Novel concept to guide systolic heart failure medication by repeated biomarker testing-results from TIME-CHF in context of predictive, preventive, and personalized medicine.

Background: It is uncertain whether repeated measurements of a multi-target biomarker panel may help to personalize medical heart failure (HF) therapy to improve outcome in chronic HF.

Methods: This analysis included 499 patients from the Trial of Intensified versus standard Medical therapy in Elderly patients with Congestive Heart Failure (TIME-CHF), aged ≥ 60 years, LVEF ≤ 45%, and NYHA ≥ II, who had repeated clinical visits within 19 months follow-up. The interaction between repeated measurements of biomarkers and treatment effects of loop diuretics, spironolactone, β-blockers, and renin-angiotensin system (RAS) inhibitors on risk of HF hospitalization or death was investigated in a hypothesis-generating analysis.

Dual-comb modelocked laser.

In this paper we present the first semiconductor disk laser (SDL) emitting simultaneously two collinearly overlapping cross-polarized gigahertz modelocked pulse trains with different pulse repetition rates. Using only a simple photo detector and a microwave spectrum analyzer directly down-converts the frequency comb difference from the optical to the microwave frequency domain. With this setup, the relative carrier-envelope-offset (CEO) frequency can be accessed directly without an f-to2f interferometer.

Novel extracellular matrix biomarkers as predictors of adverse outcome in chronic heart failure: association between biglycan and response to statin therapy in the CORONA trial.

Background: The extracellular matrix (ECM) plays an important role in left ventricular remodeling and progression of heart failure (HF). Biglycan and mimecan are ECM proteins that are abundantly expressed in cardiac tissue but have not been evaluated as prognostic markers in HF. We investigated their interaction with statin treatment and association with adverse outcome in chronic HF.

Predictive value of endostatin in chronic heart failure patients with poor kidney function.

Objectives: Increased circulating endostatin levels have been demonstrated in progressive cardiovascular (CV) and renal disorders. We investigated the predictive value of endostatin in patients with chronic heart failure (HF) and the association between endostatin and renal function.

Methods: The interaction between serum endostatin, estimated glomerular filtration rate (eGFR) and predefined endpoints, including the primary endpoint (CV death, nonfatal myocardial infarction, nonfatal stroke; n = 397), all-cause mortality (n = 410), CV death (n = 335) or the coronary endpoint (n = 317), was evaluated in 1,390 patients >60 years of age with ischemic systolic HF in the Controlled Rosuvastatin Multinational Trial in HF (CORONA) population, who were randomly assigned to 10 mg rosuvastatin or placebo.

Gigahertz self-referenceable frequency comb from a semiconductor disk laser.

We present a 1.75-GHz self-referenceable frequency comb from a vertical external-cavity surface-emitting laser (VECSEL) passively modelocked with a semiconductor saturable absorber mirror (SESAM). The VECSEL delivers 231-fs pulses with an average power of 100 mW and is optimized for stable and reliable operation.

Pulse repetition rate scaling from 5 to 100 GHz with a high-power semiconductor disk laser.

The high-power semiconductor laser studied here is a modelocked integrated external-cavity surface emitting laser (MIXSEL), which combines the gain of vertical-external-cavity surface-emitting lasers (VECSELs) with the saturable absorber of a semiconductor saturable absorber mirror (SESAM) in a single semiconductor layer stack. The MIXSEL concept allows for stable and self-starting fundamental passive modelocking in a simple straight cavity and the average power scaling is based on the semiconductor disk laser concept. Previously record-high average output power from an optically pumped MIXSEL was demonstrated, however the long pulse duration of 17 ps prevented higher pulse repetition rates and many interesting applications such as supercontinuum generation and broadband frequency comb generation.

Avosentan is protective in hypertensive nephropathy at doses not causing fluid retention.

Multiple studies indicate that endothelin antagonism may have a protective effect for chronic kidney disease. Despite that, clinical studies using avosentan have been halted due to adverse effects including fluid overload. Therefore, we aimed at investigating whether avosentan may have protective effects against hypertensive nephropathy at doses below those inducing fluid-retention.

Femtosecond pulses from a modelocked integrated external-cavity surface emitting laser (MIXSEL).

Novel surface-emitting optically pumped semiconductor lasers have demonstrated >1 W modelocked and >100 W continuous wave (cw) average output power. The modelocked integrated external-cavity surface emitting laser (MIXSEL) combines the gain of vertical-external-cavity surface-emitting lasers (VECSELs) with the saturable absorber of a semiconductor saturable absorber mirror (SESAM) in one single semiconductor structure. This unique concept allows for stable and self-starting passive modelocking in a simple straight cavity.

Brushing without brushing?--a review of the efficacy of powered toothbrushes in noncontact biofilm removal.

Objectives: The aim of the present review was to analyze the impact of the hydrodynamic effects created by powered toothbrushes on biofilm removal in vitro.

Materials And Methods: A MEDLINE search was performed for publications published by 20 May 2012; this search was complemented by a manual search. The study selection, data preparation, and validity assessment were conducted by two reviewers.

Antidiuretic effects of the endothelin receptor antagonist avosentan.

Several clinical studies have investigated the potential benefits of endothelin receptor antagonism in chronic pathologies such as diabetic kidney disease. However, fluid retention and edema have been identified as major side effects of endothelin receptor antagonists. In the present study we hypothesized that avosentan which was described as a predominant ET(A) receptor antagonist would produce fluid retention at high concentrations where non-specific blockade of ET(B) receptors may occur.

B2-kinin receptor plays a key role in B1-, angiotensin converting enzyme inhibitor-, and vascular endothelial growth factor-stimulated in vitro angiogenesis in the hypoxic mouse heart.

Aims: Angiotensin converting enzyme (ACE) inhibition reduces heart disease and vascular stiffness in hypertension and leads to kinin accumulation. In this study, we analysed the role and importance of two kinin receptor subtypes in angiogenesis during ACE inhibition in an in vitro model of angiogenesis of the mouse heart.

Methods And Results: First, we analysed the angiogenic properties of bradykinin and enalapril on wild-type C57Bl/6 and B2 receptor(-/-) mouse heart under normoxia (21% O(2)) and hypoxia (1% O(2)) in vitro and the contribution of B1 and B2 kinin receptors to this effect.

Dimethyl fumarate, a small molecule drug for psoriasis, inhibits Nuclear Factor-kappaB and reduces myocardial infarct size in rats.

Persistent Nuclear Factor-kappaB (NF-kappaB) activation is hypothesized to contribute to myocardial injuries following ischemia-reperfusion. Because inhibition or control of NF-kappaB signaling in the heart probably confers cardioprotection, we determined the potency of the NF-kappaB inhibitor dimethyl fumarate (DMF) in cardiovascular cells, and determined whether administration of DMF translates into beneficial effects in an animal model of myocardial infarction. In rat heart endothelial cells (RHEC), we analysed inhibitory effects of DMF on NF-kappaB using shift assay and immunohistofluorescence.

Mutation of the circadian clock gene Per2 alters vascular endothelial function.

Background: The circadian clock regulates biological processes including cardiovascular function and metabolism. In the present study, we investigated the role of the circadian clock gene Period2 (Per2) in endothelial function in a mouse model.

Methods And Results: Compared with the wild-type littermates, mice with Per2 mutation exhibited impaired endothelium-dependent relaxations to acetylcholine in aortic rings suspended in organ chambers.

Bradykinin is a mediator, but unlikely a trigger, of antiarrhythmic effects of ischemic preconditioning.

Objective: Brief reversible ischemic episodes (ischemic preconditioning, IPC) protect the heart against arrhythmias during a subsequent prolonged low-flow ischemia. We have recently shown that this protection involves release of bradykinin, activation of bradykinin B2 receptors followed by opening of sarcolemmal, but not mitochondrial ATP-sensitive K+ channels. The goal of this study was to clarify a trigger and/or mediator role of bradykinin in the antiarrhythmic effects of IPC during low-flow ischemia.

Interval versus continuous high-intensity exercise in chronic obstructive pulmonary disease: a randomized trial.

Background: Guidelines recommend high-intensity continuous exercise to reduce peripheral muscle dysfunction in patients with chronic obstructive pulmonary disease but acknowledge that interval exercise might be an equally effective alternative that is better tolerated by patients.

Objective: To assess whether interval exercise is no less effective than high-intensity continuous exercise and whether it is tolerated better by patients with severe chronic obstructive pulmonary disease.

Design: Randomized, noninferiority trial.

Interval exercise versus continuous exercise in patients with moderate to severe chronic obstructive pulmonary disease--study protocol for a randomised controlled trial [ISRCTN11611768].

Background: Physical exercise has become a cornerstone of management of chronic obstructive pulmonary disease (COPD) because it leads to clinically relevant improvements of exercise capacity and health-related quality of life (HRQL). Despite the scarcity of randomised trials directly comparing exercise protocols, current guidelines recommend high intensity continuous exercise for lower extremities as the probably most effective exercise modality. However, for patients admitted to inpatient respiratory rehabilitation programmes, it is often difficult to initiate such an exercise programme because they are severely limited by dyspnoea and leg fatigue and therefore unable to perform continuous exercise at higher intensities and for periods longer than 30 minutes.

Antiarrhythmic effect of ischemic preconditioning during low-flow ischemia. The role of bradykinin and sarcolemmal versus mitochondrial ATP-sensitive K(+) channels.

Short episodes of ischemia (ischemic preconditioning) protect the heart against ventricular arrhythmias during zero-flow ischemia and reperfusion. However, in clinics, many episodes of ischemia present a residual flow (low-flow ischemia). Here we examined whether ischemic preconditioning protects against ventricular arrhythmias during and after a low-flow ischemia and, if so, by what mechanism(s).

Losartan but not enalaprilat acutely reduces reperfusion ventricular tachyarrhythmias in hypertrophied rat hearts after low-flow ischaemia.

Based on clinical and experimental studies, angiotensin II receptor blockers and angiotensin converting enzyme inhibitors have been proposed to exert acute anti-arrhythmic effects in heart failure patients. Therefore, the goal of this study was to assess acute anti-arrhythmic effects of losartan and enalaprilat in hypertrophied rat hearts during low-flow ischaemia and reperfusion. In dose-finding experiments in non-hypertrophied isolated perfused hearts, we performed dose-response curves of losartan and enalaprilat studying monophasic action potential duration at 90% repolarisation (MAPD(90%)) and ventricular fibrillation (VF) threshold.

Rate response of a closed-loop stimulation pacing system to changing preload and afterload conditions.

Closed-loop stimulation (CLS) is a new sensor concept for rate adaptive pacing measuring changes in the unipolar right ventricular impedance, which correlates to changes of the right ventricular contractility and reflects the autonomic nervous innervation of the heart. Some patients do not tolerate the CLS mode because of inappropriate tachycardia, mainly related to postural changes. This study tested if the rate response of the CLS sensor is influenced not only by myocardial contractility but also by rapid changes in right ventricular filling.

Postresuscitation stunning: postfibrillatory myocardial dysfunction caused by reduced myofilament Ca2+ responsiveness after ventricular fibrillation-induced myocyte Ca2+ overload.

Introduction: Resuscitation from ventricular fibrillation (VF), particularly from prolonged VF, frequently is complicated by postfibrillatory myocardial dysfunction (postresuscitation stunning). We tested whether this dysfunction can be caused by reduced myofilament Ca2+ responsiveness after VF-induced myocyte Ca2+ overload. We also tested whether electrical defibrillation shocks contribute to this dysfunction.