40 research outputs found
LINGUISTICS OF INDIRECT INFLUENCE AS A LANGUAGE GAME IN SOCIO-POLITICAL DISCOURSE
Abstract. The article considers the methods of so-called "silence-speech" – specific speech, tactics andstrategies of which are oriented, on the one hand, to the author’s non-identification of some aspects and events of socio-political life; on the other hand, to the use of intentional ambiguity, which violates the rule of accuracy and obviousness of a speech, and at the same time makes it understandable, accessible to the target audience's perception of the speaker. As a rule, such a two-tiered textual corset of the text is formed with the help of appropriate intonation (in oral speech) and a special set of lexical means (in oral and written speech), less often this function is performed by morphological and syntactic language means. The authors of the article suggest several methods of "diagnostics" hidden semantics in the text, as well as ways to verify these "secret" meanings, using the achievements of modern linguistics, communicativistics, psycholinguistics and approaching the classical complex text analysis. Fragments of modern publicistic oral and written speech texts have become the material of this study.Keywords: mass communication, linguistics of influence, communicative efficiency, intention, perlocutiveeffect, implicit semantics, discourse analysis
Морфологические изменения желез Гардера после имплантации пленок поликапролактонных в роговицу
Имплантация пленок поликапролактона в строму роговицы глаза сопровождается развитием незначительных реактивных изменений желез Гардера в виде умеренного полнокровия сосудов, отека стромы железы, которые обусловливают неспецифические реактивные изменения в железе. Реактивные изменения железы Гардера (умеренное полнокровие сосудов, отек стромы железы) свидетельствуют об экзогенном механизме - хирургическом воздействии на морфологическую трансформацию железы
The altered serum lipidome and its diagnostic potential for Non-Alcoholic Fatty Liver (NAFL)-associated hepatocellular carcinoma
Background
Non-alcoholic fatty liver disease (NAFLD) is affecting more people globally. Indeed, NAFLD is a spectrum of metabolic dysfunctions that can progress to hepatocellular carcinoma (NAFLD-HCC). This development can occur in a non-cirrhotic liver and thus, often lack clinical surveillance. The aim of this study was to develop non-invasive surveillance method for NAFLD-HCC.
Methods
Using comprehensive ultra-high-performance liquid chromatography mass-spectrometry, we investigated 1,295 metabolites in serum from 249 patients. Area under the receiver operating characteristic curve was calculated for all detected metabolites and used to establish their diagnostic potential. Logistic regression analysis was used to establish the diagnostic score.
Findings
We show that NAFLD-HCC is characterised by a complete rearrangement of the serum lipidome, which distinguishes NAFLD-HCC from non-cancerous individuals and other HCC patients. We used machine learning to build a diagnostic model for NAFLD-HCC. We quantified predictive metabolites and developed the NAFLD-HCC Diagnostic Score (NHDS), presenting superior diagnostic potential compared to alpha-fetoprotein (AFP). Patients’ metabolic landscapes show a progressive depletion in unsaturated fatty acids and acylcarnitines during transformation. Upregulation of fatty acid transporters in NAFLD-HCC tumours contribute to fatty acid depletion in the serum.
Interpretation
NAFLD-HCC patients can be efficiently distinguished by serum metabolic alterations from the healthy population and from HCC patients related to other aetiologies (alcohol and viral hepatitis). Our model can be used for non-invasive surveillance of individuals with metabolic syndrome(s), allowing for early detection of NAFLD-HCC. Therefore, serum metabolomics may provide valuable insight to monitor patients at risk, including morbidly obese, diabetics, and NAFLD patients.
Funding
The funding sources for this study had no role in study design, data collection, data analyses, interpretation or writing of the report as it is presented herein
Cytokine Storm Combined with Humoral Immune Response Defect in Fatal Hemorrhagic Fever with Renal Syndrome Case, Tatarstan, Russia
Hemorrhagic fever with renal syndrome (HFRS) is endemic in Tatarstan, where thousands of cases are registered annually. Puumala orthohantavirus is commonly detected in human case samples as well as in captured bank voles, the rodent hosts. The pathogenesis of HFRS is still not well described, although the cytokine storm hypothesis is largely accepted. In this study, we present a comprehensive analysis of a fatal HFRS case compared with twenty four non-fatal cases where activation of the humoral and cellular immune responses, pro-inflammatory cytokines and disturbed blood coagulation were detected using immunological, histological, genetic and clinical approaches. Multiple organ failure combined with disseminated intravascular coagulation syndrome and acute renal failure was the cause of death. Decreased Interleukin (IL)-7 and increased IL-18, chemokine (C-C motif) ligand (CCL)-5, stem cell growth factor (SCGF)-b and tumor necrosis factor-beta (TNF-β) serum levels were found, supporting the cytokine storm hypothesis of hantavirus pathogenesis
Use of Biologically Active 3D Matrix for Extensive Skin Defect Treatment in Veterinary Practice: Case Report
Objectives: Large full-thickness skin defects represent a serious veterinary problem.Methods: We have developed novel bioactive 3D-matrixes based on fibrin glue Tissucol (Baxter), containing the combination of the adenoviral constructs with genes vascular endothelial growth factor 165 (VEGF165) and fibroblast growth factor two (FGF2; construct Ad5-VEGF165 + Ad5-FGF2) or multipotent mesenchymal stem cells, genetically modified with these constructs.Results:In vitro studies confirmed the biosynthesis of VEGF165 and FGF2 mRNA in the transduced cells. Ad5-VEGF165 + Ad5-FGF2- transduced multipotent mesenchymal stem cells showed an enhanced capacity to form capillary-like tubes in vitro. Bioactive 3D-matrix application enhanced granulation tissue formation and epithelialization of non-healing, large bite wounds in a dog. Successful wound healing was observed with a positive clinical outcome for the canine patient. This research and application of regenerative gene therapy alongside a novel bioactive 3D-matrix shows promising clinical applications for the future in both dogs and other mammals including humans
Proangiogenic Effect of 2A-Peptide Based Multicistronic Recombinant Constructs Encoding VEGF and FGF2 Growth Factors
Coronary artery disease remains one of the primary healthcare problems due to the high cost of treatment, increased number of patients, poor clinical outcomes, and lack of effective therapy. Though pharmacological and surgical treatments positively affect symptoms and arrest the disease progression, they generally exhibit a limited effect on the disease outcome. The development of alternative therapeutic approaches towards ischemic disease treatment, especially of decompensated forms, is therefore relevant. Therapeutic angiogenesis, stimulated by various cytokines, chemokines, and growth factors, provides the possibility of restoring functional blood flow in ischemic tissues, thereby ensuring the regeneration of the damaged area. In the current study, based on the clinically approved plasmid vector pVax1, multigenic constructs were developed encoding vascular endothelial growth factor (VEGF), fibroblast growth factors (FGF2), and the DsRed fluorescent protein, integrated via picornaviruses’ furin-2A peptide sequences. In vitro experiments demonstrated that genetically modified cells with engineered plasmid constructs expressed the target proteins. Overexpression of VEGF and FGF2 resulted in increased levels of the recombinant proteins. Concomitantly, these did not lead to a significant shift in the general secretory profile of modified HEK293T cells. Simultaneously, the secretome of genetically modified cells showed significant stimulating effects on the formation of capillary-like structures by HUVEC (endothelial cells) in vitro. Our results revealed that when the multicistronic multigene vectors encoding 2A peptide sequences are created, transient transgene co-expression is ensured. The results obtained indicated the mutual synergistic effects of the growth factors VEGF and FGF2 on the proliferation of endothelial cells in vitro. Thus, recombinant multicistronic multigenic constructs might serve as a promising approach for establishing safe and effective systems to treat ischemic diseases
Sorption Capacity of Reindeer Horn Tissue in Relation to Pb2+ Ions
В работе р ассмотрена с орбционная с пособность т кани р огов с еверных
оленей в отношении ионов Pb2+. Исследованы структурно-функциональные
особенности
строения биополимеров, входящих в состав ткани рогов северных оленей с использованием
ИК‑спектроскопии. Проведена сравнительная оценка сорбционных показателей (константы
сорбционной ёмкости, коэффициента связывающей емкости, степени сродства, а также
коэффициента интенсивности сорбции) ткани рогов и полисорба в отношении ионов свинца.
В работе показана возможность использования ткани рогов северных оленей в качестве
энтеросорбентов при хронических отравлениях солями свинцаThe paper considers the sorption capacity of reindeer horn tissue in relation to Pb2+ ions. The structural and functional features of the structure of biopolymers included in the tissue of reindeer antlers using IR spectroscopy have been studied. A comparative assessment of sorption parameters (sorption capacity constants, binding capacity coefficient, degree of affinity, as well as sorption intensity coefficient) of horn tissue and polysorb with respect to lead ions was carried out. The paper shows the possibility of using reindeer horn tissue as enterosorbents in chronic poisoning with lead salt
The altered serum lipidome and its diagnostic potential for Non-Alcoholic Fatty Liver (NAFL)-associated hepatocellular carcinoma
[Background] Non-alcoholic fatty liver disease (NAFLD) is affecting more people globally. Indeed, NAFLD is a spectrum of metabolic dysfunctions that can progress to hepatocellular carcinoma (NAFLD-HCC). This development can occur in a non-cirrhotic liver and thus, often lack clinical surveillance. The aim of this study was to develop non-invasive surveillance method for NAFLD-HCC.[Methods] Using comprehensive ultra-high-performance liquid chromatography mass-spectrometry, we investigated 1,295 metabolites in serum from 249 patients. Area under the receiver operating characteristic curve was calculated for all detected metabolites and used to establish their diagnostic potential. Logistic regression analysis was used to establish the diagnostic score.[Findings] We show that NAFLD-HCC is characterised by a complete rearrangement of the serum lipidome, which distinguishes NAFLD-HCC from non-cancerous individuals and other HCC patients. We used machine learning to build a diagnostic model for NAFLD-HCC. We quantified predictive metabolites and developed the NAFLD-HCC Diagnostic Score (NHDS), presenting superior diagnostic potential compared to alpha-fetoprotein (AFP). Patients’ metabolic landscapes show a progressive depletion in unsaturated fatty acids and acylcarnitines during transformation. Upregulation of fatty acid transporters in NAFLD-HCC tumours contribute to fatty acid depletion in the serum.[Interpretation] NAFLD-HCC patients can be efficiently distinguished by serum metabolic alterations from the healthy population and from HCC patients related to other aetiologies (alcohol and viral hepatitis). Our model can be used for non-invasive surveillance of individuals with metabolic syndrome(s), allowing for early detection of NAFLD-HCC. Therefore, serum metabolomics may provide valuable insight to monitor patients at risk, including morbidly obese, diabetics, and NAFLD patients.We thank all funding sources: The laboratory of JBA is supported by the Novo Nordisk Foundation (14040, 0058419), Danish Cancer Society (R98-A6446, R167-A10784, R278-A16638), and the Danish Medical Research Council (4183-00118A, 1030-00070B). Data used for validation in this study provided by JMB was funded by the Spanish Ministry of Economy and Competitiveness and ’Instituto de Salud Carlos III’ grants (PI18/01075, Miguel Servet Programme CON14/00129 and CPII19/00008) co-financed by ’Fondo Europeo de Desarrollo Regional’ (FEDER); CIBERehd, Spain; IKERBASQUE, Basque foundation for Science, Spain; BIOEF (Basque Foundation for Innovation and Health Research: EiTB Maratoia BIO15/CA/016/BD); Department of Health of the Basque Country (2017111010), Euskadi RIS3 (2019222054, 2020333010); Department of Industry of the Basque Country (Elkartek: KK-2020/00008), AECC Scientific Foundation and European Commission Horizon 2020 program (ESCALON project no.: 825510). Similarly, MAJ was funded by grants from the Fondo Nacional De Ciencia y Tecnología de Chile (FONDECYT #1191145 to M.A.) and the Comisión Nacional de Investigación, Ciencia y Tecnología (CONICYT, AFB170005, CARE Chile UC).Peer reviewe
TREM-2 defends the liver against hepatocellular carcinoma through multifactorial protective mechanisms
[EN] Objective Hepatocellular carcinoma (HCC) is a prevalent
and aggressive cancer usually arising on a background
of chronic liver injury involving inflammatory and hepatic
regenerative processes. The triggering receptor expressed
on myeloid cells 2 (TREM-2) is predominantly expressed in
hepatic non-parenchymal
cells and inhibits Toll-like
receptor
signalling, protecting the liver from various hepatotoxic
injuries, yet its role in liver cancer is poorly defined. Here,
we investigated the impact of TREM-2 on liver regeneration
and hepatocarcinogenesis.
Design TREM-2 expression was analysed in liver tissues
of two independent cohorts of patients with HCC and
compared with control liver samples. Experimental HCC
and liver regeneration models in wild type and Trem-2-/-
mice, and in vitro studies with hepatic stellate cells (HSCs)
and HCC spheroids were conducted.
Results TREM-2 expression was upregulated in human
HCC tissue, in mouse models of liver regeneration and
HCC. Trem-2-/- mice developed more liver tumours
irrespective of size after diethylnitrosamine (DEN)
administration, displayed exacerbated liver damage,
inflammation, oxidative stress and hepatocyte proliferation.
Administering an antioxidant diet blocked DEN-induced
hepatocarcinogenesis in both genotypes. Similarly,
Trem-2-/- animals developed more and larger tumours in
fibrosis-associated
HCC models. Trem-2-/- livers showed
increased hepatocyte proliferation and inflammation after
partial hepatectomy. Conditioned media from human HSCs
overexpressing TREM-2 inhibited human HCC spheroid
growth in vitro through attenuated Wnt ligand secretion.
Conclusion TREM-2 plays a protective role in
hepatocarcinogenesis via different pleiotropic effects,
suggesting that TREM-2 agonism should be investigated
as it might beneficially impact HCC pathogenesis in a
multifactorial manner.Spanish Ministry of Economy and Competitiveness and ’Instituto de Salud
Carlos III’ grants (MJP (PI14/00399, PI17/00022 and Ramon y Cajal Programme
RYC-2015–17755); JMB (PI12/00380, PI15/01132, PI18/01075, Miguel Servet
Programme CON14/00129 and CPII19/00008) cofinanced by ’Fondo Europeo de
Desarrollo Regional’ (FEDER); CIBERehd: MJP, JMB and LB), Spain; IKERBASQUE,
Basque foundation for Science (MJP and JMB), Spain; ’Diputación Foral de Gipuzkoa’
(MJP: DFG18/114, DFG19/081; JMB: DFG15/010, DFG16/004); BIOEF (Basque
Foundation for Innovation and Health Research: EiTB Maratoia BIO15/CA/016/
BD to JMB); Department of Health of the Basque Country (MJP: 2015111100 and
2019111024; JMB: 2017111010), Euskadi RIS3 (JMB: 2016222001, 2017222014,
2018222029, 2019222054, 2020333010) Department of Industry of the Basque
Country (JMB: Elkartek: KK-2020/00008) and AECC Scientific Foundation (JMB).
AE-B
was funded by the University of the Basque Country (UPV/EHU) (PIF2014/11)
and by the short-term
training fellowship Andrew K Burroughs (European
Association for the Study of the Liver, EASL). IL and AA-L
were funded by the
Department of Education, Language Policy and Culture of the Basque Government
(PRE_2016_1_0152 and PRE_2018_1_0184). OS and SK were funded by the
Austrian Science Fund (FWF25801-B22,
FWF-P35168
to OS and L-Mac:
F 6104-B21
to SK). FO and DAM were funded by a UK Medical Research Council programme
Grant MR/R023026/1. DAM was also funded by the CRUK programme grant
C18342/A23390, CRUK/AECC/AIRC Accelerator Award A26813 and the MRC MICA
programme grant MR/R023026/1. JBA is supported by the Danish Medical Research
Council, Danish Cancer Society, Nordisk Foundation, and APM Foundation. CJO’R
and PM-G
are supported by Marie Sklodowska-Curie
Programme and EASL Sheila
Sherlock postdoctoral fellowships
In Need for a More Holistic Perspective: Clarifying Instrumental and Non-Instrumental Approaches to Workplace Spirituality
Different approaches within the emerging literature on spirituality at work are analysed using the construct of instrumental and non-instrumental approaches. These approaches deal with either expected or unfolding effects of spirituality and have profound implications for organisations because they shed light on the issue of the manipulative or authentic application of workplace spirituality. Linking the instrumental approach to objective, and non-instrumental - to subjective research methodologies makes the ontological and epistemological assumptions of instrumentalism and non-instrumentalism explicit and enables the identification of the fundamentally different nature of the research questions originating from these two perspectives.16 page(s