The Management of High-Frequency Episodic and Chronic Migraines with Calcitonin Gene-Related Peptide Monoclonal Antibody

Introduction. High prevalence of migraine and its impact on quality of life requires the development of original agents. In 2020, fremanezumab, a new calcitonin gene-related peptide monoclonal antibody was authorized in Russia. Objective: to evaluate safety and effectiveness of fremanezumab in patients with high-frequency episodic migraine (HF EM) and chronic migraine (CM). Materials and methods. We assessed 60 patients at the age of 35.5 8.96 years (85%, females) with HFEM and CM with and without aura who were either receiving preventive treatment or not. Fremanezumab was administered subcutaneously at a single dose of 675 mg. The study participants were followed-up for efficacy in 3 months. The investigators assessed change in the number of days with headache per month as well as headache intensity, its impact on the daily activities, anxiety, and depression. Results. By the end of month 3 post dosing, the number of days with headache decreased by 50% in 76.7% of participants where 77.8% of individuals suffered from HF EM and 72.7% of individuals had CM while headache intensity decreased in all the patients equally. No response (decrease in the number of days with headache by 30%) was reported in 15% of participants including 14.8% of individuals with HF EM and 15.2% of individuals with CM. By the end of study month 3, 81% of participants demonstrated no anxiety symptoms and 79% of participants showed no depression with significant MIDAS and HIT-6 score decline in both groups. Only 3 (5%) patients noted adverse events (redness, itching at the administration site). Conclusion. We documented higher fremanezumab safety and effectiveness in patients with EM and CM in real-world practice as compared to fremanezumab safety and efficacy in randomized clinical trials. A single dose of fremanezumab (675 mg) resulted in effective migraine prevention, decline in comorbid anxiety and depression, and improved quality of life during 3-month follow-up

Vitamin D binding protein polymorphysm in patients with acute coronary syndrome in kaliningrad region

BACKGROUND: Vitamin D binding protein is a main vitamin D carrier in serum. It also has an impact on macrophagial function. Role of vitamin D and macrophages in the pathogenesis of atherosclerosis is scientifically proven but there is lack of data on vitamin D binding protein in this regard. AIMS: To evaluate the vitamin D binding protein polymorphism in patients with acute coronary syndrome without diabetes mellitus, autoimmune diseases and malignant tumors. Determine correlation, if there is, between vitamin D binding protein allele and features of acute coronary syndrome among this patient group. MATERIALS AND METHODS: It is a cross-sectional observational study. Study subjects are patients with acute coronary syndrome. Exclusion criteria are the presence of diabetes mellitus, autoimmune diseases and malignant tumors. In all participants were evaluated: predisposing factors for heart diseases, CBC, biochemical blood test, troponin, coronarography, echocardiography. The study lasted for 5 months from November 2017 until March 2018. Primary end point – assessment of vitamin D binding protein polymorphysm in this group of patients with acute coronary syndrome by means of vitamin D binding protein gene sequencing. 50 patients were enrolled into this study who were urgently admitted to hospital and diagnosed with acute coronary syndrome. Among them – 36 males and 14 females. Mean age was 60 (55;66) years. All participants were sequenced for single nucleotide polymorphysm in VDBP p.T436K (rs4588) and P.432E (rs7041). RESULTS: Gene polymorphysms of interest were found in 43 patients among 50 enrolled. Haplotype Gc1s/2 (rs7041G-rs4588A) was found in 7 (14%) patients, Gc2 (rs7041T-rs4588A) — in 9 (18%) patients, Gc1s (rs7041G-rs4588C) – in 20 (40%) patients, Gc1f (rs7041T-rs4588C) in 14 (28%). Coronarography showed that coronary artery occlusions obstructing more than 50% of vessel lumen was found in 16 patients; obstruction greater than 90% was seen in 8 patients; total occlusion – in 4 patients. CONCLUSIONS: In patient group with acute coronary syndrome prevalence of vitamin D binding protein gene polymorphysm was high – in 86% of participants. The features of Gc2 haplotype were higher frequency of recurrent myocardial infarction and total coronary artery occlusion, as well as tendency to decreased serum vitamin D3 (25(OH)D) levels

Survival, cognitive functions, and brain MRI in patients with cSVD: 5-year observation

Introduction. Contributing to high disability and mortality, cerebral small vessel disease (cSVD) is a common condition in senior and elderly individuals. Objective: to assess the 5-year survival as well as cognitive and MRI changes in patients with cSVD and cognitive impairment (CI). Materials and methods. A prospective 5-year study included 54 patients (of them 37 women; mean age: 60.51 6.76 years) with cSVD, CIs, and white matter hyperintensities (WMHs; Fazekas 23). Twenty-two subjects were followed up to assess cognitive functions and a type of CI, cSVD MRI features, WMH, white and grey matter, and cerebrospinal fluid (CSF) volume as well as microstructural brain changes and correlate cognitive and MRI parameters at 5 years timepoint after the baseline. Results. Dementia developed in 14% of the subjects and 14% of the subjects died over a 5-year period. The subjects assessed twice had controlled hypertension (HTN). CIs worsened in the domain of executive functions and memory with mixed-type CI worsening. The follow-up showed that the WMH and CSF volume increased while the white matter volume decreased and axial diffusivity increased in the corpus callosum. The CSF volume correlated with the Stroop Test results and delayed memory (r = 0.803 and r = 0.701, respectively) and with white matter atrophy (r = 0.256) while the latter correlated with the axial diffusivity increased in the corpus callosum (r = 0.560). Conclusion. cSVD with advanced WMHs is associated with high mortality and dementia progression. General cognition assessment and MRI scan are not enough sensitive to assess disorder progression over a 5-year period. Stroop Test and Delayed 10-Word Recall Test results and transition to mixed-type CI indicate CI worsening and, therefore, can be used for the follow-up assessment. Cognitive decline in extensive cSVD is mediated by the brain matter atrophy and altered CSF circulation

Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection

Cervical artery dissection (CeAD), a mural hematoma in a carotid or vertebral artery, is a major cause of ischemic stroke in young adults although relatively uncommon in the general population (incidence of 2.6/100,000 per year). Minor cervical traumas, infection, migraine and hypertension are putative risk factors, and inverse associations with obesity and hypercholesterolemia are described. No confirmed genetic susceptibility factors have been identified using candidate gene approaches. We performed genome-wide association studies (GWAS) in 1,393 CeAD cases and 14,416 controls. The rs9349379[G] allele (PHACTR1) was associated with lower CeAD risk (odds ratio (OR) = 0.75, 95% confidence interval (CI) = 0.69-0.82; P = 4.46 × 10(-10)), with confirmation in independent follow-up samples (659 CeAD cases and 2,648 controls; P = 3.91 × 10(-3); combined P = 1.00 × 10(-11)). The rs9349379[G] allele was previously shown to be associated with lower risk of migraine and increased risk of myocardial infarction. Deciphering the mechanisms underlying this pleiotropy might provide important information on the biological underpinnings of these disabling conditions

Individual investment accounts as a tool for investing in the financial market: the value-based legal approach

The article is a comprehensive study of the legal regime of Russian individual investment accounts (IIA) as a financial tool intended only for citizens, taking into account the existing legislation which deserves special attention, since it reflects key problems of the financial market. Under the sanctions imposed on the Russian Federation and economic recovery after the negative impact of the COVID-19 pandemic, the national political and legal concept is aimed at involving the population in the investment process and ensuring sustainable development. The scientific and practical value of the research results is due to the development of civil legal ideas about the legal mechanism of individual investment accounts as an instrument of tax policy, taking into account the aspects of administrative and labor law and the impact of digital technologies. The legal relations between professional participants in the securities market and citizens associated with IIAs are analyzed taking into account the methods of gaining income (value), including tax advantages. The novelty of the study is due to the systematic analysis of the dynamics of legal relations and administrative barriers which reduce the economic efficiency of IIAs. A number of problems related to the lack of comprehensive legal protection of the rights and interests of citizens-investors have been identified (safety of assets on these accounts)

Problems of modeling further development of civil legislation of the Russian Federation

The article provides of civil modeling of civil legislation development, shows its significance and peculiarities, structural elements, gives their characteristics, concludes the necessity of an integrated approach to Problem of civil models. For a long time, and to a large extent now, legislation, including civil law, is perceived as a means of legal regulation of public relations, and normative legal acts are considered mainly as the most important legal form of fixing and ensuring the proper conduct of the subjects. This "normative" approach, along with the positive ones, also contains a number of negative aspects, when there is a deep analysis of the draft legislation, the possibility and consequences of their implementation in practice, which often leads to the fact that the effectiveness of many normative acts remains low; there are many conflicts and cases of inconsistency in legislation; changes, additions and other, sometimes unsystematic, amendments to the legislation that give rise to a lot of discussions in the scientific and practical environment are constantly being made

Some issues of legal regulation of electronic commerce in the Russian Federation

Over the past ten years the Internet has developed into the global market space; now the commodities of online shops have already become accessible to the mass consumer on a global scale. The article analyzes the topical aspects of development of e-commerce in the Russian Federation and abroad (in the light of the experience of China). Special attention is devoted to the economic advantages of a segment of trade "business to customer" (B2C) and trans boundary-related legal risks that online-trade participants carry. The article outlines the prospects for the development of this sector in Russia in light of the "Strategy for the development of electronic commerce for the period until 2025"

Some issues of legal regulation of electronic commerce in the Russian Federation

Over the past ten years the Internet has developed into the global market space; now the commodities of online shops have already become accessible to the mass consumer on a global scale. The article analyzes the topical aspects of development of e-commerce in the Russian Federation and abroad (in the light of the experience of China). Special attention is devoted to the economic advantages of a segment of trade "business to customer" (B2C) and trans boundary-related legal risks that online-trade participants carry. The article outlines the prospects for the development of this sector in Russia in light of the "Strategy for the development of electronic commerce for the period until 2025"

Problems of modeling further development of civil legislation of the Russian Federation

The article provides of civil modeling of civil legislation development, shows its significance and peculiarities, structural elements, gives their characteristics, concludes the necessity of an integrated approach to Problem of civil models. For a long time, and to a large extent now, legislation, including civil law, is perceived as a means of legal regulation of public relations, and normative legal acts are considered mainly as the most important legal form of fixing and ensuring the proper conduct of the subjects. This "normative" approach, along with the positive ones, also contains a number of negative aspects, when there is a deep analysis of the draft legislation, the possibility and consequences of their implementation in practice, which often leads to the fact that the effectiveness of many normative acts remains low; there are many conflicts and cases of inconsistency in legislation; changes, additions and other, sometimes unsystematic, amendments to the legislation that give rise to a lot of discussions in the scientific and practical environment are constantly being made

High-Rise Construction in Densely Dwelled Cities: Requirements for Premises Insolation and Consequences of their Violation in Russian Law and Jurisprudence

The issues of constructing high-rise, primarily residential, buildings have a great social significance. Not every plot of land, acquired in the Russian Federation is suitable for high-rise construction. Therefore, every construction company that plans to erect a multi-apartment building, a high-rise office building, or a skyscraper must take into account not only technical norms but as well sanitary legislation regulations that set obligatory requirements about insolation of apartments. The article includes a short study of several norms in the Russian legislation regarding insolation of dwellings; analises the problems of judicial interpretation of the statutory limitations. In this aspect it researches the debatable questions arising in practice of state arbitration courts dealing with the lawsuits on allocation of land-plots by the local administration. The analysis of the judicial practice is followed by description of the difficulties facing the developers of land-plots, concerning the project and territorial planning documentation