Stressor-Induced “Inflammaging” of Vascular Smooth Muscle Cells via Nlrp3-Mediated Pro-inflammatory Auto-Loop

Calcification of the vessel wall as one structural pathology of aged vessels is associated with high cardiovascular mortality of elderly patients. Aging is linked to chronic sterile inflammation and high burden of reactive oxygen species (ROS), leading to activation of pattern recognition receptors (PRRs) such as Nlrp3 in vascular cells. The current study investigates the role of PRR activation in the calcification of vascular smooth muscle cells (VSMCs). Therefore, in vitro cell culture of primary rat VSMCs and ex vivo aortic stimulations were used to analyze osteogenic, senescence and inflammatory markers via real-time PCR, in situ RNA hybridization, Western Blot, photometric assays and histological staining. Induction of ROS and DNA-damage by doxorubicin induces a shift of VSMC phenotype toward the expression of osteogenic, senescence and inflammatory proteins. Induction of calcification is dependent on Nlrp3 activity. Il-1β as a downstream target of Nlrp3 induces the synthetic, pro-calcifying VSMC phenotype. Inhibition of PRR with subsequent reduction of chronic inflammation might be an interesting target for reduction of calcification of VSMCs, with subsequent reduction of cardiovascular mortality of patients suffering from vessel stiffness.

Reduced neutralisation of the Delta (B.1.617.2) SARS-CoV-2 variant of concern following vaccination

Vaccines are proving to be highly effective in controlling hospitalisation and deaths associated with SARS-CoV-2 infection but the emergence of viral variants with novel antigenic profiles threatens to diminish their efficacy. Assessment of the ability of sera from vaccine recipients to neutralise SARS-CoV-2 variants will inform the success of strategies for minimising COVID19 cases and the design of effective antigenic formulations. Here, we examine the sensitivity of variants of concern (VOCs) representative of the B.1.617.1 and B.1.617.2 (first associated with infections in India) and B.1.351 (first associated with infection in South Africa) lineages of SARS-CoV-2 to neutralisation by sera from individuals vaccinated with the BNT162b2 (Pfizer/BioNTech) and ChAdOx1 (Oxford/AstraZeneca) vaccines. Across all vaccinated individuals, the spike glycoproteins from B.1.617.1 and B.1.617.2 conferred reductions in neutralisation of 4.31 and 5.11-fold respectively. The reduction seen with the B.1.617.2 lineage approached that conferred by the glycoprotein from B.1.351 (South African) variant (6.29-fold reduction) that is known to be associated with reduced vaccine efficacy. Neutralising antibody titres elicited by vaccination with two doses of BNT162b2 were significantly higher than those elicited by vaccination with two doses of ChAdOx1. Fold decreases in the magnitude of neutralisation titre following two doses of BNT162b2, conferred reductions in titre of 7.77, 11.30 and 9.56-fold respectively to B.1.617.1, B.1.617.2 and B.1.351 pseudoviruses, the reduction in neutralisation of the delta variant B.1.617.2 surpassing that of B.1.351. Fold changes in those vaccinated with two doses of ChAdOx1 were 0.69, 4.01 and 1.48 respectively. The accumulation of mutations in these VOCs, and others, demonstrate the quantifiable risk of antigenic drift and subsequent reduction in vaccine efficacy. Accordingly, booster vaccines based on updated variants are likely to be required over time to prevent productive infection. This study also suggests that two dose regimes of vaccine are required for maximal BNT162b2 and ChAdOx1-induced immunity.

Direct evidence for metallic mercury causing photo-induced darkening of red cinnabar tempera paints

Photo-induced darkening of red cinnabar (HgS) has attracted the interest of many researchers as it drastically impacts the visual perception of artworks. Darkening has commonly been related to metallic mercury (Hg0) formation in the presence of chlorides. Based on the study of UV-aged cinnabar pigment and tempera paint we propose an alternative pathway for the blackening reaction of cinnabar, considering its semiconductor properties and pigment-binder interactions. We demonstrate that darkening is caused by the oxidation of cinnabar to mercury sulfates and subsequent reduction to Hg0 via photo-induced electron transfer without the involvement of chlorides, and provide direct evidence for the presence of Hg0 on UV-aged tempera paint. Photooxidation also affects the organic binder, causing a competing depletion of photo-generated holes and consequently limiting but not impeding mercury sulfate formation and subsequent reduction to Hg0. In addition, organics provide active sites for Hg0 sorption, which is ultimately responsible for the darkening of cinnabar-based paint.

Evaluation of AV-5055 as Seed Dresser in Lowland Rice Production

This experiment was established in 2020 cropping season at National Cereals Research Institute experimental field at Badeggi in Guinea Savannah agro-ecological Zone, (Latitude 9 040 Longitude 6 070 E), to assess seed dressing effect of AV-5055 on rice seed. The experiment was laid out in Randomized Complete Block Designs (RCBD), replicated three times. It consisted of four (4) treatments: application of AV-5055 rate at 0.7L, 1.2L, 1.7L per 100kg of rice seed and no application of chemical as (control). Data was taken on plant height, tiller count, days to 50% flowering, bird damage, rodent damage panicle per meter square and grain yield. The result shows that there was no significant difference (P > 0.05) in plant height, tiller count, days to 50% flowering and bird damage. However, control plot had significantly (P < 0.05) lower rodent damage (0.00) and higher grain yield (2060.00kg/ha) compared to rodent damage and grain yield in treated plots (0.33-2.33) and (1789.00-1999.03) respectively. It was concluded from the result of analysis that AV-5055 offer protection to dressed seed against bird depredation from planted field as there was no significant difference on bird depredation among the various rates of AV-5055 application. However, various rates of AV-5055 application attract picking by rodents and subsequent reduction on yield. Thus it was recommended that AV-5055 should be applied in combination with rodenticides to give perfect seed protection against birds and rodents.

Kinetic Aspects of the Electrochemical Reduction of Uranyl in HCl Solutions

The interfacial mechanism of uranyl electroreduction at Au-electrodes in HCl solutions was discussed on the light of systematic studies of cyclovoltammetry, normal pulse voltammetry, UV-Vis spectroscopy and published electroanalytical research. Voltammetric waves were numerically deconvoluted on the basis of a reaction model consisting of a first mass-controlled, quasi-reversible first electron transfer and a subsequent reduction of interfacial U(V) intermediate species with adsorption of generated U(IV) products. The dependence of the kinetic parameters on [HCl] indicates an electron transfer following an inner-sphere type mechanism assisted by electrosorption of chloride ligands. The interfacial accumulation of chloride exerts a strong electrostatic repulsion of complexed uranyl and a consequent edged drop of electron transfer rates at [HCl] ∽ 0.5 mol l-1. The electron transfer steps are followed by a chemical desorption reaction of the unstable tetravalent uranyl in U(H2O)9 4+ species. It is shown that the numerical reproduction of voltammetric waves suits as a method for calculating kinetic parameters in multi-steps electrochemical reactions.

Obesity and Atrial Fibrillation: Epidemiology, Pathogenesis and Effect of Weight Loss

The obesity epidemic continues its relentless advance and is paralleled by an increase in the incidence of AF. Several epidemiological studies have highlighted obesity as an independent risk factor for the development of AF. This relationship is likely multifactorial through a number of interacting mechanisms. Weight loss through lifestyle changes or surgery has been associated with reverse remodelling of the atrial substrate and subsequent reduction in AF, making it an essential pillar in the management of AF in obese patients. In this review, the epidemiological data that support the obesity–AF relationship, the current insights into the underlying pathophysiological mechanism, the impact of weight loss on reverse remodelling and AF reduction, and the strategies to achieve weight loss in patients with AF are discussed.

EP.WE.205Impact of the Covid-19 Pandemic on Loop Ileostomy Formation

Aim Uncertainty during the early phases of the Covid-19 pandemic regarding availability of critical care beds and peri-operative impact of SARS-CoV-2 led to changing intercollegiate guidance in favour of increased stoma formation. This study assessed the impact the Covid-19 pandemic had on loop ileostomy formation. Methods Data were reviewed from a prospectively collected database on the number of loop ileostomies formed over a 10-month period from 1st March to 31st December 2020. Comparison was made with the same period in 2019. Details were confirmed using clinical letters. Results 114 loop ileostomies were formed in the 20-month period. There was a 10.0% reduction in loop ileostomy formation in 2020 compared with 2019. The median number of loop ileostomies formed per month over the two 10-month periods was 6. This peaked at 11 in April 2020 coinciding with the first wave of Covid-19, falling in subsequent months. All 11 of these loop ileostomies were formed in colorectal cancer patients undergoing anterior resection, after appropriate counselling. Conclusions There was a reduction in the number of ileostomies formed in 2020 compared with 2019 reflecting the impact of the Covid-19 pandemic on both elective and emergency case load and presentations. These results show reactive change in surgical practice corresponding to guidance at a time of maximum uncertainty. Primary anastomosis still occurred but with an increased likelihood of a defunctioning stoma to minimise the consequences of an anastomotic leak. A subsequent reduction in stoma formation in the following months indicates that practice rapidly returned to normal.

Hypothyroidism Affects Uterine Function via the Modulation of Prostaglandin Signaling

Thyroid hormones control the functions of almost all body systems. Reproductive dysfunctions, such as abnormal sexual development, infertility, or irregularities in the reproductive cycle, might be associated with thyroid disorders. Uterine receptivity is the period when the uterus is receptive to the implantation of an embryo. During the receptivity period (implantation window), a newly formed blastocyst is incorporated into the uterine epithelium. Prostaglandins are well-known primary mediators of pathological conditions such as inflammation and cancer but are also essential for the physiology of female reproduction. The aim of this study was to evaluate the possible relationship between hypothyroidism and changes in the prostaglandin signaling pathways in the uterus and in the process of uterine receptivity in a rat model. The results show that hypothyroidism impaired uterine receptivity by decreasing the level of E2 as well as decreasing the expression of the uterine-receptivity factors homeobox A10 and osteopontin. Moreover, hypothyroidism caused changes in the expression of elements of the prostaglandin E2, F2α, and I2 signaling pathways and changed the levels of those prostaglandins in the uterine tissue. The results suggest that the mechanisms by which hypothyroidism affects female reproductive abnormalities might involve the prostaglandin signaling pathway, resulting in a subsequent reduction in uterine receptivity.

An Efficient Synthesis of 2-CF3-3-Benzylindoles

The reaction of α-CF3-β-(2-nitroaryl) enamines with benzaldehydes afforded effectively α,β-diaryl-CF3-enones having nitro group. Subsequent reduction of nitro group by NH4HCO2-Pd/C system initiated intramolecular cyclization to give 2-CF3-3-benzylindoles. Target products can be prepared in up to quantitative yields. Broad synthetic scope of the reaction was shown. Probable mechanism of indole formation is proposed.

Reduced neutralisation of the Delta (B.1.617.2) SARS-CoV-2 variant of concern following vaccination

Vaccines are proving to be highly effective in controlling hospitalisation and deaths associated with SARS-CoV-2 infection but the emergence of viral variants with novel antigenic profiles threatens to diminish their efficacy. Assessment of the ability of sera from vaccine recipients to neutralise SARS-CoV-2 variants will inform the success of strategies for minimising COVID19 cases and the design of effective antigenic formulations. Here, we examine the sensitivity of variants of concern (VOCs) representative of the B.1.617.1 and B.1.617.2 (first associated with infections in India) and B.1.351 (first associated with infection in South Africa) lineages of SARS-CoV-2 to neutralisation by sera from individuals vaccinated with the BNT162b2 (Pfizer/BioNTech) and ChAdOx1 (Oxford/AstraZeneca) vaccines. Across all vaccinated individuals, the spike glycoproteins from B.1.617.1 and B.1.617.2 conferred reductions in neutralisation of 4.31 and 5.11-fold respectively. The reduction seen with the B.1.617.2 lineage approached that conferred by the glycoprotein from B.1.351 (South African) variant (6.29-fold reduction) that is known to be associated with reduced vaccine efficacy. Neutralising antibody titres elicited by vaccination with two doses of BNT162b2 were significantly higher than those elicited by vaccination with two doses of ChAdOx1. Fold decreases in the magnitude of neutralisation titre following two doses of BNT162b2, conferred reductions in titre of 7.77, 11.30 and 9.56-fold respectively to B.1.617.1, B.1.617.2 and B.1.351 pseudoviruses, the reduction in neutralisation of the delta variant B.1.617.2 surpassing that of B.1.1351. Fold changes in those vaccinated with two doses of ChAdOx1 were 0.69, 4.01 and 1.48 respectively. The accumulation of mutations in these VOCs, and others, demonstrate the quantifiable risk of antigenic drift and subsequent reduction in vaccine efficacy. Accordingly, booster vaccines based on updated variants are likely to be required over time to prevent productive infection. This study also suggests that two dose regimes of vaccine are required for maximal BNT162b2 and ChAdOx1-induced immunity.