bluuebunny/crossref_metadata_2025 huggingface dataset:
ESAT-6 and CFP-10 antigens as a biotechnology molecule substrate. Applications in medicine
Authors: Kudlai Dmitry A. , Doktorova N. P.
Published: May 2022

Recombinant technologies have been long widely used in medicine. This article presents a review on the application of medical technologies based on ESAT-6 and CFP-10 proteins in diagnostics and prevention of tuberculosis. ESAT-6 and CFP-10 are specific proteins whose genes are encoded in the RD-1 zone (region of difference) of M. tuberculosis. M. bovis BCG and in most nontuberculous mycobacteria lack the RD-1 genome fragment. The discovery of ESAT-6 and CFP-10 antigens allowed to make the first and so far, the only breakthrough in improving the diagnostics of latent tuberculosis infection after the first tuberculin skin test (TST) was implemented. The article describes the principle of action and the experience with diagnostic tools based on ESAT-6 and CFP-10 such as in vitro interferon-gamma release assays (IGRA) and in vivo recombinant tuberculosis allergen (RTA, Diaskintest). RTA is inoculated intradermally similar to TST followed by developing delayed-type immune reaction detected in the area closest to M. tuberculosis. Combined use of ESAT-6 and CFP-10 for early detection of tuberculosis infection allowed to ameliorate for many drawbacks related to TST. High sensitivity and specificity was confirmed for ESAT-6- and CFP-10-based tests, so that former BCG vaccination had no more effect on test results and lowered frequency of false positive results due to reaction to non-tuberculous mycobacteria. The results of a large-scale meta-analysis on studies with patients at high risk demonstrated that the risk of developing tuberculosis in subjects with positive vs. negative IGRA was increased by 9.35-fold (95% confidence interval (CI [6.4813.49]), whereas for TST by 4.24-fold (95% CI [3.35.46]). 95.1%, (95% CI [95.0695.1]). Analyzing available publications demonstrated sufficient evidence base regarding efficacy of using ESAT-6CFP-10-based tests in tuberculosis diagnostics. Finally, there are also reviewed the diagnostic tests and vaccines based on using such proteins currently being under development.
Enhanced hydroxyl radical generation by human leukocytes exposed to bacterial diamines highlighting immunomodulatory effect of microbial metabolites
Authors: Godovalov Anatoliy P. , Karpunina Tamara I. , Morozov I. A.
Published: May 2022

Recently, there have been increasing an interest to study a role of polyamines in intercellular interactions, especially in the focus of inflammation, where accumulation of such polycations is observed. In this regard, products of microbial origin cadaverine and putrescine are of particular attention. The role of polyamines as scavengers of free radicals has been described, but no data of their effect on the leukocyte radical-producing activity have been obtained so far. The aim of the investigation was to study features of hydroxyl radical generation by human leukocytes exposed to microbe-derived polyamines. Materials and methods. Peripheral venous blood samples were obtained from 20 healthy donors. To assess radical production, a luminol-dependent chemiluminescence reaction was carried out with blood leukocytes pre-incubated with cadaverine (0.01 M) and putrescine (0.01 M), measured on a Luminoskan Ascent Thermo Labsystems luminometer (USA) for 180 min. For statistical analysis, an integral chemiluminescence index was used for the entire measurement period (RLU). Results and discussion. It was shown that cadaverine has a stimulating effect on the leukocyte potential to produce radicals (averaged area under the curve is 6.70.7 r.u., p 0.05). Putrescine had little effect on the radical-producing activity of human cells (2.80.4 r.u., p 0.05). This might be due to the direct influence of polycations on the mechanisms of radical generation, as well as increased activity of leukocyte diamine oxidase catalyzing the conversion of diamines into aminoaldehyde, which is accompanied by the release of hydrogen peroxide reacting with luminol. In addition, the enzyme inactivates other compounds, such as histamine leading to formation of a less pronounced clinical picture. Polyamines, particularly cadaverine and putrescine, can be referred to the factors remodeling the metabolic activity of the host leukocytes, which is aimed at maintaining the viability and increasing the number of microorganisms. Conclusion. Thus, cadaverine and putrescine produced by microorganisms, depending on the conditions of the microenvironment, might be evidently considered as mediators of the mild or asymptomatic course of inflammatory diseases, which contributes to underlying persistent potential of bacteria.
Formation of anti-infectious and post-vaccination anti-SARS-CoV-2 humoral immunity in medical workers of the perinatal center
Authors: Chistyakova G. N. , Malgina G. B. , Ustyuzhanin A. V. , Remizova I. I.
Published: May 2022

In the context of the global spread of the new coronavirus infection, studies aimed at investigating formation of anti-infectious and post-vaccination immunity are of special importance, which is necessary to prevent and reduce morbidity and mortality due to SARS-CoV-2 infection. Purpose: to assess anti-infectious immunity against SARS-CoV-2 in various forms of the disease and development of post-vaccination humoral reactions in medical workers of the perinatal center.
Materials and methods. A study of blood serum was carried out to assess SARS-CoV-2-specific IgM and IgG antibodies in 119 medical workers recovered after COVID-19, divided into groups based on the disease severity (mild, moderate and asymptomatic), as well as in 62 vaccinated employees, divided into groups according to age. Semi-quantitative measurement of virus-specific antibodies was carried out by ELISA with test systems SARS-CoV-2-IgG-ELISA-BEST and SARS-CoV-2-IgM-ELISA-BEST. Statistical processing of the research results was carried out using Microsoft Excel 2010 and Statistica 6. Quantitative characteristics were presented as median (ME), lower and upper quartiles (LQ1-UQ3); qualitative parameters as absolute value and relative number (%). Difference between groups was analyzed by using the 2 test (qualitative) and the MannWhitney U-test (quantitative).
Results. The results of the study showed that the majority of employees with a moderate-severe form of SARS-CoV-2 had a high level of IgG (PR a positivity rate of more than 9.0 arbitrary units) 9 months after the disease compared to those who suffered from mild or asymptomatic (83.3% versus 25.8% and 13.3%, p 0.017) infection. The duration of IgG circulation after former illness had no relation to its severity and patient age. The effectiveness of the primary vaccination Sputnik V and revaccination with Sputnik Light and KoviVak was 100% after inoculating the vaccine second component. The lowest level of antibodies after the first vaccination is recorded in persons over 60 years old (1.48 (1.123.25 versus PR = 8.48(5.7810.11) and 9.27 (5.8410.31) arbitrary units, p 0.017)), in comparison with young and middle-age subjects. The speed SARS-CoV-2 elimination of IgG at 6, 9 or more months after vaccination depends on relevant initial peak antibody concentration. Subjects who were initially vaccinated with the KoviVac vaccine, IgG was not detected 2 months after vaccination. The protective effect of Sputnik V, Sputnik Light, KoviVac after re-infection with SARS-CoV-2 averages 71.2%.
Conclusion. Thus, the results obtained on assessing anti-infectious and post-vaccination immunity against SARS-CoV-2 emphasize the need for further studies on a larger patient cohort, especially in those with asymptomatic infection as well as the elderly subjects.
Features of the new coronavirus COVID-19 infection in identical twins
Authors: Yudina S. M. , Kiseleva V. V. , Rusanova Tatyana S. , Ivanova I. A.
Published: May 2022

The problem of the clinical course and principles of treatment for the new coronavirus infection COVID-19 remains the most debated issue. At the same time, reliable prognostic criteria that determine characteristics of the disease course and outcome have not been established. Taking it into consideration, we present clinical cases of COVID-19 in identical twins. Patients A. and S., 39 years old, were admitted to the Regional Clinical Infectious Diseases Hospital. The patients were clinically diagnosed with COVID-19 coronavirus infection, verified, moderate form; bilateral polysegmental pneumonia of moderate severity, 1st degree respiratory failure. The course of COVID-19 coronavirus infection in identical twins markedly differed. Patient A. had peripheral blood lymphocytosis, slightly increased ESR, CRP, ferritin, IL-6, and D-dimer level. A paired twin brother (patient S.) had lymphopenia, ESR accelerated up to 20 mm/h, CRP pronouncedly increased up to 10 mg/ml, IL-6 up to 9,5 pg/ml, and D-dimer up to 750 ng/ml. Condition of the patient A. remained stable, on day 13th of treatment, the patient was discharged from the hospital. The condition of the patient S. on day 3rd of hospitalization deteriorated sharply. Considering the decrease in SpO2 level down to 88%, the damage of the lung parenchyma was more than 70%, resulting in the use of antibacterial drugs, anti-IL-6 monoclonal antibodies as well as selective reversible inhibitor of Janus-kinases 1 and 2. On day 16th of treatment, subjectively, the patient showed an improvement in general condition. During the next two days, the patients condition revealed marked positive dynamics on day 19th of hospital stay, the patient was discharged for rehabilitation. Thus, significant differences in the severity of the course of the new coronavirus infection in identical twins with similar medical history and lack of confounding comorbidities are most likely due to the initial dose of the viral load which was an important factor determining the development and course of infection.
Gene polymorphism of mannose-binding lectin-associated serine protease (MASP2) in indigenous populations of the Russian Arctic Territories
Authors: Smolnikova Marina V. , Malinchik M. A. , Tereschenko S. Y.
Published: May 2022

Mannose-binding lectin-associated serine proteases (MASP) are among of the key components in the lectin pathway (LP) of the complement activation. MASP-2 is the most studied agent among specific enzymes activating both mannose-binding lectin (MBL) and ficolins, pattern-recognition proteins involved in the elimination of pathogenic microorganisms through LP complement activation. There are some mutations in MASP2, with the most significant identified as rs72550870 (p.D120G). The homozygous GG rs72550870 is associated with congenital MASP-2 deficiency and characterized by a total lack of serum protease activity, which leads to impaired binding to lectins. This, in turn, results in severe course of infectious diseases with a high risk of adverse outcome. There seem to be some marked populational differences in the genotype and haplotype prevalence in MASP2 gene polymorphisms. To date, no data are available on the genotype distribution for the MASP2 gene in the indigenous populations of the Russian Arctic regions. The aim of the work was to study the prevalence and ethnic specificity in the distribution of allelic variants of MASP2 rs72550870 in the populations of the Taymyr Dolgan-Nenets District of the Krasnoyarsk Territory (Nenets, Dolgans, Nganasans) as well as the city of Krasnoyarsk (Russians). MASP2 genotyping was performed by using real-time PCR. The frequencies of the AG genotype associated with low MASP-2 level was 6.6% for ethnic Russian newborns in the Eastern Siberia. The prevalence of the AG genotype was significantly lower in newborns of the Arctic populations than in the Russians, being 0.3% and 0.9% for the Nenets and the Dolgan-Nganasans, respectively, which is close to the prevalence values identified for Asian and African populations (0%). No homozygous GG rs72550870 associated with congenital MASP-2 deficiency in newborns of the indigenous populations of the Taymyr Dolgan-Nenets region of Krasnoyarsk Territory (Nenets and Dolgan-Nganasans) and ethnic Caucasian subjects of the Krasnoyarsk city was detected. The frequency of the rare allelic variant G rs72550870 in ethnic Russian subjects was 3.3%, being close to the frequencies in the European populations of the world (4.0%), whereas it was 0.5% in the indigenous inhabitants of the Arctic Region. We have suggested that isolated Arctic populations encounter some intracellular infections historically later and, as contrasted with Caucasoid populations, retained a high activity in the lectin pathway of the complement activation established at the early stage of human evolution.
An impact of lactoferrin, serum albumin and secretory immunoglobulin A in actimicrobial activity of breast milk whey
Authors: Arzumanian Vera G. , Kolyganova Tatiana I. , Svitich Oxana A. , Samoylikov Pavel V. , Konanykhina Svetlana Y. , Zaytseva Tatiana A. , Zverev Vitaly V.
Published: May 2022

The contribution of the antimicrobial activity of sIgA, lactoferrin, -lactalbumin, serum albumin, and lysozyme to the total antimicrobial activity of whey was evaluated. 66 breast milk samples from healthy women aged from 23 to 45 years collected at different periods of lactation were studied. It was found that along with proceeding the lactation period, not only the total antimicrobial activity (r = 0.944) decreased, but also the activity of the low molecular weight fraction containing the sum of antimicrobial peptides (r = 0.950). The median lactoferrin level varied from 3.46 mg/ml in colostrum down to 0.94 mg/ml one year after the onset of lactation that correlated with whey activity (r = 0.616). The concentration of sIgA was peaked in the whey of colostrum (5.01 mg/ml) and significantly reduced in mature milk, remaining approximately at the same level in subsequent periods of lactation (1.0 mg/ml). Serum albumin concentration significantly decreased while proceeding through lactation period (from 5.52 to 4.68 mg/ml) and correlated with whey activity (r = 0.589). Evaluating effects of the purified -lactalbumin on C. albicans cells within the range of 520 mg/ml by spectrophotometry and microscopy showed the absence of fungicidal activity. At the same time, purified lactoferrin, IgA, lysozyme, and serum albumin demonstrated a direct fungicidal effect. The activity of the IgA preparation at a concentration relevant to the sIgA content in the whey of the first day colostrum was 50.0%, and in the whey after 12 months 31.0%; lactoferrin 26.7% and 3.4%; serum albumin 15.0% and 17.7%; lysozyme 0.1% and 1.8%. Thus, the sum of the activities of these polypeptides at concentrations typical for the first-day colostrum was 91.7%, which is comparable to the total activity of this whey 82.4%. The sum of the activities of these polypeptides, typical for 12 months of lactation, was 53.9%, and the total whey activity relevant to this period was 64.5%. Therefore, IgA and lactoferrin contribute the most significant antimicrobial activity in the whey of colostrum, whereas after 12 month-breastfeeding IgA and serum albumin become most significant.
Immunodepressive and pathogenetic mechanisms in infectious allergy
Authors: Dobrodeeva Liliya K. , Samodova A. V.
Published: May 2022

The incidence of infectious allergy has been growing mainly due to infection with Staphylococcus aureus, Streptococcus pneumoniae, Klebsiella pneumoniae, with enhancing allergic background by yeast-like fungi of the genus Candida. The frequency of infection has currently become a threat without tending to decline. Undoubtedly, Staphylococcus aureus is a pathogenic species producing highly powerful exotoxins exerting properties of cytolysin capable of disrupting the integrity of any cell wall, destroying epithelial cells, damaging mucous membranes in any organ, including the intestines, wherein it becomes accumulated at any location of staphylococcal inflammation. At the same time, almost 90% of cases of allergic reactions are diagnosed with atopic dermatitis because IgE level in some cases of infectious allergy is increased. The mechanism of the pathogenetic action of reagins is realized by re-binding of antigens to IgE fixed on mast cell and basophil surface resulting in FcR1 cross-linking and release of vasoactive mediators responsible for developing early phase of allergy. IgE concentrations, accounting for only 0.002% of the total blood immunoglobulins in an apparently healthy person, may remain low in atopic bronchial asthma, atopic dermatitis, allergic rhinoconjunctivitis, etc. IgE level is increased not only in atopy, but also in oncopathology, autoimmune diseases, whole body cooling and IgA deficiency. In allergic reactions, an increased level in the extracellular pool of various receptor structures is recorded. Of interest is a comparative analysis of the ratio between frequency of IgE reactions and CD23 shedding in infectious allergies of various etiology. The aim of the study is to establish a role of the CD23 extracellular pool in pathogenetic mechanisms of infectious allergy. There were examined 678 subjects who were at apparently healthy state at the time of the examination, including 545 females and 133 males, as well as 1481 patients with verified infectious allergy who live in the Arkhangelsk Region. It has been established that patients with staphylococcal infection had markedly aggravated symptom complex of pathological reactions linked to anemia, neutropenia and deficiency of phagocytic protection. Pathological reactions in infectious allergies are accompanied by sharply increased level of sCD23 with its abnormally high concentrations ( 200 ng/ml) found in 51.7% of cases paralleled by increased level of serum IL-10 and reagins in 21.43 and 35.7% cases, respectively, along with phagocytic defense deficit observed in 85.7% as well as accumulation of CEC in 92.86%. A parallel increase in level of sCD23 and IgE is associated with increased percentage of T helpers, cytotoxic T lymphocytes, activated T cells expressing IL-2 receptor, along with upregulated of the MHC II molecules.
Impact of Candida spp. metabolites on human skin fibroblasts
Authors: Ignatova Nadezhda I. , Zaslavskaya M. I. , Alexandrova N. A. , Orlova O. E. , Melnikov V. G.
Published: May 2022

Micromycetes spp. have been increasingly involved in the etiology of infectious diseases guiding to consider them not as important as bacterial and viral pathogens. Nowadays, a lot of severe forms of candidiasis are caused by C. auris, C. albicans, whereas C. glabrata and C. krusei are of similar importance. Members of these species were selected to investigate related metabolite action on human skin fibroblasts. Candida spp. being continuously found on the epithelium and mucosal membranes resulting in to sustained interaction between microbiota and human cells. Potential to produce metabolites containing pathogenicity factors is one of the crucial events for transition to invasive candidiasis, wherein human epithelial cells build up the front line of defense barrier preventing Candida spp. invasion into deeper host tissues. The study was aimed at assessing data on metabolite effects derived from epidemiologically relevant Candida spp. on primary human skin fibroblast culture in vitro. In particular, there were analyzed Candida spp. metabolites acting on fibroblast monolayer integrity and viability in cell suspension. It was found that Candida spp. metabolites might directly cause fibroblast death so that biocidal activity was exhibited as a strain-specific feature. A direct biocidity against dermal cells was more typical for strains C. glabrata и C. krusei, less pronounced for C. albicans and very weak for C. auris. In addition, a mechanism for secretory product-related biocidal activity derived from various Candida spp. on dermal fibroblasts in vitro revealed that it resulted in fibroblasts death 1 hour after exposure that peaked at 3 hrs. Cell death was equally proceeded via apoptosis and necrosis. Of note, biocidal effect of fungal metabolites showed no correlation with Candida-related potential to cleave intercellular junctions. It was found that C. auris metabolites showing weak biocidity against some fibroblasts simultaneously resulted in more marked disruption of cell monolayer compared to other Candida spp. Perhaps, it is just a feature of C. auris that might account for its higher invasiveness potential allowing to destroy tight human tissues more effectively compared to other Candida spp.
Obtaining immunodiagnostic preparations from Toxocara canis antigens for serodiagnostics of toxocariasis in human
Authors: Kanina Irina V. , Novak A. I. , Novak M. D. , Evdokimova O. V.
Published: May 2022

Toxocariasis is a human helminthic invasion that has a wide range of hosts with epizootic distribution. The populational seropositivity in countries with a temperate climate comprises about 37%, whereas in regions with tropical climate up to 92%. Almost all age groups of the population are at risk of invasion by toxocars. The immunological method currently retains diagnostic significance for toxocariasis, because the reaction of immune system against helminths is accompanied by developing sensitization, and techniques as well as methods of collecting clinical material to identify the migratory form of toxocarosis in humans are time-consuming and invasive. The purpose of this study is to develop an immunobiological preparation based on excretory-secretory antigens from Toxocara canis larvae for serodiagnostics of larva migrans syndrome in human by using enzyme-linked immunoassay (ELISA). Antigens were obtained from Toxocara canis larvae by culturing its eggs isolated from the uterus of female nematodes in the glutamine-supplemented medium. The preparation was purified from ballast substances by centrifugation at 8000 g for 20 minutes followed by filtration through microfiltration membrane with a pore diameter of 0,050,15 microns, type MFAS-P-1 (manufactured by CJSC STC Vladipor). Blood serum of student volunteers from countries with high incidence rate of toxocariasis were tested to detect T. canis-specific antibodies. ELISA with commercial antigens Toxocara-IgG-ELISA-BEST kit was used for selection of seropositive and seronegative sera also used as a control. Diagnostic antigenic preparations with different protein concentrations were prepared to examine seropositive sera for determining optimal dose of the antigenic drugs. Results. ELISA with standard test kit allowed to detect Toxocara-IgG antibodies in 20 sera (8%) from 250 samples, what indicates about antigenic stimulation of the immune system by helminths and suspected former disease. Analyzing experimental samples allowed to find the number of seropositive data correlated with antigenic protein concentration in preparations: at a concentration of 1,96 g/ml 5,2% of positive results were detected, 1,71 g/ml 3.2%, 0.33 g/ml 0.8% (Pearsons correlation coefficient 0,94). The number of positive sera detected with commercial antigen in ELISA kit was identical to that of positive sera detected by an experimental antigen sample with a protein concentration of 2,49 g/ml. Thus, the immunodiagnostic preparations obtained by the experimental method based on the excretory-secretory antigens from Toxocara canis are characterized by high sensitivity and can be used to detect Toxocara-IgG antibodies in ELISA. The antigen preparation protein concentration of at least 2.49 g/ml is optimal and correlates whit sensitivity of the commercial antigen of the standard ELISA.
Physicochemical and antigenic properties of the urea-extracted surface structures of Yersinia pseudotuberculosis O:1b
Authors: Kryukova Anna V. , Markov E. Yu. , Nikolaev V. B. , Popova Yu. O. , Klimov V. T. , Igumnova S. V. , Andreevskaya N. M. , Ulanskaya A. V. , Zagoskina T. Yu. , Chesnokova M. V.
Published: May 2022

Immuno-serological diagnostic tools particularly identifying pathogen antigens are the most important methods of pseudotuberculosis studies. The main immunodominant and species-specific antigens located in the surface structures of the bacterial cell are of practical interest. Thereby the aim of the work was to isolate and characterize biologically active surface structures of the pseudotuberculosis microbe. Here, the living cells of Y. pseudotuberculosis 3704 (O:1b) were lysed by using 9 M urea solution to extract antigens localized in the microbial surface structures. The subcellular fractions obtained such as outer membranes (OM), urea extract (UE) and isolated protein-lipopolysaccharide complex (PLPSC) are characterized by physical and chemical parameters. The protein content in the preparations ranged from 42% to 53%. The polypeptide band of the OM preparation, UE polypeptide and PLPSC for pseudotuberculosis microbe was presented by 14, 16 and 9 major polypeptides with molecular weight ranging from 13.9 kDa to 131.5 kDa, 13.5 kDa to 101.6 kDa, and 20.7 kDa to 66.6 kDa, respectively. Proteolytically active proteins and polypeptides were detected in isolated subcellular fractions (OM and UE) by using the radial enzyme diffusion test and substrate-gel electrophoresis found to be presented by 4 and 7 polypeptides with molecular weight ranging from 28.0 kDa to 118.0 kDa and 29.2 kDa to 97.7 kDa in the OM and UE preparation, respectively. The subcellular fractions obtained are capable to exhibit immunogenic activity after inoculation to experimental animals and antigenic activity while interacting with specific antibodies in the radial immunodiffusion (RID) assay and antibodies labeled with colloidal silver nanoparticles in dot immunoassay (DIA). OM and PLPSC preparations in DIA with immunoglobulins isolated from experimental antisera and labeled with colloidal silver nanoparticles were detected at a concentration of 0.12 g/ml (dry weight), cells of strain Y. pseudotuberculosis 3704 at a concentration of 3, 9 106 m.c./ml, which is similar to the results of DIA with immunoglobulins isolated from commercial pseudotuberculosis antiserum (St. Petersburg) and labeled with nanoparticles of colloidal silver. Thus, the subcellular fractions of pseudotuberculosis microbe isolated by using urea as a lysing and decontaminating agent retain their antigenic and immunogenic properties and enzymatic activity suggesting about their potential benefits for use to improve early diagnostics of pseudotuberculosis.
Species diversity among the genus Streptomyces members isolated from clinical material
Authors: Lyamin Artem V. , Tereshchenko V. S. , Zhestkov A. V. , Ismatullin D. D.
Published: May 2022

Recently, both in Russia and around the world, the number of cases detecting acid-fast microbial members from the order Actinomycetales while developing human bacterial infections has been increased. The most important pathogens in this bacterial order are the members from the families Mycobacteriaceae, Nocardiaceae, Gordoniaceae, Tsukamurellaceae, Promicromonosporaceae, Brevibacteriaceae, Streptomycetaceae. This work is devoted to analyzing prevalence and species diversity of representatives of the family Streptomycetaceae from the genus Streptomyces isolated from clinical material upon examining for tuberculosis. There were examined 865 cultures of clinical material samples while examining for tuberculosis, in which signs of growth of contaminating microflora were revealed, as well as 316 cultures of clinical material samples obtained during examination for tuberculosis, in which signs of growth of non-tuberculosis mycobacteria (NTM) were detected. The material was collected from January 2016 to January 2019. Samples with signs of growth of contaminating microflora allowed to identify 1,093 strains, samples with signs of growth of NTM 352 strains. Among them, the number of representatives of the genus Streptomyces comprised 39 strains. All Streptomyces strains were isolated from sputum. Variety of isolated Streptomyces: S. phaeochromogenes (13 strains), S. albus (1 train), S. avidinii (1 strain), S. badius (2 strains), S. chartreusis (2 strains), S. griseus (1 strain), S. hirsutus (2 strains), S. lavendulae (3 strains), S. violaceoruber (10 strains). Species identification was not possible for 4 strains. Analyzing the data obtained, it is possible to draw a conclusion about the moderate distribution of representatives of the genus Streptomyces in pattern of contaminating microflora while examining for tuberculosis. In pattern structure of isolated microorganisms, Streptomyces accounted for 3.3%. Among the microflora isolated from culture with signs of NTM growth, Streptomyces was presented by single strains. However, it should be noted that Streptomyces was the dominant group among acid-resistant actinomycetes in pattern of contaminating microflora and accounted for 38.3%. Taking into account the fact that a significant proportion of them were isolated as microbial associations, it can be concluded that Streptomyces turned out to be classical contaminants in this case. Nevertheless, we believe that the isolation of Streptomyces in association with clinically significant NTMs can be considered as an unfavorable factor due to the fact that antibiotic resistance genes are widespread among Streptomyces and may be transmitted to other types of microorganisms from the group of acid-resistant actinomycetes, including mycobacteria. Thus, the clinical material examining for tuberculosis is an interesting research object from which various representatives of acid-fast actinomycetes, including Streptomyces, can be isolated.
The epidemiological and clinical study of patients with clostridium difficile enterocolitis in Varna, Bulgaria
Authors: Lyutsova Ekaterina D. , Gospodinova M. D.
Published: May 2022

Introduction. Clostridium difficile infections (CDI) remain a global health concern. Currently, no unified approach to the diagnostics and determining severity of these infections despite their high urgency throughout the world was proposed. The aim of the study is to identify risk factors for CDI, investigate clinical and epidemiological features of the disease course and potential for using the ATLAS scale to assess its severity. Materials and methods. 36 CDI patients hospitalized at the Infectious Disease Clinic of Varna were analyzed during the period from January 2018 until June 2019. Clinical and epidemiologic study was conducted. The diagnosis was made by using a rapid immunochromatographic test; CDI patient stratification was performed by ATLAS scoring system. Results and discussion. Within the aforementioned period, 1100 patients were hospitalized at the Infectious Disease Clinic of Varna, and CDIs were reported in 3,3% of cases. The most affected were elderly individuals (the mean age was 69,816,4 years old) most of whom were females (92%) with only 6% of males. The following risk factors were investigated: comorbidities 32 patients (88,89%), recent hospitalization 19 patients (52,78%), antibiotic use 31 patients (86,11%). Twenty-four patients (66,67%, ATLAS score 4 points) had mild CDI, whereas moderate form of CDI was observed in 12 patients (33,33%). No severe CDI or death were observed. The characteristic clinical presentation included fever, diarrhea and abdominal cramping. The treatment was implemented according to the national and international recommendations by using oral Metronidazole for 11 patients (30,56%), Vancomycin for 12 patients (33,33%), or both for 13 patients (36,11%). Conclusion. Patients at risk with symptoms of enterocolitis and a history of antibiotic use or hospitalizations should be screened for the presence of toxin-forming strains of Clostridium difficile. According to the European Centre for Disease Prevention (ECDC) the diagnostic yield of CDI may be increased by using two-step protocol, whereas the ATLAS score system may be a useful tool for routine evaluation of patients with CDI.
Avoiding Negative Side Effects of Autonomous Systems in the Open World
Authors: Saisubramanian Sandhya , Kamar Ece , Zilberstein Shlomo
Published: May 2022

Autonomous systems that operate in the open world often use incomplete models of their environment. Model incompleteness is inevitable due to the practical limitations in precise model specification and data collection about open-world environments. Due to the limited fidelity of the model, agent actions may produce negative side effects (NSEs) when deployed. Negative side effects are undesirable, unmodeled effects of agent actions on the environment. NSEs are inherently challenging to identify at design time and may affect the reliability, usability and safety of the system. We present two complementary approaches to mitigate the NSE via: (1) learning from feedback, and (2) environment shaping. The solution approaches target settings with different assumptions and agent responsibilities. In learning from feedback, the agent learns a penalty function associated with a NSE. We investigate the efficiency of different feedback mechanisms, including human feedback and autonomous exploration. The problem is formulated as a multi-objective Markov decision process such that optimizing the agent’s assigned task is prioritized over mitigating NSE. A slack parameter denotes the maximum allowed deviation from the optimal expected reward for the agent’s task in order to mitigate NSE. In environment shaping, we examine how a human can assist an agent, beyond providing feedback, and utilize their broader scope of knowledge to mitigate the impacts of NSE. We formulate the problem as a human-agent collaboration with decoupled objectives. The agent optimizes its assigned task and may produce NSE during its operation. The human assists the agent by performing modest reconfigurations of the environment so as to mitigate the impacts of NSE, without affecting the agent’s ability to complete its assigned task. We present an algorithm for shaping and analyze its properties. Empirical evaluations demonstrate the trade-offs in the performance of different approaches in mitigating NSE in different settings.
Implications of Cyber Risk for Financial Stability
Authors: Brando Danny , Kotidis Antonis , Kovner Anna , Lee Michael Junho , Schreft Stacey L.
Published: May 2022

Cyber risk, defined as the risk of loss from dependence on computer systems and digital technologies, has grown in the financial system. Cyber events, especially cyberattacks, are among the top risks cited in financial stability surveys in the United States and globally.
Dynamic Factor Copula Models with Estimated Cluster Assignments
Authors: Oh Dong Hwan , Patton Andrew J.
Published: May 2022

This paper proposes a dynamic multi-factor copula for use in high dimensional time series applications. A novel feature of our model is that the assignment of individual variables to groups is estimated from the data, rather than being pre-assigned using SIC industry codes, market capitalization ranks, or other ad hoc methods. We adapt the k-means clustering algorithm for use in our application and show that it has excellent finite-sample properties. Applying the new model to returns on 110 US equities, we find around 20 clusters to be optimal. In out-of-sample forecasts, we find that a model with as few as five estimated clusters significantly outperforms an otherwise identical model with 21 clusters formed using two-digit SIC codes.
The effectiveness of intratissue percutaneous electrolysis for the treatment of tendinopathy: a systematic review
Authors: Augustyn Divan , Paez Arsenio
Published: May 2022

Background: Tendinopathy is highly prevalent in the general public and common in athletes. It makes up nearly 50% of all sport injuries. A number of treatment techniques with varying evidence of effectiveness are currently available. Intratissue percutaneous  electrolysis (EPI) is one such modality, however little consensus exists for EPI’s efficacy or the most effective treatment parameters.
Objective: To review and appraise available evidence for Intratissue Percutaneous Electrolysis (EPI) in the treatment of tendinopathy, examining the effectiveness of EPI in conjunction with other modalities and identifying the strengths and limitations of the evidence base for EPI in order to make evidence-based recommendation for future studies of EPI.
Methods: PubMed, Embase and Scopus were searched with keywords related to EPI and tendinopathy. Grey literature searches were conducted with Embase, OpenGrey, and ProQuest. Extensive citation searching was undertaken. Randomised controlled trials (RCTs), uncontrolled and observational studies of the application of EPI in patients aged 18-65 years with Magnetic Resonance Imaging (MRI) or clinical Ultrasonography (US) confirmed diagnosis of tendinopathy were eligible.
Results: Eleven studies met inclusion criteria: six randomised control trials (RCTs) and five uncontrolled studies. Clinical trials of EPI as an adjunct modality with physical therapy reporting greater decreased pain and return to function than treatment with physical therapy alone. The evidence for EPI is limited and influenced by small sample sizes, varying treatment protocols, clinical heterogeneity and high risk of bias.
Conclusion: It is currently not possible to conclude that EPI is an effective modality for the treatment of tendinopathy. RCTs with clearly described EPI treatment protocols, larger sample sizes and intervention reporting sufficient to support reproducibility are needed to determine the effectiveness of EPI for the treatment of tendinopathy.
Bankalarda Kâr Yönetimi Uygulamaları: Türkiye’de Katılım ve Yatırım Bankaları Üzerine Bir Analiz
Authors: ÇETİN Hüseyin , GÜÇLÜ Ali
Published: May 2022

Bu çalışmada Türkiye’de faaliyette bulunan katılım ve yatırım bankalarının kâr yönetimi davranışları tespit edilmeye çalışılmıştır. Bankalar kâr yönetim faaliyetlerini genelde mali tablolarında bulunan ve tahakkuk esaslı değişkenler vasıtasıyla gerçekleştirmektedir. Çalışma bu bankaların 2005-2019 yılları arasındaki verileri analiz edilerek yapılmıştır. Analiz yöntemi olarak panel veri analizi kullanılmıştır. Analiz bulgularına göre bankaların mali tablolarında yer alan özel karşılıklar değişkenini kullanarak kâr yönetimi faaliyetinde bulundukları tespit edilmiştir. Ancak özel karşılıklar bağımlı değişkeni ile enflasyon, faiz ve büyüme gibi makroekonomik değişkenler arasında anlamlı istatistiki bir ilişki tespit edilememiştir.
Scaffolding through cognitive mapping based on diagnosing students difficulties in solving problem
Authors: BUHAERAH Buhaerah , NASİR Muhammad , JUSOFF Kamarusaman
Published: May 2022

This study shows the diagnosis of difficulties faced by students when solving problems with a system of linear equations with three variables and efforts to overcome them by providing scaffolding interventions. The approach used in this study is qualitative. The sample selection using a purposive sampling technique was made by giving three math problems, the topic of a system of linear equations with two variables, then three students were selected to be the research subjects. The selection of students is determined based on the category of communication skills and low, medium, or high mathematical abilities. The research data were obtained from 3 sources: test sheets, semi-structured interviews, and the results of student work after scaffolding was given. Several research results show students' difficulties in solving three-variable linear equation systems problems based on Polya-based cognitive mapping: first, the difficulty in understanding the problem. This difficulty arises because of mental holes that students should not have at grade levels, such as knowledge of fractions, algebra, basic concepts of triangles, and others. Second: Difficulty compiling a solution. This can be seen when students cannot correctly model contextual problems into mathematical models. Third, the implementation of the complete plan can be identified through students' mistakes when performing arithmetical algebraic operations and applying appropriate mathematical rules/principles, the leading cause of which can occur due to inaccuracy and misconceptions about mathematical concepts. The researchers tried to overcome these problems by providing Level 2 scaffolding with the techniques proposed by Angirelli, including (explaining, reviewing, and restructuring).
[RETRACTED] Monjour CBD Gummies Shocking Reviews Ingredients, Cost, Price, Where To buy! v1
Authors: CBD Gummies Uly
Published: May 2022

[RETRACTED]

Monjour's CBD Gummies are available in blueberry, strawberry, and wild berry flavors. These gummies are naturally formulated that contain all natural elements!
[RETRACTED] Kerassentials Fungus Reviews - Is It Fake Or Trusted? v1
Authors: not provided kerassentialsfungusreviews
Published: May 2022

[RETRACTED]

Kerassentials Fungus Reviews - Is It Fake Or Trusted?
Are Adolescents in One‐Parent Families a Previously Unnoticed Group in Inclusive Career Guidance?
Authors: Klein Jerusha , Driesel‐Lange Katja , Ohlemann Svenja
Published: May 2022

In Germany, schools are largely responsible for adolescents’ career development. Corresponding interventions in career guidance must take into account various endogenous and exogenous factors of individualized development to foster successful post‐school transitions. Parents, in particular, are one of the most significant influencing factors when it comes to shaping after‐school plans usually having a highly positive effect along with teacher support. Children in one‐parent families constitute a group that has received little attention so far in the context of career guidance analysis. They are at a higher risk of social decline into precarious circumstances and of living in families with lower education levels as well as less parental care time. In addition, one‐parent families more often report that they are unable to adequately support their children concerning career development, ultimately impacting the children’s post‐school transition. Based on the theoretical model of career competence, a sample from eight German schools (N = 1998) is used to investigate to what extent adolescents in one‐parent families differ from their peers in other family compositions regarding both support and development of career competence. Each school’s location and teacher support are included in the calculations. This study shows that adolescents in one‐parent families display below‐average levels concerning three of the analysed facets (occupational knowledge, exploration, and self‐regulation).
Mints-cabinet of the University of St. vladimir in the First Years of Existence. 1834–1842
Authors:   National museum of Ukrainian history, Zraziuk Zinaida
Published: May 2022

The article is devoted to the first years of existence of the Mints cabinet of the University of St. Volodymyr. Kyiv University of St. Volodymyr was created by decree of Emperor Nicholas I on November 8th (20th) 1833. However, back in September 1833, the State Trustee of the Kyiv Educational District Egor Fedorovich von Bradke issued an order according to which all collections, including numismatic ones, from the Kremenets Lyceum and Vilnius University, closed after the Polish uprising of 1830–1831, should be moved to Kyiv. Actually, this date can be considered the beginning of the existence of the Mints cabinet of St. Volodymyr. In early 1834 M. Y. Yakubovych brought numismatic collection of Kremenets Lyceum from Vilnius to Kyiv. Since at that time Kyiv University did not have its own building, several private houses in Pechersk were rented for this work. M. Y. Yakubovych reported to the University Council that the Kremenets collection consists of 8636 of ancient coins and 9200 coins and medals of the new age. In January 1834, P. O. Yarkovsky was appointed to the post of chief librarian and curator of Mints cabinet. In 1834 he was sent on a business trip to Vilnius, where he had to accept the property and library of the University of Vilnius. In September 1835, along with the library and property, the numismatic collection of Vilnius University, consisting of 2783 coins, arrived in Kyiv. In the following years, the collections of of Theophilpolskyi nobility county school, Uman basilian county school, Lutsk gymnasium were also transferred to the Mints cabinet. In April 1835, the first addition in the «new» Kyiv collection was recorded. Among the donors – the first rector of the University M. O. Maksymovych, governor G. S. Loshkarev, amateur researcher of ancient Kyiv O. S. Anenkov, etc. By the end of 1836, the collection received more than 500 coins and medals. Since 1838, one of the important sources of replenishment of the numismatic collection were treasures, which, by order of Kyiv, Podolskyi, Volyn Governor-General began to come to the university for consideration. During the period from 1838 to 1842, about 20 treasures were examined in the Mints Cabinet. In the new university building, the Mints cabinet received room № 21 on the third floor for arranging the exposition and storing coins. In fact, the Mints cabinet became the first museum institution in Kyiv.
Weight systems of ancient civilizations in Korea and Japan
Authors:   Taras Shevchenko National University of Kyiv, Zubko Andrii
Published: May 2022

Ancient civilizations in Central Asia and the Far East have appeared after a long period of developing social relations, material and spiritual culture of the population of this vast region of the Earth. In Central Asia, economic development was based on animal husbandry, and in the Far East, on land cultivation. Continuous growth of production and trade took place simultaneously with state formation that continued over millenniums. First proto – state formations of this region have created unified length, weight and volume measures that were indispensable for a successful economic development. The needs of trade necessitated the advent of monetary units that long have been closely related to weight measures. Gradually, every state saw the adoption of unified monetary – weight systems. It has long been known that the development of production and trade, social processes, state building takes place in those regions where several types of economy coexist. The type of farm is determined by natural conditions. There are several natural areas in the Far East. The first is the forest zone of Siberia and Primorie, where the population was engaged in hunting and forestry. The second – the area of steppes and deserts of Manchuria, Mongolia, the plateaus of Tibet, suitable for livestock. The third is the area of the Yellow River and Yangtze River valleys, where irrigated agriculture developed and the Chinese began cultivating rice for the first time in the world. Fourth – the area of the Yellow Sea coast, the coast of Korea, the Japanese islands, where the population was engaged in sea fishing and trade. In the interaction and complementarity of all these forms of economy arose the civilizations of the Far East. In the Far East, the geographical location of the Korean Peninsula is compared with Italy, the Japanese Islands – with England and Ireland. It is on the shores of navigable rivers, the Yellow Sea coast, the Korean Peninsula, the Japanese islands for thousands of years the most intensive development of production, domestic and foreign trade, and in modern times there was an industrial revolution. This work describes the development and mutual influence of weight systems used by ancient civilizations in Central Asia and the Far East in the course of international trade. Weight norms and their correlation with each other and with monetary denominations in every separate country have been determined.