Дискурсний аналіз оповідань А. К. Дойла "Пригоди Шерлока Холмса" мовою оригіналу (Discourse analysis of the stories The Adventures of Sherlock Holmes by A. C. Doyle in the original)

У тезах досліджується специфіка детективного дискурсу, а також засоби когезії та континууму, притаманні цьому жанру, на прикладі чотирьох оповідань А. К. Дойла із циклу «Пригоди Шерлока Холмса». (This research explores the distinguishing features of detective discourse as well as means of cohesion and continuum, peculiar to this genre, using the example of four detective stories from the collection «The Adventures of Sherlock Holmes» by A. C. Doyle.

НЕВЕРБАЛЬНІ ЗАСОБИ СПІЛКУВАННЯ В МОВНИХ ТРАДИЦІЯХ СПОЛУЧЕНИХ ШТАТІВ АМЕРИКИ ТА КАНАДИ (UNVERBAL MEANS OF COMMUNICATION IN LANGUAGE TRADITIONS OF THE UNITED STATES OF AMERICA AND CANADA)

У тезах досліджено невербальні засоби спілкування, які широко застосовують у Сполучених Штатах Америки й Канаді, і вплив їх на міжособистісну комунікацію. Проаналізовано вплив національно-культурних чинників на процес спілкування. (This thesis explores the non-verbal means of communication widely used in the United States of America and Canada and impact of these means on the interpersonal communication. There is also an analysis of the impact of the national and cultural factors on the process of communication.

Assessment of self-perceived knowledge of key clinical pharmacology concepts and educational needs among European Paediatric Intensive Care Units: an ESPNIC survey

Background: Knowledge of clinical pharmacology concepts is essential to improve patients’ outcomes. Scarce data is available on the utilisation of these concepts in the paediatric intensive care unit (PICU). We aimed to investigate the self-perceived knowledge of clinical pharmacology concepts, educational needs and identify priorities for pharmacological research across European PICUs. Methods: From July to November 2022 an online survey was distributed to evaluate i) the self-reported knowledge, and ii) application of key pharmacology concepts in clinical practice (using a likert scale from 1 = never apply to 10 = always apply); iii) need for additional education on them; and iv) key areas for future pharmacological research. The survey was distributed to European Society of Paediatric and Neonatal Intensive Care (ESPNIC) members and other European national PICUs societies members. Results: Two-hundred-thirty-seven responses from 149 PICUs were collected. 54% of PICUs reported to have a clinical pharmacologist available for consultation during drug prescription and 65% of them regularly contact them during the prescribing process. Among clinical pharmacology concepts the parameter with the highest self-reported knowledge was half-life (99%) and the lowest were pharmacodynamics and volume-of-distribution (92%). The reported median application of these concepts in clinical practice ranged between 5/10 and 7/10. Most of the respondents reported the need for additional education on specific pharmacology concepts. Reported priorities for drug research mostly involved analgesics/sedatives (87%), antimicrobials (86%), and cardiovascular medications (55%). Conclusions: Self-reported knowledge on clinical pharmacology concepts seems good, but self-perceived clinical application may improve and most of the respondents report a need for additional education. These findings call for concerted multidisciplinary efforts to streamline education and guidelines to fill this gap

A Comparison of Red Fluorescent Proteins to Model DNA Vaccine Expression by Whole Animal In Vivo Imaging

DNA vaccines can be manufactured cheaply, easily and rapidly and have performed well in pre-clinical animal studies. However, clinical trials have so far been disappointing, failing to evoke a strong immune response, possibly due to poor antigen expression. To improve antigen expression, improved technology to monitor DNA vaccine transfection efficiency is required. In the current study, we compared plasmid encoded tdTomato, mCherry, Katushka, tdKatushka2 and luciferase as reporter proteins for whole animal in vivo imaging. The intramuscular, subcutaneous and tattooing routes were compared and electroporation was used to enhance expression. We observed that overall, fluorescent proteins were not a good tool to assess expression from DNA plasmids, with a highly heterogeneous response between animals. Of the proteins used, intramuscular delivery of DNA encoding either tdTomato or luciferase gave the clearest signal, with some Katushka and tdKatushka2 signal observed. Subcutaneous delivery was weakly visible and nothing was observed following DNA tattooing. DNA encoding haemagglutinin was used to determine whether immune responses mirrored visible expression levels. A protective immune response against H1N1 influenza was induced by all routes, even after a single dose of DNA, though qualitative differences were observed, with tattooing leading to high antibody responses and subcutaneous DNA leading to high CD8 responses. We conclude that of the reporter proteins used, expression from DNA plasmids can best be assessed using tdTomato or luciferase. But, the disconnect between visible expression level and immunogenicity suggests that in vivo whole animal imaging of fluorescent proteins has limited utility for predicting DNA vaccine efficacy

Towards an international language for incontinence-associated dermatitis (IAD): design and evaluation of psychometric properties of the Ghent Global IAD Categorization Tool (GLOBIAD) in 30 countries

Background Incontinence-associated dermatitis (IAD) is a specific type of irritant contact dermatitis with different severity levels. An internationally accepted instrument to assess the severity of IAD in adults, with established diagnostic accuracy, agreement and reliability, is needed to support clinical practice and research. Objectives To design the Ghent Global IAD Categorization Tool (GLOBIAD) and evaluate its psychometric properties. Methods The design was based on expert consultation using a three-round Delphi procedure with 34 experts from 13 countries. The instrument was tested using IAD photographs, which reflected different severity levels, in a sample of 823 healthcare professionals from 30 countries. Measures for diagnostic accuracy (sensitivity and specificity), agreement, interrater reliability (multirater Fleiss kappa) and intrarater reliability (Cohen’s kappa) were assessed. Results The GLOBIAD consists of two categories based on the presence of persistent redness (category 1) and skin loss (category 2), both of which are subdivided based on the presence of clinical signs of infection. The agreement for differentiating between category 1 and category 2 was 0 86 [95% confidence interval (CI) 0 86–0 87], with a sensitivity of 90% and a specificity of 84%. The overall agreement was 0 55 (95% CI 0 55–0 56). The Fleiss kappa for differentiating between category 1 and category 2 was 0 65 (95% CI 0 65–0 65). The overall Fleiss kappa was 0 41 (95% CI 0 41–0 41). The Cohen’s kappa for differentiating between category 1 and category 2 was 0 76 (95% CI 0 75–0 77). The overall Cohen’s kappa was 0 61 (95% CI 0 59–0 62). Conclusions The development of the GLOBIAD is a major step towards a better systematic assessment of IAD in clinical practice and research worldwide. However, further validation is needed.info:eu-repo/semantics/acceptedVersio

Dendritic Cells Transfected with scFv from Mab 7.B12 Mimicking Original Antigen gp43 Induces Protection against Experimental Paracoccidioidomycosis

Paracoccidioidomycosis (PCM), endemic in Latin America, is a progressive systemic mycosis caused by Paracoccidioides brasiliensis (P. brasiliensis), which primarily attacks lung tissue. Dendritic cells (DCs) are able to initiate a response in naïve T cells, and they also participate in Th-cell education. Furthermore, these cells have been used for therapy in several disease models. Here we transfected DCs with a plasmid (pMAC/PS-scFv) encoding a single chain variable fragment (scFv) of an anti-Id antibody that is capable of mimicking gp43, the main antigenic component of P. brasiliensis. First, Balb/c mice were immunized subcutaneously with pMAC/PS-scFv and, after seven days, scFv protein was presented to the regional lymph nodes cells. Moreover, we showed that the DCs transfected with scFv were capable of efficiently activating proliferation of total lymph node cells and inducing a decrease in lung infection. Therefore, our results suggested that the use of scFv-transfected DCs may be a promising therapy in the paracoccidioidomycosis (PCM) model

Integrative genetic map of repetitive DNA in the sole Solea senegalensis genome shows a Rex transposon located in a proto-sex chromosome

Repetitive sequences play an essential role in the structural and functional evolution of the genome, particularly in the sexual chromosomes. The Senegalese sole (Solea senegalensis) is a valuable flatfish in aquaculture albeit few studies have addressed the mapping and characterization of repetitive DNA families. Here we analyzed the Simple Sequence Repeats (SSRs) and Transposable elements (TEs) content from fifty-seven BAC clones (spanning 7.9 Mb) of this species, located in chromosomes by multiple fluorescence in situ hybridization (m-BAC-FISH) technique. The SSR analysis revealed an average density of 675.1 loci per Mb and a high abundance (59.69%) of dinucleotide coverage was observed, being 'AC' the most abundant. An SSR-FISH analysis using eleven probes was also carried out and seven of the 11 probes yielded positive signals. 'AC' probes were present as large clusters in almost all chromosomes, supporting the bioinformatic analysis. Regarding TEs, DNA transposons (Class II) were the most abundant. In Class I, LINE elements were the most abundant and the hAT family was the most represented in Class II. Rex/Babar subfamily, observed in two BAC clones mapping to chromosome pair 1, showed the longest match. This chromosome pair has been recently reported as a putative sexual proto-chromosome in this species, highlighting the possible role of the Rex element in the evolution of this chromosome. In the Rex1 phylogenetic tree, the Senegalese sole Rex1 retrotransposon could be associated with one of the four major ancient lineages in fish genomes, in which it is included O. latipes

Synthesis, X-ray Analysis, and Biological Evaluation of a New Class of Stereopure Lactam-Based HIV-1 Protease Inhibitors

In an effort to identify a new class of druglike HIV-1 protease inhibitors, four different stereopure beta-hydroxy gamma-lactam-containing inhibitors have been synthesized, biologically evaluated, and cocrystallized. The impact of the tether length of the central spacer (two or three carbons) was also investigated. A compound with a shorter tether and (3R,4S) absolute configuration exhibited high activity with a K-i of 2.1 nM and an EC50 of 0.64 mu M. Further optimization by decoration of the P1' side chain furnished an even more potent HIV-1 protease inhibitor (K-i = 0.8 nM, EC50 = 0.04 mu M). According to X-ray analysis, the new class of inhibitors did not fully succeed in forming two symmetric hydrogen bonds to the catalytic aspartates. The crystal structures of the complexes further explain the difference in potency between the shorter inhibitors (two-carbon spacer) and the longer inhibitors (three-carbon spacer)

Inborn errors of OAS-RNase L in SARS-CoV-2-related multisystem inflammatory syndrome in children

Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1, OAS2, or RNASEL in five unrelated children with MIS-C. The cytosolic double-stranded RNA (dsRNA)-sensing OAS1 and OAS2 generate 2'-5'-linked oligoadenylates (2-5A) that activate the single-stranded RNA-degrading ribonuclease L (RNase L). Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNase L deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulation. Exogenous 2-5A suppresses cytokine production in OAS1-deficient but not RNase L-deficient cells. Cytokine production in RNase L-deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by mitochondrial antiviral-signaling protein (MAVS) deficiency. Recessive OAS-RNase L deficiencies in these patients unleash the production of SARS-CoV-2-triggered, MAVS-mediated inflammatory cytokines by mononuclear phagocytes, thereby underlying MIS-C