Social work in psychiatry

The analysis of activity of a social service shows that the social experts participating in rendering of the mediko-social help to patients in establishments of public health services, realise the socially-psychological, socially-pedagogical and socially-legal activity directed on restoration, preservation and strengthening of their health.Анализ деятельности социальной службы показывает, что социальные специалисты, участвующие в оказании медико­социальной помощи пациентам в учреждениях здравоохранения, реализуют социально-психологическую, социально-педагогическую и социально-правовую деятельность, направленную на восстановление, сохранение и укрепление их здоровья

Prevalence of cognitive disorders in elderly residents: epidemiological information obtained in the implementation of the program of urban organization of interagency cooperation in Nizhny Tagil

The limited epidemiological data on prevalence in the national population of mental disorders in older age groups leads to misunderstanding scale of the problem of cognitive disorders among elderly citizens of our country that determines the absence of an organized system of integrated medical and psycho-social care for the elderly with cognitive impairment. The results of the organizational and epidemiological prospective study of the occurrence of cognitive disorders in the population of the city of Nizhny Tagil. This study was carried out in the framework of the organization of the urban program of interagency cooperation in providing assistance to elderly citizens with cognitive disabilities (2012-2014 years). High prevalence of cognitive disorders of varying severity in the urban population, which allows you to build a prospective outlook for the problem.Ограниченность эпидемиологических сведений о распространенности в отечественной популяции психических расстройств у лиц старших возрастных групп ведет к непониманию масштаба проблемы когнитивных расстройств среди пожилых граждан нашей страны, что определяет отсутствие организованной системы комплексной медико-психосоциальной помощи лицам пожилого возраста с когнитивными нарушениями. Приведены результаты организационно-эпидемиологического проспективного исследования встречаемости когнитивных расстройств в популяция города Нижний Тагил. Данное исследование осуществлялось в рамках городской программы организации межведомственного взаимодействия при оказании помощи пожилым горожанам с когнитивными расстройствами (2012-2014 г.г.). Выявлена высокая распространенность когнитивных расстройств разной степени выраженности в городской популяции, что позволяет строить проспективный прогноз в отношении данной проблемы

The PYRIN Domain-only Protein POP1 Inhibits Inflammasome Assembly and Ameliorates Inflammatory Disease

SummaryIn response to infections and tissue damage, ASC-containing inflammasome protein complexes are assembled that promote caspase-1 activation, IL-1β and IL-18 processing and release, pyroptosis, and the release of ASC particles. However, excessive or persistent activation of the inflammasome causes inflammatory diseases. Therefore, a well-balanced inflammasome response is crucial for the maintenance of homeostasis. We show that the PYD-only protein POP1 inhibited ASC-dependent inflammasome assembly by preventing inflammasome nucleation, and consequently interfered with caspase-1 activation, IL-1β and IL-18 release, pyroptosis, and the release of ASC particles. There is no mouse ortholog for POP1, but transgenic expression of human POP1 in monocytes, macrophages, and dendritic cells protected mice from systemic inflammation triggered by molecular PAMPs, inflammasome component NLRP3 mutation, and ASC danger particles. POP1 expression was regulated by TLR and IL-1R signaling, and we propose that POP1 provides a regulatory feedback loop that shuts down excessive inflammatory responses and thereby prevents systemic inflammation

Analysis of acute poisonings in the region in the periods between 1996-2006

The aim is the study epidemiology of acute poisonings in the period between 1996 -2006 years. All cases of acute poisonings we analysed accodinig to the centre of Hygiene and epidemiology of Sverdlovsk region. The problems of epidemiology sitiuation of acute poisonings in Sverdlovsk region were discovered.Целью работы явилось изучение эпидемиологической ситуации в Свердловской области в период 1996 по 2006 г. Исследование построено на данных анализа экстренных извещений на каждый случай отравления с последующей компьютерной обработкой материала (токсикологический мониториг). Данные эпидемиологического анализа свидетельствуют о не благополучной ситуации в Свердловской области

The Human Lung Cell Atlas: A High-Resolution Reference Map of the Human Lung in Health and Disease.

Lung disease accounts for every sixth death globally. Profiling the molecular state of all lung cell types in health and disease is currently revolutionizing the identification of disease mechanisms and will aid the design of novel diagnostic and personalized therapeutic regimens. Recent progress in high-throughput techniques for single-cell genomic and transcriptomic analyses has opened up new possibilities to study individual cells within a tissue, classify these into cell types, and characterize variations in their molecular profiles as a function of genetics, environment, cell-cell interactions, developmental processes, aging, or disease. Integration of these cell state definitions with spatial information allows the in-depth molecular description of cellular neighborhoods and tissue microenvironments, including the tissue resident structural and immune cells, the tissue matrix, and the microbiome. The Human Cell Atlas consortium aims to characterize all cells in the healthy human body and has prioritized lung tissue as one of the flagship projects. Here, we present the rationale, the approach, and the expected impact of a Human Lung Cell Atlas.Supported by the Helmholtz Association and the German Center for Lung Research (DZL) (H.B.S.); the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement 753039 (L.M.S.); U.K. Medical Research Council grant G0900424 (E.L.R.); National Institutes of Health (NIH) grants ES013995, HL071643, and AG049665, and Veterans Administration grant BX000201 and Department of Defense grant PR141319 (G.R.S.B.); NIH grants HL135124 and AI135964 and Department of Defense grant PR141319 (A.V.M.); NIH grants R01HL141852, R01HL127349, UHHL3123886, U01HL122626, and UG3TR002445, and Department of Defence grant PR151124 (N.K.); and the Netherlands Lung Foundation grants 5.1.14.020 and 4.1.18.226 (M.C.N.)

Mitochondria Regulate Proliferation in Adult Cardiac Myocytes

Newborn mammalian cardiomyocytes quickly transition from a fetal to an adult phenotype that utilizes mitochondrial oxidative phosphorylation but loses mitotic capacity. We tested whether forced reversal of adult cardiomyocytes back to a fetal glycolytic phenotype would restore proliferative capacity. We deleted Uqcrfs1 (mitochondrial Rieske iron-sulfur protein, RISP) in hearts of adult mice. As RISP protein decreased, heart mitochondrial function declined, and glucose utilization increased. Simultaneously, the hearts underwent hyperplastic remodeling during which cardiomyocyte number doubled without cellular hypertrophy. Cellular energy supply was preserved, AMPK activation was absent, and mTOR activation was evident. In ischemic hearts with RISP deletion, new cardiomyocytes migrated into the infarcted region, suggesting the potential for therapeutic cardiac regeneration. RNA sequencing revealed upregulation of genes associated with cardiac development and proliferation. Metabolomic analysis revealed a decrease in α-ketoglutarate (required for TET-mediated demethylation) and an increase in S-adenosylmethionine (required for methyltransferase activity). Analysis revealed an increase in methylated CpGs near gene transcriptional start sites. Genes that were both differentially expressed and differentially methylated were linked to upregulated cardiac developmental pathways. We conclude that decreased mitochondrial function and increased glucose utilization can restore mitotic capacity in adult cardiomyocytes, resulting in the generation of new heart cells, potentially through the modification of substrates that regulate epigenetic modification of genes required for proliferation

The local and systemic response to SARS-CoV-2 infection in children and adults

While a substantial proportion of adults infected with SARS-CoV-2 progress to develop severe disease, children rarely manifest respiratory complications. Therefore, understanding differences in the local and systemic response to SARS-CoV-2 infection between children and adults may provide important clues about the pathogenesis of SARS-CoV-2 infection. To address this, we first generated a healthy reference multi-omics single cell data set from children (n=30) in whom we have profiled triple matched samples: nasal and tracheal brushings and PBMCs, where we track the developmental changes for 42 airway and 31 blood cell populations from infancy, through childhood to adolescence. This has revealed the presence of naive B and T lymphocytes in neonates and infants with a unique gene expression signature bearing hallmarks of innate immunity. We then contrast the healthy reference with equivalent data from severe paediatric and adult COVID-19 patients (total n=27), from the same three types of samples: upper and lower airways and blood. We found striking differences: children with COVID-19 as opposed to adults had a higher proportion of innate lymphoid and non-clonally expanded naive T cells in peripheral blood, and a limited interferon-response signature. In the airway epithelium, we found the highest viral load in goblet and ciliated cells and describe a novel inflammatory epithelial cell population. These cells represent a transitional regenerative state between secretory and ciliated cells; they were found in healthy children and were enriched in paediatric and adult COVID-19 patients. Epithelial cells display an antiviral and neutrophil-recruiting gene signature that is weaker in severe paediatric versus adult COVID-19. Our matched blood and airway samples allowed us to study the spatial dynamics of infection. Lastly, we provide a user-friendly interface for this data1 as a highly granular reference for the study of immune responses in airways and blood in children

Exceptional Hyperthyroidism and a Role for both Major Histocompatibility Class I and Class II Genes in a Murine Model of Graves' Disease

Autoimmune hyperthyroidism, Graves' disease, can be induced by immunizing susceptible strains of mice with adenovirus encoding the human thyrotropin receptor (TSHR) or its A-subunit. Studies in two small families of recombinant inbred strains showed that susceptibility to developing TSHR antibodies (measured by TSH binding inhibition, TBI) was linked to the MHC region whereas genes on different chromosomes contributed to hyperthyroidism. We have now investigated TSHR antibody production and hyperthyroidism induced by TSHR A-subunit adenovirus immunization of a larger family of strains (26 of the AXB and BXA strains). Analysis of the combined AXB and BXA families provided unexpected insight into several aspects of Graves' disease. First, extreme thyroid hyperplasia and hyperthyroidism in one remarkable strain, BXA13, reflected an inability to generate non-functional TSHR antibodies measured by ELISA. Although neutral TSHR antibodies have been detected in Graves' sera, pathogenic, functional TSHR antibodies in Graves' patients are undetectable by ELISA. Therefore, this strain immunized with A-subunit-adenovirus that generates only functional TSHR antibodies may provide an improved model for studies of induced Graves' disease. Second, our combined analysis of linkage data from this and previous work strengthens the evidence that gene variants in the immunoglobulin heavy chain V region contribute to generating thyroid stimulating antibodies. Third, a broad region that encompasses the MHC region on mouse chomosome 17 is linked to the development of TSHR antibodies (measured by TBI). Most importantly, unlike other strains, TBI linkage in the AXB and BXA families to MHC class I and class II genes provides an explanation for the unresolved class I/class II difference in humans

Modified Vaccinia Virus Ankara Preferentially Targets Antigen Presenting Cells In Vitro, Ex Vivo and In Vivo

Modified Vaccinia virus Ankara (MVA) is a promising vaccine vector with an excellent safety profile. However, despite extensive pre-clinical and clinical testing, surprisingly little is known about the cellular tropism of MVA, especially in relevant animal species. Here, we performed in vitro, ex vivo and in vivo experiments with recombinant MVA expressing green fluorescent protein (rMVA-GFP). In both human peripheral blood mononuclear cells and mouse lung explants, rMVA-GFP predominantly infected antigen presenting cells. Subsequent in vivo experiments performed in mice, ferrets and non-human primates indicated that preferential targeting of dendritic cells and alveolar macrophages was observed after respiratory administration, although subtle differences were observed between the respective animal species. Following intramuscular injection, rMVA-GFP was detected in interdigitating cells between myocytes, but also in myocytes themselves. These data are important in advancing our understanding of the basis for the immunogenicity of MVA-based vaccines and aid rational vaccine design and delivery strategies