Bulk and Surface Magnetization of Co atoms in Rutile Ti_[1-x]Co_xO_[2-delta] Thin Films Revealed by X-Ray Magnetic Circular Dichroism

We have studied magnetism in Ti_[1-x]Co_xO_[2-\delta] thin films with various x and \delta by soft x-ray magnetic circular dichroism (XMCD) measurements at the Co L_[2,3] absorption edges. The estimated ferromagnetic moment by XMCD was 0.15-0.24 \mu\beta/Co in the surface, while in the bulk it was 0.82-2.25 \mu\beta/Co, which is in the same range as the saturation magnetization of 1.0-1.5 \mu\beta/Co. Theseresults suggest that the intrinsic origin of the erromagnetism. The smaller moment of Co atom at surface is an indication of a magnetically dead layer of a few nm thick at the surface of the thin films.Comment: This Paper is accepted in J. of Phys: Conds. Matte

Parkinson's Disease in Central Asian and Transcaucasian Countries: A Review of Epidemiology, Genetics, Clinical Characteristics, and Access to Care

Our understanding of Parkinson’s disease (PD) has significantly accelerated over the last few years, but predominant advances have been made in developed, Western countries. Little is known about PD in the Central Asian (CA) and Transcaucasian (TC) countries. Here, we review the clinical characteristics, treatments used, epidemiology, and genetics of PD in CA and TC countries via a methodological search in MEDLINE, EMBASE, Scopus, Web of Science, and Google Scholar databases. For the acquisition of PD care-related data, the search was extended to the local web resources. Our findings showed that PD prevalence in the region is averaging 62 per 100,000 population. The mean age of onset is 56.4 ± 2.8 in females and 63.3 ± 3.5 in males. Large-scale national studies on PD prevalence from the region are currently lacking. A limited number of genetic studies with small cohorts and inconclusive results were identified. The G2019S LRRK2 mutation, the commonest mutation in PD worldwide, was found in 5.7% of patients with idiopathic PD and 17.6% of familial cases in 153 Uzbek patients. Our review highlighted systematic deficiencies in PD health care in the region including lacks of neurologists specializing in PD, delays in PD diagnosis, absence of specialized PD nurses and PD rehab services, limited access to PD medications and surgery, and the unavailability of PD infusion therapies. Overall, this article demonstrated the paucity of data on this common neurological disorder in CA and TC countries and identified a number of healthcare areas that require an urgent consideration. We conclude that well-designed large-scale epidemiological, genetic, and clinical studies are desperately needed in this region. Healthcare professionals, local and national institutions, and stakeholders must come together to address deficiencies in PD healthcare systems in CA and TC countries

Elevated levels of proinflammatory cytokines in cerebrospinal fluid of multiple sclerosis patients

© 2017 Khaibullin, Ivanova, Martynova, Cherepnev, Khabirov, Granatov, Rizvanov and Khaiboullina.Multiple sclerosis (MS) is an autoimmune neurodegenerative disease characterized by chronic brain inflammation. Leukocyte infiltration of brain tissue causes inflammation, demyelination, and the subsequent formation of sclerotic plaques, which are a hallmark of MS. Activation of proinflammatory cytokines is essential for regulation of lymphocyte migration across the blood-brain barrier. We demonstrate increased levels of many cytokines, including IL-2RA, CCL5, CCL11, MIF, CXCL1, CXCL10, IFNγ, SCF, and TRAIL, were upregulated in cerebrospinal fluid (CSF), whereas IL-17, CCL2, CCL3, CCL4, and IL-12(p40) were activated in MS serum. Interaction analysis of cytokines in CSF demonstrated a connection between IFNγ and CCL5 as well as MIF. Many cells can contribute to production of these cytokines including CD8 and Th1 lymphocytes and astrocytes. Therefore, we suggest that IFNγ released by Th1 lymphocytes can activate astrocytes, which then produce chemoattractants, including CCL5 and MIF. These chemokines promote an inflammatory milieu and interact with multiple chemokines including CCL27 and CXCL1. Of special note, upregulation of CCL27 was found in CSF of MS cases. This observation is the first to demonstrate CCL27 as a potential contributor of brain pathology in MS. Our data suggest that CCL27 may be involved in activation and migration of autoreactive encephalitogenic immune effectors in the brain. Further, our data support the role of Th1 lymphocytes in the pathogenesis of brain inflammation in MS, with several cytokines playing a central role

A glimpse of the genetics of young-onset Parkinson's disease in Central Asia

Background: Knowledge of the genetic background of many human diseases is currently lacking from genetically undiscovered regions, including Central Asia. Kazakhstan is the first Central Asian country where the genetic studies of Parkinson's disease (PD) have been emerging since it had become a member of the International Parkinson Disease Genomics Consortium. Here we report on the results of whole‐exome sequencing (WES) in 50 young‐onset PD (YOPD) cases from Kazakhstan. / Methodology: WES was performed on 50 unrelated individuals with YOPD from Kazakhstan. Exome data were screened for novel/ultra‐rare deleterious variants in known and candidate PD genes. Copy number variants and small indels were also called. / Results: Only three cases (6%) were found to be positive for known PD genes including two unrelated familial PD cases with LRRK2 p.(Arg1441Cys) and one case with a homozygous pathogenic PRKN p.(Arg84Trp) variant. Four cases had novel and ultra‐rare variants of uncertain significance in LRRK2, DNAJC13, and VPS35. Novel deleterious variants were found in candidate Mendelian PD genes including CSMD1, TNR, EIF4G1, and ATP13A3. Eight cases harbored the East Asian‐specific LRRK2 p.(Ala419Val) variant. Conclusions The low diagnostic yield in our study might imply that a significant proportion of YOPD cases in Central Asia remains unresolved. Therefore, a better understanding of the genetic architecture of PD among populations of Central Asian ancestry and the pathogenicity of numerous rare variants should be further investigated. WES is a valuable technique for large‐scale YOPD genetic studies in Central Asia

Разработка компьютерного модуля для прогнозирования и оценки эффективности базисной терапии рассеянного склероза

in the present research is shown that using information and computer technologies can automate the pharmacoeconomic evaluation of the rationality of the appointment and a forecast of efficiency of basic therapy of multiple sclerosis. Criteria of efficiency of immunomodulatory therapy of the multiple sclerosis, taking into account the individual characteristics of each patient, are selected.в данной работе показано, что благодаря использованию информаци онно-компьютерных технологий, возможно автоматизировать фармакоэкономическую оценку рациональности назначения и прогноза эффективности базисной терапии рассеянного склероза. Отобраны критерии эффективности иммуномодулирующей терапии рассеянного склероза, учитывающие индивидуальные особенности каждого больного

Divergent immunomodulation capacity of individual myelin peptides-components of liposomal therapeutic against multiple sclerosis

© 2017 Ivanova, Khaiboullina, Gomzikova, Martynova, Ferreira, Garanina, Sakhapov, Lomakin, Khaibullin, Granatov, Khabirov, Rizvanov, Gabibov and Belogurov. Multiple sclerosis (MS) is an autoimmune disease characterized by demyelination and consequent neuron injury. Although the pathogenesis of MS is largely unknown, a breach in immune self-tolerance to myelin followed by development of autoreactive encephalitogenic T cells is suggested to play the central role. The myelin basic protein (MBP) is believed to be one of the main targets for autoreactive lymphocytes. Recently, immunodominant MBP peptides encapsulated into the mannosylated liposomes, referred as Xemys, were shown to suppress development of experimental autoimmune encephalomyelitis, a rodent model of MS, and furthermore passed the initial stage of clinical trials. Here, we investigated the role of individual polypeptide components [MBP peptides 46-62 (GH17), 124-139 (GK16), and 147-170 (QR24)] of this liposomal peptide therapeutic in cytokine release and activation of immune cells from MS patients and healthy donors. The overall effects were assessed using peripheral blood mononuclear cells (PBMCs), whereas alterations in antigen-presenting capacities were studied utilizing plasmacytoid dendritic cells (pDCs). Among three MBP-immunodominant peptides, QR24 and GK16 activated leukocytes, while GH17 was characterized by an immunosuppressive effect. Peptides QR24 and GK16 upregulated CD4 over CD8 T cells and induced proliferation of CD25 + cells, whereas GH17 decreased the CD4/CD8 T cell ratio and had limited effects on CD25 + T cells. Accordingly, components of liposomal peptide therapeutic differed in upregulation of cytokines upon addition to PBMCs and pDCs. Peptide QR24 was evidently more effective in upregulation of pro-inflammatory cytokines, whereas GH17 significantly increased production of IL-10 through treated cells. Altogether, these data suggest a complexity of action of the liposomal peptide therapeutic that does not seem to involve simple helper T cells (Th)-shift but rather the rebalancing of the immune system

РЕЗУЛЬТАТЫ ОТКРЫТОГО СРАВНИТЕЛЬНОГО РАНДОМИЗИРОВАННОГО КЛИНИЧЕСКОГО ИССЛЕДОВАНИЯ ЭФФЕКТИВНОСТИ И БЕЗОПАСНОСТИ ПРЕПАРАТА АКСОГЛАТИРАН® ФС (ЗАО «Ф-СИНТЕЗ», РОССИЯ) В СРАВНЕНИИ С ПРЕПАРАТОМ КОПАКСОН®-ТЕВА (ТЕВА ФАРМАЦЕВТИЧЕСКИЕ ПРЕДПРИЯТИЯ ЛТД., ИЗРАИЛЬ) У ПАЦИЕНТОВ С РЕЦИДИВИРУЮЩИМ РЕМИТТИРУЮЩИМ РАССЕЯННЫМ СКЛЕРОЗОМ

Objective. Comparison of Axoglatiran® FS (F-Sintez,  Russia) and Copaxone®-Teva (Teva Pharmaceutical Industries Ltd.,  Israel) efficiency and safety in patients with relapsing-remitting multiple sclerosis. Materials and methods. In the study 150 patients with relapsing-remitting multiple sclerosis were randomized into 2 groups: patients in the 1st group (n = 100) received treatment with Axoglatiran® FS, patients in the 2nd group (n = 50) received treatment with Copaxone®-Teva. Vital signs of every patient in the study were monitored accompanied by physical examinations, neurological examinations with EDSS (Expanded Disability Status Scale) and MSFC (Multiple Sclerosis Functional Composite) evaluations, magnetic resonance imaging of the brain and lab tests. Results. Mean age (M ± SD) of the patients in the 1st group was 32.8 ± 8.7 years (20–54  years), percentages of men and women were 34 and 66 % respectively, mean age of multiple sclerosis onset was 27.93 ± 7.72 years (11–48 years). Median (Me), lower and upper quartiles estimates [LQ; UQ] on the EDSS scale were 2 [1.5; 3.0] steps (1.0–4.5  steps). In the 2nd group mean age of the patients was 35.2 ± 9.5 years (18–57  years), percentages of men and women were 24 and 76 % respectively, mean age of multiple sclerosis onset was 26.5 ± 6.9 years (18–47  years), EDSS estimates were 2.25 [1.5; 3.5] steps (1–5  steps). In the 1st group 88 (88 %) patients completed the study, in the 2nd  group 44 (88 %) patients completed the study. Among them in 73 (82.95 %) patients in the 1st group and 34 (77.27 %) patients in the 2nd  group the disease didn’t exacerbate (p > 0.05). In both groups no progression according to the EDSS and MSFC scale was observed (p > 0.05). Magnetic resonance imaging data showed that dynamics of the total number of T2 lesions, contrast-enhancing T1 lesions, atrophy degree estimated using internuclear index were comparable in both groups (p > 0.05). Safety profiles of Axoglatiran® FS and Copaxone®Teva were evaluated as satisfactory in both groups: local reactions were the most common adverse event (57.7 and 63.0 % in the 1st  and 2nd groups respectively).Conclusion. Efficiency, safety and tolerability of Axoglatiran® FS is comparable with the reference medicine Copaxone®-Teva in patients with relapsing-remitting multiple sclerosis. This result allows to recommend the use of Axoglatiran® FS in clinical practice.Цель исследования. Сравнение эффективности и безопасности применения препарата Аксоглатиран®  ФС (ЗАО «Ф-Синтез», Россия) и препарата Копаксон®-Тева (Тева Фармацевтические Предприятия Лтд., Израиль) у пациентов с рецидивирующим ремиттирующим рассеянным склерозом.Материалы и методы. Всего в исследование были включены 150 больных рецидивирующим ремиттирующим рассеянным склерозом, рандомизированных в 2 группы: пациенты 1-й группы (n = 100) получали лечение препаратом Аксоглатиран® ФС, пациенты 2-й группы (n = 50) – препаратом Копаксон®-Тева. Всем больным осуществляли анализ жизненно важных показателей, физикальный осмотр, неврологический осмотр с оценкой по EDSS (ExpandedDisabilityStatusScale, расширенная шкала оценки степени инвалидизации), MSFC (MultipleSclerosisFunctionalComposite, комплексная функциональная шкала), магнитно-резонансную томографию головного мозга, лабораторные анализы.Результаты. Средний возраст (M ± SD) пациентов 1-й группы составил 32,8 ± 8,7 года (20–54 года), доля мужчин и женщин – 34 и 66 % соответственно, средний возраст дебюта рассеянного склероза – 27,93 ± 7,72 года (11–48 лет). Оценка медианы (Me), нижнего и верхнего квартилей [LQ; UQ] по шкале EDSS – 2 [1,5; 3,0] балла (1,0–4,5 балла). Во 2-й группе средний возраст пациентов – 35,2 ± 9,5 года (18–57 лет), доля мужчин и женщин – 24 и 76 % соответственно, средний возраст дебюта рассеянного склероза – 26,5 ± 6,9 года (18–47  лет), оценка по EDSS – 2,25 [1,5; 3,5] балла (1–5  баллов). В 1-й группе исследование в полном объеме завершили 88 (88 %) пациентов, во 2-й – 44 (88 %). Из них 73 (82,95 %) больных 1-й группы и 34 (77,27 %) пациента 2-й группы не имели обострений (p > 0,05). В обеих группах прогрессирования по оценкам EDSS и MSFC не отмечено (p > 0,05). По данным магнитно-резонансной томографии динамика общего количества Т2-очагов, контрастируемых Т1-очагов, объема Т2-очагов, критерия атрофии по межъядерному показателю в обеих группах была сопоставимой (p > 0,05). Профиль безопасности применения препаратов Аксоглатиран® ФС и Копаксон®-Тева был оценен как удовлетворительный в обеих группах: чаще наблюдались местные реакции (57,7 и 63,0 % в 1-й и 2-й группах соответственно).Выводы. Эффективность, безопасность и переносимость исследуемого препарата Аксоглатиран® ФС сопоставимы с референтным препаратом Копаксон®-Тева у пациентов с рецидивирующим ремиттирующим рассеянным склерозом, что позволяет рекомендовать его для внедрения в клиническую практику

Phase Behavior of Aqueous Na-K-Mg-Ca-CI-NO3 Mixtures: Isopiestic Measurements and Thermodynamic Modeling

A comprehensive model has been established for calculating thermodynamic properties of multicomponent aqueous systems containing the Na{sup +}, K{sup +}, Mg{sup 2+}, Ca{sup 2+}, Cl{sup -}, and NO{sub 3}{sup -} ions. The thermodynamic framework is based on a previously developed model for mixed-solvent electrolyte solutions. The framework has been designed to reproduce the properties of salt solutions at temperatures ranging from the freezing point to 300 C and concentrations ranging from infinite dilution to the fused salt limit. The model has been parameterized using a combination of an extensive literature database and new isopiestic measurements for thirteen salt mixtures at 140 C. The measurements have been performed using Oak Ridge National Laboratory's (ORNL) previously designed gravimetric isopiestic apparatus, which makes it possible to detect solid phase precipitation. Water activities are reported for mixtures with a fixed ratio of salts as a function of the total apparent salt mole fraction. The isopiestic measurements reported here simultaneously reflect two fundamental properties of the system, i.e., the activity of water as a function of solution concentration and the occurrence of solid-liquid transitions. The thermodynamic model accurately reproduces the new isopiestic data as well as literature data for binary, ternary and higher-order subsystems. Because of its high accuracy in calculating vapor-liquid and solid-liquid equilibria, the model is suitable for studying deliquescence behavior of multicomponent salt systems