The stochastic digital human is now enrolling for in silico imaging trials -- Methods and tools for generating digital cohorts

Randomized clinical trials, while often viewed as the highest evidentiary bar by which to judge the quality of a medical intervention, are far from perfect. In silico imaging trials are computational studies that seek to ascertain the performance of a medical device by collecting this information entirely via computer simulations. The benefits of in silico trials for evaluating new technology include significant resource and time savings, minimization of subject risk, the ability to study devices that are not achievable in the physical world, allow for the rapid and effective investigation of new technologies and ensure representation from all relevant subgroups. To conduct in silico trials, digital representations of humans are needed. We review the latest developments in methods and tools for obtaining digital humans for in silico imaging studies. First, we introduce terminology and a classification of digital human models. Second, we survey available methodologies for generating digital humans with healthy and diseased status and examine briefly the role of augmentation methods. Finally, we discuss the trade-offs of four approaches for sampling digital cohorts and the associated potential for study bias with selecting specific patient distributions

Composition and medicinal uses of echinacea species in Russia and abroad

The article is an overview of current data on Echinacea purpurea, used in Russia and in the world as a powerful immunomodulator. Related species have a similar composition and are used in the world as analogues, the pharmacological effect of their raw materials and drugs are also discussed in the work.В статье представлен обзор современных данных об эхинацеи пурпурной, применяемой в России и в мире в качестве мощного иммуномодулятора. Родственные виды имеют схожий состав и используются в мире как аналоги, фармакологическое действие их сырья и препараты также представлены в работе

Tick-borne infection: evaluation of humoral immunity

The article presents an analysis of the humoral immune response in tick-borne infections (tick-borne encephalitis and Lyme borreliosis) based on an assessment of the level of antibodies of the IgM and IgG classes at different periods of the disease (observation). The antibodies M and G class to tick-borne encephalitis virus (TBE) and Lyme Borreliosis (LB) pathogen were detected using ELISA and immunoblotting methods. The results of studies conducted for 2018 on the basis of the MAU Clinical and Diagnostic Center (Yekaterinburg) are usedВ статье представлен анализ гуморального иммунного ответа при клещевых инфекциях (клещевой вирусный энцефалит и Лайм- боррелиоз) на основе оценки уровня антител классов IgM и IgG в разные периоды болезни (наблюдения). Иммуноглобулины M и G к вирусу клещевого энцефалита (КЭ) и возбудителю Лайм-Боррелиза (ЛБ) выявляли с помощью методов ИФА и иммунноблоттинга. Использованы результаты исследований, проведённых в 2018 году на базе МАУ «Клинико- иагностический центр» (город Екатеринбург

Nodular Dermatitis: Emergence of Novel Poxviral Infection in Russia

Nodular dermatitis, (dermatitis nodularis), is an exotic for the Russian Federation poxviral disease. Some epizootical characteristics of it, problems of laboratory diagnostics, and possible reasons of extension of agent spread areal are discussed in this review. Phylogenetic analysis of P32 gene nucleotide sequences of dermatitis nodularis virus has also been conducted. It is noted that taking into account the economic loss caused by the disease and possibility of its import into non-enzootic regions, it is necessary to use existing effective means of specific prophylacsis extensively. The swift outspread of the disease in the Russian Federation should be considered as the risk factor for biological safety of our country

Current State of the Development of Next-Generation Vaccines against Ebola Virus Disease

Representative of Ebolavirus gender, Filoviridae family, Ebola virus is an etiological agent of particularly dangerous viral fever, the lethality of which comes up to 88 %. According to the leading specialists and experts in the sphere, vaccination is the most effective and cost-efficient method for the protection from epidemic spread. Objective of the review is to analyze current state of the development of next generation vaccines against Ebola fever. It is established that focus areas of the activities are the construction of vaccines on the basis of alpha-virus replicons, virus-like particles, and the development of DNA-vaccines and vector recombinant vaccines. The paper discusses the most significant achievements in the sphere of obtainment of potent therapies for prophylaxis as regards Ebola fever. To date manufactured, using various approaches, have been the next-generation vaccine preparations, for a number of which high protective capacity is demonstrated in the course of experiments on the nonhuman primates. The most advanced and prospective prototype is the vector recombinant vesicular stomatitis virus-based vaccine

MOLECULAR-BIOLOGICAL PECULIARITIES OF ARENAVIRUS REPRODUCTION IN SENSITIVE CELLS

The Arenaviridae family consists of a large group of single strand ambisense RNA viruses that are separated phylogenetically, serologically and geographically into Old World and New World viruses. Recent studies indicate that cellular entry of arenaviruses requires a series of cellular protein interaction and molecular mechanisms. The arenaviruses entry into cells is initiated by the interaction of viral glycoprotein with one or more receptors on the surface of host cells. The main host cell factors that are involved in filovirus entry are attachment factors (α-dystroglycan for Old World and human transferrin receptor 1 for New World viruses), endolisosomal host cell factors (cathepsins B and L and Niemann-Pick C1 protein). The review presents the modern knowledge about the role of structural proteins of arenaviruses and some cell factors in pathogenesis of the diseases, caused by arenaviruses

Attempt to assess direct interactions between tumor burden, myeloid-derived suppressor cells and PD-1- and TIM-3-expressing T cells in multiple myeloma patients

The avoidance of immune surveillance by malignant plasma cells (PCs) in multiple myeloma (MM) is mediated by different mechanisms, among which an induction of T cell exhaustion and expansion of myeloid-derived suppressor cells (MDSCs) appear to play substantial roles, but it is still a lack of data on possible MDSC-mediated induction of T cell exhaustion. The aim of the present work was to evaluate possible relationship between frequencies of MM PCs, MDSCs and phenotypically exhausted PD-1+ and TIM-3+ T cells in bone marrow (BM) samples and peripheral blood (PB) of MM patients at various disease stages. Peripheral blood (n = 88) and BM samples (n = 56) were obtained from MM patients (newly diagnosed (n = 6), patients in remission (n = 71) and with progressive disease (n = 11)). Frequencies of T cells expressing checkpoint receptors PD-1 and TIM-3, polymorphonuclear MDSCs (PMN-MDSCs, Lin-CD14-HLA-DR- CD33+CD15+/CD66b+), monocyte MDSCs (M-MDSCs, CD14+HLA-DRlow/-), early MDSCs (E-MDSCs, Lin-HLA-DR-CD33+CD15-/CD66b-), and MM PCs (CD45dimCD38+CD138+CD56+CD19-CD117+CD27- CD81-) were assessed with flow cytometry. Circulating and BM-resident PD-1+/TIM-3+T cell subsets, BM E-MDSCs, as soon as MM PCs and serum beta2-microglobulin (B2-M) levels were gradually increased in patients at different stages. Despite that, there were no associations between the markers of tumor load and the studied cell subsets. In patients in remission, BM PMN-MDSCs negatively correlated with CD4+T cells, CD4+PD-1+ and CD8+TIM-3+T cell subsets; there were positive correlations between BM E-MDSCs and CD4+PD-1+TIM-3+ cells and PB M-MDSCs and CD8+PD-1+ and (as a trend) CD8+TIM-3+T cells. We found no associations for the samples of patients at diagnosis and with progression. We can conclude that a possible mutual influence of malignant PCs, MDSCs and PD-1+/TIM-3+T cells is nonlinear, especially during a manifest tumor growth at diagnosis and progression. The detected negative correlations between resident PMN- MDSCs and T cell subsets might be associated with MDSC suppressive function, affecting both predominantly activated PD-1+ cells and exhausted TIM-3+ subsets. The positive correlations between BM E-MDSCs and CD4+PD-1+TIM-3+ cell subset and circulating M-MDSCs and PD-1+ and TIM-3+ CD8+T cells might confirm an ability of MDSCs to induce T cell exhaustion

Impact of the COVID-19 pandemic on suicidal behavior: a literary review

The paper presents a literature review of the impact of various aspects of the COVID-19 pandemic on suicidal behavior, including the neurotropic influence of the virus SARS-COV-2, psychogenic factors, and global socio-economic changesПредставлен литературный обзор влияния различных аспектов пандемии COVID-19 на суицидальное поведение, в том числе нейротропного влияния самого вируса SARS-COV-2, психогенных факторов и глобальных социально-экономических изменений

Participation of biological and psychosocial factors in the pathogenesis of schizophrenoform postnatal psychosis: a literary review

In connection with the current socio-demographic situation in the country and in the world, the study of the pathogenic characteristics of postpartum psychosis is highly relevant. The aim of this work was to analyze the literature data on the factors of the pathogenesis of schizophreniform postpartum psychoses. The application of the general scientific method and the analysis of publications in the PubMed, Cyberleninka, e-Library databases helped to confirm the multifactorial nature of postpartum psychoses, proceeding with schizophreniform symptoms, indicating that genetic changes in the coding of neurophysiological mechanisms that manifest themselves after delivery can play a significant role in their genesis. Women in relation to nonspecific influences, and the action of acute or chronic stress factors play the role of triggers for the implementation of the pathogenic cascade, which phenomenologically can be realized into a psychotic disorder. Thus, the formation of postpartum schizophreniform psychoses follows the concept of stress vulnerabilityВ связи со сложившейся социально-демографической ситуацией в стране и в мире изучение патогенетических особенностей послеродовых психозов является весьма актуальным. Целью данной работы являлся анализ ли тературных данных о факторах патогенеза шизофреноформных послеродовых психозов. Применение обще- научного метода и анализ публикаций баз данных PubMed, Cyberleninka, e-Library позволили подтвердить полифакторность послеродовых психозов, протекающих с шизофреноформной симптоматикой, указав, что в их генезе существенную роль могут играть генетические изменения в кодировании нейрофизиологических механизмов, проявляющиеся после родоразрешения, что повышает уязвимость женщины по отношению к неспец ифическим воздействиям, а действие острого или хронического стрессовых факторов играют роль пусковых механизмов для реализации патогенетического каскада, который феноменологически может реализоваться в психотическое расстройство. Таким образом, формирование послеродовых шизофреноформных психозов следует концепции стресс-уязвимост

Some features of suicidal behavior of the population of the Sverdlovsk region under conditions in the COVID-19 pandemic

The paper presents a comparative analysis of the number of completed suicides from different sources without checking statistical reliability. The features of suicidal attempts, personal meanings and suicidal behavior motives of 704 patients among all age groups who committed suicidal attempts against the background of the COVID-19 pandemic (in the second and third quarters of 2020) identified. Comparisons made with the control group of 755 patients who committed suicide attempts in the fourth quarter of 2019 and in the first quarter of 2020. There is an increase in the proportion of those who committed suicide attempts of such personal meaning of suicidal behavior as protest (p≤0.01), as well as such social motives of suicidal behavior as material difficulties (p≤0.001) and domestic difficulties (p≤0.01)В статье представлен сравнительный анализ данных по завершенным суицидам, полученным из разных источников без проверки статистической достоверности. Выявлены особенности суицидальных попыток, личностных смыслов и мотивов суицидального поведения 704 пациентов среди всех возрастных групп, совершивших суицидальные попытки на фоне пандемии COVID-19 (во II и III кварталах 2020 г.). Проведено сравнение с контрольной группой, состоящей из 755 пациентов, совершивших суицидальные попытки в IV квартале 2019 г. и в I квартале 2020 г. Выявлено увеличение удельной доли среди совершивших суицидальные попытки такого личностного смысла суицидального поведения, как протест (р ≤ 0,01), а также таких социальных мотивов суицидального поведения, как материальные трудности (р ≤ 0,001) и бытовые трудности (р ≤ 0,01)