Cardiac Function in Patients with Angina

It is a great honour and pleasure for me to be invited to this meeting, commemorating the introduction by your former member, T. Lauder Brunton, of amyl nitrite as a potent remedy for anginal pain, one hundred years ago.For some years, I have been interested in the haemodynamic consequences of coronary heart disease, the most common cause of anginal pain. That this symptom is due to an improper balance between the myocardial demand for energy and the supply available from the coronary circulation has been more or less generally accepted for a long time. This view seems, for instance, to have been held by Allan Burns in his book on cardiology printed in this city in 1809. The exact cause of the pain is still uncertain. It seems, however, to be linked to inadequate delivery of oxygen to the myocardium, either generally or locally. And metabolic studies (Cohen el al. 1965) have indicated changes probably due to hypoxia in patients with coronary heart disease not only during but also in the intervals between attacks of angina pectoris. If reduction of the coronary circulation and abnormal metabolism are common in these patients, it is reasonable to expect a reduction in ventricular function as well. However, one of the main symptoms of impaired left heart function, namely dyspnoea, has not been generally regarded as a feature of this condition (P. Wood 1953)

Early Validation of High-Tech Start-ups by Using Big Data

Source at https://circulareconomy.europa.eu/platform/en/news-and-events/all-events/ispim-innovation-conference-2023.Majority of the start-ups fail in the early stage of the development due to lack of validation. This paper focuses on high-tech start-ups and investigates the use of data and/or big data at this stage. The study found that early-stage start-ups fail because they create products or services not needed in the market. Early validation through an agile approach can help these young companies to manoeuver through a turbulent external environment. The results show that big data or data can act as a support at this stage. However, there are various barriers that need to be addressed for successful data adoption. The paper proposes an early validation user guide (EVU) to overcome these barriers and make data adoption easier. The EVU can provide start-ups the tools to use big data or data as a support for early validation based on the market context of the start-ups

Cell cycle-specific UNG2 phosphorylations regulate protein turnover, activity and association with RPA

Human UNG2 is a multifunctional glycosylase that removes uracil near replication forks and in non-replicating DNA, and is important for affinity maturation of antibodies in B cells. How these diverse functions are regulated remains obscure. Here, we report three new phosphoforms of the non-catalytic domain that confer distinct functional properties to UNG2. These are apparently generated by cyclin-dependent kinases through stepwise phosphorylation of S23, T60 and S64 in the cell cycle. Phosphorylation of S23 in late G1/early S confers increased association with replication protein A (RPA) and replicating chromatin and markedly increases the catalytic turnover of UNG2. Conversely, progressive phosphorylation of T60 and S64 throughout S phase mediates reduced binding to RPA and flag UNG2 for breakdown in G2 by forming a cyclin E/c-myc-like phosphodegron. The enhanced catalytic turnover of UNG2 p-S23 likely optimises the protein to excise uracil along with rapidly moving replication forks. Our findings may aid further studies of how UNG2 initiates mutagenic rather than repair processing of activation-induced deaminase-generated uracil at Ig loci in B cells

Res Medica, April 1967, Special Issue – Lauder Brunton Centenary Symposium on Angina Pectoris

WelcomeHistorical SessionOpening AddressLauder BruntonHistory of Angina Pathophysiological SessionThe Pathology of AnginaExperimental Studies on the Myocardial Collateral CirculationFirst DiscussionCoronary Blood Flow and Myocardial Metabolism in Angina PectorisCardiac Function in Patients with AnginaSecond Discussion Therapeutic SessionThe Modern EpidemicIs Angina Preventable?Third DiscussionChest Pain, Exercise Electrocardiography and Coronary Arteriography(Correlative Studies in Angina PectorisPrognosis of Angina PectorisPanel DiscussionSumming U

Risk Categorization Using New American College of Cardiology/American Heart Association Guidelines for Cholesterol Management and Its Relation to Alirocumab Treatment Following Acute Coronary Syndromes

10.1161/CIRCULATIONAHA.119.042551CIRCULATION140191578-158

Effect of Alirocumab on Mortality After Acute Coronary Syndromes An Analysis of the ODYSSEY OUTCOMES Randomized Clinical Trial

10.1161/CIRCULATIONAHA.118.038840CIRCULATION1402103-11

Alirocumab and cardiovascular outcomes after acute coronary syndrome

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