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Despite many recent advances on cancer novel therapies, researchers have yet a long way to cure cancer. They have to deal with tough challenges before they can reach success. Nonetheless, it seems that recently developed immunotherapy-based therapy approaches such as adoptive cell transfer (ACT) have emerged as a promising therapeutic strategy against various kinds of tumors even the cancers in the blood (liquid cancers). The hematological (liquid) cancers are hard to be targeted by usual cancer therapies, for they do not form localized solid tumors. Until recently, two types of ACTs have been developed and introduced; tumor-infiltrating lymphocytes (TILs) and chimeric antigen receptor (CAR)-T cells which the latter is the subject of our discussion. It is interesting about engineered CAR-T cells that they are genetically endowed with unique cancer-specific characteristics, so they can use the potency of the host immune system to fight against either solid or liquid cancers. Multiple myeloma (MM) or simply referred to as myeloma is a type of hematological malignancy that affects the plasma cells. The cancerous plasma cells produce immunoglobulins (antibodies) uncontrollably which consequently damage the tissues and organs and break the immune system function. Although the last few years have seen significant progressions in the treatment of MM, still a complete remission remains unconvincing. MM is a medically challenging and stubborn disease with a disappointingly low rate of survival rate. When comparing the three most occurring blood cancers (i.e., lymphoma, leukemia, and myeloma), myeloma has the lowest 5-year survival rate (around 40%). A low survival rate indicates a high mortality rate with difficulty in treatment. Therefore, novel CAR-T cell-based therapies or combination therapies along with CAT-T cells may bring new hope for multiple myeloma patients. CAR-T cell therapy has a high potential to improve the remission success rate in patients with MM. To date, many preclinical and clinical trial studies have been conducted to investigate the ability and capacity of CAR T cells in targeting the antigens on myeloma cells. Despite the problems and obstacles, CAR-T cell experiments in MM patients revealed a robust therapeutic potential. However, several factors might be considered during CAR-T cell therapy for better response and reduced side effects. Also, incorporating the CAT-T cell method into a combinational treatment schedule may be a promising approach. In this paper, with a greater emphasis on CAR-T cell application in the treatment of MM, we will discuss and introduce CAR-T cell’s history and functions, their limitations, and the solutions to defeat the limitations and different types of modifications on CAR-T cells.

Adoptive cell therapy has received a great deal of interest in the treatment of advanced cancers that are resistant to traditional therapy. The tremendous success of chimeric antigen receptor (CAR)-engineered T (CAR-T) cells in the treatment of cancer, especially hematological cancers, has exposed CAR’s potential. However, the toxicity and significant limitations of CAR-T cell immunotherapy prompted research into other immune cells as potential candidates for CAR engineering. NK cells are a major component of the innate immune system, especially for tumor immunosurveillance. They have a higher propensity for immunotherapy in hematologic malignancies because they can detect and eliminate cancerous cells more effectively. In comparison to CAR-T cells, CAR-NK cells can be prepared from allogeneic donors and are safer with a lower chance of cytokine release syndrome and graft-versus-host disease, as well as being a more efficient antitumor activity with high efficiency for off-the-shelf production. Moreover, CAR-NK cells may be modified to target various antigens while also increasing their expansion and survival in vivo. Extensive preclinical research has shown that NK cells can be effectively engineered to express CARs with substantial cytotoxic activity against both hematological and solid tumors, establishing evidence for potential clinical trials of CAR-NK cells. In this review, we discuss recent advances in CAR-NK cell engineering in a variety of hematological malignancies, as well as the main challenges that influence the outcomes of CAR-NK cell-based tumor immunotherapies.

Acute myeloid leukemia (AML) is a serious, life-threatening, and hardly curable hematological malignancy that affects the myeloid cell progenies and challenges patients of all ages but mostly occurs in adults. Although several therapies are available including chemotherapy, allogeneic hematopoietic stem cell transplantation (alloHSCT), and receptor-antagonist drugs, the 5-year survival of patients is quietly disappointing, less than 30%. alloHSCT is the major curative approach for AML with promising results but the treatment has severe adverse effects such as graft-versus-host disease (GVHD). Therefore, as an alternative, more efficient and less harmful immunotherapy-based approaches such as the adoptive transferring T cell therapy are in development for the treatment of AML. As such, chimeric antigen receptor (CAR) T cells are engineered T cells which have been developed in recent years as a breakthrough in cancer therapy. Interestingly, CAR T cells are effective against both solid tumors and hematological cancers such as AML. Gradually, CAR T cell therapy found its way into cancer therapy and was widely used for the treatment of hematologic malignancies with successful results particularly with somewhat better results in hematological cancer in comparison to solid tumors. The AML is generally fatal, therapy-resistant, and sometimes refractory disease with a disappointing low survival rate and weak prognosis. The 5-year survival rate for AML is only about 30%. However, the survival rate seems to be age-dependent. Novel CAR T cell therapy is a light at the end of the tunnel. The CD19 is an important target antigen in AML and lymphoma and the CAR T cells are engineered to target the CD19. In addition, a lot of research goes on the discovery of novel target antigens with therapeutic efficacy and utilizable for generating CAR T cells against various types of cancers. In recent years, many pieces of research on screening and identification of novel AML antigen targets with the goal of generation of effective anti-cancer CAR T cells have led to new therapies with strong cytotoxicity against cancerous cells and impressive clinical outcomes. Also, more recently, an improved version of CAR T cells which were called modified or smartly reprogrammed CAR T cells has been designed with less unwelcome effects, less toxicity against normal cells, more safety, more specificity, longer persistence, and proliferation capability. The purpose of this review is to discuss and explain the most recent advances in CAR T cell-based therapies targeting AML antigens and review the results of preclinical and clinical trials. Moreover, we will criticize the clinical challenges, side effects, and the different strategies for CAR T cell therapy.

© 2020 Elsevier B.V. Herein, the synthesis, design, and the physicochemical characterization of phosphorus functionalized thiazolotriazole (PFT) compound are presented. The PFT tests on the biological activity revealed butyrylcholinesterase inhibition that was confirmed and explained with molecular docking studies. The pronounced reduction of optical density and biological activity was found as a result of irradiation of the PFT water solution with laser beam at wavelength 266 nm. The observed phenomenon was explained on the base of molecular dynamics, docking, and density functional theory modeling by the formation of PFT conformers via laser-induced phosphonate group twisting. The reorganization of the PFT geometry was found to be a reason of butyrylcholinesterase inhibition mechanism change and the site-specificity loss. These results demonstrate that PFT combines photoswitching and bioactive properties in one molecule that makes it promising as a molecular basis for the further design of bioactive substances with photosensitive properties based on the mechanism of the phosphonate group phototwisting.

© 2019, Springer Science+Business Media, LLC, part of Springer Nature. The objective of the present study was to elucidate the effect of perinatal cobalt chloride (CoCl2) exposure on extramedullary erythropoiesis in suckling mice in relation to iron (Fe) content and transferrin receptor (TfR) expression. Pregnant ICR mice were subjected to a daily dose of 75 mg CoCl2/kg body weight 2–3 days prior and 18 days after delivery. Co exposure significantly increased erythrocyte count (RBC), and reduced the erythrocytic parameters mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) in the offspring. Total iron-binding capacity (TIBC) was decreased while bilirubin values were ~ 1.2-fold higher in the metal-exposed mice. Perinatal CoCl2 treatment also induced pathohistological changes in target organs (spleen, liver, and kidneys) as altered organ weight indices, leukocyte infiltration, abundant Kupffer cells in the liver, increased mesangial cellularity, and reduced capsular space in the kidney. CoCl2 administration induced significant 68-, 3.8-, 41.3-, and 162-fold increase of Co content in the kidney, spleen, liver, and RBC, respectively. Fe content in the target organs of CoCl2-treated mice was also significantly elevated. Immunohistochemical analysis demonstrated that TfR1 was well expressed in the renal tubules, hepatocytes, the red pulp, and marginal zone of white pulp in the spleen. TfR2 showed similar expression pattern, but its expression was stronger in the spleen and liver samples of Co-treated mice compared with that of the untreated controls. The results demonstrate that exposure to CoCl2 during late pregnancy and early postnatal period affects body and organ weights and alters hematological and biochemical parameters, iron content, and TfR expression in target organs.

© 2019, Springer Science+Business Media, LLC, part of Springer Nature. The objective of the present study was to elucidate the effect of perinatal cobalt chloride (CoCl2) exposure on extramedullary erythropoiesis in suckling mice in relation to iron (Fe) content and transferrin receptor (TfR) expression. Pregnant ICR mice were subjected to a daily dose of 75 mg CoCl2/kg body weight 2–3 days prior and 18 days after delivery. Co exposure significantly increased erythrocyte count (RBC), and reduced the erythrocytic parameters mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) in the offspring. Total iron-binding capacity (TIBC) was decreased while bilirubin values were ~ 1.2-fold higher in the metal-exposed mice. Perinatal CoCl2 treatment also induced pathohistological changes in target organs (spleen, liver, and kidneys) as altered organ weight indices, leukocyte infiltration, abundant Kupffer cells in the liver, increased mesangial cellularity, and reduced capsular space in the kidney. CoCl2 administration induced significant 68-, 3.8-, 41.3-, and 162-fold increase of Co content in the kidney, spleen, liver, and RBC, respectively. Fe content in the target organs of CoCl2-treated mice was also significantly elevated. Immunohistochemical analysis demonstrated that TfR1 was well expressed in the renal tubules, hepatocytes, the red pulp, and marginal zone of white pulp in the spleen. TfR2 showed similar expression pattern, but its expression was stronger in the spleen and liver samples of Co-treated mice compared with that of the untreated controls. The results demonstrate that exposure to CoCl2 during late pregnancy and early postnatal period affects body and organ weights and alters hematological and biochemical parameters, iron content, and TfR expression in target organs.

© 2019, © 2019 Informa UK Limited, trading as Taylor  &  Francis Group. Introduction: Due to the polymorphic clinical presentations and manifestations of systemic lupus erythematosus (SLE), biomarkers with enough diagnostic and prognostic value are of paramount importance. Recently, anti-double stranded DNA (anti-dsDNA) auto-antibodies have been proposed to monitor the response to different therapies. It has also been suggested that they should be employed as entry markers in trial studies. However, their clinical use remains still debated and, sometimes, controversial, due to conflicting findings reported. Areas covered: Through an extensive literature review, we evaluated changes in anti-dsDNA auto-antibodies levels before and after the administration of the treatment (either biological or non-biological). Expert opinion: Anti-dsDNA auto-antibodies related findings are still difficult to compare mainly because of the different detecting methods employed, even though in most studies included in this review a consistent decreasing pattern after the treatment seems to emerge. Hence, if properly standardized, anti-dsDNA auto-antibody profile may be a reliable biomarker to monitor the effectiveness of biologics as well as of non-biological drugs, especially if grouped in composite outcomes scores, such as the ‘Lupus Multivariable Outcome Score’ (LUMOS) or measured with other biomarkers, such as anti-nucleosome auto-antibodies. We recommend the assessment of anti-dsDNA auto-antibodies levels in both daily practice and research settings.

This study aimed to investigate the effects of propofol through evaluating its interaction with nitric oxide (NO), hydrogen sulfide (H2S), and carbon monoxide (CO). Wistar male rats were divided in 4 groups: (1) bolus injection of propofol (1% 10 mg/mL, 100 mg/kg bw, i.p.); (2) Nω-nitro-l-arginine methyl ester (L-NAME; NO synthase inhibitor, 60 mg/kg bw, i.p.) + bolus injection of propofol (1% 10 mg/mL, 100 mg/kg bw, i.p.); (3) DL-propargylglycine (DL-PAG; H2S synthase inhibitor, 50 mg/kg bw, i.p.) + bolus injection of propofol (1% 10 mg/mL, 100 mg/kg bw, i.p.); (4) zinc protoporphyrin IX (ZnPPIX; CO synthase inhibitor, 50 μmol/kg bw, i.p.) + bolus injection of propofol (1% 10 mg/mL, 100 mg/kg bw, i.p.). Increased levels of albumins, low-density lipoproteins, alkaline phosphatase, amylase, high-sensitivity Troponin T, and fibrinogen were found in L-NAME + propofol group. Platelet crit, platelet count, total cholesterol, and high-density lipoproteins were elevated in ZnPPIX + propofol group. Hydrogen peroxide was increased in all groups treated with gasotransmitters inhibitors. Reduced glutathione was reduced in all groups, superoxide dismutase activity only in L-NAME + propofol. The effect of propofol on various biochemical, haematological, and oxidative stress markers may be at least in part mediated through interaction with 3 estimated gasotransmitters.

© 2019, Springer-Verlag GmbH Germany, part of Springer Nature. Astrocytes, a class of morphologically and functionally diverse primary homeostatic neuroglia, are key keepers of neural tissue homeostasis and fundamental contributors to brain defence in pathological contexts. Failure of astroglial support and defence facilitate the evolution of neurological diseases, which often results in aberrant synaptic transmission, neurodegeneration and death of neurones. In Alzheimer’s disease (AD), astrocytes undergo complex and multifaceted metamorphoses ranging from atrophy with loss of function to reactive astrogliosis with hypertrophy. Astroglial asthenia underlies reduced homeostatic support and neuroprotection that may account for impaired synaptic transmission and neuronal demise. Reactive astrogliosis which mainly develops in astrocytes associated with senile plaque is prominent at the early to moderate stages of AD manifested by mild cognitive impairment; downregulation of astrogliosis (reflecting astroglial paralysis) is associated with late stages of the disease characterised by severe dementia. Cell-specific therapies aimed at boosting astroglial supportive and defensive capabilities and preventing astroglial paralysis may offer new directions in preventing, arresting, or even curing AD-linked neurodegeneration.

© 2019 The Author(s) Antiviral interferons (IFN-alpha/beta) are possibly responsible for the high tolerance of bats to zoonotic viruses. Previous studies focused on the IFN system of megabats (suborder Yinpterochiroptera). We present statistically robust RNA sequencing (RNA-seq) data on transcriptomes of cells from the “microbat” Myotis daubentonii (suborder Yangochiroptera) responding at 6 and 24 h to either an IFN-inducing virus or treatment with IFN. Our data reveal genes triggered only by virus, either in both humans and Myotis (CCL4, IFNL3, CH25H), or exclusively in Myotis (STEAP4). Myotis cells also express a series of conserved IFN-stimulated genes (ISGs) and an unusually high paralog number of the antiviral ISG BST2 (tetherin) but lack several ISGs that were described for megabats (EMC2, FILIP1, IL17RC, OTOGL, SLC24A1). Also, in contrast to megabats, we detected neither different IFN-alpha subtypes nor an unusually high baseline expression of IFNs. Thus, Yangochiroptera microbats, represented by Myotis, may possess an IFN system with distinctive features. Biological Sciences; Immunity; Omics; Transcriptomics

© 2019, Springer Science+Business Media, LLC, part of Springer Nature. Modern antimicrobial preservatives authorized for use in dosage form technology are reviewed. The nomenclature and various classifications of preservatives according to chemical nature, mechanism and spectrum of antimicrobial action, optimum effective concentrations for antimicrobial activity, and separate factors affecting the activity of antimicrobial preservatives in various dosage forms, e.g., optimum solution pH values and specific adsorbents reducing preservative activity, are presented. Antimicrobial preservatives used widely in pharmaceutical technology, i.e., parabens, sorbic acid and its salts, benzoic acid and its salts, and benzalkonium chloride, are discussed in detail. Ascience-based approach to selecting antimicrobial preservatives is shown to produce the most stable and safest medicines.

© 2019, Pediatria Ltd. All rights reserved. Objective of the research: To study the effect of different temperature conditions and shelf life of expressed mother and donor breast milk (BM) on its microbiological safety. Materials and methods: N open prospective study was performed, which included 120 lactating women. BM samples were microbiologically evaluated under various storage conditions. Seeding of biological material was performed by a semi-quantitative method. Species identification of the obtained microorganisms was performed using a MALDI-TOF-MS Biotyper MicroFlex mass spectrometer and a VITEK bacteriological analyzer. Results: In 66% of women, samples of expressed BM showed an increase (103–105 CFU/ml) of conditionally pathogenic bacteria (CPB) with a predominance of S. epidermidis (55%). None of the samples of the expressed BM stored for 3 hours at room temperature (t° + 23°C) during the day in the refrigerator (t° + 4–6°C) and for 1 month in the freezer (t ° –18°C), the growth of CPB was not recorded. However, a decrease in the growth of bacteria total number was revealed, including S. epidermidis, when storing expressed milk for 24 hours at t° + 4–6°С and for 1 month at t° –18°С. It was found that BM pasteurization leads to a significant decrease in the number of CPB. The study revealed no increase in the total number of bacteria during storage of donor milk at t° –18°C for both 1 and 3 months.

© 2019 The Journal of Rheumatology. All rights reserved. Objective. To determine whether neutropenia is associated with increased risk for infection in patients with systemic juvenile idiopathic arthritis (sJIA) and polyarticular-course juvenile idiopathic arthritis (pcJIA) treated with tocilizumab (TCZ). Methods. Data up to Week 104 from 2 phase III trials of intravenous TCZ in sJIA (n = 112; ClinicalTrials.gov, NCT00642460) and pcJIA (n = 188; ClinicalTrials.gov, NCT00988221) were pooled. Worst common toxicity criteria grade and lowest observed absolute neutrophil count (ANC) were identified for each patient. Associations between patient characteristics and lowest observed ANC were tested using univariate regression analysis. Infection and serious infection rates per 100 patient-years (PY) in periods associated with grades 1/2 and 3/4 neutrophil counts were compared with rates associated with normal neutrophil counts. Results.ANC decreased to grade ≥ 3 in 25.0% and 5.9% of sJIA and pcJIA patients, respectively, and decreases were transient. Young age (p = 0.047) and methotrexate use (p = 0.012) were positively associated with neutropenia in patients with sJIA but not in patients with pcJIA. The rate of serious infections in patients with sJIA (10.9/100 PY; 95% CI 6.8-16.5) tended to be higher than in patients with pcJIA (5.2/100 PY; 95% CI 3-8.5). No increase in rates of serious or nonserious infections was observed during periods of neutropenia in either trial. Conclusion. Patients with JIA treated with TCZ experienced transient neutropenia that was not associated with an increased number of infections.

© 2018 Elsevier Ltd In this review, we describe dielectric properties of biological tissues and liquids in the context of terahertz (THz) biophotonics. We discuss a model of the THz dielectric permittivity of water and water-containing media, which yields analysis of the relaxation and damped resonant molecules modes. We briefly describe modern techniques of THz spectroscopy and imaging employed in biophotonics with a strong emphasize on a THz time-domain spectroscopy. Furthermore, we consider the methods of sub-wavelength resolution THz imaging and the problem of THz wave delivery to hard to access tissues and internal organs. We consider the THz dielectric properties of biological solutions and liquids. Although strong absorption by water molecules prevents THz-waves from penetration of hydrated tissues and probing biological molecules in aqueous solutions, we discuss approaches for overcoming these drawbacks – novel techniques of freezing and temporal dehydration by application of hyperosmotic agents which have a potential for cancer detection. We review recent applications of THz technology in diagnosis of malignancies and aiding histology paying particular attention to the origin of contrast observed between healthy and pathological tissues. We consider recent applications of THz reflectometry in sensing the thinning dynamics of human pre-corneal tear film. Modern modalities of THz imaging, which relies on the concepts of multi-spectral and multi-temporal domains and employing the principles of color vision, phase analysis and tomography are discussed. Novel methods of THz spectra analysis based on machine learning, pattern recognition, chemical imaging and the revealing of the spatial distribution of various substances in a tissue, are analyzed. Advanced thermal model describing biological object irradiated by THz waves and phantoms mimicking the optical properties of tissues at THz frequencies are presented. Finally, application of the high-resolution THz spectroscopy in analytic chemistry, biology and medicine are described.

© 2018 IEEE. We have proposed a method of THz solid immersion microscopy, which yields imaging soft biological tissues with the sub-wavelength resolution up to 0.2-wavelengths. To achieve this advanced resolution, it employs a solid immersion phenomenon - i.e. a reduction in the dimensions of the THz beam caustic by its formation on a small distance behind the medium featuring high refractive index. We have assembled an experimental setup, which realizes the principles of the THz solid immersion microscopy, and proposed an approach for handling the soft tissue at the object plane. This setup uses a backward-wave oscillator, as a source of continuous-wave THz radiation, and a Golay cell, as a detector of the THz field intensity. We have examined the resolution of the THz solid immersion microscopy using both numerical simulations and experimental studies. Finally, in order to highlight the prospective of the proposed THz imaging modality, we have applied the experimental setup for imaging of representative examples of biological tissues.

Copyright © 2018. All rights reserved. Objective: Evaluate growth in patients with polyarticular-course juvenile idiopathic arthritis (pcJIA) treated with tocilizumab (TCZ) for up to 2 years in a phase III trial. Methods: Patients with pcJIA lasting at least 6 months and inadequate response to methotrexate received open-label TCZ intravenously every 4 weeks (randomly assigned to 8 or 10 mg/kg if they weighed < 30 kg; received 8 mg/kg if they weighed ≥ 30 kg) for 16 weeks. Patients with JIA American College of Rheumatology 30 response at Week 16 were randomly assigned to TCZ or placebo for 24 weeks, with an open-label extension through Week 104. Mean ± SD height velocity (cm/yr) and World Health Organization (WHO) height SD score (SDS) were measured in patients receiving ≥ 1 dose of TCZ who did not receive growth hormone and in patients whose baseline Tanner stage was ≤ 3. Results: The study included 187 of 188 patients (99.5%) with mean WHO height SDS -0.5 ± 1.2, which was unrelated to age or disease duration (Spearman rank correlations r = 0.08 and r = -0.12, respectively). There were 123 patients at Tanner stage ≤ 3 at baseline, among whom 103 completed the study with 2 years of height SDS data. Mean height SDS increased from baseline to year 2 (+0.40, p < 0.0001). In 74 of 103 patients (72%), height SDS was greater than at baseline, and mean height velocity was 6.7 ± 2.0 cm/year. Conclusion. Among patients with pcJIA at Tanner stage ≤ 3 at baseline, 72% (74/103) had increased height SDS at the end of the study.

© 2018, © 2018 Taylor  &  Francis. “The Four Horsemen” was the nickname given to the four neurologists—Abraham Baker, Francis Forster, Russell DeJong, and Adolph Sahs—who were most instrumental in founding and developing the American Academy of Neurology (AAN) beginning around 1948. Forster later humorously added “and their nags” to the epithet to reflect the cohesion of the founders and their wives. This article presents the personal recollections of these founders from correspondence and oral histories. When the AAN was founded, private-practice neurologists and residents were excluded from the academically oriented and restrictive American Neurological Association (ANA). Baker conceptualized the AAN as an inclusive professional society that would accept all neurologists of whatever age and level of training, and that would strive to strengthen their knowledge, competencies, and skills through continuing medical education and guideline development. Baker recruited supportive colleagues to help create and develop the organization. Their intention was not to compete with or subvert the ANA, but to offer an inclusive professional organization for all neurologists. Nevertheless, their efforts produced opposition among ANA members. To defuse the antagonism, neurologist Alphonse Vonderahe proposed an influential House–Senate formulation of the AAN–ANA relationship, modeled after the U.S. Congress, both as a supporting rationale for the AAN and as a conceptual model for the functional relationship between the two organizations. The inclusive approach greatly augmented the ranks of the fledgling AAN, whereas those of the ANA stayed relatively stagnant, with the AAN ultimately becoming the dominant neurological society. These neurologic pioneers laid the groundwork for an invigorated, well-trained, scientifically based specialty of neurology in the second half of the twentieth century.

© 2018, The Author(s). Efficacy and safety of tocilizumab (TCZ), an interleukin-6 receptor inhibitor, were demonstrated in juvenile idiopathic arthritis (JIA) with polyarticular course (pJIA) in the CHERISH trial. This observational, III phase study evaluated long-term treatment of TCZ in pJIA patients was conducted by members of the Pediatric Rheumatology International Trials Organization (PRINTO) from Poland and Russia. Forty-one patients, who had completed the CHERISH core study (104 weeks), were extensionally treated with TCZ (8 mg/kg, intravenous infusion every 4 weeks). Total treatment time was from 131 to 193 weeks. The long-term safety (the primary endpoint) and efficacy were evaluated. All patients achieved ACR70 response in the core study and continued to achieve at least ACR50 response up to week 24 of this study. The safety population comprised 46.41 patient-years (PY). Rates per 100 PY of adverse (AEs) and serious events (SAEs) were 181.0 and 6.46, respectively. Pharyngitis and respiratory tract infections were the most common AEs. Except one AE (severe neutropenia), all others were classified as mild (24.4%) or moderate (29.3%). The incidence of SAEs was low (7.3%). No new safety findings were observed. The safety profile of over 2.5-year treatment with TCZ is consistent with the pre-marketing CHERISH clinical trial. Presented data and continued efficacy response support the use of TCZ in pJIA. EUDRACT No: 2011-001607-12. https://clinicaltrials.gov/ct2/show/study/NCT01575769?term=ML27783.

© 2018. ASERS Publishing. All rights reserved. The paper understands cross-border natural resources as a totality of characteristics of local ecological systems, which can act as regulators of human’s life space. Authors state that uniqueness of this phenomenon is defined by the fact that all natural resources act as a single system of planet scale. The problem distinguished in the paper is based on the fact that in the period of ecological systems and natural resources development a little attention is paid to cross-border management on the part of nations they belong to. The research subject is an indicator of stability and quality of management of cross-border natural resources in the aspect of their even existing and carrying out of their functions. Scientific novelty of the research is that it’s proved for the first time that each ecological system has s number of parameters, one of which shows how much it resistant to human impact. The system of providing biodiversity is one of such parameters. In the paper the legal characteristics of the issue are identified with the actual state of interstate cooperation and the opportunity of its expansion within the already existing interstate formation is determined. The example of such formation is European Union. The areas of further research can be defined as an expansion of specified cooperation of Asian and South American continent.