University of Lorraine

About: University of Lorraine is a education organization based out in Nancy, France. It is known for research contribution in the topics: Population & Context (language use). The organization has 11942 authors who have published 25010 publications receiving 425227 citations. The organization is also known as: Lorraine University.

Effects of sodium-glucose cotransporter 2 inhibitors for the treatment of patients with heart failure - Proposal of a novel mechanism of action

Abstract: Importance Only 1 class of glucose-lowering agents—sodium-glucose cotransporter 2 (SGLT2) inhibitors—has been reported to decrease the risk of cardiovascular events primarily by reducing the risk of the development or progression of heart failure. In a landmark trial called Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes [EMPA-REG Outcomes], long-term treatment with empagliflozin prevented fatal and nonfatal heart failure events but did not reduce the risk of myocardial infarction or stroke in diabetic patients. Observations The beneficial effect of SGLT2 inhibitors on heart failure cannot be explained by their actions on glycemic control or as osmotic diuretics. Instead, in the kidneys, SGLT2 functionally interacts with the sodium-hydrogen exchanger, which is responsible for the majority of sodium tubular reuptake following filtration. The activity of sodium-hydrogen exchanger is markedly increased in patients with heart failure and may be responsible for both resistance to diuretics and to endogenous natriuretic peptides. In addition, in the heart, empagliflozin appears to inhibit sodium-hydrogen exchange, which may in turn lead to a reduction in cardiac injury, hypertrophy, fibrosis, remodeling, and systolic dysfunction. Furthermore, the major pathophysiological derangements of heart failure and a preserved ejection fraction may be mitigated by the actions of SGLT2 inhibitors to reduce blood pressure, body weight, and fluid retention as well as to improve renal function. The benefits of spironolactone in patients with heart failure with either a reduced or a preserved ejection fraction may also be attributable to the actions of the drug to inhibit the sodium-hydrogen exchange mechanism. Conclusions and Relevance The benefits of SGLT2 inhibitors in heart failure may be mediated by the inhibition of sodium-hydrogen exchange rather than the effect on glucose reabsorption. This hypothesis has important implications for the design and analysis of large-scale outcomes trials involving diabetic or nondiabetic patients with chronic heart failure.

A heuristic quasi-polynomial algorithm for discrete logarithm in finite fields of small characteristic

Abstract: The difficulty of computing discrete logarithms in fields \(\mathbb{F}_{q^k}\) depends on the relative sizes of k and q. Until recently all the cases had a sub-exponential complexity of type L(1/3), similar to the factorization problem. In 2013, Joux designed a new algorithm with a complexity of L(1/4 + e) in small characteristic. In the same spirit, we propose in this article another heuristic algorithm that provides a quasi-polynomial complexity when q is of size at most comparable with k. By quasi-polynomial, we mean a runtime of n O(logn) where n is the bit-size of the input. For larger values of q that stay below the limit \(L_{q^k}(1/3)\), our algorithm loses its quasi-polynomial nature, but still surpasses the Function Field Sieve. Complexity results in this article rely on heuristics which have been checked experimentally.