Charles University in Prague

About: Charles University in Prague is a education organization based out in Prague, Czechia. It is known for research contribution in the topics: Population & Large Hadron Collider. The organization has 32392 authors who have published 74435 publications receiving 1804208 citations.

Fatty acids as biocompounds: their role in human metabolism, health and disease--a review. Part 1: classification, dietary sources and biological functions.

Abstract: Background. Fatty acids are substantial components of lipids and cell membranes in the form of phospholipids. This review consists of two parts. The present part aims at describing fatty acid classification, dietary sources and biological functions. The second part will focus on fatty acid physiological roles and applications in human health and disease. Results. In humans, not all fatty acids can be produced endogenously due to the absence of certain desaturases. Thus, specific fatty acids termed essential (linoleic, alpha-linolenic) need to be taken from the diet. Other fatty acids whose synthesis depends on essential fatty acid intake include eicosapentaenoic acid and docosahexaenoic acid, found in oily fish. Dietary sources of saturated fatty acids are animal products (butter, lard) and tropical plant oils (coconut, palm), whereas sources of unsaturated fatty acids are vegetable oils (such as olive, sunflower, and soybean oils) and marine products (algae and fish oils). Saturated fatty acids have been related to adverse health effects, whereas unsaturated fatty acids, especially monounsaturated and n-3 polyunsaturated, are thought to be protective. In addition, trans fatty acids have been shown to have negative effects on health, whereas conjugated fatty acids might be beneficial. Lastly, fatty acids are the main components of lipid classes (triacylglycerols, phospholipids, cholesteryl esters, non-esterified fatty acids). Conclusion. Fatty acids are important biocompounds which take part in complex metabolic pathways, thus having major biological roles. They are obtained from various dietary sources which determine the type of fat consumed and consequently health outcome.

Accuracy of Quantum Chemical Methods for Large Noncovalent Complexes

Abstract: We evaluate the performance of the most widely used wave function, density functional theory, and semiempirical methods for the description of noncovalent interactions in a set of larger, mostly dispersion-stabilized noncovalent complexes (the L7 data set). The methods tested include MP2, MP3, SCS-MP2, SCS(MI)-MP2, MP2.5, MP2.X, MP2C, DFT-D, DFT-D3 (B3-LYP-D3, B-LYP-D3, TPSS-D3, PW6B95-D3, M06-2X-D3), and M06-2X, and semiempirical methods augmented with dispersion and hydrogen bonding corrections: SCC-DFTB-D, PM6-D, PM6-DH2, and PM6-D3H4. The test complexes are the octadecane dimer, the guanine trimer, the circumcoronene···adenine dimer, the coronene dimer, the guanine-cytosine dimer, the circumcoronene···guanine-cytosine dimer, and an amyloid fragment trimer containing phenylalanine residues. The best performing method is MP2.5 with relative root-mean-square deviation (rRMSD) of 4%. It can thus be recommended as an alternative to the CCSD(T)/CBS (alternatively QCISD(T)/CBS) benchmark for molecular system...

Lipid-lowering nutraceuticals in clinical practice: position paper from an International Lipid Expert Panel.

Abstract: In recent years, there has been growing interest in the possible use of nutraceuticals to improve and optimize dyslipidemia control and therapy. Based on the data from available studies, nutraceuticals might help patients obtain theraputic lipid goals and reduce cardiovascular residual risk. Some nutraceuticals have essential lipid-lowering properties confirmed in studies; some might also have possible positive effects on nonlipid cardiovascular risk factors and have been shown to improve early markers of vascular health such as endothelial function and pulse wave velocity. However, the clinical evidence supporting the use of a single lipid-lowering nutraceutical or a combination of them is largely variable and, for many of the nutraceuticals, the evidence is very limited and, therefore, often debatable. The purpose of this position paper is to provide consensus-based recommendations for the optimal use of lipid-lowering nutraceuticals to manage dyslipidemia in patients who are still not on statin therapy, patients who are on statin or combination therapy but have not achieved lipid goals, and patients with statin intolerance. This statement is intended for physicians and other healthcare professionals engaged in the diagnosis and management of patients with lipid disorders, especially in the primary care setting.

Ceftazidime-avibactam versus meropenem in nosocomial pneumonia, including ventilator-associated pneumonia (REPROVE): a randomised, double-blind, phase 3 non-inferiority trial

Abstract: Summary Background Nosocomial pneumonia is commonly associated with antimicrobial-resistant Gram-negative pathogens. We aimed to assess the efficacy and safety of ceftazidime-avibactam in patients with nosocomial pneumonia, including ventilator-associated pneumonia, compared with meropenem in a multinational, phase 3, double-blind, non-inferiority trial (REPROVE). Methods Adults with nosocomial pneumonia (including ventilator-associated pneumonia), enrolled at 136 centres in 23 countries, were randomly assigned (1:1) to 2000 mg ceftazidime and 500 mg avibactam (by 2 h intravenous infusion every 8 h) or 1000 mg meropenem (by 30-min intravenous infusion every 8 h) for 7–14 days; regimens were adjusted for renal function. Computer-generated randomisation codes were stratified by infection type and geographical region with a block size of four. Participants and investigators were masked to treatment assignment. The primary endpoint was clinical cure at the test-of-cure visit (21–25 days after randomisation). Non-inferiority was concluded if the lower limit of the two-sided 95% CI for the treatment difference was greater than −12·5% in the coprimary clinically modified intention-to-treat and clinically evaluable populations. This trial is registered with ClinicalTrials.gov (NCT01808092) and EudraCT (2012-004006-96). Findings Between April 13, 2013, and Dec 11, 2015, 879 patients were randomly assigned. 808 patients were included in the safety population, 726 were included in the clinically modified intention-to-treat population, and 527 were included in the clinically evaluable population. Predominant Gram-negative baseline pathogens in the microbiologically modified intention-to-treat population (n=355) were Klebsiella pneumoniae (37%) and Pseudomonas aeruginosa (30%); 28% were ceftazidime-non-susceptible. In the clinically modified intention-to-treat population, 245 (68·8%) of 356 patients in the ceftazidime-avibactam group were clinically cured, compared with 270 (73·0%) of 370 patients in the meropenem group (difference −4·2% [95% CI −10·8 to 2·5]). In the clinically evaluable population, 199 (77·4%) of 257 participants were clinically cured in the ceftazidime-avibactam group, compared with 211 (78·1%) of 270 in the meropenem group (difference −0·7% [95% CI −7·9 to 6·4]). Adverse events occurred in 302 (75%) of 405 patients in the ceftazidime-avibactam group versus 299 (74%) of 403 in the meropenem group (safety population), and were mostly mild or moderate in intensity and unrelated to study treatment. Serious adverse events occurred in 75 (19%) patients in the ceftazidime-avibactam group and 54 (13%) patients in the meropenem group. Four serious adverse events (all in the ceftazidime-avibactam group) were judged to be treatment related. Interpretation Ceftazidime-avibactam was non-inferior to meropenem in the treatment of nosocomial pneumonia. These results support a role for ceftazidime-avibactam as a potential alternative to carbapenems in patients with nosocomial pneumonia (including ventilator-associated pneumonia) caused by Gram-negative pathogens. Funding AstraZeneca.

SOFA/DCUP: architecture for component trading and dynamic updating

Abstract: In this paper the authors address some of the challenges of the current technologies in the area of component-based programming and automated software downloading. These challenges include: component updating at runtime of affected applications, adopting the "true-push" model in order to allow for silent software modification (e.g., for removing minor implementation errors), and finding a way to integrate these technologies and electronic commerce in software components. To respond to these challenges, the SOFA (SOFtware Appliances) architecture, the SOFA component model and its extension, DCUP (Dynamic Component UPdating), are introduced. SOFA and DCUP provide a small set of well scaling orthogonal abstractions (easily mapped to Java and CORBA) which address three areas: the background for electronic commerce, the component model, and support for dynamic component updating in running applications. The updating granularity can scale anything from minor implementation changes to a major reconfiguration.