Efficacy and safety of CDR132L in patients with reduced left ventricular ejection fraction after myocardial infarction: Rationale and design of the HF-REVERT trial.

Aim: Inhibition of microRNA (miR)-132 effectively prevents and reverses adverse cardiac remodelling, making it an attractive heart failure (HF) target. CDR132L, a synthetic antisense oligonucleotide selectively blocking pathologically elevated miR-132, demonstrated beneficial effects on left ventricular (LV) structure and function in relevant preclinical models, and was safe and well tolerated in a Phase 1b study in stable chronic HF patients. Patients with acute myocardial infarction (MI) and subsequent LV dysfunction and remodelling have limited therapeutic options, and may profit from early CDR132L treatment.

Incubation characteristics, growth performance, carcass characteristics and meat quality of Saxonian Chicken and German Langshan bantam breeds in a free-range rearing system.

In the absence of evidence-based findings for Saxonian Chicken (SaChi) and German Langshan bantam (GLB), which are indigenous endangered German fancy chicken breeds, the objective of the present study was to characterise their growth performance and meat potential in an extensive free-range system METHODS: A total of 340 hatching eggs from SaChi and 439 eggs from GLB were provided by private breeders, from which 263 SaChi (77.3%) and 174 GLB (39.6%) hatched (p < 0.

Classical Xanthinuria in Nine Israeli Families and Two Isolated Cases from Germany: Molecular, Biochemical and Population Genetics Aspects.

Classical xanthinuria is a rare autosomal recessive metabolic disorder caused by variants in the (type I) or (type II) genes. Thirteen Israeli kindred (five Jewish and eight Arab) and two isolated cases from Germany were studied between the years 1997 and 2013. Four and a branch of a fifth of these families were previously described.

Novel antisense therapy targeting microRNA-132 in patients with heart failure: results of a first-in-human Phase 1b randomized, double-blind, placebo-controlled study.

Aims: Cardiac microRNA-132-3p (miR-132) levels are increased in patients with heart failure (HF) and mechanistically drive cardiac remodelling processes. CDR132L, a specific antisense oligonucleotide, is a first-in-class miR-132 inhibitor that attenuates and even reverses HF in preclinical models. The aim of the current clinical Phase 1b study was to assess safety, pharmacokinetics, target engagement, and exploratory pharmacodynamic effects of CDR132L in patients on standard-of-care therapy for chronic ischaemic HF in a randomized, placebo-controlled, double-blind, dose-escalation study (NCT04045405).

Rigorous Lower Bounds for the Ground State Energy of Molecules by Employing Necessary N-Representability Conditions.

Electronic structure calculations, in particular the computation of the ground state energy, lead to challenging problems in optimization. These problems are of enormous importance in quantum chemistry for calculations of properties of solids and molecules. Minimization methods for computing the ground state energy can be developed by employing a variational approach, where the second-order reduced density matrix defines the variable.