Effect of hormone replacement therapy on vasomotor function of the coronary microcirculation in post-menopausal women with medically treated cardiovascular risk factors

Aims The aim of this study was to evaluate the effect of hormone replacement therapy (HRT) on coronary vasomotor function in post-menopausal women (PM) with medically treated cardiovascular risk factors (RFs) in a cross-sectional and a longitudinal follow-up (FU) study. Methods and results Myocardial blood flow (MBF) response to cold pressor testing (CPT) and during pharmacologically induced hyperaemia was measured with positron emission tomography in pre-menopausal women (CON), in PM with HRT and without HRT, and repeated in PM after a mean FU of 24 ± 14 months. When compared with CON at baseline, the endothelium-related change in MBF (ΔMBF) to CPT progressively declined in PM with HRT and without HRT (0.35 ± 0.23 vs. 0.24 ± 0.20 and 0.16 ± 0.12 mL/g/min; P = 0.171 and P = 0.021). In PM without HRT and in those with HRT at baseline but with discontinuation of HRT during FU, the endothelium-related ΔMBF to CPT was significantly less at FU than at baseline (0.05 ± 0.19 vs. 0.16 ± 0.12 and −0.03 ± 0.14 vs. 0.25 ± 0.18 mL/g/min; P = 0.023 and P = 0.001), whereas no significant change was observed in PM with HRT (0.19 ± 0.22 vs. 0.23 ± 0.22 mL/g/min; P = 0.453). Impaired hyperaemic MBFs when compared with CON were not significantly altered from those at baseline exam. Conclusion Long-term administration of oestrogen may contribute to maintain endothelium-dependent coronary function in PM with medically treated cardiovascular RF

Checking Whether an Automaton Is Monotonic Is NP-complete

An automaton is monotonic if its states can be arranged in a linear order that is preserved by the action of every letter. We prove that the problem of deciding whether a given automaton is monotonic is NP-complete. The same result is obtained for oriented automata, whose states can be arranged in a cyclic order. Moreover, both problems remain hard under the restriction to binary input alphabets.Comment: 13 pages, 4 figures. CIAA 2015. The final publication is available at http://link.springer.com/chapter/10.1007/978-3-319-22360-5_2

Improvement in coronary endothelial function is independently associated with a slowed progression of coronary artery calcification in type 2 diabetes mellitus

Aims To examine a relationship between alterations of structure and function of the arterial wall in response to glucose-lowering therapy in type 2 diabetes mellitus (DM) after a 1-year follow-up (FU). Methods and results In DM (n = 22) and in healthy controls (n = 17), coronary artery calcification (CAC) was assessed with electron beam tomography and carotid intima-media thickness (IMT) with ultrasound, whereas coronary function was determined with positron emission tomography-measured myocardial blood flow (MBF) at rest, during cold pressor testing (CPT), and during adenosine stimulation at baseline and after FU. The decrease in plasma glucose in DM after a mean FU of 14 ± 1.9 months correlated with a lower progression of CAC and carotid IMT (r = 0.48, P ≤ 0.036 and r = 0.46, P ≤ 0.055) and with an improvement in endothelium-related ΔMBF to CPT and to adenosine (r = 0.46, P ≤ 0.038 and r = 0.36, P ≤ 0.056). After adjusting for metabolic parameters by multivariate analysis, the increases in ΔMBF to CPT after glucose-lowering treatment remained a statistically significant independent predictor of the progression of CAC (P ≤ 0.001 by one-way analysis of variance). Conclusion In DM, glucose-lowering treatment may beneficially affect structure and function of the vascular wall, whereas the observed improvement in endothelium-related coronary artery function may also mediate direct preventive effects on the progression of CA

Double-Stranded RNA Attenuates the Barrier Function of Human Pulmonary Artery Endothelial Cells

Circulating RNA may result from excessive cell damage or acute viral infection and can interact with vascular endothelial cells. Despite the obvious clinical implications associated with the presence of circulating RNA, its pathological effects on endothelial cells and the governing molecular mechanisms are still not fully elucidated. We analyzed the effects of double stranded RNA on primary human pulmonary artery endothelial cells (hPAECs). The effect of natural and synthetic double-stranded RNA (dsRNA) on hPAECs was investigated using trans-endothelial electric resistance, molecule trafficking, calcium (Ca2+) homeostasis, gene expression and proliferation studies. Furthermore, the morphology and mechanical changes of the cells caused by synthetic dsRNA was followed by in-situ atomic force microscopy, by vascular-endothelial cadherin and F-actin staining. Our results indicated that exposure of hPAECs to synthetic dsRNA led to functional deficits. This was reflected by morphological and mechanical changes and an increase in the permeability of the endothelial monolayer. hPAECs treated with synthetic dsRNA accumulated in the G1 phase of the cell cycle. Additionally, the proliferation rate of the cells in the presence of synthetic dsRNA was significantly decreased. Furthermore, we found that natural and synthetic dsRNA modulated Ca2+ signaling in hPAECs by inhibiting the sarco-endoplasmic Ca2+-ATPase (SERCA) which is involved in the regulation of the intracellular Ca2+ homeostasis and thus cell growth. Even upon synthetic dsRNA stimulation silencing of SERCA3 preserved the endothelial monolayer integrity. Our data identify novel mechanisms by which dsRNA can disrupt endothelial barrier function and these may be relevant in inflammatory processes

A Fast Algorithm Finding the Shortest Reset Words

In this paper we present a new fast algorithm finding minimal reset words for finite synchronizing automata. The problem is know to be computationally hard, and our algorithm is exponential. Yet, it is faster than the algorithms used so far and it works well in practice. The main idea is to use a bidirectional BFS and radix (Patricia) tries to store and compare resulted subsets. We give both theoretical and practical arguments showing that the branching factor is reduced efficiently. As a practical test we perform an experimental study of the length of the shortest reset word for random automata with $n$ states and 2 input letters. We follow Skvorsov and Tipikin, who have performed such a study using a SAT solver and considering automata up to $n=100$ states. With our algorithm we are able to consider much larger sample of automata with up to $n=300$ states. In particular, we obtain a new more precise estimation of the expected length of the shortest reset word $\approx 2.5\sqrt{n-5}$.Comment: COCOON 2013. The final publication is available at http://link.springer.com/chapter/10.1007%2F978-3-642-38768-5_1

Valuation and estimation from experience

The processing of sequentially presented numerical information is a prerequisite for decisions from experience, where people learn about potential outcomes and their associated probabilities and then make choices between gambles. Little is known, however, about how people's preference for choosing a gamble is affected by how they perceive and process numerical information. To address this, we conducted a series of experiments wherein participants repeatedly sampled numbers from continuous outcome distributions. They were incentivized either to estimate the means of the numbers or to state their minimum selling prices to forgo a consequential draw from the distributions (i.e., the certainty equivalents or valuations). We found that participants valued distributions below their means, valued high-variance sequences lower than low-variance sequences, and valued left-skewed sequences lower than right-skewed sequences. Though less pronounced, similar patterns occurred in the mean estimation task where preferences should not play a role. These results are not consistent with prior findings in decision from experience such as the overweighting of high numbers and the underweighting of rare events. Rather, the qualitative effects, as well as the similarity of effects in valuation and estimation, are consistent with the assumption that people process numbers on a compressed mental number line in valuations from experience

Pre-cooling for endurance exercise performance in the heat: a systematic review.

PMCID: PMC3568721The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1741-7015/10/166. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Endurance exercise capacity diminishes under hot environmental conditions. Time to exhaustion can be increased by lowering body temperature prior to exercise (pre-cooling). This systematic literature review synthesizes the current findings of the effects of pre-cooling on endurance exercise performance, providing guidance for clinical practice and further research

Updated Clinical Classification of Pulmonary Hypertension

In 1998, a clinical classification of pulmonary hypertension (PH) was established, categorizing PH into groups which share similar pathological and hemodynamic characteristics and therapeutic approaches. During the 5th World Symposium held in Nice, France, in 2013, the consensus was reached to maintain the general scheme of previous clinical classifications. However, modifications and updates especially for Group 1 patients (pulmonary arterial hypertension [PAH]) were proposed. The main change was to withdraw persistent pulmonary hypertension of the newborn (PPHN) from Group 1 because this entity carries more differences than similarities with other PAH subgroups. In the current classification, PPHN is now designated number 1. Pulmonary hypertension associated with chronic hemolytic anemia has been moved from Group 1 PAH to Group 5, unclear/multifactorial mechanism. In addition, it was decided to add specific items related to pediatric pulmonary hypertension in order to create a comprehensive, common classification for both adults and children. Therefore, congenital or acquired left-heart inflow/outflow obstructive lesions and congenital cardiomyopathies have been added to Group 2, and segmental pulmonary hypertension has been added to Group 5. Last, there were no changes for Groups 2, 3, and 4