Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Social Housing: an Economic Issue

The paper presents briefly the situation of the social housing market in general, with accents on the Romanian situation, in the contexts of a mortgage crisis in the United States and of a need to adhere to the European level of dwelling supply. The need for financing of a social housing system, through various means is obvious, mostly when the conclusion of the paper is that there are no recent studies on the Romanian market (the latest publicly available study being conducted in 2004, before the crises and the increases in the prices of the houses). The paper is considering a series of solutions for financing a social housing system, having in view a series of articles on the subject.social housing, Romania, financing, mortgage

Transaortic Shallow Septal Myectomy and Cutting of Secondary Fibrotic Mitral Valve Chordae—A 5-Year Single-Center Experience in the Treatment of Hypertrophic Obstructive Cardiomyopathy

Background: Anomalies of the mitral apparatus have been shown to contribute to left ventricular outflow obstruction in patients with hypertrophic cardiomyopathy (HCM). We report our 5-year single-center experience with a shallow myectomy procedure associated with transaortic mitral valve repair in a cohort of HCM patients. Methods: We studied 83 consecutive patients who underwent surgical treatment of symptomatic left ventricular outflow obstruction. In all study patients, a transaortic shallow septal myectomy was performed. Fibrous or muscular structures connecting the papillary muscles to the septum or free wall were resected, and fibrotic secondary chordae of the anterior mitral valve were cut selectively. Results: We report one death (1.2%) during hospitalization, no iatrogenic ventricular septal defects, and two (2.4%) mitral valve replacements. At discharge, no patients were in New York Heart Association (NYHA) Class III/IV, from 49 (59%) preoperatively. Mean maximal septal thickness decreased from 24 ± 6 to 16 ± 3 mm. Mean outflow gradient decreased from 93 ± 33 to 13 ± 11 mmHg. Grade 3 or 4 mitral regurgitation was noticed in one patient postoperatively, from 32 (39%) before surgery. Conclusions: Shallow septal myectomy associated with secondary mitral valve chordal cutting and papillary muscle mobilization provided excellent results offering adequate treatment of outflow obstruction

Statistical Analysis of Long- and Short-Range Forces Involved in Bacterial Adhesion to Substratum Surfaces as Measured Using Atomic Force Microscopy ▿

Surface thermodynamic analyses of microbial adhesion using measured contact angles on solid substrata and microbial cell surfaces are widely employed to determine the nature of the adhesion forces, i.e., the interplay between Lifshitz-van der Waals and acid-base forces. While surface thermodynamic analyses are often viewed critically, atomic force microscopy (AFM) can also provide information on the nature of the adhesion forces by means of Poisson analysis of the measured forces. This review first presents a description of Poisson analysis and its underlying assumptions. The data available from the literature for different combinations of bacterial strains and substrata are then summarized, leading to the conclusion that bacterial adhesion to surfaces is generally dominated by short-range, attractive acid-base interactions, in combination with long-range, weaker Lifshitz-van der Waals forces. This is in line with the findings of surface thermodynamic analyses of bacterial adhesion. Comparison with single-molecule ligand-receptor forces from the literature suggests that the short-range-force contribution from Poisson analysis involves a discrete adhesive bacterial cell surface site rather than a single molecular force. The adhesion force arising from these cell surface sites and the number of sites available may differ from strain to strain. Force spectroscopy, however, involves the tedious task of identifying the minor peaks in the AFM retraction force-distance curve. This step can be avoided by carrying out Poisson analysis on the work of adhesion, which can also be derived from retraction force-distance curves. This newly proposed way of performing Poisson analysis confirms that multiple molecular bonds, rather than a single molecular bond, contribute to a discrete adhesive bacterial cell surface site

Nanomechanics of yeast surfaces revealed by AFM

Despite the large and well-documented characterization of the microbial cell wall in terms of chemical composition, the determination of the mechanical properties of surface molecules in relation to their function remains a key challenge in cell biology.The emergence of powerful tools allowing molecular manipulations has already revolutionized our understanding of the surface properties of fungal cells. At the frontier between nanophysics and molecular biology, atomic force microscopy (AFM), and more specifically single-molecule force spectroscopy (SMFS), has strongly contributed to our current knowledge of the cell wall organization and nanomechanical properties. However, due to the complexity of the technique, measurements on live cells are still at their infancy.In this chapter, we describe the cell wall composition and recapitulate the principles of AFM as well as the main current methodologies used to perform AFM measurements on live cells, including sample immobilization and tip functionalization.The current status of the progress in probing nanomechanics of the yeast surface is illustrated through three recent breakthrough studies. Determination of the cell wall nanostructure and elasticity is presented through two examples: the mechanical response of mannoproteins from brewing yeasts and elasticity measurements on lacking polysaccharide mutant strains. Additionally, an elegant study on force-induced unfolding and clustering of adhesion proteins located at the cell surface is also presented