The Crisis of Values of the Late-Victorian Society in England (On the Example of the Tales of Writer O. Wilde)

The study is devoted to criticism of the moral attitudes of the Late-Victorian Society in England (1880–1900 years), which was expressed by the famous british writer Oscar Wilde in one of his collections of fairy tales: «The Happy Prince and the other tales» (1888). In it, Oscar Wilde reflects the plight of the working class in England, as well as the hypocritical attitude towards it’s poverty of the Church of England.Исследование посвящено анализу критики моральных установок поздневикторианского общества в Англии (1880–1900), известным британским писателем Оскаром Уайльдом в сборнике сказок «Счастливый принц и другие сказки» (1888). В ней Уайльд показывает бедственное положение рабочего класса в Англии, а также лицемерное к этому отношение англиканского общества

Oscar Wilde at the pre-revolutionary Russia

Представлен краткий обзор дореволюционной историографии, посвященной Оскару Уайльду. Показано, что творчество писателя получило признание в литературных кругах дореволюционной России.The article presents the short review of popularisation of Oscar Wilde works at the pre-revolutionary Russia. The author proves that the writer’s work was recognized in the literary circles of Russia at the beginning of the 19th century

Loss of neuronal integrity during progressive HIV-1 infection of humanized mice.

Neuronal damage induced by ongoing human immunodeficiency virus type 1 (HIV-1) infection was investigated in humanized NOD/scid-IL-2Rγ(c)(null) mice transplanted at birth with human CD34-positive hematopoietic stem cells. Mice infected at 5 months of age and followed for up to 15 weeks maintained significant plasma viral loads and showed reduced numbers of CD4(+) T-cells. Prospective serial proton magnetic resonance spectroscopy tests showed selective reductions in cortical N-acetyl aspartate in infected animals. Diffusion tensor imaging revealed structural changes in cortical gray matter. Postmortem immunofluorescence brain tissue examinations for neuronal and glial markers, captured by multispectral imaging microscopy and quantified by morphometric and fluorescence emission, showed regional reduction of neuronal soma and synaptic architectures. This was evidenced by loss of microtubule-associated protein 2, synaptophysin, and neurofilament antigens. This study is the first, to our knowledge, demonstrating lost neuronal integrity after HIV-1 infection in humanized mice. As such, the model permits studies of the relationships between ongoing viral replication and virus-associated neurodegeneration

CD4+ Effector T cells Accelerate Alzheimer\u27s Disease in Mice

BACKGROUND: Alzheimer\u27s disease (AD) is a progressive neurodegenerative disorder characterized by pathological deposition of misfolded self-protein amyloid beta (Aβ) which in kind facilitates tau aggregation and neurodegeneration. Neuroinflammation is accepted as a key disease driver caused by innate microglia activation. Recently, adaptive immune alterations have been uncovered that begin early and persist throughout the disease. How these occur and whether they can be harnessed to halt disease progress is unclear. We propose that self-antigens would induct autoreactive effector T cells (Teffs) that drive pro-inflammatory and neurodestructive immunity leading to cognitive impairments. Here, we investigated the role of effector immunity and how it could affect cellular-level disease pathobiology in an AD animal model. METHODS: In this report, we developed and characterized cloned lines of amyloid beta (Aβ) reactive type 1 T helper (Th1) and type 17 Th (Th17) cells to study their role in AD pathogenesis. The cellular phenotype and antigen-specificity of Aβ-specific Th1 and Th17 clones were confirmed using flow cytometry, immunoblot staining and Aβ T cell epitope loaded haplotype-matched major histocompatibility complex II IA RESULTS: The propagated Aβ-Th1 and Aβ-Th17 clones were confirmed stable and long-lived. Treatment of APP/PS1 mice with Aβ reactive Teffs accelerated memory impairment and systemic inflammation, increased amyloid burden, elevated microglia activation, and exacerbated neuroinflammation. Both Th1 and Th17 Aβ-reactive Teffs progressed AD pathology by downregulating anti-inflammatory and immunosuppressive regulatory T cells (Tregs) as recorded in the periphery and within the central nervous system. CONCLUSIONS: These results underscore an important pathological role for CD4+ Teffs in AD progression. We posit that aberrant disease-associated effector T cell immune responses can be controlled. One solution is by Aβ reactive Tregs

Improvements and Limitations of Humanized Mouse Models for HIV Research: NIH/NIAID “Meet the Experts” 2015 Workshop Summary

The number of humanized mouse models for the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) and other infectious diseases has expanded rapidly over the past 8 years. Highly immunodeficient mouse strains, such as NOD/SCID/gamma chainnull (NSG, NOG), support better human hematopoietic cell engraftment. Another improvement is the derivation of highly immunodeficient mice, transgenic with human leukocyte antigens (HLAs) and cytokines that supported development of HLA-restricted human T cells and heightened human myeloid cell engraftment. Humanized mice are also used to study the HIV reservoir using new imaging techniques. Despite these advances, there are still limitations in HIV immune responses and deficits in lymphoid structures in these models in addition to xenogeneic graft-versus-host responses. To understand and disseminate the improvements and limitations of humanized mouse models to the scientific community, the NIH sponsored and convened a meeting on April 15, 2015 to discuss the state of knowledge concerning these questions and best practices for selecting a humanized mouse model for a particular scientific investigation. This report summarizes the findings of the NIH meeting

Abrogated Inflammatory Response Promotes Neurogenesis in a Murine Model of Japanese Encephalitis

Japanese encephalitis virus (JEV) induces neuroinflammation with typical features of viral encephalitis, including inflammatory cell infiltration, activation of microglia, and neuronal degeneration. The detrimental effects of inflammation on neurogenesis have been reported in various models of acute and chronic inflammation. We investigated whether JEV-induced inflammation has similar adverse effects on neurogenesis and whether those effects can be reversed using an anti-inflammatory compound minocycline.Here, using in vitro studies and mouse models, we observed that an acute inflammatory milieu is created in the subventricular neurogenic niche following Japanese encephalitis (JE) and a resultant impairment in neurogenesis occurs, which can be reversed with minocycline treatment. Immunohistological studies showed that proliferating cells were replenished and the population of migrating neuroblasts was restored in the niche following minocycline treatment. In vitro, we checked for the efficacy of minocycline as an anti-inflammatory compound and cytokine bead array showed that production of cyto/chemokines decreased in JEV-activated BV2 cells. Furthermore, mouse neurospheres grown in the conditioned media from JEV-activated microglia exhibit arrest in both proliferation and differentiation of the spheres compared to conditioned media from control microglia. These effects were completely reversed when conditioned media from JEV-activated and minocycline treated microglia was used.This study provides conclusive evidence that JEV-activated microglia and the resultant inflammatory molecules are anti-proliferative and anti-neurogenic for NSPCs growth and development, and therefore contribute to the viral neuropathogenesis. The role of minocycline in restoring neurogenesis may implicate enhanced neuronal repair and attenuation of the neuropsychiatric sequelae in JE survivors

Modern Approaches to the Diagnosis and treatment of <i>Clostridioides difficile (C. difficile)</i>-associated Disease in Adults (literature Review and Expert Council Resolution)

Aim: to review the modern approaches to the diagnosis and treatment of C. difficile-associated disease in adults and present the resolution of the Expert Council held on March 25, 2023 in Moscow.General provisions. C. difficile is the most important nosocomial pathogen which spores are also commonly found in the environment. Microbiota impairment, primarily due to the use of antibacterial drugs, is a key stage in the development of C. difficile-associated disease. A search for an infection should be carried out only in patients with diarrhea, and it is advisable to use at least 2 laboratory methods. The drug of choice for first-line treatment is vancomycin. If drug treatment is ineffective or the patient has recurrent clostridial infection, fecal microbiota transplantation should be considered. The probiotic strain Saccharomyces boulardii CNCM I-745 has a direct inhibitory effect on C. difficile toxin A, promotes normalization of the intestinal microbiota composition, and decreases the inflammatory reaction in colonic mucosa colonized with a toxigenic strain of C. difficile.Conclusions. Addition of the probiotic strain Saccharomyces boulardii CNCM I-745 to antibacterial therapy promotes both primary and secondary prevention of C. difficile-associated disease

Modern Approaches to <i>H. pylori</i> Eradication Therapy in Adults (Literature Review and Resolution of Experts Council)

Aim: to analyze current approaches to H. pylori eradication therapy in adults and present the materials of Experts Council held on December 9, 2022 in Moscow.General statements. H. pylori infection is the main etiological factor of gastritis, peptic ulcer, and gastric cancer. Eradication of H. pylori is recognized as a necessary measure to reduce the incidence of these diseases. The approaches to selecting an eradication regimen should be optimized to take into account epidemiological trends and achieve better treatment outcomes. The updated Maastricht VI Consensus Report presents the means to overcome the difficulties in selecting an approach to the treatment of H. pylori infection. However, eradication therapy remains challenging due to adverse events (primarily antibiotic-associated diarrhea), poor treatment tolerance and patient compliance. Eradication therapy can be optimized by supplementing treatment regimens with strain-specific probiotics that reduce adverse events, improve patient compliance and eradication rates, such as Saccharomyces boulardii CNCM I-745 strain with established efficacy.Conclusion. The inclusion of certain probiotics in eradication regimens improves treatment tolerance, reduces the risk of adverse events, improves patient compliance and eradication rates