Determination of poloidal mode numbers of MHD modes and their radial location using a soft x-ray camera array in the Wendelstein 7-X stellarator

A forward modeling technique is developed for determining the characteristic features of observed MHD modes from the line-of-sight data of the soft x-ray (SXR) tomography diagnostics in the Wendelstein 7-X (W7-X) stellarator. In particular, forward modeling is used to evaluate the poloidal mode numbers m, radial location, poloidal rotation direction and ballooning character of the MHD modes. The poloidal mode structures have been modeled by the radially localized Gaussian-shaped emission regions rotating along the magnetic surfaces. In the present study the cases of rigid-shape emission regions and flexible emission regions are modeled. Various mode phase velocity dependences on the magnetic surface position are simulated. The modeled phase dynamics of line-integrated oscillations and the distribution of oscillation amplitudes are compared with the experimental signals of the SXR cameras which observe the plasma at various viewing angles in the poloidal cross-section. Application of this technique enables describing of the 1–50 kHz modes. In particular, in the discharge W7X-PID 20180918.045 three identified branches with the poloidal mode numbers m= 8, m= 10 and m= 11 localized at ρ ≈ 0.3 are rotating in the clockwise poloidal direction. The present paper reports the first application of the forward modeling technique to the data from the SXR diagnostics in W7-X. The high m-modes are identified by forward modeling in W7-X

Gene Expression and DNA Methylation Alterations During Non-alcoholic Steatohepatitis-Associated Liver Carcinogenesis

Hepatocellular carcinoma (HCC) is one of the most aggressive human cancers. HCC is characterized by an acquisition of multiple abnormal phenotypes driven by genetic and epigenetic alterations, especially abnormal DNA methylation. Most of the existing clinical and experimental reports provide only a snapshot of abnormal DNA methylation patterns in HCC rather than their dynamic changes. This makes it difficult to elucidate the significance of these changes in the development of HCC. In the present study, we investigated hepatic gene expression and gene-specific DNA methylation alterations in mice using the Stelic Animal Model (STAM) of non-alcoholic steatohepatitis (NASH)-derived liver carcinogenesis. Analysis of the DNA methylation status in aberrantly expressed epigenetically regulated genes showed the accumulation of DNA methylation abnormalities during the development of HCC, with the greatest number of aberrantly methylated genes being found in full-fledged HCC. Among these genes, only one gene, tubulin, beta 2B class IIB (Tubb2b), was increasingly hypomethylated and over-expressed during the progression of the carcinogenic process. Furthermore, the TUBB2B gene was also over-expressed and hypomethylated in poorly differentiated human HepG2 cells as compared to well-differentiated HepaRG cells. The results of this study indicate that unique gene-expression alterations mediated by aberrant DNA methylation of selective genes may contribute to the development of HCC and may have diagnostic value as the disease-specific indicator

Gliclazide MR in the structure of antihyperglycemic therapy according to the data of Moscow region diabetes register

Background: Sulfonylureas (SU) are often used for second and third line type 2 diabetes mellitus (T2DM) therapy. Currently, there are no unified recommendations governing the choice of drugs for the second line therapy. This requires clarification.Aim: To examine Moscow Region DM register data for assessing ongoing antihyperglycemic therapy and its correspondence to current local and international T2DM treatment recommendations, as well as actual clinical recommendations for the treatment of T2DM patients and COVID-19.Materials and methods: The structure of glucose-lowering therapy with non-insulin drugs (NID) was studied in T2DM patients according to the data T2DM register of Moscow region. The analysis was carried out on 06.02.2021. We analyzed the general group of T2DM patients (237479 people), group 60 years and older (188644 patients), T2DM patients who have had COVID-19. Newly diagnosed T2DM individuals were analyzed for 2020 (5088 people).Results: Glucose-lowering therapy is received by 97.6% of T2DM patients. Of these, 79.07% take NID, insulin + NID - 11.37%. Monotherapy is received by 44.4% of patients, a combination of two drugs - 29.3%, out of three - 5.3% of patients. Metformin is the leader in prescribing NID (69.4% of all T2DM patients and 81.3% in newly diagnosed patients). SU are in second place in T2DM treatment (50% of all patients, 24.1% in newly diagnosed patients), iIDPP-4 is in third place (12.1% and 12.6%, respectively). Among patients of 60 and more years old, 25.99% of patients take gliclazide MR, 14.3% glibenclamide, 7.7% glimepiride. Mortality from COVID-19 depends on the diabetes duration.Conclusion: According to the DM register, half of the T2DM patients and a quarter of T2DM newly diagnosed patients get SU. As a first-line drug, SU is on the second place after metformin and are most often used in double and triple combinations of T2DM therapy. In the older age group on SU, preference is given to gliclazide MR

The glucose-lowering therapy structure in special groups of type 2 diabetes mellitus patients based on data from the Moscow region register

BACKGROUND: Data of real clinical practice in diabetes mellitus (DM) register allow to evaluate features and trends in structure of glucose-lowering therapy (GLT). AIM: Тo analyze of structure of GLT received by patients with type 2 diabetes mellitus (T2DM) in Moscow region for 2018 and to evaluate its dynamics over 15 years. METHODS: Analysis of GLT structure was carried out on basis of data from register of patients with DM in Moscow region, which is part of National register of diabetes mellitus in Russian Federation. In March 2018 it contained data on 211,792 T2DM patients of Moscow region. Structure of GLT administration was evaluated according T2DM duration, patient’s age and presence of cardiovascular diseases (CVD). Dynamics of GLT is analyzed from 2004 to 2018 yrs. RESULTS: In 2018 non-insulin glucose-lowering drugs (NIGD) prescription prevailed (78.3%), insulin therapy was prescribed in 18.5% of patients, 3.2% of patients did not receive drug therapy. Most commonly prescribed NIGD were metformin (69.3%) and sulfonylurea (51.3%). Older patients more often than younger did not use GLT at all and less frequently received insulin therapy and iDPP-4. Insulin therapy was prescribed twice as often in patients with CVD compared with patients without CVD (29.6% and 15.5%). NIGD monotherapy has been less commonly used in patients with CVD (67.3% and 81.2%). Glucagon-like peptide-1 receptor agonists (GLP-1 RA) were prescribed to patients with CVD GLP-1 RA – in 0.1% of cases, without CVD in 0.3% of cases, and sodium-glucose cotransporter 2 (SGLT2) inhibitors in 1.1% and 0.6%. correspondently. CONCLUSION: Metformin was most commonly prescribed drug in GLT structure for T2DM patients in the Moscow region in 2018 yr. Percentage of new drugs in the structure of GLT increased mainly due to iDPP-4, and secondly due to SGLT2 inhibitors. New classes of GLT were more often prescribed to patients of younger age, with diabetes duration up to 10 years, overweight or obese. Administration of NIGD with proven cardiovascular protection in presence of CVD is almost two times less than for those without CVD

Клинико-экономическая оценка терапии острого повреждения почек при сепсисе продолжительными комбинированными методами заместительной почечной терапии

Objective: complex assessment of clinical and economic effectiveness as well as saving of the state budget assets within the therapy of patients with sepsis/septic shock based on different technologies of blood purification.Methods. Evaluation of direct and indirect costs of the eight blood purifcation methods. The target population includes adult patients 18+ with septic acute kidney injury. The study was conducted in compliance with acting Standards on Clinical Economic Studies used in the Russian Federation.The study methods included evaluation of existing randomized clinical studies and trials with data from network meta-analyses and systematic reviews of the target technologies. The direct medical and indirect non-medical costs were calculated and analyzed in respect of cost-effectiveness  and budget impact analyses.Results. Direct and indirect costs were calculated for the sorption devices oXiris (Baxter International Inc.), Toraymyxin (Toray Medical Co.), Alteco LPS Adsorber (Alteco Medical AB), Toxipak (POKARD NPF), Desepta.LPS (BIOTECH M NPP), CytoSorb (CytoSorbents Inc.), HA330 (Jafron Biomedical Co.), Desepta (BIOTECH M NPP) for two time-horizons: 1-year period and 5-years period with discounting. For both periods, the use of oXiris hemoflter results in the least economic burden for the state budget.Conclusion. The use of blood purifcation in septic patients therapy is associated with considerable direct and indirect fnancial expenses, the amount of which and consequential budget saving depend on the technology of blood purifcation applied. The actual tariff compensation policy evidently demands revising.Цель исследования: комплексная оценка клинико-экономической эффективности и экономии бюджетных средств при использовании разных технологий экстракорпоральной гемокоррекции (ЭГК) при лечении больных с сепсисом / септическим шоком.Методика. Предмет исследования – фармако-экономические показатели прямых медицинских и непрямых затрат при использовании восьми технологий ЭГ. Целевая популяция – пациенты старше 18 лет с сепсис-ассоциированным острым повреждением почек. Исследование осуществлено в соответствии с действующим отраслевым стандартом «Клинико-экономические исследования», применяемым в России.Методология предполагала оценку имеющихся рандомизированных клинических исследований, а также исследований, включающих данные сетевых метаанализов и систематических обзоров применения изучаемых технологий. Произведен расчет прямых медицинских и непрямых немедицинских затрат с анализом по критериям «затраты ‒ эффективность», «влияние на бюджет».Результаты. Определена величина прямых и косвенных затрат при использовании сорбционных устройств oXiris (Baxter International Inc.), Toraymyxin (Toray Medical Co.), Alteco LPS Adsorber (Alteco Medical AB), Toxipak (НПФ ПОКАРД), Desepta.LPS (НПП Биотех М), CytoSorb (CytoSorbents Inc.), HA330 (Jafron Biomedical Co.), Desepta (НПП Биотех М) в расчете на применение технологий в течение 1 года и на временной 5-летний горизонт. Показано, что среди всех технологий в оба этих периода наименьшую нагрузку на бюджет оказывает использование гемофильтра oXiris.Выводы. Использование экстракорпоральной гемокоррекции при лечении больных с сепсисом сопровождается большими прямыми и косвенными финансовыми затратами, величина которых и экономия бюджетных средств зависят от применяемой технологии. Порядок компенсации затрат на экстракорпоральную гемокоррекцию при сепсисе, реализуемый в настоящее время в рамках модели, основанной на клинико-статистических группах, требует пересмотра

Оценка организации медицинской помощи и лекарственного обеспечения при ревматических заболеваниях и социально-экономического бремени этих болезней в Российской Федерации

This article reviews data on the assessment of the incidence of rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA, arthropathic psoriasis), as well as related disability and the economic burden of these nosological entities, including their therapy with biological agents. It considers the issues of organization and quality of medical care, drug supply, normative and legal regulation. The paper also shows the important epidemiological and socioeconomic importance of RA, AS, and PsA in Russia, points out the regional peculiarities of medical care and drug provision, and proposes solutions for their optimization at the federal and local levels. In preparing this investigation, the authors have taken into account the opinions of many specialists and experts in this field from different subjects of the Russian Federation.Представлен обзор данных, касающихся оценки заболеваемости ревматоидным артритом (РА), анкилозирующим спондилитом (АС) и псориатическим артритом (ПсА, артропатический псориаз), а также связанных с этими заболеваниями потери трудоспособности, инвалидизации и экономического бремени, включая терапию генно-инженерными биологическими препаратами (ГИБП). Рассмотрены вопросы организации и качества медицинской помощи, лекарственного обеспечения, нормативно-правового регулирования. Показано важное эпидемиологическое и социально-экономическое значение РА, АС и ПсА в России, отмечены региональные особенности оказания медицинской помощи и лекарственного обеспечения и предложены решения для их оптимизации на федеральном и местном уровнях. При подготовке исследования были учтены мнения многих специалистов и экспертов в данной области из различных субъектов Российской Федерации

Disease and treatment-related burden in patients with acromegaly who are biochemically controlled on injectable somatostatin receptor ligands

Medical treatment for acromegaly commonly involves receiving intramuscular or deep subcutaneous injections of somatostatin receptor ligands (SRLs) in most patients. In addition to side effects of treatment, acromegaly patients often still experience disease symptoms even when therapy is successful in controlling GH and IGF-1 levels. Symptoms and side effects can negatively impact patients' health-related quality of life. In this study, we examine the disease- and treatment-related burden associated with SRL injections as reported through the use of the Acromegaly Treatment Satisfaction Questionnaire (Acro-TSQ(C)) and clinician-reported symptom severity through the Acromegaly Index of Severity (AIS). Patients included in this analysis were enrolled in a randomized phase 3 study, were biochemically-controlled (an IGF-1 = 6 months with a stable dose of either long- acting octreotide or lanreotide monotherapy for >= 4 months. The sample (N = 91) was 65% female, 91% Caucasian, with a mean [standard deviation (SD)] age of 53 (1) years. Two-thirds of patients reported that they still experience acromegaly symptoms; 82% of these said they experience symptoms all of the time. Three-fourths experienced gastrointestinal (GI) side effects after injections, and 77% experienced treatment-related injection site reactions (ISRs). Patients commonly reported that these interfered with their daily life, leisure, and work activities. Those with higher symptom severity, as measured by the AIS, scored significantly worse on several Acro-TSQ domains: Symptom Interference, GI Interference, Treatment Satisfaction, and Emotional Reaction. Despite being biochemically controlled with injectable SRLs, most patients reported experiencing acromegaly symptoms that interfere with daily life, leisure, and work. GI side effects and ISRs were also common. This study highlights the significant disease burden that still persists for patients with acromegaly that have achieved biochemical control with the use of injectable SRLs.Diabetes mellitus: pathophysiological changes and therap