Comparison of multianalyte proficiency test results by sum of ranking differences, principal component analysis, and hierarchical cluster analysis

Sum of ranking differences (SRD) was applied for comparing multianalyte results obtained by several analytical methods used in one or in different laboratories, i.e., for ranking the overall performances of the methods (or laboratories) in simultaneous determination of the same set of analytes. The data sets for testing of the SRD applicability contained the results reported during one of the proficiency tests (PTs) organized by EU Reference Laboratory for Polycyclic Aromatic Hydrocarbons (EU-RL-PAH). In this way, the SRD was also tested as a discriminant method alternative to existing average performance scores used to compare mutlianalyte PT results. SRD should be used along with the z scores-the most commonly used PT performance statistics. SRD was further developed to handle the same rankings (ties) among laboratories. Two benchmark concentration series were selected as reference: (a) the assigned PAH concentrations (determined precisely beforehand by the EU-RL-PAH) and (b) the averages of all individual PAH concentrations determined by each laboratory. Ranking relative to the assigned values and also to the average (or median) values pointed to the laboratories with the most extreme results, as well as revealed groups of laboratories with similar overall performances. SRD reveals differences between methods or laboratories even if classical test(s) cannot. The ranking was validated using comparison of ranks by random numbers (a randomization test) and using seven folds cross-validation, which highlighted the similarities among the (methods used in) laboratories. Principal component analysis and hierarchical cluster analysis justified the findings based on SRD ranking/grouping. If the PAH-concentrations are row-scaled, (i.e., z scores are analyzed as input for ranking) SRD can still be used for checking the normality of errors. Moreover, cross-validation of SRD on z scores groups the laboratories similarly. The SRD technique is general in nature, i.e., it can be applied to any experimental problem in which multianalyte results obtained either by several analytical procedures, analysts, instruments, or laboratories need to be compared. [Figure not available: see fulltext.] © 2013 Springer-Verlag Berlin Heidelberg

The Role of Non-Native Interactions in the Folding of Knotted Proteins: Insights from Molecular Dynamics Simulations

For several decades, the presence of knots in naturally-occurring proteins was largely ruled out a priori for its supposed incompatibility with the efficiency and robustness of folding processes. For this very same reason, the later discovery of several unrelated families of knotted proteins motivated researchers to look into the physico-chemical mechanisms governing the concerted sequence of folding steps leading to the consistent formation of the same knot type in the same protein location. Besides experiments, computational studies are providing considerable insight into these mechanisms. Here, we revisit a number of such recent investigations within a common conceptual and methodological framework. By considering studies employing protein models with different structural resolution (coarse-grained or atomistic) and various force fields (from pure native-centric to realistic atomistic ones), we focus on the role of native and non-native interactions. For various unrelated instances of knotted proteins, non-native interactions are shown to be very important for favoring the emergence of conformations primed for successful self-knotting events

Real-life data on the efficacy and safety of ombitasvir/paritaprevir//ritonavir + dasabuvir + ribavirin in the patients with genotype 1 chronic hepatitis c virus infection in serbia

© 2019, Inst. Sci. inf., Univ. Defence in Belgrade. All rights reserved. Background/Aim. The era of direct-acting antiviral (DAA) regimen in the treatment of chronic hepatitis C virus (HCV) started in 2011. The aim of this study was to assess the antiviral efficacy and safety of DAA regimen, ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) + dasabuvir (DSV) + ribavirin (RBV), in patients with chronic HCV infection, genotype Methods. The real-life data were collected. The study was multicentric and included seven infectious diseases and hepatology departments in Serbia. A total of 21 patients were enrolled in the OBV/PTV/r + DSV + RBV early access program, 20 of which were previously treated with pegylated interferon + RBV, while 1 was treatment-naive. All patients received the adequate doses of these antiviral drugs. RBV was not given to the patients with HCV genotype 1b infection according to the therapeutic protocol. For the majority of patient, the treatment duration lasted for 12 weeks. For the patients with liver cirrhosis, who were infected with HCV genotype 1a, the duration of treatment was 24 weeks. Viremia was assessed at four points in time: At baseline, 4 weeks after the treatment beginning (rapid viral response, RVR), 12 or 24 weeks after the treatment beginning (end of treatment response – ETR) and 12 weeks after the end of treatment (sustained viral response – SVR). SVR, as a confirmation of the absence of HCV was considered as endpoint of successful treatment. Results. Complete RVR, ETR and SVR were achieved in 64.71%, 85.71% and 95.24% of the patients, respectively. Only 3 patients had mild adverse effects which did not required dose reduction. Conclusion. The treatment of the patients with a chronic HCV infection with OBV/PTV/r + DSV + RBV resulted in excellent antiviral activity and tolerability. Apstrakt Uvod/Cilj. Era direktno delujućeg antivirusnog (DAA) režima lečenja bolesnika sa hroničnom hepatitis C virusnom (HCV) infekcijom započela je 2011. godine. Cilj rada bio je ispitivanje efikasnosti i bezbednosti DAA režima ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) + dasabuvir (DSV) + ribavirin (RBV), kod bolesnika sa genotip 1 HCV infekci jom u Srbiji. Metode. U multicentričnu studiju je bilo uključeno sedam centara u Srbiji. Prikupljeni su podaci iz realnog života. U rani pristupni program OBV/PTV/r + DSV + RBV bio je uključen 21 bolesnik od kojih jedan nije prethodno lečen, dok je ostalih 20 prethodno lečeno pegilovanim interferonom i RBV. Svi bolesnici su dobijali odgovarajuće doze lekova. Bolesnici sa HCV genotipom 1b nisu dobijali RBV u skladu sa terapijskim protokolom. Za većinu bolesnika trajanje terapije je iznosilo 12 nedelja. Za četvoro bolesnika sa cirozom i HCV genotipom 1a trajanje terapije je iznosilo 24 nedelje. Viremija je određivana četiri puta: Pre početka terapije, 4 nedelje posle početka terapije (rapidni virusološko odgovor – RVR), 12 ili 24 nedelje nakon početka terapije (kraj terapije – ETR) i 12 nedelja nakon završetka terapije (stabilan virusološki odgovor – SVR). Postignut SVR kao potvrda odsustva virusne RNK u serumu, smatran je završnicom uspešnog lečenja. Rezultati. Kompletan RVR, ETR i SVR postignut je kod 64,71%, 85,71%, i 95,24% bolesnika sukcesivno. Samo 3 bolesnika imali su blage neželjene efekte koji nisu zahtevali korekciju doze lekova. Zaključak. Lečenje bolesnika sa hroničnom HCV infekcijom sa OBV/PTV/r + DSV + RBV pokazalo je odličnu antivirusnu aktivnost i podnošljivost

Pomegranate Peel Extract Attenuates Isoprenaline-Induced Takotsubo-like Myocardial Injury in Rats

Takotsubo syndrome (TTS) is an acute heart failure syndrome characterised by catecholamine-induced oxidative tissue damage. Punica granatum, a fruit-bearing tree, is known to have high polyphenolic content and has been proven to be a potent antioxidant. This study aimed to investigate the effects of pomegranate peel extract (PoPEx) pre-treatment on isoprenaline-induced takotsubo-like myocardial injury in rats. Male Wistar rats were randomised into four groups. Animals in the PoPEx(P) and PoPEx + isoprenaline group (P + I) were pre-treated for 7 days with 100 mg/kg/day of PoPEx. On the sixth and the seventh day, TTS-like syndrome was induced in rats from the isoprenaline(I) and P + I groups by administering 85 mg/kg/day of isoprenaline. PoPEx pre-treatment led to the elevation of superoxide dismutase and catalase (p p p 2O2, O2− (p 2− (p < 0.001), in the P + I group, when compared to the I group. In addition, a significant reduction in the levels of cardiac damage markers, as well as a reduction in the extent of cardiac damage, was found. In conclusion, PoPEx pre-treatment significantly attenuated the isoprenaline-induced myocardial damage, primarily via the preservation of endogenous antioxidant capacity in the rat model of takotsubo-like cardiomyopathy