the silicon wafer and the quartz window on the temperature of the heater are accounted. It is shown that temperature bistability in the silicon wafer initiates an induced bistability into the quartz window that does not reveal bistable behavior because of the linear temperature dependence of its total optical characteristics. A possibility for simulation of the quartz window by spectral restriction of the heater radiation is confirmed. The availability of the weak bistable effect in the mode of zero effective heat exchange coefficient of a non-radiative component of the thermal flux removed from the working wafer has been obtained.

Structural Changes of the Liver Vessels in Compensated and Decompensated Coarctation of Aorta in Experimental Studies

Our studies allowed us to establish that simulating coarctation of aorta in laboratory animals results in tone reduction of vessels carrying blood to the liver and from it and a subsequent development of their intima atrophy. In spite of that fact the number of vessels containing intimal musculature, muscularelastic sphincters and polypoid pulvini in the arterial bed flow increases and in the major outflowing veins, on the contrary, thinning of their muscular tori takes place. Appearance and functioning in the hepatic vessels of adaptive formations contributes to keeping up homeostasis at the microcirculatory level. With cardiac decompensation decreasing because of venous plethora, hypotonia and atrophy of the intima of the vessels responsible for the blood inflow to the liver and the outflow from it progress. Besides, the number of arteries and the rate of development of arteries with adaptive smooth muscle formations in the arteries, as well as in hepatic veins with muscular tori decreases dramatically. The reason of compensatory reaction failure is a long-term hypoxia leading to vessel and their adaptive formation sclerosis. The consequence of the exhaustion of the above-mentioned mechanisms is development of perisinusoidal fibrosis and depression of the transcapillary metabolism.

Multiagent Approach to Adsorption-Diffusion-Reaction Processes Modeling by the Method of Likelihood Cellular Automat

The discrete three-dimensional model of the adsorption-diffusion process was developed with three states using the comers of blocks within the framework of the theory of CA （cellular automata）. The construction of an asynchronous cellular automaton was used for the modeling, The implementation of the algorithm leads to a huge variety of dynamical regimes some of which are moving from the general chaos into a state of local and then global synchronization （within the framework of the model）.

Diastolic Dysfunction and Left Ventricle Remodeling in Men with Impaired Fasting Glucose

Background: Early disturbances of carbohydrate metabolism are an independent risk factor of development of cardiovascular diseases. Objective: The diastolic dysfunction and left ventricle remodeling depending on presence of impaired fasting glucose were examined. Methods: The characteristics of heart remodeling and fasting glucose of capillary blood were studied in 85 men aged 30 to 63 years without coronary heart disease. Results: In male patients with impaired fasting glucose in comparison of persons with level of glucose less than 5.6 mM/l, more pronounced diastolic dysfunction and left ventricle remodeling associated with more often presence III degree of peripheral obesity. Conclusion: Impaired fasting glucose in men increases probability of development of heart remodeling.

The Activity of Antioxidative Enzymes of Neutrophils in Patients with Unfavorable Outcome of Acute Coronary Syndrome

Background: There is a necessity for an establishment of specific markers of oxidative stress for screening in populations of high risk and an estimation of efficiency antioxidative therapies. Objective: Studying the activity of antioxidative enzymes at neutrophils in patients with acute coronary syndrome depending on outcome during the year. Methods: Intracellular metabolism of neutrophils was studied in 108 patients, of whom, in 58 persons has been diagnosed acute coronary syndrome, and 50 individuals were without coronary heart disease. Results: In patients with acute coronary syndrome, in comparison with patients without coronary heart disease, growth of production of superoxide anion on background reduction of glutathione reductase activity in neutrophils was revealed. The greatest reduction in parameters of glutathione reductase and catalase at simultaneous growth of activity of NAD(P)H oxidase and myeloperoxidase at neutrophils was observed in patients with fatal outcome during the year. Conclusion: The decrease of efficiency antioxidative protection of neutrophils associates with risk of fatal outcome in patients with acute coronary syndrome.

Developing an Efficient Technology for Key Intermediates Production Used in Enzymatic Synthesis of Cladribine and Nelarabine

The pilot-scale process for preparing 2-amino-6-chloro-9-（2＇,3＇,5＇-tri-O-acetyl-Dq3-ribofuranosyl）-purine and 2-chloroadenosine has been developed with a total yield of the desired compounds 73% and 44.5%, respectively. These compounds are useful intermediates for enzymatic synthesis of active pharmaceutical ingredients Nelarabine and Cladribine. The starting material--commercially avaliable guanosine--was acetylated with acetic anhydride, yielding 2,3,5-tri-O-acetylguanosine, which was further deoxyhalogenated with phosphorous oxychloride in presence of tetraethylammonia chloride. Diazotization of the resulting intermediate with tert-butylnitrite leads to the corresponding ribofuranosyl-substituted 2,6-dichloropurine, which was converted to 6-chloroadenosine by reaction with methanolic ammonia.

Influence of Antirisk Factors of Cardiovascular Diseases on Intracellular Metabolism of Neutrophils in Men with Obesity

Background: The factor promoting development of oxidative stress at obesity can be the neutro-phils. Objective: To study the influence antirisk factors of cardiovascular diseases on intracellular metabolism of neutrophils in men with peripheral obesity. Methods: In 103 male patients aged 23 to 64 years without coronary heart disease, we studied the presence obesity, antirisk factors of cardiovascular diseases, and the metabolic activity of neutrophils. Results: It is identified that obesity in men associates with more rare use of crude vegetables or fruits every day, and also low physical activity. The daily uses of crude vegetables or fruits, and also the increase of physical activity in obese men promote increase intracellular activity of antioxidative protection at neutrophils. Conclusion: The antirisk factors of cardiovascular diseases increase activity antioxidative protection of neutrophils in men with peripheral obesity, reducing the probability of development of oxidative stress.

Verbal Abuse Russian View

An important part of human communication--verbal abuse--shows signs of specifically national features. So far the Russian language of law is sadly lacking a few terms necessary in legal procedures concerning cases of human rights violation. The ＂Westernization＂ of Russian collectivist mentality makes the solution of the problem still more urgent.

The underground organ microbial complexes of moorland spotted orchid <i>Dactylorhiza maculata</i>(L.) Soó(Orchidaceae)

This paper is focused on the first study of microbiota of a moderate climate orchid from Northern hemisphere—Moorland Spotted Orchid Dactylorhiza maculata (L.) Soó growing in its natural habitat. There have been obtained detailed data concerning bacterial communities from rhizosphere and inner tissues of young and old tubers. It was done using the biomarker analysis method where the markers were detected by gas chromatography—mass-spectrometry. It is shown that the number of bacterial genera and the bacteria amount (105 - 108 CFU per gram of dry weight) in D. maculata microbial complexes decreases from rhizosphere to old tuber to young. At the same time all three bacterial cenoses closely resemble each other in biodiversity. Their constant members are gg. Hyphomicrobium, Methylococcus, Nitrobacter, Pseudomonas and Sphingomonas (Proteobacteria), Bacillus and Clostridium (Firmicutes), Rhodococcus and Streptomyces (Actinobacteria). There were found differences peculiar to the taxonomic structure of each microbial complex. The rhizosphere is dominated by Actinobacteria while in inner tissues Proteobacteria are prevalent. The bacteria of gg. Ochrobactrum, Xanthomonas, Butyrivibrio, Corynebacterium, Mycobacterium, Propionibacterium, Sphingobacterium and specific iron reducers were shown to belong to rhizosphere community. Genera of Agrobacterium and Bifidobacterium were found only in the endophytic microbiota of the young tuber while g. Aeromonas

Interpretation of the"Catastrophe"of Quasars on the Basis of New Decisions of the Problem of the Reverse Compton-Effect

In a model based on a search with increased accuracy of calculations-four times-of all the roots of the equations for the velocities of electrons in the inverse Compton effect,it is established that for new values of the roots of the equations(corresponding to the laws of conservation of momentum and energy),the recoil electrons remain ultra-relativistic,according to the authors,allows to eliminate the reverse Compton catastrophe of quasars.The maximum value of the scattering angle of the formed particles was found to explain the thin quasar jets.

Development of the Atomic Force Microscopy Research Technique for the Nanostructures on the Vertical Edge of Thin Insulating Film

In this work, a development of a method of a thin insulating film vertical edge visualization of metal-insulator-metal （MIM） memory cells with atomic force microscopy （AFM） using a modified Omicron UHV AFM/STM microscope was performed. This included a development of a technique of the AFM visualization of segments of a vertical edge of thin insulator SiO2 film structures on a conductive substrate, a comparison of AFM topography and current profilograms for the edge profiles, and an Omicron microscope custom upgrade. The latter allowed us to perform the AFM probe positioning to any specific area of the sample in the scanning plane by two coordinates with an order of precision of 1 micrometer. The method is illustrated with the experimental results of AFM investigations of the special MIM structures with comb-type topology, and of the cells of functioning memory matrices with 20 nm thin silicon dioxide film open edge perimeter and TiN lower electrode, including topography/current profilograms. As a conclusion, our ongoing work on the AFM visualization of a complete perimeter of a SiO2 open edge of memory cells with a special new topology with a goal to visualize conductive phase nanoparticles during switching processes is briefly overviewed.

On the Relationship between Statistical and Phenomenological Models of the Thermodynamic Systems

The paper deals with the performing of a critical analysis of the problems arising in matching the classical models of the statistical and phenomenological thermodynamics. The performed analysis shows that some concepts of the statistical and phenomenological methods of describing the classical systems do not quite correlate with each other. Particularly, in these methods various caloric ideal gas equations of state are employed, while the possibility existing in the thermodynamic cyclic processes to obtain the same distributions both due to a change of the particle concentration and owing to a change of temperature is not allowed for in the statistical methods. The above-mentioned difference of the equations of state is cleared away when using in the statistical functions corresponding to the canonical Gibbs equations instead of the Planck’s constant a new scale factor that depends on the parameters of a system and coincides with the Planck’s constant in going of the system to the degenerate state. Under such an approach, the statistical entropy is transformed into one of the forms of heat capacity. In its turn, the agreement of the methods under consideration in the question as to the dependence of the molecular distributions on the concentration of particles, apparently, will call for further refinement of the physical model of ideal gas and the techniques for its statistical description.