Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

SMALL-FORMAT “NEWS FLOW” MEDIATEXTS IN THE FOCUS OF LINGUISTICS: GENRE AND LANGUAGE PECULIARITIES

Today the media sphere is one of the most active functional areas of the modern Russian language, and it demonstrates the major current trends of modern Russian speech in the most vivid way. This is what conditions the study of small-format texts of the “news flow”, which belong to the basic and most widespread media texts. These texts are characterized by a stable structure and certain genre and linguistic features, the description of which is the purpose of the study. News stories of news agencies, captions, news tickers and other text materials of T.V. news programs were chosen as sources of material. It is small-format news media texts that represent media speech “in its pure form”. The volume of such texts varies from a single utterance to texts of an average volume, consisting of 4-6 paragraphs (up to 5000 characters). The nature of the genre determines the placement of information in these texts according to the “inverted pyramid” principle, well-known in journalistic practice, as well as the prevalence of the informative component, semantic density, syntactic minimalism in such texts. The article considers the main common feature of small-format news media texts - linguistic asceticism, consisting in “anti-creativity”, “neutrality” of speech, absence of distinct metaphorical and evaluative linguistic means, in simple syntactic structures. The most striking linguistic features of these texts, which singles them out in a separate group, include a large number of abbreviations, borrowings, structures that indicate the source of the news information. Small-format news media texts have significant linguodidactic potential. A stable structure and fairly rigid regulation of the language give grounds for their more active use as didactic material in the practice of teaching Russian as a foreign language (RFL) and Russian as a non-native language (RNL)

Linezolid-dependent function and structure adaptation of ribosomes in a Staphylococcus epidermidis strain exhibiting linezolid dependence

Linezolid-dependent growth was recently reported in Staphylococcus epidermidis clinical strains carrying mutations associated with linezolid resistance. To investigate this unexpected behavior at the molecular level, we isolated active ribosomes from one of the linezolid-dependent strains and we compared them with ribosomes isolated from a wild-type strain. Both strains were grown in the absence and presence of linezolid. Detailed biochemical and structural analyses revealed essential differences in the function and structure of isolated ribosomes which were assembled in the presence of linezolid. The catalytic activity of peptidyltransferase was found to be significantly higher in the ribosomes derived from the linezolid-dependent strain. Interestingly, the same ribosomes exhibited an abnormal ribosomal subunit dissociation profile on a sucrose gradient in the absence of linezolid, but the profile was restored after treatment of the ribosomes with an excess of the antibiotic. Our study suggests that linezolid most likely modified the ribosomal assembly procedure, leading to a new functional ribosomal population active only in the presence of linezolid. Therefore, the higher growth rate of the partially linezolid-dependent strains could be attributed to the functional and structural adaptations of ribosomes to linezolid. Copyright © 2014, American Society for Microbiology. All Rights Reserved

Optical Biometry Derived Axial Length Measurements Following Intravitreal Anti-Vascular Endothelial Growth Factor Treatment for Macular Edema.

To evaluate axial length (AL) alterations in patients with macular disease over the course of intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment. In this prospective, comparative study, 33 patients with macular edema underwent unilaterally intravitreal anti-VEGF therapy and were followed for two months; the contralateral eyes were considered as controls. Central retinal thickness (CRT) was measured with spectral-domain optical coherence tomography and AL with an IOL-Master optical biometer. CRT of the treated eyes decreased by 35.33 ± 65.59 μm (range, -222.00-67 μm), while AL increased by 0.008 ± 0.062 mm (range, -0.11-0.18 mm). CRT of the control group decreased by 9.82 ± 65.40 μm (range, -203-182 μm), and AL increased by 0.011 ± 0.129 mm (range, -0.20-0.67 mm). No significant correlation was detected between CRT and AL parameters (rhos=0.026, P=0.882). Anti-VEGF administration has no significant impact on optical biometry-derived AL measurements

Performance indicators for European bridge management

Bridge management as a part of road infrastructure network includes a series of activities that are interconnected in order to achieve its optimal value, including balancing of required costs, potential risks and overall bridge performance. In this context, different performance levels within bridge management are identified and discussed in this paper. Moreover, bridge performance aspects are overviewed, based on a set of national practice codes/guidelines and research accomplishments related to bridge management across the Europe. In sequence, the categorization of Performance Indicators (PI), within the Key Performance Indictors (KPI) umbrella, is described in relation to Performance Goals (PG) and Performance Thresholds (PT) at different levels taking into account different aspects. In addition, a reference to monitoring based PI is also made and to how they frame in current practices of road bridge management. In order to improve the existent performance assessment methods, further research activities and developments are herein foreseen focusing on the management of roadway bridges. In addition to giving a review on systematization of PIs, the main contribution of this paper is a reflection on extraction and categorization of key performance indicators to improve existing assessment methods within management system of road bridges.This article is based upon the work from COST Action TU1406, Quality specifications for roadway bridges, standardization at a European level (BridgeSpec), supported by COST (European Cooperation in Science and Technology). The authors would also like to acknowledge the financial support of the "ATCZ190 SAFEBRIDGE" project by the European Regional Development Fund within the European Union Program "INTERREG AUSTRIA-CZECH REPUBLIC

Optical Biometry Derived Axial Length Measurements Following Intravitreal Anti-Vascular Endothelial Growth Factor Treatment for Macular Edema

Purpose: To evaluate axial length (AL) alterations in patients with macular disease over the course of intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment. Methods: In this prospective, comparative study, 33 patients with macular edema underwent unilaterally intravitreal anti-VEGF therapy and were followed for two months; the contralateral eyes were considered as controls. Central retinal thickness (CRT) was measured with spectral-domain optical coherence tomography and AL with an IOL-Master optical biometer. Results: CRT of the treated eyes decreased by 35.33 ± 65.59 μm (range, –222.00–67 μm), while AL increased by 0.008 ± 0.062 mm (range, –0.11–0.18 mm). CRT of the control group decreased by 9.82 ± 65.40 μm (range, –203–182 μm), and AL increased by 0.011 ± 0.129 mm (range, –0.20–0.67 mm). No significant correlation was detected between CRT and AL parameters (rhos=0.026, P=0.882). Conclusions: Anti-VEGF administration has no significant impact on optical biometry-derived AL measurements. © Taylor & Francis

Flying under the radar: DNA barcoding ray wings in Greece detects protected species and umbrella labelling terms

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordMislabeling of seafood products and marketing of protected species remains a worldwide issue despite the labeling regulations set at a local, European and International level. DNA barcoding has proven to be the most popular and accurate method of detection of fraudulent seafood products. This study investigated the batoid meat market of Greece, the mislabeling rates and the protected species occurrence. A total of 114 ray products were collected from fishmongers, open markets, supermarkets, and restaurants across eight Greek cities. The cytochrome oxidase subunit I (COI) gene was used to analyze samples, and the sequences were compared against genetic databases for species identification. At least 13 species across nine genera were identified. The results did not indicate significant differences in species utilization among cities, retailers, and labels. However, in the pairwise comparisons, Athens differed from all other locations and a similar trend was followed by the label “salachi”. Moderate mislabeling levels were recorded (13.5%), while 3.5% of the identified samples belonged to species with prohibitions on landings, confirming an ongoing market for protected species. Overall, 19.8% of the samples originated from species that are locally listed in threatened categories of the IUCN Red List of species.Fisheries Society of the British Isles (FSBI)Save Our Seas Foundation (SOSF