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Osteoarthritis (OA) is the most common joint disease. Searching for new treatment methods and regimens for OA is relevant.Objective: to evaluate the efficiency and safety of therapy with a symptomatic sustained-release drug (Alflutop) in combination with intra-articular hyaluronic acid (HA) injection versus monotherapy with HA in patients with knee OA in routine clinical practice.Patients and methods. A post-registration open-labeled prospective comparative randomized study was conducted to assess the results of treatment in 76 patients (31 men and 45 women; mean age, 49.3±8.5 years; body mass index, 28.4±0.8 kg/m2 ) in two clinical centers in Yekaterinburg and Perm. The patients were randomized into two equal groups, were homogeneous in terms of gender, the frequency of comorbidities, and vital signs (blood pressure, heart rate, and respiratory rate).Group 1 patients received Alflutop as 1-ml daily intramuscular injections (a total of 20 injections) + 2 ml of 1% intraarticular (IA) HA solution injections three times at 1-week intervals; Group 2 patients were given 2 ml of 1% intraarticular HA solution injections three times at 1-week intervals. As an additional therapy, the use of meloxicam 7.5–15 mg/day was permitted, and, if non-steroidal anti-inflammatory drugs were contraindicated, paracetamol 1–3 g/day might be used.Results and discussion. During treatment, both groups of patients showed improvement (compared to the baseline levels). At the same time, evaluating the intergroup values revealed clear differences: a more pronounced decrease in all WOMAC indicators in Group 1 patients: pain scores, 2 [1; 3] vs. 4 [2; 5] in Group 2 (p

The article is devoted to the development of a conceptual model patent of the patent analytics module integrated into the SAP corporate information system. It has been shown that patent research plays an important role in the strategic development of an enterprise based on the study of market trends. It has been proven that since the future strategy of the company depends on such a large dataset and the person is not able to assess the situation efficiently and consider a broad introduction, reengineering of the process of data collection and analysis is required, on which the fate of the enterprise depends. The primary purpose of this module is to provide automation of this kind of analysis and planning of strategic development of the enterprise. Moreover, the information collected by the system will help to correctly allocate funds for research and development programs.

in 3 mL on patients with knee osteoarthritis (OA) in a multicenter prospective study. Materials and methods. 79 outpatients (predominantly females 81.0%) from 5 RF constituent territories with primary tibiofemoral KellgrenLawrence score grade II or III knee OA, 40 mm pain intensity during walking on visual analogue scale (VAS), requiring NSAIDs intake (for at least 30 days during 3 months prior to enrollment) were included into the study after signing the informed consent form. Mean age was 60.38.7 years, mean BMI 29.24.7 kg/m2, disease duration 6 (310) years. Grade II OA was documented in 68.4% of patients, Grade III in 31.6%. The study lasted for 6 months. Efficacy and safety evaluations were made based on VAS pain assessment, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) [WOMAC pain (0500), WOMAC function (01700), WOMAC stiffness (0200)], VAS patients health status, EQ-5D-based assessment of patients quality of life, global physicians and patients efficacy assessment, and daily NSAIDs requirements. Results. Obtained results demonstrate statistically significant VAS pain reduction during walking already in 1 week after intra-articular injection of the combination [respectively, 62 (5572) and 41 (3251) mm, р0.0001]. Moreover, pain continued to subside during all 3 months of follow up [in 1 month 28 (2042), in 3 month 22 (1437) mm]. A significant pan reduction achieved at Mo 3 persisted until Mo 6 20 (1442) mm, without documented pain increase. Similar trends were observed with total WOMAC score [1125 (8991540) at baseline, and 552 (309837) mm by the end of the study, p0.0001], and all WOMAC sub-scores [268 (189312) baseline WOMAC pain, 91 (48171) mm by the end of the study p0.0001; stiffness 101 (59130) and 40 (2061) mm, p0.0001; function 802 (6471095) and 402 (191638) mm, p0.0001, respectively]. Median time to the onset of therapeutic effect was 7 (518) days. Statistically significant improvement of patients quality of life by EQ-5D and general health status was observed during all follow up period [respectively, 0.52 (-0.020.59) and 0.69 (0.590.80), р0.0001; 48 (3060) and 72 (6080) mm, р0.0001]. One injection of the drug resulted in dose reduction or discontinuation of NSAIDs therapy: at baseline 76 patients (96.2%) were taking NSAIDs, in one week 31 (39.2%) patients discontinued NSAIDs, in 1 month 72.2%, in 3 months 73.4%, and by the end of the study at Mo 6 54.4% were not taking NSAIDs. These data were consistent with physicians and patients global assessment of the efficacy of treatment, who stated significant improvement and improvement in the majority of cases, with only few no effect or worsening cases documented in analyzed population. Adverse events, such as worsening of pain and/or swelling of the joint, were documented in 8 patients (10.1%); they resolved spontaneously or following NSAIDs intake. Conclusion. These results suggest that intra-articular injections of hyaluronic acid plus chondroitin sulfate in patients with knee OA are efficient and safe. A single injection of the drug resulted in statistically significant reduction of pain and stiffness, reduction in NSAIDs intake, as well as improvement in patients quality of life and function.

Diabetes mellitus (DM) can lead to the development of late complications. In addition to the traditional late complications, a high prevalence of damage to the musculoskeletal system in diabetes was noted. The most appropriate term that reflects the defeat of the musculoskeletal system in diabetes is limited joints mobility syndrome (LJM). Damage to the hands in the presence of open painless stiffness of the joints, fixed flexion contractures, impaired fine motor skills of the hands and grip forces. Subsequently, it became clear that, over time, the restriction of joint mobility develops not only in the small joints of the hands, but also in other large and small joints of the limbs. Traditionally, LJM syndrome pays low attention on the part of practitioners in comparison with other micro- and macrovascular complications of diabetes, even though LJM can significantly impair functional activity, self-care, and impair the quality of life. It is assumed that damage to the periarticular tissues and joints in DM is caused by the accumulation of end glycation products. A decisive place in the diagnosis of LJM is the clinical examination. In the presence of LJM syndrome, the osteoarticular structures of the feet can be affected, timely diagnosis can lead to the development of diabetic foot syndrome.

The paper provides a review of the data available in the literature on the relationship of pain to the risk of OA progression. Network analyses and numerous studies, including those conducted at the V.A. Nasonova Research Institute of Rheumatology, have confirmed that pain syndrome is one of the significant predictors of knee OA progression. The major class of medications for OA pain includes nonsteroidal anti-inflammatory drugs. The paper gives data on the efficacy of meloxicam in OA patients, which is widely used in both Russia and other countries of the world. Meloxicam is characterized by a good safety profile in the gastrointestinal tract, cardiovascular and renal systems. It is the drug of choice in patients with musculoskeletal diseases, in particular OA. Good results in severe pain syndrome have been shown by a step-by-step regimen of meloxicam when the injection formulation of the drug is used in the first days of treatment, and then, to consolidate what has been gained from therapy, its oral dosage form is administered in terms of concomitant diseases.

Osteoarthritis (OA) belongs to diseases with high comorbidity and most frequently concurrent with obesity, diabetes mellitus (DM), hypertension, and other cardiovascular diseases (coronary heart disease, atherosclerosis), gastrointestinal tract diseases, and chronic diseases of the lung and kidney. Irrational treatment of OA in the presence of comorbidity and without considering characteristics of drug interactions leads to a pronounced increase in the number of adverse reactions (ARs) and to aggravation of the course of all concomitant diseases. From this point of view, therapy seems to be relevant when the latter involves drugs that have both symptom- and structure-modifying properties and have a high safety profile.Objective: to compare the safety of alternating and standard treatment regimens with Alflutop® in patients with knee OA.Patients and methods. 130 patients were enrolled in the trial who had Kellgren-Lawrence Grade II–III primary tibiofemoral knee OA with pain intensity on walking ≥40 mm on a visual analogue scale and who needed to take nonsteroidal anti-inflammatory drugs (≥30 days in the previous 3 months). The patients were randomized into two groups: Group 1 was prescribed Alflutop® 1.0 ml intramuscularly (IM) daily for 20 days (a standard regimen); Group 2 was given 2 ml IM every other day (a total of 10 injections) (an alternating regimen). The duration of follow-up was 14 weeks. The safety of Alflutop® was evaluated by the incidence of ARs and serious ARs (SARs) varying in severity according to medical records, laboratory tests, physical examination, assessment of a patient' vital signs, and electrocardiography (ECG). The patients were examined at the beginning, at the end, and 1 month after therapy.Results and discussion. No SARs were recorded during the study period and follow-up. There were 10 ARs in the group of patients receiving Alflutop® in the standard regimen and 19 ARs in the other group (the alternating regimen). All ARs corresponded to mild and moderate severity, were unassociated with the test drug, and resolved by the end of the follow-up. 12-lead ECG identified only clinically insignificant abnormalities in the patients of both groups. Patients without DM displayed no clinically significant increase in glucose levels. Those with DM had no increased glycemia tendency. Biochemical studies in both groups revealed only clinically insignificant abnormalities, the frequency of which was insignificant.Conclusion. This study has confirmed the comparable high safety of Alflutop® in both standard and alternative therapy regimens. It has also shown that the drug has a good safety profile and can be recommended for wide clinical application in any use regimen: 1 ml daily (a total of 20 injections) or 2 ml every other day (a total of 10 injections).

The results of the development of an effective intelligent system for technical diagnostics of reinforced concrete structures are presented. The category of technical condition is the main criterion in deciding on the degree of accident or the need to take measures to bring it to further safe operation of a building construction. For the purposes of this study, an expert system was developed based on the mathematical apparatus of the theory of fuzzy sets and fuzzy logic, which can take into account the scatter of individual opinions of experts, significantly reduce the examination time and improve the quality of the diagnostics. A hierarchical structure of the organization of expert knowledge is proposed for assessing the technical condition of building structures taking into account the universality of information and the possibility of its expansion based on ontological analysis. Moreover, a technique was developed for formalizing expert information using membership functions for input and output control parameters. To implement a fuzzy logical inference, an algorithm adapted to the given problem is developed. A computer program has been developed that implements the method of identification of the category of technical condition of building structures on the basis of fuzzy knowledge bases. The results of using this program in a survey of a real industrial building are given. The results of the technical state evaluation examined structure, obtained using the expert system, are confirmed by expert opinions of specialists who did not participate in the creation of the program and have extensive experience in examining the building structures. The present work is motivated by a need to transfer knowledge from the technical books and experienced experts in the domain field of diagnostics of building structures to make that knowledge and expertise available to practicing engineers.

The article analyzes the facts of the collecting the data on the development of the Soviet industry in Ukrainian industrial areas by the German researchers in Ukraine during the World War II and its further processing. The primary focus of this economical and statistical researching was on evolution of the Soviet industry since the early 1920 s and its functioning in Ukraine during the Nazi occupation. The main purpose was the investigation of the Soviet experience of industrialization, the role and the significance of the industrial areas created around the Ukrainian cities of Kharkiv and Dnipropetrovsk. The forms of the collecting of the information about economics and industry of Ukraine and its main results are characterized: review of the special literature and bibliographies in local libraries in occupied Ukraine, and questionnaire studies for the purpose of gathering information from directors of enterprises and workers. It has been established that the significant contribution to these studies of the Ukrainian industrial areas during the World War II has been made by German economist Walter Thoms, the dean of the Faculty for public policy and economics at the Heidelberg University in Germany (1939-1945). Problems of the Soviet enterprises functioning, social welfare of the Soviet industry workers and their professional education were a major focus of his academic interest. W. Thoms prepared two questionnaires for the survey in Kharkiv and Dnipropetrovsk. The survey findings were to be processed at the University of Heidelberg after the war. Directions for future research have been set, first of all the activities of W. Thoms during World War II in the occupied territories, as well as the search for materials on economic statistics that have been brought out of Ukraine during World War II.

The purpose of the research is to characterize the documents of the Main Office for Science (German: Haupamt Wissenschaft) by the Commissioner of the Fuehrer for the Supervision of the Entire Intellectual and Ideo-logical Schooling and Training of the NSDAP (German: Beauftragter des Fьhrers fьr die Ьberwachung der gesamten geistigen und weltanschaulichen Schulung und Erziehung der NSDAP, and related materials of A. Rosenberg’s other structures as the sources on the ideological component of the Third Reich’s struggle against Bolshevism and their significance for information or ideological component of the Nazi occupation policy in the occupied territo-ries of Eastern Europe. The research methodology consists of historical-archival, historical-comparative research methods, source analysis methods. The scientific novelty is determined by the fact that the materials of the Rosenberg Office and the documents of the Main Office for Science, in particular, have not yet been the subject of a separate comprehensive scientific archival and source review for their possible use as the historical sources on the ideological component of Nazi policy, vision of connection between science and ideology, participation of the Main Office for Science in the so-called «ideological struggle» against Bolshevism, collection of scientific informa-tion in the occupied territories of Eastern Europe, in particular, the USSR. Although these documents are familiar to German researchers, the latter used them as the sources to determine the Rosenberg Office›s place in the NSDAP system and its significance for domestic party policy in the Third Reich. Conclusions. The analysis of the documents from the Main Office for Science of the Rosenberg Office allows us to conclude that a number of his documents for 1942-1945, as well as related documents of the Special Staff Science (German: Sonderstab Wissenschaft), which represented the interests of the department at the Special Command Force of Reichsleiter Alfred Rosenberg orReichsleiter Rosenberg Taskforce (German: Einsatzstab Reichsleiter Rosenberg), contain the interesting and valuable information not only on the connection between National Socialist ideology and science but also on the collection and processing of various information about the state of science in the Soviet Union, especially the materials of scientific content, consolidated data about state of Soviet scientific institutions during the Nazi occupation, etc. This information has so far been little known or not introduced into scientific circulation at all, but it may be useful to researchers of the history of World War II.

The article analyzes official newsletter “Mitteilungsblatt” that has been published by the Commissioner of the Fuehrer for the Supervision of the Entire Intellectual and Ideological Schooling and Training of the NSDAP (aka Dienststelle Rosenberg) as a source for supporting an ideology as a component of the Nazi policy in the occupied European countries, of the Nazi propaganda and political education. The main data of the Mitteilungsblatt is characterized: its publication frequency, structure, mission, target audience, its place amongst print publications that were published by the Dienststelle Rosenberg, as well as its completeness and current storage location. It has been established that the official publications of the Dienststelle Rosenberg have not been considered until this point by researchers as sources on the history of National Socialism and political education in the Third Reich. Subject matters of the Mitteilungsblatt have been described and it has been found that a prevalent part of its papers deals with the Soviet Union, namely communist ideology and propaganda and their effect on Soviet people, communist morality, economic policy (collectivization and industrialization), militarization propaganda and preparations for a war long before the World War II began. It has been established that the Mitteilungsblatt was intended for use by the ideological education and political training of the Nazi party members, military officers, public servants of the German occupation authorities.

The intelligent and digital technologies implementation into the civil engineer expert activities is able to provide alternative solutions to different qualifications specialists. This will increase the speed of data processing and the reliability of the expert opinion on the technical condition of the operated construction objects as well as will allow assessing their real residual resource for making a decision on the possibility of further exploitation. The ontology and the original technology for the main system components determination are necessary to achieve the goal (the confinement model) used for the structural and functional analysis of the knowledge system. The entire technologies set for the architectural and construction objects (digital documentation, scan results, thermal imager data, non-destructive survey methods data), data about structure’s defects and damage, appropriate software as well as intelligent technologies (fuzzy logic, neural networks) are used for more thoroughly diagnose certain construction parts and transmit digital information to determine the technical condition category. Also, this data set can be used for following situations: a control of the dynamics of changes in the technical state of a construction object, an improvement the accuracy of determining the scope of repair work, an enhancement the quality of project documentation, methods for assessing the quality of restoration work and measures for the conservation of architectural monuments, etc.

Pallister-Killian syndrome (PKS) is a rare inherited disease with multiple congenital anomalies, profound intellectual disability, and the presence in the karyotype of sSMC - i(12)(p10). The frequency of PKS may be underestimated due to problems with cytogenetic diagnosis caused by tissue-specific mosaicism and usually a low percentage of peripheral blood cells containing sSMC. Such tissue-specific mosaicism also complicates a detailed analysis of the sSMC, which, along with the assessment of mosaicism in different tissues, is an important part of cytogenetic diagnosis in PKS. Unfortunately, a full-fledged diagnosis in PKS is either practically impossible or complicated. On the one hand, this is due to problems with the biopsy of various tissues (skin biopsy with fibroblast culture is most often used in practice); on the other - a low percentage of dividing peripheral blood cells containing sSMC, which often significantly complicates the analysis of its composition and organization. In the present study, a detailed analysis of sSMC was carried out in a patient with a characteristic clinical picture of PKS. A relatively high percentage of peripheral blood cells with sSMC (50%) made it possible to perform a detailed molecular cytogenetic analysis of de novo sSMC using chromosomal in situ suppression hybridization (CISS-hybridization), multicolor FISH (mFISH), multicolor chromosome banding (MCB), array CGH (aCGH), and quantitative real-time PCR (qPCR), and short tandem repeat (STR) - analysis. As a result, it was found that the sSMC is not a typical PKS derivative of chromosome 12. In contrast to the classical i(12)(p10) for PKS, the patient's cells contained an acrocentric chromosome consisting of 12p material. Clusters of telomeric repeats were found at the both ends of the sSMC. Furthemore, the results of aCGH and qPCR indicate the presence of interstitial 8.9 Mb duplication at 12p13.1-p12.1 within the sSMC, which leads to different representations of DNA from different segments of 12p within cells containing sSMC. The obtained data raise the question of the instability of the sSMC and, as a consequence, the possible presence of additional rearrangements, which, in traditional cytogenetic analysis of patients with PKS, are usually described as i(12)(p10). [ABSTRACT FROM AUTHOR]

For the first time, the paper presents in detail the prevalence of osteoarthritis (OA) and considers the predictors of disease development and progression. The clinical classification of OA and its place in the ICD-10 are described. The clinical presentation of the disease is characterized in detail according to the localization of the process. It is noted that there is a change in the understanding of OA as a classic model of nociceptive pain. The paper depicts clinical, laboratory, and instrumental methods for diagnosing the disease, as well as classification and diagnostic criteria; much attention is paid to the current principles of OA therapy according to the Russian clinical recommendations and the guidelines of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the European League Against Rheumatism (EULAR).

Aim. To find the relationship between bone mineral density (BMD) and risk of knee OA progression in a 5-year prospective study. Materials and methods. 110 females with knee OA were examined twice with 5-year interval. Examination included filling questionnaires, VAS pain assessment, plain knee radiography and axial skeleton densitometry. I stage knee OA was established in 33 (30%) patients, II stage - in 46 (41.8%), III stage - in 26 (23.6%), and IV - in 5 (4.5%). Normal lumbar vertebrae densitometry BMD values were found in 45 patients (40.9%), osteopenia - corresponding BMD values - in 33 (30.0%), and osteoporosis - in 32 (29.1%). Normal femoral neck BMD values were identified in 60 (54.5%) patients, osteopenia - level BMD - in 48 (43.7%), osteoporosis - in 2 (1.8%). In all premenopausal patients (n=15) axial skeleton BMD values were normal. Results. In 5-year interval radiographic progression was established in 40 patients (Group 2), while in 70 (Group 1) patients no progression occurred. Both groups were comparable in terms of age and disease duration, although, more patients from Group 2 tended to have normal baseline densitometry BMD values - both in lumbar vertebrae and femoral neck: 47.5% vs 37.1%, and 62.5% vs 44.3% as compared to Group 1 patients. Patients from Group 1 more often had BMD values corresponding to osteoporosis and osteopenia: 32.9% vs 22.5%, and 55.7% vs 37.5%, respectively, as compared to Group 2 patients, although not achieving statistical significance. These differences were still identifiable after 5-year interval. Absolute BMD values at the second examination in 5 years were indicative of statistically significant increase in femoral neck and total hip BMD in Group 2 patients with knee OA progression: 0.79±0.11 vs 0.73±0.16, р

Many patients with osteoarthritis (OA) tend to have comorbidities. This tendency is more frequently observed to increase with age. One of the comorbidities is type 2 diabetes mellitus (T2DM). Due to the higher prevalence of coexistence of these two conditions, it has been suggested that T2DM-associated hyperglycemia may adversely affect joint tissues and increase OA severity. However, the molecular mechanisms in the development of DM in patients with OA remain unclear.Objective: to trace the dynamics of T2DM development in patients with OA at the level of the expression of genes associated with glucose metabolism, joint destruction, and general regulation of metabolic processes.Patients and methods. Three patients with OA were followed up for 4—6 years, including the year of onset of T2DM. The clinical condition of the patients was analyzed once a year. Total RNA was annually isolated from their blood and used to determine the level of gene expression by real-time polymerase chain reaction.Results and discussion. The development of T2DM was shown to be accompanied by the increased expression of genes related to glycolysis, Krebs cycle, pentose phosphate pathway, matrix metalloproteinases and regulators of AMPKand mTOR metabolism. By contrast, the level of the hypoxia regulator HIF1a and hexosamine pathway genes was decreased.Conclusion. The occurrence of T2DM in the presence of OA is likely to be associated with the higher needs for cells for ATP energy and is accompanied by activation of the glucose assimilation pathways, as well as by the increased expression of the genes responsible for extracellular matrix destruction. This may be caused by impaired protein glycosylation due to inhibition of the hexosamine pathway.

Recurrent pregnancy loss (RPL) is a severe reproductive pathology with a significant component of unexplained etiology. Extended homozygous regions as a possible etiological factor for RPL were sought in the genomes of embryos. Twenty-two paired first-trimester spontaneously aborted embryos from eleven women with recurrent miscarriage were analyzed. All embryos had normal karyotypes according to metaphase karyotyping and conventional comparative genomic hybridization. SurePrint G3 Human CGH + SNP 4 × 180K microarrays (Agilent Technologies) were used to search for homozygous regions. As a result, 39 runs of homozygosity (ROH) were identified in extraembryonic tissues of 15 abortuses. Verification of recurrent homozygous regions was performed by Sanger sequencing. The presence of occasional heterozygous SNPs was shown in 25 extended ROHs, which may indicate that they did not arise de novo but were inherited from parents. In the course of inheritance in a series of generations, they may accumulate mutations, leading to heterozygosity for several sites in the initially homozygous population-specific regions. Homozygotization of recessive mutations is one of the putative mechanisms of the influence of such inherited ROHs on RPL development. The high frequency of extended ROHs detected in the present study may point to a role of inbreeding in RPL etiology. Homozygous regions may also occur due to uniparental disomy, and abnormalities of genomic imprinting may be another mechanism responsible for the pathological manifestation of ROHs in embryogenesis. Indeed, five predicted imprinted genes were identified within ROHs according to the Geneimprint database: OBSCN, HIST3H2BB, LMX1B, CELF4, and FAM59A. This work reports the first finding of a high frequency of extended ROHs in spontaneously aborted embryos with normal karyotypes from families with RPL.

The aim of the research is to analyse the documents of the Reichsleiter Rosenberg Headquarters archives as sources for the use of Soviet film strips and documentary film strips confiscated throughout the Nazi-occupied territory of the USSR, that is the films of various kinds and contents, for propaganda and political training, both in different Nazi civilian institutions and within military structures of The Third Reich, devoted to theideological struggle against the Soviet Union and Bolshevism during the Second World War. The methodology of research is comprised of the historical-archival and historicalcomparative research methods, as well as methods of source analysis. The use of such methodology made it possible to determine the content as well as determine the informational potential of this kind of documents in the archive of the Reichsleiter Rosenberg Headquarters, which covers the issue of confiscation of Soviet documentary films on the occupied territories, inventory and processing, export to the Third Reich, as well as their use in anti-Soviet propaganda. Scientific novelty of the research. The documents of the Reichsleiter Rosenberg Headquarters, dedicated to one of the aspects of its activities on the Nazi-occupied territory of the USSR, namely the confiscation of documentary films, which have not been put into scientific circulation until today are the objects of this research and source study. A separate place in the study also covers the issue of the use of the resources by both the Operational Headquarters and other Nazi structures of Soviet films of scientific and popular science content, documentaries, and newsreels in political education and in specialised training during World War II, which until now have not been the subject of scientific research, neither in Ukraine nor abroad. Conclusions. The carried out source analysis of the documents allows us to conclude that the Reichsleiter Rosenberg Headquarters, in addition to cultural values - art objects, confiscated in the USSR and exported to the Reich, collections of film materials as sources both for learning about life in the Soviet Union. Evidences for this notion are supplied by the various documents from the Headquarters archives - reports of employees, lists of confiscated films and correspondence.

Skin fibroblasts from a patient with neurodevelopmental and speech delay, anxiety disorder, macrocephaly, microorchidism, multiple anomalies of internal organs and ring chromosome 13 were reprogrammed into induced pluripotent stem cells (iPSCs) to generate a clonal stem cell line IMGTi003-A (iTAF6-6). IMGTi003-A pluripotency was demonstrated by three germ layer differentiation capacity in vitro, and this cell line had a mosaic karyotype with 46,XY,r(13) as a predominant cell subpopulation. IMGTi003-A line is a good model for studying of the mitotic instability of the ring chromosome 13.

The paper describes a clinical case of adverse reaction (AR) to leflunomide (LEF) in a female patient with rheumatoid arthritis (RA). In 2007 to 2017, the female patient with a reliable diagnosis of RA took LEF (Arava) at a dose of 20 mg/day, which showed a good clinical effect. However, the patient developed atypical bone cysts in the hands, feet, right elbow, and left heel 10 years after start of therapy. The differential diagnosis with deep mycosis, tuberculosis, cancer pathology, endocrine system disease, and AR to the long-term use of LEF was made to clarify the nature of bone cysts.

Ring chromosomes are structural aberrations commonly associated with disease phenotype. We consider necessary to create the iPSCs with a ring chromosome 8, which can be used for disease modeling and related research. The ICGi025-A iPSCs line was obtained by the reprogramming of the skin fibroblasts from a 1-year-old boy with 46,XY,r(8)/45,XY,–8 mosaicism, developmental delay, microcephaly, dysmorphic features, diffuse muscle hypotonia, moderate proximal muscle weakness, feeding problems, and motor alalia. The iPSCs had expression of the pluripotency-associated markers. In vitro differentiated cells expressed the markers of the cells of three germ layers. That data allowed us to conclude that ICGi025-A cells were pluripotent.

Ring chromosome 18 is a rare chromosomal disorders that usually originate de novo and correlate with clinical manifestation: developmental delay as well as microcephaly, brain and ocular malformations, hypotonia and skeletal abnormalities. We generate iPSC clonal cell line ICGi024-A with pluripotency properties which were demonstrated in vitro by three germ layer differentiation capacity. ICGi024-A can be used for disease modeling and fundamental investigation of ring chromosome instability.

A variety of hypotheses have been proposed to explain the association between trisomy and increasing maternal age in humans, virtually all of which assume that the underlying mechanisms involve meiotic errors. However, recently Hultén and colleagues [Hulten et al., 2010b] proposed a provocative model-the Oocyte Mosaicism Selection Model (OMSM)-that links age-dependent trisomy 21 to pre-meiotic errors in the ovary. Specifically, they propose that nondisjunctional events occur in a proportion of germ cells as they mitotically proliferate, resulting in mosaicism for trisomy 21. Assuming that the presence of an additional chromosome 21 delays meiotic progression, these cells would be ovulated later in reproductive life, resulting in an age-dependent increase in aneuploid eggs. Because this model has important clinical implications, we initiated studies to test it. We first analyzed oocytes from two trisomy 21 fetuses, combining immunostaining with FISH to determine the likelihood of detecting the additional chromosome 21 at different stages of meiosis. The detection of trisomy was enhanced during the earliest stage of prophase (leptotene), before homologs synapsed. Accordingly, in subsequent studies we examined the chromosome content of leptotene oocytes in seven second trimester female fetuses, analyzing three chromosomes commonly associated with human trisomies (i.e., 13, 16, and 21). In contrast to the prediction of the OMSM, we found no evidence of trisomy mosaicism for any chromosome. We conclude that errors in pre-meiotic germ cells are not a major contributor to human aneuploidy and do not provide an explanation for the age-related increase in trisomic conceptions.

Своевременная техническая диагностика конструкций зданий и сооружений является важным условием обеспе­чения их безопасности. Объективность и достоверность информации, предоставляемой экспертами о техническом состоянии строительного объекта, в большой степени зависят от опыта эксперта, то есть от человеческого фактора. Внедрение интеллектуальных технологий в экспертную деятельность инженера-строителя мотивировано необходи­мостью передачи знаний опытных экспертов специалистам разной квалификации для расширения и укрепления их профессиональных возможностей. Логика рассуждений человека-эксперта в интеллектуальной системе должна легко поддаваться машинной обработке. Для этого её необходимо структурировать в виде концептуальной схемы системы знаний. Представлен эффективный метод конфайнмент-моделирования на примере создания концептуальной структуры базы знаний (БЗ) технической диагностики конструкций зданий и сооружений, который позволяет унифицировать процесс разработки онтологических баз знаний, помогает от­сеивать неважные факторы и сосредоточиться на тех, которые действительно влияют на результат. Разработанная структура является основой для реализации следующего этапа - по­строения интегрированной базы знаний интеллектуальной системы диагностики технического состояния строительных объектов разных конструктивных форм и назначения, вы­полненных из разных материалов, которая должна также включать: методы цифровой обработки результатов лазерного сканирования повреждений конструкций; методы оценки ри­сков и определения остаточного ресурса конструкций зданий и сооружений с использованием теории нечётких множеств и нечёткой логики; оценку экономического эффекта от ме­роприятий по обеспечению конструкционной безопасности.

This paper presents the results of numerical modeling and full-scale experiments of the failure process of a glued laminated timber beam with rigid joint in the middle. All the connecting parts are made of carbon fiber. The structural analysis is done with the finite element method (ANSYS software). The nonlinear problem was solved. The contact interaction of the structural elements in the process of deformation and fracture, as well as orthotropy of the wood, the transversely isotropic properties of the plates, and the real diagrams of the deformation of carbon fiber dowel pins were taken into account. The influence of the structural parameters of the joint on the position of the most loaded dowel pin in the joint and the bearing capacity of the general structure are investigated. To verify the structural analysis results, field tests were carried out before destruction by a stepwise increasing load on a personally designed stand. The destruction of the structure occurred according to the forecast of the numerical model as a result of the mutual slip of the glued wood layers and the destruction of the polymer matrix of the glued dowel pins with the beginning of the formation of plastic joints and the formation of cracks in the wood at the junction.

The article considers a promising technology for self-shaping glued wooden elements of curved forms. This method is based on rheological processes occurring in wood, such as dehumidification and swelling of wood and its anisotropic properties. To predict the final curved shape of the wooden structure, the authors analyzed existing rheological models of wood and concluded that the rheological model proposed by European researchers includes the most complete list of factors that affect the process of deformation of wood: elastic and plastic deformation, drying and swelling of wood, deformation of viscous-elastic creep and mechanical sorption deformation. Based on the results of experimental studies and numerical modeling of the change in the curvature of glued wooden elements, which were made by European researchers, it was found that the proposed rheological model of wood needs to be clarified, namely, the correction of hygro-expansion coefficients depending on the moisture content of wood. A further direction of the authors’ research will be aimed at conducting model experiments to determine the hygro-expansion coefficients of different grades of wood depending on the thickness of the wooden elements and the orientation of the layers in the glued structure.

The human induced pluripotent stem cell (iPSC) lines, ICGi009-A, ICGi009-B, ICGi013-A and ICGi013-B, were generated from skin fibroblasts of two siblings with intellectual disability. Both patients were carriers of CNTN6 gene microdeletion (Kashevarova et al., 2014). iPSC lines have normal karyotype, express pluripotency markers, are able to differentiate in vitro into derivatives of all three germ layers and represent a unique tool to study neurodevelopmental disorders.

Skin fibroblasts from a patient with intellectual disability and ring chromosome 22 were reprogrammed into induced pluripotent stem cells (iPSCs) to establish a clonal stem cell lines, IMGTi001-A (iTAF5-29) and IMGTi001-B (iTAF5-32). Because of ring chromosome mitotic instability these cell lines show mosaic karyotypes with 46,XX,r(22) in >83% cells, 45,XX,-22 as minor class and sporadically cells with other karyotypes. Differentiation in derivatives of all three germ layers was shown in teratoma assay for IMGTi001-A, and in embryoid bodies for both cell lines. To our knowledge, human iPSC lines with ring chromosome are described for the first time.

Objective: to evaluate the efficacy and safety of Chondroguard® in the combined (intra-articular (IA) + intramuscular (IM)) and IM injection in patients with knee osteoarthritis (OA).Patients and methods. The study enrolled 150 patients with knee OA who were divided into two groups with 75 patients in each group. Group 1 received the drug (100 mg/ml) intramuscularly: 25 injections every other day, the first three injections at a dose of 100 mg, the fourth injection was started with a dose of 200 mg. Group 2 had five IA injections into the target joint at a daily dose of 200 mg with an interval of 3 days between injections, then 16 IM injections at 200 mg every other day. All the patients were prescribed nonsteroidal anti-inflammatory drugs (NSAIDs), such as meloxicam 15 mg. To determine the efficiency of treatment, the investigators estimated the following parameters: pain intensity on a visual analogue scale (VAS), the total WOMAC index and its components (pain, stiffness, and functional insufficiency), sensory and affective-emotional pain characteristics (for the target joint) according to McGill Pain Questionnaire (MPQ) scores. Clinical and biochemical blood tests, clinical urinalysis, coagulogram, and electrocardiography were performed in all the patients at the beginning and the end of the study.Results and discussion. Comparison of two Chondroguard® regimens showed that by the end of treatment, the pain intensity on VAS was significantly lower in Group 2 (IA + IM administration) than in Group 1 (16.81±13.49 and 21.88±13.24, respectively; p

Objective: to investigate the effect of diacerein (Diaflex) on some components of metabolic syndrome (MS) in patients with knee osteoarthritis (OA).Subjects and methods. The multicenter open-label prospective study covered 55 patients aged 45 to 74 years with Kellgren–Lawrence Stage II–III knee OA and MS, with a pain intensity of >40 mm on a visual analogue scale, and with a disease duration of 1 to 30 years. The therapy duration was 6 months: Diaflex 50 mg/day for one month, then 50 mg twice daily for 5 months; the patients were followed up for the succeeding 3 months. During each visit, the efficiency and safety of treatment were evaluated; moreover, blood biochemical values were taken into account at the beginning and at the end of therapy.Results and discussion. There was a statistically significant improvement in WOMAC index (all its components and total value) and quality of life using EQ-5D in the first month of therapy and throughout the follow-up. Analysis based on the OMERACT-OARSI criteria indicated high treatment response rates in 92.5% of the patients at the end of therapy and in 92.2% three months after its completion. The body mass index and levels of low-density lipoproteins, triglycerides, glucose, and uric acid significantly decreased during treatment. Adverse events were detected in a small number (5.5%) of cases.Conclusion. Diaflex is an effective and safe drug in the treatment of knee OA in patients with MS. During therapy, there is a rapid and considerable reduction in pain and stiffness and an improvement in the functional state. In addition, the pleiotropic effects of the drug make it possible not only to effectively reduce weight, but also perhaps to improve the course of MS-associated conditions by the observed corrections of metabolic disturbances.

Abstract Background Ring chromosome instability may influence a patient’s phenotype and challenge its interpretation. Results Here, we report a 4-year-old girl with a compound phenotype. Cytogenetic analysis revealed her karyotype to be 46,XX,r(22). aCGH identified a 180 kb 22q13.32 duplication, a de novo 2.024 Mb subtelomeric 22q13.32-q13.33 deletion, which is associated with Phelan-McDermid syndrome, and a maternal single gene 382-kb TUSC7 deletion of uncertain clinical significance located in the region of the 3q13.31 deletion syndrome. All chromosomal aberrations were confirmed by real-time PCR in lymphocytes and detected in skin fibroblasts. The deletions were also found in the buccal epithelium. According to FISH analysis, 8% and 24% of the patient’s lymphocytes and skin fibroblasts, respectively, had monosomy 22. Conclusions We believe that a combination of 22q13.32-q13.33 deletion and monosomy 22 in a portion of cells can better define the clinical phenotype of the patient. Importantly, the in vivo presence of monosomic cells indicates ring chromosome instability, which may favor karyotype correction that is significant for the development of chromosomal therapy protocols.

Glycosaminoglycan-peptide complex (GPC) (Rumalon®) is an injectable slow-release anti-inflammatory agent (SRIA) that has complex anti-inflammatory and metabolic effects. GPC has been successfully used in the treatment of osteoarthritis (OA) for several decades. The agent now returns again to Russian clinical practice. Objective: to evaluate the efficacy and tolerability of GPC in patients with knee OA, in whom other SRIAs have been previously ineffective.Subjects and methods. A study group consisted of 104 patients (92.3% women) (mean age, 63.2±8.5 years; body mass index (BMI), 28.5±5.4 kg/m2) with severe joint pain (≥40 mm on a 100-mm visual analogue scale (VAS)) and/or the need to regularly use nonsteroidal anti-inflammatory drugs (NSAIDs). All the patients received oral SRIAs in the last 6 months and had no improvement. At baseline, VAS pain intensity was 59.4±13.1 mm; the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain was 227.3±90.8; WOMAC stiffness, 97.9±42.1; WOMAC function, 769.2±326.1; total WOMAC scores, 1095.1±426.6. GPC was used by the standard scheme: 25 intramuscular injections every other day per treatment cycle; the results of treatment were assessed at 8 and 12 weeks by VAS and WOMAC pain scores, needs for NSAIDs, satisfaction with treatment (measured on a 1- to 5-pont scale where 1 = no improvement or deterioration and 5 = the best result).Results and discussion. At 8 and 12 weeks, VAS pain scores decreased by 30.1±18.3% and 36.9±16.9%, respectively; the reductions in WOMAC pain scores were 29.8±16.3 and 38.2±23.4%; WOMAC stiffness scores, 29.2±15.4 and 31.6±17.4%; WOMAC function scores, 27.7±14.7 and 30.6±18.4%; and total WOMAC scores, 27.2±13.5 and 33.6±18.0%. The changes in pain intensity and WOMAC scores were statistically significant in both followup periods (p

Objective/introduction. Evaluation of efficacy and safety of diacerein therapy in patients with knee joint osteoarthritis (OA) and metabolic syndrome (MS). Materials and methods. 55 outpatients (50 women and 5 men) with MS and stage 2-3 OA of knee joint according to Kellgren-Lawrence, with intensity of pain syndrome > 40 mm according to visual analogue scale (VAS) from 4 Russian Federation subjects were enrolled in the study. Average age of patients was 59.7 ± 7.3 years , mean BMI is 33 ± 5,49 kg/m2, the duration of the disease is 8 (5-10 years). Duration of the study was 9 months (6 months of therapy: 1 capsule (50 mg) per day for the first month, 2 capsules (100 mg) per day for the next 5 months, and follow-up for 3 months). Evaluation of the efficacy and safety of the treatment was conducted according to generally accepted criteria. All patients were underwent biochemical tests at the beginning and at the end of therapy. Results. The study resulted in a statistically significant reduction in pain when walking according to VAS as early as in 1 month from the beginning of treatment; the further significant improvement was observed during the entire 6-month therapy. Withdrawal of therapy (the observation period was 3 months) didn’t increase the pain syndrome. Evaluation according to Womac index also revealed identical regularity. A statistically significant improvement in the quality of life according to EQ-5D was also identified during the whole period of observation. By the end of the therapy, 92.5% of the patients were OMERACT - OARSI - responders and 64.2% of patients had completely withdrawn from NSAID. Against the background of the therapy, there was a significant decrease in BMI, LDL, TG, glucose, uric acid levels. Conclusion: The data obtained make it possible to recommend diacerein as a basic therapy for OA in patients with MS. On the background of therapy, the patients showed statistically significantly reduction in pain, stiffness, the need for NSAIDs, improved the quality of life and the function of the joints. In addition, the body weight decreases reliably, the lipidogram, carbohydrate and protein metabolism parameters also improved.

Objective. To evaluate the efficacy, tolerability and safety of the drug Diacerein (Artrocker) in patients with osteoarthritis (OA) of the hip joints after continuous administration for 4 months and the duration of the drug effects for 2 months. Materials and methods. The study included 30 patients with significant (by ARA criteria) OA of the hip joints of Stage 2-3 according to Kellgren-Lawrence. The average age of patients was 63.6 ± 5.8 years. Patients took Artrocker for the first 2 weeks by 50 mg (1 capsule), and then by 100 per day (2 capsules). Evaluation of the therapy effectiveness was evaluated by the WOMAC index (pain, stiffness and functional impairment), dynamics of the index in % relative to the initial visit; the health questionnaire EQ-5D; the test «get up and go», assessment of the therapy effectiveness by physician and patient overall assessment of tolerability. Results. The decrease in the intensity of pain and stiffness on the WOMAC index were noted by the end of the first month of therapy and persisted for the whole observation period (245,6 ± 64,3 and 142.5 ± 67,3 and 97.8 ± 35.6 and 64,3 ± 30,1; p = 0,000 respectively). Significant improvement of the functional status of the joints was achieved at the end of the treatment period, which remained until the end of observation (854,6 ± 306,8 and 637,2 ± of 253.7, p = 0.000). The decrease in total WOMAC index was recorded at visit 3 (1182,6 ± 834,2 358,6 and ± 322,1 p = 0,000). Statistically significant improvement of the test «get up and go» assessment of general health and quality of life according to EQ-5D were observed from the third visit to the end of the observation. Evaluation of tolerance to treatment done by a patient and a doctor did not differ from each other: the excellent tolerability was noted for 27.5% of patients, good-65,5%, and satisfactory - for 7% of patients. Only one adverse event – nausea – was noted in the study, which was the reason for the discontinuation of the drug and withdrawl of the patient from the study.

Interpreting the clinical significance of small supernumerary marker chromosomes (sSMCs) in prenatal diagnosis is still an urgent problem in genetic counselling regarding the fate of a pregnancy. We present a case of prenatal diagnosis of mosaic sSMC(10) in a foetus with a normal phenotype. Comprehensive cytogenomic analyses by array-based comparative genomic hybridization (aCGH), sSMC microdissection with next-generation sequencing (NGS) of microdissected library, fluorescence in situ hybridization (FISH) with locus-specific and telomere-specific DNA probes and quantitative real-time PCR revealed that sSMC(10) had a ring structure and was derived from the pericentromeric region of chromosome 10 with involvement of the 10p11.21-p11.1 and 10q11.21-q11.23 at 1.243 Mb and 7.173 Mb in size, respectively. We observed a difference in the length of sSMC(10) between NGS data of the DNA library derived from a single copy of sSMC(10), and aCGH results that may indicate instability and structural mosaicism for ring chromosomes in foetal cells. The presence of a 9 Mb euchromatin region in the analysed sSMC(10) did not lead to clinical manifestations, and a healthy girl was born at term. We suggest that the ring structure of sSMCs could influence sSMC manifestations and should be taken into account in genetic counselling during prenatal diagnosis.