The role of endothelial enzymes NOS, VAP-1 and CD73 in acute lung injury

Acute lung injury (ALI) is a syndrome of acute hypoxemic respiratory failure with bilateral pulmonary infiltrates that is not caused by left atrial hypertension. Since there is no effective treatment available, this frequent clinical syndrome significantly contributes to mortality of both medical and surgical patients. Great majority of the patients with the syndrome suffers from indirect ALI caused by systemic inflammatory response syndrome (SIRS). Sepsis, trauma, major surgery and severe burns, which represent the most common triggers of SIRS, often induce an overwhelming inflammatory reaction leading to dysfunction of several vital organs. Studies of indirect ALI due to SIRS revealed that respiratory dysfunction results from increased permeability of endothelium. Disruption of endothelial barrier allows extravasation of protein-rich liquid and neutrophils to pulmonary parenchyma. Both under normal conditions and in inflammation, endothelial barrier function is regulated by numerous mechanisms. Endothelial enzymes represent one of the critical control points of vascular permeability and leukocyte trafficking. Some endothelial enzymes prevent disruption of endothelial barrier by production of anti-inflammatory substances. For instance, nitric oxide synthase (NOS) down-regulates leukocyte extravasation in inflammation by generation of nitric oxide. CD73 decreases vascular leakage and neutrophil emigration to inflamed tissues by generation of adenosine. On the other hand, vascular adhesion protein-1 (VAP-1) mediates leukocyte trafficking to the sites of inflammation both by generation of pro-inflammatory substances and by physically acting as an adhesion molecule. The aims of this study were to define the role of endothelial enzymes NOS, CD73 and VAP-1 in acute lung injury. Our data suggest that increasing substrate availability for NOS reduces both lung edema and neutrophil infiltration and this effect is not enhanced by concomitant administration of antioxidants. CD73 protects from vascular leakage in ALI and its up-regulation by interferon-β represents a novel therapeutic strategy for treatment of this syndrome. Enzymatic activity of VAP-1 mediates neutrophil infiltration in ALI and its inhibition represents an attractive approach to treat ALI.Siirretty Doriast

Preparation of Project For Small Entrepreneur Financed From European Funds

Diplomová práce se zabývá problematikou financování projektů z fondů Evropské unie, předfinancováním či spolufinancováním projektů z bankovních produktů a zpracovává také příklad postupu při žádání o dotaci z fondů EU. Úvodní část je věnovaná teoretickým informacím, které se týkají fondů Evropské unie. Hlavní textová část práce popisuje a analyzuje jednotlivé možnosti financování projektů ze zdrojů EU.Dále se také zabývá bankovními produkty na trhu , které lze využít pro spolufinancování projektů. V závěrečné části práce se snažím o vytvoření přehledného a praktického průvodce podnikatele fondy EU.My graduation theses is analyzing questions of project funding from EU financial resources, cofinancing projects form commercial banks products and is also dealing with process of applying of financial resources from EU funds. First part is dealing with theoretical informations connected to EU funds. Main part is describing and analyzing single possibilities of financing projects form EU funds. This part is describing commercial banks products, which can be used to cofinancing of projects as well. In final part am trying to create transparent and practical guide book for entrepreneur through EU funds.

Creation of the System for Management and Evaluation of Employee in Customer's Support Center

Diplomová práce se zabývá problematikou hodnocení zaměstnanců a jejich řízení s hodnocením spojeným v zákaznickém centru nadnárodní společnosti. Úvodní část je věnována teoretickým podkladům, které se zabývají řízením lidských zdrojů, a to zejména oblastí hodnocení a řízení výkonu zaměstnance. Analytická část práce popisuje a posuzuje současný systém hodnocení a řízení zaměstnanců, který je používán v popisovaném týmu. Cílem analytické části je nalezení a identifikace nedostatků používaného systému. Závěrečná část diplomové práce je věnována autorovým návrhům řešení. Výstupem je soubor doporučení a návrhů změn k odstranění nedostatků zjištěných analýzou současného stavu.The diploma thesis deals with question of evaluation and with evaluation connected managing, of employees in Customer's Support Center. The opening part of this work is devoted to theoretical source materials connected to human resource management and dealing mainly with evaluation and management of employee’s performance. The analytical part of the work describes and rates the current system of evaluation and management of employee in a described work team. The aim of the analytical part is to find and identify shortcomings of the current system in force. The final part is devoted to author's proposed solutions. The output is a set of recommendations and solutions on how to relieve the shortages identified by the analytical part.

Microfluidic Overhauser DNP chip for signal-enhanced compact NMR

Nuclear magnetic resonance at low field strength is an insensitive spectroscopic technique, precluding portable applications with small sample volumes, such as needed for biomarker detection in body fluids. Here we report a compact double resonant chip stack system that implements in situ dynamic nuclear polarisation of a 130 nL sample volume, achieving signal enhancements of up to − 60 w.r.t. the thermal equilibrium level at a microwave power level of 0.5 W. This work overcomes instrumental barriers to the use of NMR detection for point-of-care applications

Outcome of patients receiving a continuous flow left ventricular assist device - a retrospective single center study

Objectives. We present the outcome of the first 80 patients receiving a continuous flow left ventricular assist device at Helsinki University Hospital between December 2011 and November 2018. Design. This was a single-center retrospective study. We describe our patient management in detail. The primary end-points were death, heart transplantation, or pump explant. Data was reported in accordance with the Interagency Registry for Mechanical Circulatory Support protocol. All patients receiving an assist device during the study period were included in the data analysis. Results. Mean patient age was 53 +/- 12 years at implantation and 85% were male. Most patients suffered from dilated (48%), or ischemic (40%) cardiomyopathy. One-third of patients were bridged with venoarterial extracorporeal membrane oxygenation to assist device implantation. Implant strategy was bridge to transplant or bridge to decision in most patients (88%). Mean follow-up time on pump was 529 +/- 467 days. Survival was 98, 92, 85, 79 and 71% at 1, 3, 12, 24 and 36 months, respectively. Most common causes of death were multi-organ failure, right heart failure, or stroke. Only three patients (4%) had suspected pump thrombosis, two of which resolved with medical treatment and one resulting in death. Pump exchange or explant were not performed in a single patient. Neurological events occurred in 18%, non-disabling stroke in 8%, and fatal stroke in 4% of the patients. The incidence of device-related infection was 10%. Conclusions. Survival rates were good, although one third of patients were bridged with temporary circulatory support. We report a high level of freedom from pump thrombosis, fatal stroke, and driveline infection.Peer reviewe

Feedback GAP : study protocol for a cluster-randomized trial of goal setting and action plans to increase the effectiveness of audit and feedback interventions in primary care

Peer reviewedPublisher PD

Process engineering advances in pharmaceutical and chemical industries: digital process design, advanced rectification and continuous filtration

This review paper presents some of the topics discussed at the 2018 ‘Chemical process development trends’ seminar organized by the Swiss Process and Chemical Engineers Society in Basel, Switzerland. The first subject covers the use of computer aided tools for systematic reaction route selection, the second one addresses the recent development in the field of process intensification with a focus on reactive distillation and dividing wall column technology, and the third topic highlights recent developments in the field of continuous filtration in the pharmaceutical industry

The 85$Rb(p,n)85Sr reaction and the modified proton optical potential

The cross sections of the astrophysically relevant 85$Rb(p,n)85Srg,m reaction have been measured between Ec.m. = 2.16 and 3.96 MeV. The cross sections have been derived by measuring the gamma radiation following the beta decay of the reaction products. A comparison with the predictions of Hauser-Feshbach calculations using the NON-SMOKER code confirms a recently derived modification of the global optical proton potential.Comment: CGS XIII conferenc

Operating Room of the Future (FOR) Digital Healthcare Transformation in the Age of Artificial Intelligence

New technologies are emerging under the umbrella of digital transformation in healthcare such as artificial intelligence (AI) and medical analytics to provide insights beyond the abilities of human experts. Because AI is increasingly used to support doctors in decision-making, pattern recognition, and risk assessment, it will most likely transform healthcare services and the way doctors deliver those services. However, little is known about what triggers such transformation and how the European Union (EU) and Norway launch new initiatives to foster the development of such technologies. We present the case of Operating Room of the Future (FOR), a research infrastructure and an integrated university clinic which investigates most modern technologies such as artificial intelligence (AI), machine learning (ML), and deep learning (DL) to support the analysis of medical images. Practitioners can benefit from strategies related to AI development in multiple health fields to best combine medical expertise with AI-enabled computational rationality.publishedVersio