Benefit of thrombolytic therapy in patients with acute stroke, who are on anticoagulant treatment, is not well addressed. The aim of this study was to investigate whether apixaban can modify the thrombolytic efficacy of alteplase in vitro . Static and flow models and two variants of red blood cell (RBC) dominant clots, with and without apixaban, were used. Clots were prepared from the blood of healthy human donors and subsequently exposed to alteplase treatment. Apixaban and alteplase were used in clinically relevant concentrations. Clot lysis in the static model was determined both by clot weight and spectrophotometric determination of RBC release. Clot lysis in the flow model was determined by measuring recanalization time, clot length and spectrophotometric determination of RBC release. In the static model, clots without apixaban; compared to those with apixaban had alteplase-induced mass loss 54 ± 8% vs. 53 ± 8%, p = 1.00; RBC release 0.14 ± 0.04 vs. 0.12 ± 0.04, p = 0.14, respectively. Very similar results were obtained if plasma was used instead of physiological buffered saline as the incubation medium. In the flow model, clot lysis without apixaban; compared to those with apixaban was as follows: recanalization time 107 ± 46 min vs. 127 ± 31 min, p = 1.00; recanalization frequency 90 ± 22% vs. 90 ± 22%, p = 1.00; clot volume reduction 32 ± 15% vs. 34 ± 10%, p = 1.00; RBC release 0.029 ± 0.007 vs. 0.022 ± 0.007, p = 0.16, respectively. Apixaban had no positive effect on alteplase-induced thrombolysis in both the in vitro static and flow models. Our data support current clinical practice, such that thrombolysis is contraindicated in stroke treatment for patients who have been treated with anticoagulants.
Severe chronic obstructive pulmonary disease (COPD) is a progressive disease associated with excessive mortality; however, mechanisms driving disease progression remain unclear [1]. A pro-inflammatory state, metabolic impairments and respiratory muscle weakness contribute to deterioration of lung function [1, 2]. Furthermore, a poor COPD prognosis appears to be associated with unintentional weight loss [3, 4], which has been observed in ∼50% of severe COPD patients [5]. Oxygen administration inhibits spontaneous and ANP-stimulated lipolysis in adipose tissue in severe COPD
Irisin, an adipomyokine identified in 2012, has been investigated in association with common pregnancy complications, including gestational diabetes mellitus, preeclampsia, and intrauterine growth restriction. The objective of this study is to examine the potential role of irisin in preterm birth (PTB) by comparing its level between mothers with term and preterm labor. Maternal peripheral blood and cord blood samples were collected from 30 mothers who delivered prematurely and from 35 mothers who delivered at term. Irisin concentrations were measured in all samples using ELISA, and four common single nucleotide polymorphisms in the irisin gene were determined (rs16835198, rs726344, rs3480, and rs1746661). Univariable and multivariable regression modeling was applied to evaluate maternal and cord blood irisin concentrations in relation to preterm/term labor. Irisin concentration in umbilical cord blood was found to be associated with PTB in the univariable model (p = 0.046). On the other hand, no differences in maternal blood irisin levels between mothers with preterm and term deliveries were established. To the best of our knowledge, this is the first study determining irisin levels in term and preterm deliveries in maternal peripheral blood and umbilical cord blood. Our study shows a possible association between cord blood irisin concentration and PTB occurrence.
Intravenous thrombolysis with a recombinant tissue plasminogen activator (rt-PA) is the first-line treatment of acute ischemic stroke. However, successful recanalization is relatively low and the underlying processes are not completely understood. The goal was to provide insights into clinically important factors potentially limiting rt-PA efficacy such as clot size, rt-PA concentration, clot age and also rt-PA in combination with heparin anticoagulant. We established a static in vitro thrombolytic model based on red blood cell (RBC) dominant clots prepared using spontaneous clotting from the blood of healthy donors. Thrombolysis was determined by clot mass loss and by RBC release. The rt-PA became increasingly less efficient for clots larger than 50 μl at a clinically relevant concentration of 1.3 mg/l. A tenfold decrease or increase in concentration induced only a 2-fold decrease or increase in clot degradation. Clot age did not affect rt-PA-induced thrombolysis but 2-hours-old clots were degraded more readily due to higher activity of spontaneous thrombolysis, as compared to 5-hours-old clots. Finally, heparin (50 and 100 IU/ml) did not influence the rt-PA-induced thrombolysis. Our study provided in vitro evidence for a clot size threshold: clots larger than 50 μl are hard to degrade by rt-PA. Increasing rt-PA concentration provided limited thrombolytic efficacy improvement, whereas heparin addition had no effect. However, the higher susceptibility of younger clots to thrombolysis may prompt a shortened time from the onset of stroke to rt-PA treatment.
In recent years, several computer-aided diagnosis systems emerged for the diagnosis of thyroid gland disorders using ultrasound imaging. These systems based on machine learning algorithms may offer a second opinion to radiologists by evaluating a malignancy risk of thyroid tissue, thus increasing the overall diagnostic accuracy of ultrasound imaging. Although current computer-aided diagnosis systems exhibit promising results, their use in clinical practice is limited. One of the main limitations is that the majority of them use direction-dependent features. Our intention has been to design a computer-aided diagnosis system, which will use only direction-independent features, that is, it will not be dependent on the orientation and the inclination angle of the ultrasound probe when acquiring the image. We have, therefore, applied histogram analysis and segmentation-based fractal texture analysis algorithm, which calculates direction-independent features only. In our study, 40 thyroid nodules (20 malignant and 20 benign) were used to extract several features, such as histogram parameters, fractal dimension, and mean brightness value in different grayscale bands (obtained by 2-threshold binary decomposition). The features were then used in support vector machine and random forests classifiers to differentiate nodules into malignant and benign classes. Using leave-one-out cross-validation method, the overall accuracy was 92.42% for random forests and 94.64% for support vector machine. Results show that both methods are useful in practice; however, support vector machine provides better results for this application. Proposed computer-aided diagnosis system can provide support to radiologists in their current diagnosis of thyroid nodules, whereby it can optimize the overall accuracy of ultrasound imaging.
The aortic endothelium from rats has been examined by scanning (SEM) and transmission electron microscopy (TEM) following nicotine administration or cigarette smoking. Nicotine was administered to rats by subcutaneous injections at concentrations of 1, 5, 10 and 20 mg/kg or by continuous subcutaneous pumps delivering a solution of 0.54 g/ml of nicotine at the rate of 1 microliter/h for 7 days. Animals were exposed to fresh smoke from eight cigarettes, each yielding 19 mg tar and 1.5 mg nicotine. Twenty minutes after subcutaneous injections, no endothelial abnormalities were evident by SEM, apart from at the high dose where minimal endothelial damage was seen. Limited endothelial damage was discerned following nicotine infusion and this consisted of microvillus formation, platelet adhesion and some cell separation. TEM revealed no endothelial changes in any of the animals. Cigarette smoking, however, resulted in considerable endothelial morphological changes consisting of the formation of blebs, microvillus-like projections, increased numbers of plasmalemmal vesicles and an increase in the numbers of Weibel-Palade bodies. The results suggest that components of cigarette smoke other than nicotine are responsible for the endothelial cell changes associated with smoking.
In this paper we propose a modified MSE based automatic blind modulation recognition (ABMR) algorithm for recognizing different rectangular QAM signals. The proposed method is robust to preprocessing errors like error in estimation of carrier frequency, synchronization and extraction of constellation from real band-pass signals. The performance of the proposed algorithm has been evaluated in the both noisy and faded channel through computer simulation
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