12 research outputs found

    Redo Root Replacement using the Ross in Valsalva Technique.

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    The Ross procedure is an alternative option for young and middle-aged patients needing aortic valve replacement. We present an interesting case where the patient had a preexisting aortic homograft that was implanted because of previous infective endocarditis with aortic root abscess. The patient presented with biological degeneration of the homograft with resultant severe stenosis as well as insufficiency. We performed a redo root surgery to replace the homograft with the Ross procedure by using the autograft inclusion into a vascular graft technique. The dissection was carried out by performing external dissection of the aortic root. Redo root replacement is a difficult procedure, however external root dissection is a safe and easy technique that can be used in such a difficult scenario

    Impacts of Nitrogen Fertilizer Application and Mulching on the Morpho-Physiological and Yield-Related Traits in Cotton

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    Cotton is a global cash crop with a significant contribution in the world economy. Optimum nutrient and water supply are most important for sustainable cotton production under warmer and dry environments. Field experiments were carried out to evaluate the cumulative impacts of various nitrogen doses and mulches on sustainable cotton production under semi-arid conditions during 2018 and 2019. Four nitrogen doses; 0, 70, 140, and 210 kg ha−1 and three types of mulch: control (without mulch), natural mulch (5 tons/ha wheat straw), and chemical mulch (methanol (30%). Nitrogen 210 kg ha−1 with natural mulching increased 40.5% gunning out turn, 30.0% fiber length, 31.7% fiber strength, 32.6% fiber fineness, 20.8% fiber uniformity, and 34.0% fiber elongation. Shoot nitrogen, phosphorous, potassium, calcium, and magnesium contents were maximum where 210 kg ha−1 nitrogen and mulch was applied. Natural mulch reduced the soil temperature as compared to chemical and no mulch conditions. The soil temperature was 0.5 to 1.8 ℃ lower in mulching treatments as compared to the control. Maximum economic yield was around 90% higher in natural mulch with the 210 kg ha−1 nitrogen application. It is concluded that optimum nitrogen application with natural mulch not only enhanced plant growth and development but also induced sustainability in quality cotton production under semi-arid conditions

    Effects of canagliflozin on human myocardial redox signalling: clinical implications

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    Aims Recent clinical trials indicate that sodium-glucose cotransporter 2 (SGLT2) inhibitors improve cardiovascular outcomes in heart failure patients, but the underlying mechanisms remain unknown. We explored the direct effects of canagliflozin, an SGLT2 inhibitor with mild SGLT1 inhibitory effects, on myocardial redox signalling in humans. Methods and results Study 1 included 364 patients undergoing cardiac surgery. Right atrial appendage biopsies were harvested to quantify superoxide (⁠O.−2⁠) sources and the expression of inflammation, fibrosis, and myocardial stretch genes. In Study 2, atrial tissue from 51 patients was used ex vivo to study the direct effects of canagliflozin on NADPH oxidase activity and nitric oxide synthase (NOS) uncoupling. Differentiated H9C2 and primary human cardiomyocytes (hCM) were used to further characterize the underlying mechanisms (Study 3). SGLT1 was abundantly expressed in human atrial tissue and hCM, contrary to SGLT2. Myocardial SGLT1 expression was positively associated with O.−2 production and pro-fibrotic, pro-inflammatory, and wall stretch gene expression. Canagliflozin reduced NADPH oxidase activity via AMP kinase (AMPK)/Rac1signalling and improved NOS coupling via increased tetrahydrobiopterin bioavailability ex vivo and in vitro. These were attenuated by knocking down SGLT1 in hCM. Canagliflozin had striking ex vivo transcriptomic effects on myocardial redox signalling, suppressing apoptotic and inflammatory pathways in hCM. Conclusions We demonstrate for the first time that canagliflozin suppresses myocardial NADPH oxidase activity and improves NOS coupling via SGLT1/AMPK/Rac1 signalling, leading to global anti-inflammatory and anti-apoptotic effects in the human myocardium. These findings reveal a novel mechanism contributing to the beneficial cardiac effects of canagliflozin

    Constructing custom-made radiotranscriptomic signatures of vascular inflammation from routine CT angiograms: a prospective outcomes validation study in COVID-19.

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    BackgroundDirect evaluation of vascular inflammation in patients with COVID-19 would facilitate more efficient trials of new treatments and identify patients at risk of long-term complications who might respond to treatment. We aimed to develop a novel artificial intelligence (AI)-assisted image analysis platform that quantifies cytokine-driven vascular inflammation from routine CT angiograms, and sought to validate its prognostic value in COVID-19.MethodsFor this prospective outcomes validation study, we developed a radiotranscriptomic platform that uses RNA sequencing data from human internal mammary artery biopsies to develop novel radiomic signatures of vascular inflammation from CT angiography images. We then used this platform to train a radiotranscriptomic signature (C19-RS), derived from the perivascular space around the aorta and the internal mammary artery, to best describe cytokine-driven vascular inflammation. The prognostic value of C19-RS was validated externally in 435 patients (331 from study arm 3 and 104 from study arm 4) admitted to hospital with or without COVID-19, undergoing clinically indicated pulmonary CT angiography, in three UK National Health Service (NHS) trusts (Oxford, Leicester, and Bath). We evaluated the diagnostic and prognostic value of C19-RS for death in hospital due to COVID-19, did sensitivity analyses based on dexamethasone treatment, and investigated the correlation of C19-RS with systemic transcriptomic changes.FindingsPatients with COVID-19 had higher C19-RS than those without (adjusted odds ratio [OR] 2·97 [95% CI 1·43-6·27], p=0·0038), and those infected with the B.1.1.7 (alpha) SARS-CoV-2 variant had higher C19-RS values than those infected with the wild-type SARS-CoV-2 variant (adjusted OR 1·89 [95% CI 1·17-3·20] per SD, p=0·012). C19-RS had prognostic value for in-hospital mortality in COVID-19 in two testing cohorts (high [≥6·99] vs low [InterpretationRadiotranscriptomic analysis of CT angiography scans introduces a potentially powerful new platform for the development of non-invasive imaging biomarkers. Application of this platform in routine CT pulmonary angiography scans done in patients with COVID-19 produced the radiotranscriptomic signature C19-RS, a marker of cytokine-driven inflammation driving systemic activation of coagulation and responsible for adverse clinical outcomes, which predicts in-hospital mortality and might allow targeted therapy.FundingEngineering and Physical Sciences Research Council, British Heart Foundation, Oxford BHF Centre of Research Excellence, Innovate UK, NIHR Oxford Biomedical Research Centre, Wellcome Trust, Onassis Foundation
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