Stability of single skyrmionic bits.

The switching between topologically distinct skyrmionic and ferromagnetic states has been proposed as a bit operation for information storage. While long lifetimes of the bits are required for data storage devices, the lifetimes of skyrmions have not been addressed so far. Here we show by means of atomistic Monte Carlo simulations that the field-dependent mean lifetimes of the skyrmionic and ferromagnetic states have a high asymmetry with respect to the critical magnetic field, at which these lifetimes are identical. According to our calculations, the main reason for the enhanced stability of skyrmions is a different field dependence of skyrmionic and ferromagnetic activation energies and a lower attempt frequency of skyrmions rather than the height of energy barriers. We use this knowledge to propose a procedure for the determination of effective material parameters and the quantification of the Monte Carlo timescale from the comparison of theoretical and experimental data.

NT-pro-BNP predicts worsening renal function in patients with chronic systolic heart failure.

BACKGROUND: Worsening renal function (WRF) is frequently observed in patients with heart failure and is associated with worse outcome. The aim of this study was to examine the association of the cardiac serum marker N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) and WRF. METHODS: A total of 125 consecutive patients of a tertiary care outpatient clinic for heart failure prospectively underwent evaluation of renal function every 6 months. The association of baseline NT-pro-BNP with WRF was analysed during a follow up of 18 months. RESULTS: Twenty-eight (22.4%) patients developed WRF (increase in serum creatinine ≥0.3 mg/dL). Patients with WRF (2870 pg/mL, interquartile range (IQR) 1063-4765) had significantly higher baseline NT-pro-BNP values than patients without WRF (547 pg/mL, IQR 173-1454). The risk for WRF increased by 4.0 (95% CI 2.1-7.5) for each standard deviation of log NT-pro-BNP. In multivariable analysis including age, baseline renal function, ejection fraction, New York Heart Association class and diuretic dose, only NT-pro-BNP and diabetes were independent predictors of WRF. At a cut-off level of 696 pg/mL, NT-pro-BNP showed a sensitivity of 92.9% and a negative predictive value of 96.4% for WRF. CONCLUSION: NT-pro-BNP is a strong independent predictor of WRF within 18 months in patients with systolic heart failure with a high negative predictive value. Further studies are needed to evaluate reno-protective strategies in patients with elevated NT-pro-BNP.

Delta-glycated hemoglobin: a novel independent risk factor for cardiovascular events in patients without diabetes mellitus.

BACKGROUND: A single measurement of glycated hemoglobin (HbA1c) is a weak predictor for cardiovascular events in patients without Type 2 diabetes mellitus. We hypothesized that dynamic changes in HbA1c (Delta-HbA1c) would better predict cardiovascular outcome than a single value. METHODS: In 99 consecutive patients with stable coronary artery disease (CAD) and without diabetes mellitus who were seen twice in our outpatient clinic (4-6 months apart) in 1998, Delta-HbA1c (follow-up HbA1c--baseline HbA1c) was assessed. Between August and September 2007 (mean observation period 9.1 yr), patients and their physicians were contacted by telephone to evaluate the incidence of cardiovascular endpoints. The combined primary endpoint of our study was defined as the incidence of myocardial infarction, stroke or death from any cause. The endpoints were validated by chart review. RESULTS: Multivariate analysis demonstrated that the change of HbA1c between first and second examination in 1998 was the most powerful parameter for prediction of the combined primary endpoint in the next 9 yr. The hazard ratio was 5.03 [95% confidence interval (CI) 1.4-17.9] for any increase in HbA1c and 1.99 (95%CI 1.3-3.0) for an HbA1c increase of 0.3%. In addition, Kaplan-Meier survival analysis showed a significant association between endpoint-free survival and dynamic changes in HbA1c. CONCLUSIONS: Hence, changes in the glucometabolic milieu within 4-6 months calculated by the difference of two values of HbA1c affect the long-term prognosis of patients with CAD but without diabetes mellitus.

An increase in HbA1c after percutaneous coronary intervention raises the risk for restenosis in patients without Type 2 diabetes mellitus.

AIMS: The influence of dynamic changes in glycated haemoglobin (HbA(1c)) on restenosis after elective percutaneous coronary intervention (PCI) in patients without diabetes has not been analysed. Therefore, the rate of restenosis was investigated after elective PCI in 101 consecutive patients without diabetes mellitus in relation to dynamic changes of HbA(1c) levels. METHODS: Follow-up angiography was performed in all patients 4-6 months after intervention. RESULTS: Multivariate analysis demonstrated that the change in HbA(1c) between first and second coronary angiography was the most powerful metabolic parameter for prediction of restenosis. The odds ratio for restenosis was 3.0 (95% CI 1.0-9.0) for any increase in HbA(1c) and 1.9 (95% CI 1.1-3.5) for an HbA(1c) increase of 0.2%. CONCLUSIONS: Hence, chronic changes in the glucometabolic environment influence the incidence of restenosis after PCI in patients without diabetes.

Activation of the calcineurin/NFAT signalling cascade starts early in human hypertrophic myocardium.

Cardiac hypertrophy is an independent risk factor for heart failure. Recent studies on gene regulation of proteins have involved intracellular Ca2+ homeostasis. The Ca2+-sensitive phosphatase, calcineurin, is one potential regulator of the hypertrophic response, so we aimed to investigate the calcineurin-dependent signal pathway at different stages of hypertrophy in human myocardium. We found the calcineurin pathway to be significantly activated in hypertrophic compared with non-hypertrophic myocardium as demonstrated by increased calcineurin activity and expression of calcineurin A-beta and B, and GATA-4, and a shift of phosphorylated cytoplasmic NFAT-3 into the nucleus as dephosphorylated nuclear NFAT-3. There was a tendency for these changes to be more pronounced in the decompensated compared with the compensated hypertrophic myocardium. The present study provides evidence for significant activation of the Ca2+-triggered calcineurin pathway in hypertrophic humans. Already present in compensated hypertrophy it showed a tendency to a further increase following transition to decompensated hypertrophy.

Hypertension guidelines and their limitations--the impact of physicians' compliance as evaluated by guideline awareness.

OBJECTIVE: The initial step of an optimal therapeutic strategy for patients with arterial hypertension is the recognition and acceptance of new recommendations by the physicians themselves. This guideline awareness of the physicians has never been evaluated in detail. DESIGN: The awareness of content of current recommendations in hypertension diagnosis, treatment and treatment control was therefore assessed in primary care physicians using a questionnaire. The guidelines of the German Hypertension Society were used as the reference standard. PARTICIPANTS: A total of 24 899 German physicians, including all internists, all cardiologists and 22% of general practitioners were contacted in a nationwide survey. MAIN OUTCOME MEASURES: The number of answers in agreement with the guideline was used as a measure of guideline awareness. Adequate awareness of content of guideline recommendations was defined as the correct answer to five out of eight questions; the correct answers had to include the appropriate definition of hypertension. RESULTS: The analysis was based on 11 547 returned questionnaires (47.1%). An adequate guideline awareness was found in 23.7% of the total study population, especially in 37.1% of cardiologists, in 25.6% of internists and in 18.8% of general practitioners. While the guideline awareness was significantly influenced by the duration of private practice, regional and municipal factors had only minor influence on the results. CONCLUSION: The impact of hypertension guidelines on actual medical knowledge is modest. Thus, the information strategies about current treatment guidelines must be improved and tailored to the needs of physicians in clinical practice to ultimately improve patient care.

[Guideline-adequate knowledge in internists and general practitioners about the diagnosis and treatment of arterial hypertension]. / Leitlinienadäquate Kenntnisse von Internisten und Allgemeinmedizinern am Beispiel der arteriellen Hypertonie.

Only a small proportion of patients with arterial hypertension are adequately treated. Although a possible cause for this fact may be the deficient knowledge of physicians about diagnosis and treatment of arterial hypertension, to date no studies have addressed this important problem in Germany. Therefore, we have reviewed the knowledge of internists and general practitioners about diagnosis and treatment of arterial hypertension using a questionnaire. The guidelines of the German Hypertension Society were used as the reference standard. The questionnaire was sent out in December 1999 to all internists (n = 15,952) and to a random sample of general practitioners (n = 8947) who work as statutory health insurance physicians. A total of 11,547 questionnaires were sent back and could be analysed. Adequate guideline knowledge was assumed if five out of eight questions were correctly answered; the correct answers had to include the correct definition of arterial hypertension (> 140/90 mmHg). The correct definition of arterial hypertension was known by 4103/11,547 participants (36%). An adequate guideline knowledge was found in 18.8% of the general practitioners and in 26.6% of the internists. There were no relevant regional differences. The level of awareness about diagnosis and treatment of arterial hypertension is insufficient among internists and general practitioners. This insufficient knowledge may in part explain the inadequate care for patients with arterial hypertension. Thus, the implementation and evaluation of new information and training strategies are mandatory to improve the care for patients with arterial hypertension.

Interface-mediated death of unconditioned Tetrahymena cells: effect of the medium composition.

We have previously shown that the cell death of Tetrahymena thermophila in low inocula cultures in a chemically-defined medium is not apoptotic. The death is caused by a cell lysis occurring at the medium-air interface and can be prevented by the addition of insulin or Pluronic F-68. Here, we report that cell death can also be caused by the medium. The specific effects of several medium constituents were tested in the presence and absence of an interface. Four of the 19 amino acids (arginine, aspartic acid, glutamic acid, and histidine in millimolar concentration) as well as Ca2+ (68 microM) and Mg2+ (2 mM) and trace metal ions (micromolar concentrations) are all sufficient to induce the interface-mediated death. The effect of the amino acids and the salt ions Ca2+ and Mg2+ can be abolished by the addition of insulin (10(-6) M) or Pluronic F-68 (0.01% w/v), whereas insulin/Pluronic F-68 only postpones the death induced by trace metal ions. On the basis of our findings, a new recipe for a chemically-defined medium has been formulated. Single cells can grow in this medium in the presence of medium-air interface without any supplements.

Expression of Tetrahymena snRNA gene variants including a U1 gene with mutations in the 5' splice site recognition sequence.

The expression of U1, U2 and U5 snRNA gene variants has been studied under different physiological states of Tetrahymena. Variants of all three snRNA genes are expressed. Among the snRNAs detected is U1-3, a variant with 66 mutations compared to the normal U1 snRNA. Three of these mutations affect the 5' splice site recognition sequence. The U1-3 snRNA is present in a few hundred copies per cell. The expression of Tetrahymena snRNA genes is independent of the physiological state of the cell.

Surface mediated death of unconditioned Tetrahymena cells: effect of physical parameters, growth factors, hormones, and surfactants.

A new form of cell death has been observed. The death occurs at liquid-air interfaces when Tetrahymena cells are grown in a chemically defined medium (CDM) at low inocula. The cells die by lysis at the liquid-air interface (medium surface), which they reach due to negative gravitaxis as well as positive aerotaxis. When the cells are grown in a closed compartment, with no liquid-air interface, the death is not observed, and the cells proliferate. Cloning of cells in CDM is thus possible. The addition of effectors such as NGF (10(-11) M), EGF (10(-10) M), PDGF (10(-10) M), and insulin (10(-7) M) to cells in CDM prevents the surface mediated death. Since detergents/surfactants like SDS (7 x 10(-5) M), NP-40 (2 x 10(-5) M), Tween 80 (10(-4))% w/v), Pluronic F-68 (10(-7) M), and the biosurfactant surfactin (10(-6) M) have the same effect, we suggest that the effectors act by stimulating the cells to exudate surfactant(s) of their own. Furthermore, lyzed cells and exudates from living cells (pre-conditioned medium) prevent the death. In conditions with liquid-air interfaces, certain physical parameters are of great importance for the survival of cells at low inocula. The parameters are the distance to the surface, the temperature, and the inoculum. By increasing the height of the medium, lowering the temperature, and increasing the inoculum of the culture, the survival can be greatly enhanced. There is no evidence for programmed cell death (PCD) or apoptosis.