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In the cardiovascular system, atherogenic low-density lipoproteins (LDL) and the protective hormone adiponectin bind to the same receptor, T-cadherin. In this study, we tested the hypothesis that the ratio of circulating LDL to high-molecular weight (HMW) adiponectin could predict the development of atherosclerosis. Using enzyme-linked immunosorbent assay, we measured the level of circulating HMW adiponectin in the blood of donors together with ultrasound measuring of intima-media thickness (IMT) of carotid arteries. Single-nucleotide polymorphisms in the T-cadherin gene were identified using polymerase chain reaction. We found that carotid artery IMT is inversely correlated with the level of HMW in male subjects. We also found that the G allele of rs12444338 SNP in the T-cadherin gene correlates with a lower level of circulating T-cadherin and thinner IMT and therefore could be considered as an atheroprotective genotype. Despite our data, we could not provide direct evidence for the initial study hypothesis. However, we did uncover an important correlation between circulating T-cadherin and thinner carotid IMT.

Vericiguat is indicated to reduce the risk of cardiovascular death and hospitalisation for heart failure in patients with heart failure and reduced ejection fraction (HFrEF) following a recent worsening event. The aim of the VICTOR trial was to assess the effect of vericiguat in patients with HFrEF without recent heart failure worsening. In this double-blind, placebo-controlled, phase 3 trial, conducted at 482 sites across 36 countries, patients aged 18 years or older with HFrEF (left ventricular ejection fraction of ≤40%) without heart failure hospitalisation within 6 months or outpatient intravenous diuretic use within 3 months before randomisation were randomly assigned (1:1) using an intervention randomisation system with interactive response technology to oral vericiguat (target 10 mg dose) or matching placebo. The primary composite endpoint was time to cardiovascular death or heart failure hospitalisation. Efficacy endpoints were assessed in the intention-to-treat population. Adverse events were assessed in all randomly assigned patients who received at least one dose of study drug (safety population). This trial is registered with ClinicalTrials.gov, NCT05093933, and is complete. Between Nov 2, 2021, and Dec 21, 2023, 10 921 patients were screened and 6105 were randomly assigned: 3053 to vericiguat and 3052 to placebo. The median age was 68·0 years (IQR 61·0–75·0), 1440 (23·6%) patients were women, 4665 (76·4%) were men, 3934 (64·4%) were White, and 2899 (47·5%) had no previous hospitalisation for heart failure. During a median follow-up of 18·5 months (IQR 13·6–24·7), primary outcome events occurred in 549 (18·0%) patients in the vericiguat group and 584 (19·1%) patients in the placebo group (hazard ratio [HR] 0·93 [95% CI 0·83–1·04]; p=0·22). As prespecified in the protocol, because the primary endpoint was not statistically significant, all analyses of secondary and exploratory endpoints are considered nominal. Cardiovascular death occurred in 292 (9·6%) patients in the vericiguat group and 346 (11·3%) patients in the placebo group (HR 0·83 [95% CI 0·71–0·97]). Hospitalisation for heart failure occurred in 348 (11·4%) patients in the vericiguat group and in 362 (11·9%) patients in the placebo group (HR 0·95 [95% CI 0·82–1·10]). Serious adverse events occurred in 717 (23·5%) of 3049 patients in the vericiguat group and 751 (24·6%) of 3049 patients in the placebo group. The most common adverse event was symptomatic hypotension (345 [11·3%] patients in the vericiguat group and 281 [9·2%] in the placebo group). All-cause death occurred in 377 (12·3%) patients in the vericiguat group and 440 (14·4%) patients in the placebo group (HR 0·84 [95% CI 0·74–0·97]). Among patients with HFrEF and no recent worsening, vericiguat did not reduce the risk of a composite endpoint of time to cardiovascular death or heart failure hospitalisation. Fewer cardiovascular deaths were observed in the vericiguat group than in the placebo group. Merck Sharp & Dohme (a subsidiary of Merck) and Bayer.

Following completion of the VICTORIA trial, vericiguat was approved for the treatment of worsening heart failure with reduced ejection fraction (HFrEF) and received a class IIb recommendation in European and North American guidelines. The subsequent VICTOR trial evaluated the use of vericiguat in patients with HFrEF and no recent worsening. We aimed to assess the effect of vericiguat on clinical endpoints through pooled analyses of patient-level data from the VICTORIA and VICTOR trials. This prespecified, pooled individual participant-level analysis was conducted on data from two trials: VICTORIA, which was active from Sept 25, 2016, to Sept 2, 2019 in 42 countries, and VICTOR, which was active from Nov 2, 2021, to Feb 5, 2025 in 36 countries. The VICTORIA trial enrolled adult (aged ≥18 years) participants with HFrEF with recent worsening (defined as either hospitalisation for heart failure within the previous 6 months or outpatient use of intravenous diuretics within the previous 3 months) and increased NT-proBNP concentrations; the VICTOR trial had similar eligibility criteria but participants had no recent worsening of heart failure. Participants in both trials received contemporary background guideline-directed heart failure therapy as appropriate. The primary endpoint was a composite endpoint of cardiovascular death or hospitalisation for heart failure (also assessed individually). This study is registered with PROSPERO, CRD420251065636. Data from 11 155 patients (5050 in the VICTORIA trial and 6105 in the VICTOR trial) were included in the pooled analysis. The primary endpoint of cardiovascular death or hospitalisation for heart failure occurred in 1446 (25·9%) of 5579 patients in the vericiguat group and 1556 (27·9%) of 5576 patients in the placebo group (hazard ratio [HR] 0·91 [95% CI 0·85–0·98]; p=0·0088), with similar reductions in its individual components of cardiovascular death (0·89 [0·80–0·98]; p=0·020) and hospitalisation for heart failure (0·92 [0·84–1·00]; p=0·043) as first events. Vericiguat reduced the risk of hospitalisation for heart failure and cardiovascular death in patients with HFrEF across a broad range of clinical severity, including those receiving contemporary guideline-directed medical therapy. Vericiguat might be suitable as an additional treatment option for selected patients with HFrEF. Merck Sharp & Dohme (a subsidiary of Merck) and Bayer.

Speakers and writers of English can choose whether to mark a high level of sentience in a nonhuman animal, by selecting the human and gendered terms (he, she, who) rather than the inanimate and ungendered terms (it, which). This article reports an investigation of the Anglo-American literature, to explore the extent to which speakers and writers use gendered pronouns 'he' and 'she' where the antecedent is a nonhuman animal. The authors also attempt to identify pragmatic factors and metaphoric associations that trigger personalizing of animals in literature and everyday conversations.

Speakers and writers of English can choose whether to mark a high level of sentience in a nonhuman animal by selecting the human and gendered terms (he, she, who) rather than the inanimate and ungendered terms (it, which). This paper reports an investigation of the Anglo-American literature to explore the extent to which speakers and writers use gendered pronouns ‘he’ and ‘she’ where the antecedent is a nonhuman animal. We also attempt to identify pragmatic factors and metaphoric associations that trigger personalizing of animals in literature and everyday conversations.

The article deals with the personification of Nature in modern English. The author attempted to carry out analysis of the cognitive metaphor Nature is Woman and the gender-conceptual structure in Anglo-American culture. Proceeding from the assumption that any personification is sexification that is cultural assumptions and beliefs underlie all kinds of personification, the writer claims that the concept of Nature comprises biological, social-cultural and psychological attributes pertaining to the feminine beginning which allows including the concept of Nature in the category of feminine gender and using ‘she’ as co-referring pronoun.

The article deals with the personification of Nature in modern English. The author attempted to carry out analysis of the cognitive metaphor Nature is Woman and the gender-conceptual structure in Anglo-American culture. Proceeding from the assumption that any personification is sexification that is cultural assumptions and beliefs underlie all kinds of personification, the writer claims that the concept of Nature comprises biological, social-cultural and psychological attributes pertaining to the feminine beginning which allows including the concept of Nature in the category of feminine gender and using 'she' as co-referring pronoun. [PUBLICATION ABSTRACT]

The article deals with the personification of Nature in modern English. The author attempted to carry out analy- sis of the cognitive metaphor Nature is Woman and the gender-conceptual structure in Anglo-American culture. Proceeding from the assumption that any personification is sexification that is cultural assumptions and beliefs underlie all kinds of personification, the writer claims that the concept of Nature comprises biological, social-cultural and psychological attributes pertaining to the feminine beginning which allows including the concept of Nature in the category of feminine gender and using ‘she’ as co-referring pronoun.

In the article, we analyze the metaphoric associations which are the basis for the personification of countries in English. We try to find out in what discourse types countries and cities are personalized. We identify the main factors which stand behind the use of she-reference with countries.

In the article, we analyze the metaphoric associations which are the basis for the personification of countries in English. We try to find out in what discourse types countries and cities are personalized. We identify the main factors which stand behind the use of she-reference with countries. [PUBLICATION ABSTRACT]