Sex- and age-related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long-Term Registry

Aims: This study aimed to assess age- and sex-related differences in management and 1-year risk for all-cause mortality and hospitalization in chronic heart failure (HF) patients. Methods and results: Of 16 354 patients included in the European Society of Cardiology Heart Failure Long-Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline-directed medical therapy (GDMT) were high (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P\ua0 64 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1-year follow-up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all-cause mortality were lower in women than in men (7.1% vs. 8.7%; P\ua0=\ua00.015), as were rates of all-cause hospitalization (21.9% vs. 27.3%; P\ua075 years. Conclusions: There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all-cause mortality in patients with LVEF 6445%

Enantiodivergent, Biocatalytic Routes to Both Taxol Side Chain Antipodes

Two enantiocomplementary bakers\u27 yeast enzymes reduced an alpha-chloro-beta-keto ester to yield precursors for both enantiomers of the N-benzoyl phenylisoserine Taxol side chain. After base-mediated ring closure of the chlorohydrin enantiomers, the epoxides were converted directly to the oxazoline form of the target molecules using a Ritter reaction with benzonitrile. These were hydrolyzed to the ethyl ester form of the Taxol side chain enantiomers under acidic conditions. This brief and atom-efficient route to both target enantiomers demonstrates both the synthetic utility of individual yeast reductases and the power of genomic strategies in making these catalysts available

Regio and enantioselective reduction of t-butyl 6-chloro-3,5-dioxohexanoate with baker's yeast

Whole baker's yeast cells reduce t-butyl 6-chloro-3,5-dioxohexanoate regioselectively to the corresponding C5 hydroxy keto ester. While the (R)-alcohol was favored, the enantioselectivity was poor (41% ee). A variety of process conditions were evaluated in order to improve both the enantioselectivity and yield of this reduction. Including a nonpolar resin in the reaction mixture afforded the (R)-alcohol in 94% ee and 50% isolated yield. The enantio selectivity was further improved to >99% ee by substituting purified YGL157w in place of whole yeast cells. This reductase was identified by screening a collection of yeast enzymes uncovered by genome sequence analysis. (C) 2004 Elsevier Ltd. All rights reserved

Stereoselective, Biocatalytic Reductions of α-chloro-β-keto Esters

Homochiral glycidic esters are versatile intermediates that can be converted into a variety of high-value products. Optically active glycidates can be prepared by a number of routes including asymmetric Darzens reactions, chiral alkene oxidation methodologies, and ring closure of homochiral α-halo-β-hydroxy esters (see ref 1 and references cited therein). We were particularly interested in the last strategy because asymmetric reductions of α-chloro-β-keto esters might afford each of the four possible glycidate precursors via dynamic kinetic resolution processes from single, inexpensive starting materials (Scheme 1). Here, we explore the potential of individual reductase enzymes from baker\u27s yeast (Saccharomyces cerevisiae) as solutions to the problem of obtaining homochiral glycidate precursors. Reductions of α-chloro-β-keto esters by whole cells of commercial baker\u27s yeast generally produce disappointing mixtures of alcohol diastereomers.2-5 Recent work has revealed that the yeast genome encodes a large number of reductases,6 and it seemed likely that their simultaneous participation was mainly responsible for the modest stereoselectivities commonly observed in yeast-mediated ketone reductions.7-9 In response, we have adapted a fusion protein strategy10 that allows the properties of yeast reductases to be assessed individually, so that enzymes yielding homochiral products can be uncovered.11,12 Moreover, after a reductase with the desired properties has been identified, whole Escherichia coli cells expressing the same protein can be employed for bioconversions on preparative scales using glucose fed-batch conditions.13 Cellular metabolic pathways supply NADPH and the whole cells display very high stereoselectivities because they express only a single yeast reductase

Relationship between nutritional status and length of hospital stay among patients with atrial fibrillation – a result of the nutritional status heart study

Background: Nutritional status is related to the prognosis and length of hospital stay (LOHS) of patients with atrial fibrillation (AF). This study aimed to assess how nutritional status affects LOHS for patients with AF. Methods: We performed retrospective analysis of the medical records of 1,813 patients admitted urgently with a diagnosis of AF to the Institute of Heart Diseases of the University Clinical Hospital in Wroclaw, Poland. Results: In total, 1,813 patients were included in the analysis. The average LOHS in the entire group was 3.53 ± 3.41 days. The mean BMI was 28.7 kg/m2 (SD: 5.02). Patients who were hospitalized longer were statistically more likely to have a Nutritional Risk Score (NRS) ≥3 (p = 0.028). A higher percentage of longer hospitalized patients with LDL levels below 70 mg/dl (p < 0.001) and those with HDL ≥40 mg/dl (p < 0.001) were observed. Study participants with NRS ≥3 were an older group (M = 76.3 years), with longer mean LOHS (M = 4.44 days). The predictors of LOHS in the univariate model were age (OR = 1.04), LDL (OR = 0.99), HDL (OR = 0.98), TC (OR = 0.996), CRP (OR = 1, 02, p < 0.001), lymphocytes (OR = 0.97, p = 0.008) and in the multivariate model were age, LDL (mg/dl), HDL (mg/dl), Na, and K. Conclusion: For nutritional status, factors indicating the risk of prolonged hospitalization in patients with AF are malnutrition, lower serum LDL, HDL, potassium, and sodium levels identified at the time of admission to the cardiology department. Assessment of nutritional status in patients with AF is important both in the context of evaluating obesity and malnutrition status, as both conditions can alter the prognosis of patients. Further studies are needed to determine the exact impact of the above on the risk of prolonged hospitalization

Superhydrophobic functionalization of cutinase activated poly(lactic acid) surfaces

Superhydrophobic materials have focused the interest of many researchers due to their potential in a wide spectrum of applications like microfluidics or biosensors in the biomedical field. Typically, the increased surface roughness at the micro or nano scale needed for superhydrophobic surfaces is achieved by coating of different substances, which in combination with a lower surface energy lead to Water Contact Angle (WCA) values greater than 150\uc2\ub0. Here, limited enzymatic surface hydrolyis poly(lactic acid) (PLA) was combined with spin coating of a steraic alkene ketene dimer (AKD) layer. The selective enzymatic hydrolysis creates, in a gentle and controlled way, new hydroxylic and carboxylic groups on the polymer surface without damaging the material bulk properties like alkaline treatment does. The creation of new hydrophilic surface groups lead to a significant increase in the hydrophilicity, decreasing the WCA to less than 30\uc2\ub0 while raising the roughness from an Rrmsof 50.5 to 90.8 nm concomittantly increasing the exposed surface vs. the projected one by 13.2%. Coupling of PLA hydroxy groups with AKD was demonstrated by using a PLA model substrate and subsequent identification of the reaction product via LC-TOF/MS. On the PLA film, FTIR based detection of the characteristic \uce\ub2-ketoester bond peak between the AKD and enzymatically generated hydroxy groups on the surface confirmed successful coupling. Scanning Electron Microscopy (SEM) & Atomic Force Microscopy (AFM) imaging confirmed the presence of fractal structures after curation of the enzymatically activated PLA film. The suitable size, 4.15 \uce\ubcm on the lateral dimension and 0.7 \uce\ubcm on height of the structures, together with the high density of these fractal structures lead to a superhydrophobic surface (WCA >150\uc2\ub0). This process represents an alternative to produce chemically inert superhydrophobic bio-based polyesters surfaces, by combining mild biocatalytic activation of a polyester film with non-toxic chemicals in an environmentally friendly manner