Fact-Fiction as an Epistolary Forming Component of the Novel by B. Bainbridge According to Queeney

In this article the correlation between fictional and documentary origins in the novel According to Queeney by Beryl Bainbridge is analysed. This novel belongs to the genre of biographical novel. The researcher analyses the peculiarities of this correlation in epistolary part of novel, which occupies one of the main parts in the narrative texture of the novel. Bainbridge, describing the life of the character, relies on authentic facts, and herewith interprets them according to her vision.В статье анализируется соотношение вымышленного и документального начал в романе Берил Бейнбридж «Согласно Куини», представляющем собой жанр романизированной биографии. Исследователь анализирует особенности этого соотношения в эпистолярной части романа, занимающей одно из главных мест в повествовательной ткани произведения. Бейнбридж, описывая жизнь героя, опирается на подлинные факты и при этом интерпретирует их согласно своему, авторскому, видению

THE ARCHITECTURAL TOURISTIC AND RECREATIONAL SYSTEM: STRUCTURE, PROPERTIES, RELATIONSHIPS

The aim is to determine the possibility of organizing the architectural environment as a system based on the fundamental principle of a single criterion helps to avoid errors arising from the integrated multi-factor approach to the problem under study.Methods. Architectural tourism and recreation system (ATRS) is a part of demoekosystem and has all its inherent properties.Results. Applying systematic approach to construction of architectural tourism and recreation system helps to identify the main factors that affect the system and form its boundaries. The identified properties and principles of interaction between the elements allow to build the ontological (essential), functional and mathematical models.Main conclusions. System approach allows to solve such important economic problems as tourism development in the Russian Federation

Management of a Female Patient with Irritable Bowel Syndrome and Somatoform Disorder

Aim: to demonstrate the management of a patient with somatization disorder and irritable bowel syndrome.Key points. A 41-yo female patient was admitted with complains of spastic lower abdomen pain, hard stool once every 1–2 days under laxative treatment (macrogol), bloating, anxiety, waiting for confirmation of a life threatening illness, internal stress, difficulty in falling asleep, shallow sleep. Has a long history of disease, characterized by the appearance of a variety of somatic symptoms (headache, tachycardia, joint pain, stool disorders, abdominal pain, etc.) during periods of emotional tension, lack of data suggesting organic disease. No abnormal changes were detected in examination at the clinic (complete blood count, serum chemistry tests, urinalysis or fecal tests, hydrogen and methane breath tests with lactulose, abdominal ultrasound, esophagogastroduodenoscopy, colonoscopy). With the prior agreement of patient, she was consulted by a psychiatrist and diagnosed with somatization disorder and mild anxiety disorder. On discharge from hospital recommended cognitive-behavioral therapy, continue taking macrogol, as well as treatment with Kolofort. After 3 months of complex treatment, there was a significant decrease in the severity of both the symptoms of irritable bowel syndrome and anxiety disorder.Conclusion. For patients whose complaints meet the diagnostic criteria for IBS, a two-stage differential diagnosis may be justified: at the first stage, differentiation of IBS and organic diseases of the gastrointestinal tract is carried out; at the second stage - IBS and somatization disorder. Kolofort can be the drug of choice both in patients with IBS and the pharmacological part of therapy in patients with somatization disorder

Increased liver stiffness promotes hepatitis B progression by impairing innate immunity in CCl4-induced fibrotic HBV\u3csup\u3e+\u3c/sup\u3e transgenic mice

Background: Hepatitis B virus (HBV) infection develops as an acute or chronic liver disease, which progresses from steatosis, hepatitis, and fibrosis to end-stage liver diseases such as cirrhosis and hepatocellular carcinoma (HCC). An increased stromal stiffness accompanies fibrosis in chronic liver diseases and is considered a strong predictor for disease progression. The goal of this study was to establish the mechanisms by which enhanced liver stiffness regulates HBV infectivity in the fibrotic liver tissue. Methods: For in vitro studies, HBV-transfected HepG2.2.15 cells were cultured on polydimethylsiloxane gels coated by polyelectrolyte multilayer films of 2 kPa (soft) or 24 kPa (stiff) rigidity mimicking the stiffness of the healthy or fibrotic liver. For in vivo studies, hepatic fibrosis was induced in C57Bl/6 parental and HBV+ transgenic (HBVTg) mice by injecting CCl4 twice a week for 6 weeks. Results: We found higher levels of HBV markers in stiff gel-attached hepatocytes accompanied by up-regulated OPN content in cell supernatants as well as suppression of anti-viral interferon-stimulated genes (ISGs). This indicates that pre-requisite “fibrotic” stiffness increases osteopontin (OPN) content and releases and suppresses anti-viral innate immunity, causing a subsequent rise in HBV markers expression in hepatocytes. In vitro results were corroborated by data from HBVTg mice administered CCl4 (HBVTg CCl4). These mice showed higher HBV RNA, DNA, HBV core antigen (HBcAg), and HBV surface antigen (HBsAg) levels after liver fibrosis induction as judged by a rise in Col1a1, SMA, MMPs, and TIMPs mRNAs and by increased liver stiffness. Importantly, CCl4-induced the pro-fibrotic activation of liver cells, and liver stiffness was higher in HBVTg mice compared with control mice. Elevation of HBV markers and OPN levels corresponded to decreased ISG activation in HBVTg CCl4 mice vs HBVTg control mice. Conclusion: Based on our data, we conclude that liver stiffness enhances OPN levels to limit anti-viral ISG activation in hepatocytes and promote an increase in HBV infectivity, thereby contributing to end-stage liver disease progression

Alcohol-Induced Lysosomal Damage and Suppression of Lysosome Biogenesis Contribute to Hepatotoxicity in HIV-Exposed Liver Cells

Although the causes of hepatotoxicity among alcohol-abusing HIV patients are multifactorial, alcohol remains the least explored “second hit” for HIV-related hepatotoxicity. Here, we investigated whether metabolically derived acetaldehyde impairs lysosomes to enhance HIV-induced hepatotoxicity. We exposed Cytochrome P450 2E1 (CYP2E1)-expressing Huh 7.5 (also known as RLW) cells to an acetaldehyde-generating system (AGS) for 24 h. We then infected (or not) the cells with HIV-1ADA then exposed them again to AGS for another 48 h. Lysosome damage was assessed by galectin 3/LAMP1 co-localization and cathepsin leakage. Expression of lysosome biogenesis–transcription factor, TFEB, was measured by its protein levels and by in situ immunofluorescence. Exposure of cells to both AGS + HIV caused the greatest amount of lysosome leakage and its impaired lysosomal biogenesis, leading to intrinsic apoptosis. Furthermore, the movement of TFEB from cytosol to the nucleus via microtubules was impaired by AGS exposure. The latter impairment appeared to occur by acetylation of α-tubulin. Moreover, ZKSCAN3, a repressor of lysosome gene activation by TFEB, was amplified by AGS. Both these changes contributed to AGS-elicited disruption of lysosome biogenesis. Our findings indicate that metabolically generated acetaldehyde damages lysosomes and likely prevents their repair and restoration, thereby exacerbating HIV-induced hepatotoxicity

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

Role of apoptotic hepatocytes in HCV dissemination: regulation by acetaldehyde

Alcohol consumption exacerbates hepatitis C virus (HCV) pathogenesis and promotes disease progression, although the mechanisms are not quite clear. We have previously observed that acetaldehyde (Ach) continuously produced by the acetaldehyde-generating system (AGS), temporarily enhanced HCV RNA levels, followed by a decrease to normal or lower levels, which corresponded to apoptosis induction. Here, we studied whether Ach-induced apoptosis caused depletion of HCV-infected cells and what role apoptotic bodies (AB) play in HCV-alcohol crosstalk. In liver cells exposed to AGS, we observed the induction of miR-122 and miR-34a. As miR-34a has been associated with apoptotic signaling and miR-122 with HCV replication, these findings may suggest that cells with intensive viral replication undergo apoptosis. Furthermore, when AGS-induced apoptosis was blocked by a pan-caspase inhibitor, the expression of HCV RNA was not changed. AB from HCV-infected cells contained HCV core protein and the assembled HCV particle that infect intact hepatocytes, thereby promoting the spread of infection. In addition, AB are captured by macrophages to switch their cytokine profile to the proinflammatory one. Macrophages exposed to HCV+ AB expressed more IL-1β, IL-18, IL-6, and IL-10 mRNAs compared with those exposed to HCV-AB. The generation of AB from AGS-treated HCV-infected cells even enhanced the induction of aforementioned cytokines. We conclude that HCV and alcohol metabolites trigger the formation of AB containing HCV particles. The consequent spread of HCV to neighboring hepatocytes via infected AB, as well as the induction of liver inflammation by AB-mediated macrophage activation potentially exacerbate the HCV infection course by alcohol and worsen disease progression

Direct and Indirect Methods for Studying Human Gut Microbiota

Aim: To review the main methods of intestinal microbiota studying.Key points. Currently, molecular genetic methods are used mainly for basic research and do not have a unified protocol for data analysis, which makes it difficult to implement them in clinical practice. Measurement of short chain fatty acids (SCFA) concentrations in plasma provides the data, which can serve as an indirect biomarker of the colonic microbiota composition. However, currently available evidence is insufficient to relate the obtained values (SCFA levels and ratio) to a particular disease with a high degree of certainty. Trimethylamine N-oxide (TMAO) levels in the blood plasma and urine can also reflect the presence of specific bacterial clusters containing genes Cut, CntA/CntB and YeaW/YeaX. Therefore, further studies are required to reveal possible correlations between certain disorders and such parameters as the composition of gut microbiota, dietary patterns and TMAO concentration. Gas biomarkers, i.e. hydrogen, methane and hydrogen sulphide, have been studied in more detail and are better understood as compared to other biomarkers of the gut microbiome composition and functionality. The main advantage of gas biomarkers is that they can be measured multiple times using non-invasive techniques. These measurements provide information on the relative proportion of hydrogenic (i.e. hydrogen producing) and hydrogenotrophic (i.e. methanogenic and sulfate-reducing) microorganisms. In its turn, this opens up the possibility of developing new approaches to correction of individual microbiota components.Conclusions. Integration of the data obtained by gut microbiota studies at the genome, transcriptome and metabolome levels would allow a comprehensive analysis of microbial community function and its interaction with the human organism. This approach may increase our understanding of the pathogenesis of various diseases as well open up new opportunities for prevention and treatment

ELECTRONIC ABSORPTION SPECTRA OF PRASEODIMIUM(III) IONS IN ALKALI CHLORIDE MELTS

Electronic absorption spectra of Pr(III) ions were recorded in fused alkali chlorides. To assess the effect of temperature and solvent melt cations on the spectra the measurements were performed between 350 and 850 oC in the melts based on individual alkali metal chlorides (LiCl, NaCl, KCl and CsCl) and several mixtures (LiCl–KCl, NaCl–CsCl and LiCl–KCl–CsCl eutectics and NaCl–KCl equimolar mixture)

ELECTRONIC ABSORPTION SPECTRA OF ERBIUM(III) IONS IN ALKALI CHLORIDE MELTS

Electronic absorption spectra of Er(III) ions were recorded in the melts based on individual alkali chlorides and their mixtures: LiCl, NaCl, KCl, CsCl, binary LiCl–KCl and NaCl–CsCl eutectics, ternary LiCl–KCl–CsCl eutectic and NaCl–KCl equimolar mixture. The spectra were measured between 350 and 850 oC. The effect of temperature and alkali cations forming the second coordination sphere on the spectra and erbium speciation is discussed