Chemical Modification of Reactive Multilayered Films Fabricated from Poly(2-Alkenyl Azlactone)s: Design of Surfaces that Prevent or Promote Mammalian Cell Adhesion and Bacterial Biofilm growth

We report an approach to the design of reactive polymer films that can be functionalized post-fabrication to either prevent or promote the attachment and growth of cells. Our approach is based on the reactive layer-bylayer assembly of covalently crosslinked thin films using a synthetic polyamine and a polymer containing reactive azlactone functionality. Our results demonstrate (i) that the residual azlactone functionality in these films can be exploited to immobilize amine-functionalized chemical motifs similar to those that promote or prevent cell and protein adhesion when assembled as self-assembled monolayers on gold-coated surfaces and (ii) that the immobilization of these motifs changes significantly the behaviors and interactions of cells with the surfaces of these polymer films. We demonstrate that films treated with the hydrophobic molecule decylamine support the attachment and growth of mammalian cells in vitro. In contrast, films treated with the hydrophilic carbohydrate D-glucamine prevent cell adhesion and growth almost completely. The results of additional experiments suggest that these large differences in cell behavior can be understood, at least in part, in terms of differences in the abilities of these two different chemical motifs to promote or prevent the adsorption of protein onto film-coated surfaces. We demonstrate further that this approach can be used to pattern regions of these reactive films that resist the initial attachment and subsequent invasion of mammalian cells for periods of at least one month in the presence of serum-containing cell culture media. Finally, we report that films that prevent the adhesion and growth of mammalian cells also prevent the initial formation of bacterial biofilms when incubated in the presence of the clinically relevant pathogen Pseudomonas aeruginosa. The results of these studies, collectively, suggest the basis of general approaches to the fabrication and functionalization of thin films that prevent, promote, or pattern cell growth or the formation of biofilms on surfaces of interest in the contexts of both fundamental biological studies and a broad range of other practical applications

Enzyme inhibitors as controllers of neurodegenerative diseases: An update of in vitro effects of medicinal plants

Considering the increase of the elderly population in recent years, the growing prevalence of age-related neurodegenerative diseases (NDDs), including Alzheimer's disease (AD) and Parkinson's disease (PD), has become one of the leading healthcare problems. Currently, available therapies for AD and PD are still limited, while medicinal plants used in traditional medicine for millennia can inhibit enzymes involved in the neurodegeneration processes in AD (acetylcholinesterase, AChE, and butyrylcholinesterase, BChE) and PD (tyrosinase, TYR), hence their inhibiting effects are continuously being investigated especially in the past decade. This study was aimed to review data on medicinal plants as potential cholinesterases and TYR inhibitors reported from January 2018 until May 2021. The literature search was performed using several online bibliographical databases (Scopus, Web of Science, Science Direct, Google Scholar, PubMed, and ResearchGate) and two websites. Data analysis showed that the highest number of representatives belongs to Lamiaceae family (up to 20%), followed by Asteraceae. Almost half of the tested samples were prepared from whole plant/aerial plant parts followed by leaves. The most frequently tested preparations were methanolic extracts (about 25% of the samples examined). Additionally, synergistic interactions between different herbs and/or isolated compounds were considered as a promising strategy for further research. The presented data showed that medicinal plants preparations represent an unlimited source for research of new and more effective AD and PD treatments. This review will provide a useful starting point for further research on this topic

EMISSION LINE ASSIMETRY IN ACTIVE GALAXIES: Mrk 533 AND Mrk 110

Abstract. In this work emission line asymmetries detected in two different types of Active Galactic Nuclei (AGN) -Seyfert 1 galaxy Mrk 110 and Seyfert 2 galaxy Mrk 533 were analyzed. Since emission lines in two galaxies arise in different emitting regions, detailed spectrum analysis gave the insight into kinematical properties of the Narrow Line and the Broad Line region (NLR and BLR) of this galaxies. We used several methods in the analysis procedure: (a) in order to analyse line profiles we performed profile decomposition into Gaussian components, (b) to study kinematical properties of the gas in the stellar disk, we used the model of "tilted-rings" (Begeman 1989), (c) to determine the sources of ionization of emitting region, we used the Veilleux and Osterbrock diagnostic diagram (Veilleux and Osterbrock 1987), (d) thermodynamical properties of the BLR were determined using the Boltzman plot method We showed that the red-shift and asymmetry of emission lines in Mrk 110 are probable caused by the strong gravitational field of the super massive black hole in the center of this galaxy. On the other hand, detailed analysis of 3D spectrophotometric observation of Mrk 533 made possible to map the outflow velocities from the very center of this galaxy, as well as shock waves in the circum-nuclear region, and to analyse the increase of the blue asymmetry with the increase of the outflow velocity (in more details se

Impact of clinical phenotypes on management and outcomes in European atrial fibrillation patients: a report from the ESC-EHRA EURObservational Research Programme in AF (EORP-AF) General Long-Term Registry

Background: Epidemiological studies in atrial fibrillation (AF) illustrate that clinical complexity increase the risk of major adverse outcomes. We aimed to describe European AF patients\u2019 clinical phenotypes and analyse the differential clinical course. Methods: We performed a hierarchical cluster analysis based on Ward\u2019s Method and Squared Euclidean Distance using 22 clinical binary variables, identifying the optimal number of clusters. We investigated differences in clinical management, use of healthcare resources and outcomes in a cohort of European AF patients from a Europe-wide observational registry. Results: A total of 9363 were available for this analysis. We identified three clusters: Cluster 1 (n = 3634; 38.8%) characterized by older patients and prevalent non-cardiac comorbidities; Cluster 2 (n = 2774; 29.6%) characterized by younger patients with low prevalence of comorbidities; Cluster 3 (n = 2955;31.6%) characterized by patients\u2019 prevalent cardiovascular risk factors/comorbidities. Over a mean follow-up of 22.5 months, Cluster 3 had the highest rate of cardiovascular events, all-cause death, and the composite outcome (combining the previous two) compared to Cluster 1 and Cluster 2 (all P <.001). An adjusted Cox regression showed that compared to Cluster 2, Cluster 3 (hazard ratio (HR) 2.87, 95% confidence interval (CI) 2.27\u20133.62; HR 3.42, 95%CI 2.72\u20134.31; HR 2.79, 95%CI 2.32\u20133.35), and Cluster 1 (HR 1.88, 95%CI 1.48\u20132.38; HR 2.50, 95%CI 1.98\u20133.15; HR 2.09, 95%CI 1.74\u20132.51) reported a higher risk for the three outcomes respectively. Conclusions: In European AF patients, three main clusters were identified, differentiated by differential presence of comorbidities. Both non-cardiac and cardiac comorbidities clusters were found to be associated with an increased risk of major adverse outcomes

AN ANALYTICAL METHOD OF ESTIMATING VALUE-AT-RISK ON THE

ABSTRACT: This paper presents market risk evaluation for a portfolio consisting of shares that are continuously traded on the Belgrade Stock Exchange, by applying the Value-at-Risk model – the analytical method. It describes the manner of analytical method application and compares the results obtained by implementing this method at different confidence levels. Method verification was carried out on the basis of the failure rate that demonstrated the confidence level for which this method was acceptable in view of the given conditions. KEY WORDS: market risk, Value-at-risk (VaR) model, analytical method, financia