The recovery of endothelial function in novel coronavirus infection COVID-19 (review)

Endothelial dysfunction is a  valued part in  the  pathogenesis of  many diseases and conditions including the  active phase of COVID-19 and postcovid syndrome. The review presents both the viral and autoimmune pathways for endothelial and glycocalyx lesions and the  clinical impacts of  such a  lesion in  comorbid patients. Both endothelium and glycocalyx affected by the SARS-CoV-2 virus are considered as the main goal for therapy in outpatient patients and patients with postcovid syndrome. The glycosaminoglycans belonged natural components of vascular wall seem appropriate pathogenetically in order to recovery the endothelial barrier. The review demonstrates the advantages and limitations of using sulodexide in patients with COVID-19. This article presents a clinical case of a patient with confirmed COVID-19 of moderate severity, with the presence of risk factors for thrombosis, who developed a post-covid syndrome, a heterogeneous symptom complex that developed after the acute phase of COVID-19 infection. The post-covid period was marked by symptoms of rapid fatigue, tachycardia, shortness of breath. By day 25-26, itching and red rash appeared, and there was moderate swelling of the shins and feet of both lower extremities. Taking into account the clinical picture and laboratory findings, a decision was made to cancel the previously prescribed low-molecularweight heparin and prescribe sulodexide at a dose of 500 LU 2 times a day for a course of 28 days. On the 4th-5th day after the  start of  treatment there was a  decrease in  the  area  of  skin  rash, cessation of  itching, almost complete disappearance of the cutaneous vascular pattern and reduction in the severity of edema. This clinical case demonstrates endothelial damage caused by COVID-19, which makes it advisable to use angioprotective drugs

Cocliques of maximal size in the prime graph of a finite simple group

In this paper we continue our investgation of the prime graph of a finite simple group started in http://arxiv.org/abs/math/0506294 (the printed version appeared in [1]). We describe all cocliques of maximal size for all finite simple groups and also we correct mistakes and misprints from our previous paper. The list of correction is given in Appendix of the present paper.Comment: published version with correction

Beyond crisis talk: Interrogating migration and crises in Europe

Commencing with some recent examples drawn from Anglophone media, this introductory article reflects on the multiple ways in which crisis and migration have been interconnected over the last decade in public discourse, political debates and academic research. It underlines how crisis has not simply become a key descriptor of specific events, but continues to operate as a powerful narrative device that structures knowledge of migration and shapes policy decisions and governance structures. It explains the rationale for choosing Europe as a multidimensional setting for investigating the diverse links between migration and crisis. It ends with a summary of the contributions that are divided into four thematic strands: relationships between the economic crisis and migrant workers and their families; the Mediterranean in crisis; political and public discourses about the post-2015 ‘migration crisis’; and ethnographies of everyday experiences of the ‘refugee crisis’ on the part of migrants, activists and local people

Graded associative conformal algebras of finite type

In this paper, we consider graded associative conformal algebras. The class of these objects includes pseudo-algebras over non-cocommutative Hopf algebras of regular functions on some linear algebraic groups. In particular, an associative conformal algebra which is graded by a finite group $\Gamma$ is a pseudo-algebra over the coordinate Hopf algebra of a linear algebraic group $G$ such that the identity component $G^0$ is the affine line and $G/G^0\simeq \Gamma$. A classification of simple and semisimple graded associative conformal algebras of finite type is obtained

Формализованная оценка системной тромбогенности у пациентов с ишемическим инсультом, развившимся на фоне истинной полицитемии

Introduction. Thrombosis diagnosis and prevention in patients with Polycythemia vera (PV) suffered an ischemic stroke (IS) are still open. The aim was to find the reasons for systemic thrombogenicity and to compare the applicability of the main scales assessing thrombosis risk in patients with PV suffered IS.Materials and methods. We followed up 127 people (42-75 y.o.), of which 68 were patients with PV suffered IS (group I) and 59 non-PV-patients with ischemic stroke (group II). Clinical study included common blood analysis, rheological properties of erythrocytes, coagulation and endothelial parameters, cytokines, inflammation markers, angiogenesis markers, and testing for the V617F mutation in the JAK2 gene. The follow up included common and neurological examinations as well, and the assesment of thrombosis risk factors with both Caprini scale and CHA2DS2-VASc scale. All patients were examined twice as in the acute period of IS as well as in 16-18 months.Results. Between the groups no significant differences were found for the NIHSS average score and for Bartel index as well.The Caprini score belonged to the “very high risk” (score > 6) in both groups in the acute period of IS. At the same time, the score “8-10 points” prevailed in group II (68%) whereas the score “11-12 points” prevailed in group I.In the acute time of IS the CHA2DS2-VASc score revealed 12% of patients from both groups who had a score of “3-4 points” (moderate risk of thrombosis).In group I thrombotic complications rate correlated significantly with the JAK2V617F gene allelicloading (r = 0.236; p < 0.05), and the development of recurrence cerebrovascular disorders correlated significantly with Caprini score (r = 0.241; p < 0.05), but not with CHA2DS2-VASc score.Aiming to predict thrombotic complications in PV-patients the threshold (cut off) points were established for those markers as factor VIII, factor VII, red blood cell deformability, thrombin activated fibrinolysis inhibitor (TAFI), red blood cell count, white blood cell count, t-PA, VEGF-A, p-thrombomodulin, and ADAMTS-13.This pattern of parameters showed the odds ratio of thrombotic complications 10.3 (95% CI 7.6-13.8) in PV-patients in thelong-term period.At the end of the follow up the Caprini score showed a trend towards a decreasing in total while the CHA2DS2-VASc score remained virtually unchanged.Conclusion. We assume the accurate assessment of thrombotic risk in patients with Polycythemia vera suffered an ischemic stroke requires a proposed pattern of parameters including the test for JAK2V617F allelicloading and the calculation of Caprini score but not CHA2DS2-VASc score. Final results may provoke to change standard antithrombotic therapy in those patients towards its intensification due to pathogenetic featues of cancer-associated thrombosis.Цель. Целью нашего исследования было выявление причин системной тромбогенности и сравнительный анализ применимости основных шкал оценки степени риска развития тромбозов у пациентов с истинной полицитемией, перенесших ишемический инсульт.Материалы и методы. Обследовано 127 человек (возраст от 42 до 75 лет), из которых 68 пациентов перенесли ишемический инсульт (ИИ) на фоне ИП (I группа), и 59 пациентов перенесли ишемический инсульт, но не имели ИП (II группа). Клиниколабораторное обследование включало общий анализ крови, исследование реологических характеристик эритроцитов, исследование параметров системы гемостаза и функции эндотелия, определение цитокинов, маркеров воспаления активности ангиогенеза, а также количественное молекулярно-генетическое исследование мутации V617F в гене JAK2. Клиническое обследование включало общий и неврологический осмотры, уточнение клинических факторов риска, сбор анамнеза, а также оценку риска развития венозных тромбоэмболических осложнений (ВТЭО) по шкалам Caprini и CHA2DS2-VASc. Все пациенты были обследованы в острейшем периоде ИИ и спустя 16-18 мес.Результаты. При оценке неврологических симптомов в остром периоде ИИ в обеих группах средняя оценка по шкале NIHSS и по индексу Бартель статистически значимо не различались между группами. Оценка по шкале Caprini в остром периоде ИИ была в категории «очень высокий риск» (количество баллов > 6) у пациентов обеих групп. При этом во II группе преобладала оценка «8-10 баллов» (68%), тогда как в I группе больных преобладала оценка «11-12 баллов». Оценка по шкале CHA2DS2-VASc в остром периоде ИИ выявила в обеих группах по 12% пациентов с оценкой «3-4 балла» (умеренный риск тромбоза). В I группе частота тромботических осложнений достоверно коррелировала с величиной аллельной нагрузки гена JAK2V617F (r = 0,236; p < 0,05), а возникновение повторных нарушений мозгового кровообращения с количеством баллов по шкале Caprini (r = 0,241; p < 0,05), но не по шкале CHA2DS2-VASc. Проведение ROC-анализа для прогноза тромботических осложнений у пациентов I группы позволило установить пороговые значения наиболее информативных лабораторных маркеров: фактор VIII, фактор VII, деформируемость эритроцитов, активируемый тромбином ингибитор фибринолиза (TAFI), количество эритроцитов, количество лейкоцитов, концентрация t-PA, концентрация VEGF-А, концентрация p-тромбомодулина и концентрация ADAMTS-13. При использовании этой панели параметров отношение шансов возникновения тромботических осложнений в отдаленном периоде у пациентов I группы составило 10,3 раза (95% ДИ 7,6-13,8). В конце периода наблюдения установлено, что по шкале Caprini отмечена тенденция к общему снижению суммарного балла, тогда как оценка по шкале CHA2DS2-VASc практически не изменилась.Заключение. Учитывая роль ИП в формировании системной тромбогенности и, как следствие, в величине риска развития ВТЭО, для более точной характеристики групп риска уместно использовать шкалу Caprini, а также паттерн показателей, включающий величину аллельной нагрузки JAK2V617F и объединенную предиктивную панель лабораторных маркеров. Тем самым это может явиться обоснованием для изменения схем стандартной антитромботической терапии у таких больных в сторону ее усиления и с учетом особенностей патогенеза рак-ассоциированного тромбоза

Опыт лечения пациентов с артериальными и венозными тромбозами при COVID-19: клинические наблюдения

Background. COVID-19 is represented by a large number of different phenotypes, ranging from asymptomatic progress to the development of severe multiple organ dysfunction syndrome. The mechanisms of development of multiple organ dysfunction syndrome are multifactorial, including hypercoagulation with the formation of blood clots. They are often diagnosed as thrombotic complications with detection of blood clots not only in the veins and pulmonary arteries, but also in the heart and main arteries. An observational study shows that the incidence of venous and arterial thrombosis is as high as 31% in patients with COVID-19 pneumonia. However, large studies have not yet been conducted.Aim. To generalize and analyze our own observations of the clinical course of patients with thrombosis and COVID-19.Methods. The study included 5 male patients who had arterial and venous thrombosis and COVID-19 positive test. Results The experience of treatment of 5 patients with COVID-19 with arterial and venous thrombosis was analyzed. All patients showed characteristic changes in the coagulogram. The patient who, upon admission, had a negative test for COVID-19, and characteristic changes in the coagulogram appeared on the day of recurrent thrombosis, was of greatest interest. All patients received standard treatment and were discharged with improvement after testing negative for COVID-19.Conclusion. Generalization of the clinical course of patients with COVID-19 and thrombosis of various vascular regions allowed us to develop treatment tactics for these groups of patients.Актуальность. COVID-19 представлен большим количеством фенотипов, варьирующих от бессимптомного течения до тяжелой полиорганной недостаточности. Механизмы развития синдрома полиорганной недостаточности имеют множество факторов, в том числе гиперкоагуляцию с образованием тромбов. Часто их диагностируют как тромботические осложнения с выявлением тромбов не только в венах и легочных артериях, но в сердце и магистральных артериях. Результаты исследования показывают, что частота венозных и артериальных тромбозов достигает 31% среди пациентов с пневмонией, вызванной COVID-19.Цель. Обобщить и проанализировать клинические случаи лечения больных тромбозами и COVID-19.Материалы и методы. В исследование включены пять больных мужского пола с тромбозами артерий и вен, а также положительным тестом на COVID-19.Результаты. У всех пациентов наблюдались характерные изменения в коагулограмме. Наибольший интерес представляет больной, у которого при поступлении был отрицательный тест на COVID-19, а значимые изменения показателей коагулограммы отмечены в день рецидива тромбоза. Все пациенты получали стандартное лечение и выписаны после улучшения состояния и отрицательным результатом теста на COVID-19.Заключение. Обобщение клинического течения больных COVID-19 и тромбозами различных сосудистых регионов позволило более подробно исследовать данный вопрос и предложить тактику лечения данных пациентов

Relativistic Compression and Expansion of Experiential Time in the Left and Right Space

Time, space and numbers are closely linked in the physical world. However, the relativistic-like effects on time perception of spatial and magnitude factors remain poorly investigated. Here we wanted to investigate whether duration judgments of digit visual stimuli are biased depending on the side of space where the stimuli are presented and on the magnitude of the stimulus itself. Different groups of healthy subjects performed duration judgment tasks on various types of visual stimuli. In the first two experiments visual stimuli were constituted by digit pairs (1 and 9), presented in the centre of the screen or in the right and left space. In a third experiment visual stimuli were constituted by black circles. The duration of the reference stimulus was fixed at 300 ms. Subjects had to indicate the relative duration of the test stimulus compared with the reference one. The main results showed that, regardless of digit magnitude, duration of stimuli presented in the left hemispace is underestimated and that of stimuli presented in the right hemispace is overestimated. On the other hand, in midline position, duration judgments are affected by the numerical magnitude of the presented stimulus, with time underestimation of stimuli of low magnitude and time overestimation of stimuli of high magnitude. These results argue for the presence of strict interactions between space, time and magnitude representation on the human brain

Genetic inhibition of neurotransmission reveals role of glutamatergic input to dopamine neurons in high-effort behavior

Midbrain dopamine neurons are crucial for many behavioral and cognitive functions. As the major excitatory input, glutamatergic afferents are important for control of the activity and plasticity of dopamine neurons. However, the role of glutamatergic input as a whole onto dopamine neurons remains unclear. Here we developed a mouse line in which glutamatergic inputs onto dopamine neurons are specifically impaired, and utilized this genetic model to directly test the role of glutamatergic inputs in dopamine-related functions. We found that while motor coordination and reward learning were largely unchanged, these animals showed prominent deficits in effort-related behavioral tasks. These results provide genetic evidence that glutamatergic transmission onto dopaminergic neurons underlies incentive motivation, a willingness to exert high levels of effort to obtain reinforcers, and have important implications for understanding the normal function of the midbrain dopamine system.Fil: Hutchison, M. A.. National Institutes of Health; Estados UnidosFil: Gu, X.. National Institutes of Health; Estados UnidosFil: Adrover, Martín Federico. National Institutes of Health; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Lee, M. R.. National Institutes of Health; Estados UnidosFil: Hnasko, T. S.. University of California at San Diego; Estados UnidosFil: Alvarez, V. A.. National Institutes of Health; Estados UnidosFil: Lu, W.. National Institutes of Health; Estados Unido

Влияние Эреспала на клиническое течение и показатели воспаления у больных хронической обструктивной болезнью легких

We studied effects of Eurespal (fenspirid) on clinical course and inflammation in COPD patients. The trial included 2 stages: 3-week therapy of exacerbation and 3-month outpatient treatment in stable condition. The drug was given twice a day, 160 mg dally. We assessed scoring of main clinical signs, lung function parameters, bronchoscopic findings, laboratory markers of inflammation, antioxidant status, and quality of life, performed cytological and cytochemical investigation of induced sputum (IS). During the exacerbation Eurespal had early and distinct cough-inhibiting and mucolytic effects, reduced bronchial obstruction, bronchial inflammation severity, decreased C-reactive protein level, IS cytosis, and neutrophil percentage (p < 0.01), increased IS concentration of lyzosomal and cationic proteins (p < 0.01) and serum level of total antioxidants (in 46.2 % of the patients compared with 26.3 % under the typical therapy). Three-month treatment with Eurespal in COPD patients resulted in further positive shifts in clinical and laboratory inflammation markers, IS cytological and cytochemical parameters. The results show Eurespal to increase the efficiency of the COPD treatment and could be included in the complex therapy of COPD. It has high antiinflammatory activity, inhibits bronchial obstruction progressing and improves quality of life of COPD patients.Изучали влияние Эреспала (фенспирид) на клиническое течение и показатели воспаления у больных ХОБЛ. Исследование проводили в 2 этапа: в течение 3 нед. терапии при обострении заболевания и на протяжении 3 мес. амбулаторного лечения в период клинической ремиссии. Эреспал назначали в дозе 160 мг в сутки при 2-кратном приеме. Оценивали основные клинические симптомы в баллах, ФВД, данные бронхоскопии, лабораторные показатели воспаления, антиоксидантного статуса, качество жизни (КЖ). Проводили цитологическое и цитохимическое исследование индуцированной мокроты (ИМ). При обострении ХОБЛ терапия Эреспалом оказывала ранний и отчетливый противокашлевый, муколитический эффекты, сопровождалась уменьшением обструкции, интенсивности воспаления в бронхах, достоверным уменьшением С-реактивного белка, снижением цитоза в ИМ, процентного содержания нейтрофилов (р < 0,01) и повышением в них лизосомально-катионных белков (р < 0,01), увеличением общих антиоксидантов в сыворотке крови (у 46,2 % больных, по сравнению 26,3 % в группе традиционной терапии). Длительное (в течение 3 мес.) лечение Эреспалом больных ХОБЛ обеспечивало дальнейшую положительную динамику клинико-лабораторных показателей воспаления, данных цитологического и цитохимического исследования ИМ. Результаты исследования позволяют считать, что включение Эреспала в комплексную терапию ХОБЛ повышает эффективность лечения как при обострении, так и в стадии относительной ремиссии заболевания, оказывая выраженное противовоспалительное действие; предупреждает нарастание обструкции, улучшает КЖ больных

High Cooperativity of the SV40 Major Capsid Protein VP1 in Virus Assembly

SV40 is a small, non enveloped DNA virus with an icosahedral capsid of 45 nm. The outer shell is composed of pentamers of the major capsid protein, VP1, linked via their flexible carboxy-terminal arms. Its morphogenesis occurs by assembly of capsomers around the viral minichromosome. However the steps leading to the formation of mature virus are poorly understood. Intermediates of the assembly reaction could not be isolated from cells infected with wt SV40. Here we have used recombinant VP1 produced in insect cells for in vitro assembly studies around supercoiled heterologous plasmid DNA carrying a reporter gene. This strategy yields infective nanoparticles, affording a simple quantitative transduction assay. We show that VP1 assembles under physiological conditions into uniform nanoparticles of the same shape, size and CsCl density as the wild type virus. The stoichiometry is one DNA molecule per capsid. VP1 deleted in the C-arm, which is unable to assemble but can bind DNA, was inactive indicating genuine assembly rather than non-specific DNA-binding. The reaction requires host enzymatic activities, consistent with the participation of chaperones, as recently shown. Our results demonstrate dramatic cooperativity of VP1, with a Hill coefficient of ∼6. These findings suggest that assembly may be a concerted reaction. We propose that concerted assembly is facilitated by simultaneous binding of multiple capsomers to a single DNA molecule, as we have recently reported, thus increasing their local concentration. Emerging principles of SV40 assembly may help understanding assembly of other complex systems. In addition, the SV40-based nanoparticles described here are potential gene therapy vectors that combine efficient gene delivery with safety and flexibility