Elevated serum lactate in emergency department patients predicts hospital admission unrelated to diagnosis – but not more

Purpose: The value of lactate as a screening biomarker in the emergency department is debated. We analysed all unselected patients in the emergency department with serum lactate measured with regard to different outcome parameters.

Material and Methods: In a retrospective single centre study, we analysed all digitalized patient data of a two-week period of all patients ≥18 where a serum lactate was measured. The lactate levels as well as demographic and other laboratory data were correlated in a logistic regression analysis, univariable as well as multivariable, with the outcome parameters.

Results: A total of 1157 patients contacted the emergency department of which 587 were included. The average lactate level was 2,08?mmol/l (SD ±1.51, median 1.73). A total of 313 patients were admitted to hospital, 274 treated as outpatients. Their median lactate levels were 2.0?mmol/l (min/max 0.6–18?mmol/l) and 1.5?mmol/l (min/max 0.5–7.4?mmol/l), respectively. Univariable regression analysis for hospital admission showed an odds ratio of 1756 (p?p?=?0.004). There was no correlation with admission to ICU, length of stay or a relation to a certain diagnostic group.

Conclusions: Screening lactate levels in unselected emergency department patients do not have a clinical relevance yet.     

Apolipoprotein A-V is a potential target for treating coronary artery disease: evidence from genetic and metabolomic analyses

Triglyceride (TG)-lowering LPL variants in combination with genetic LDL-C-lowering variants are associated with reduced risk of coronary artery disease (CAD). Genetic variation in the APOA5 gene encoding apolipoprotein A-V also strongly affects TG levels, but the potential clinical impact and underlying mechanisms are yet to be resolved. Here, we aimed to study the effects of APOA5 genetic variation on CAD risk and plasma lipoproteins through factorial genetic association analyses. Using data from 309,780 European-ancestry participants from the UK Biobank, we evaluated the effects of lower TG levels as a result of genetic variation in APOA5 and/or LPL on CAD risk with or without a background of reduced LDL-C. Next, we compared lower TG levels via APOA5 and LPL variation with over 100 lipoprotein measurements in a combined sample from the Netherlands Epidemiology of Obesity study (N = 4,838) and the Oxford Biobank (N = 6,999). We found that lower TG levels due to combined APOA5 and LPL variation and genetically-influenced lower LDL-C levels afforded the largest reduction in CAD risk (odds ratio: 0.78 (0.73–0.82)). Compared to patients with genetically-influenced lower TG via LPL, genetically-influenced lower TG via APOA5 had similar and independent, but notably larger, effects on the lipoprotein profile. Our results suggest that lower TG levels as a result of APOA5 variation have strong beneficial effects on CAD risk and the lipoprotein profile, which suggest apo A-V may be a potential novel therapeutic target for CAD prevention.     

Generation of rubella virus-neutralising antibodies by vaccination with synthetic peptides

Abstract Four short peptides from rubella virus proteins E1 and E2, predicted to contain B cell epitopes, were used to vaccinate BALB/c mice. Sera from peptide-vaccinated animals reacted with viral antigens in ELISA and three of the four induced virus-neutralising antibody (nAb) responses. Peptide PY4, in contrast to the others, induced IgG2a responses upon vaccination and stimulated spleen cells in vitro produced IFNγ in the absence of IL-5. It was reasoned that vaccination with PY4 caused Th1 subset activation, the appropriate type of response for anti-viral immunity and hence the efficient neutralising antibody response. Presentation of peptide for vaccination proved to be as important as the sequence. Similar profiles of IgG1 and IgG2a were detected in the sera of mice vaccinated with PY4 in Freund's complete adjuvant or alum; however nAb responses were not found when alum was used.     

Confidence Limits for the Ratio of Two Binomial Proportions Based on Likelihood Scores: Non-Iterative Method

The interval estimation of the ratio of two binomial proportions based on the score statistic is superior over other methods. Iterative algorithms for calculating the approximate confidence interval have been provided by, e.g., KOOPMAN (1984, Biometrics 40:513–517) and GART and NAM (1988a, Biometrics 44:323–338). This note presents the analytical solutions for upper and lower confidence limits in a closed form and gives examples for numerical illustration. The non-iterative method is generally more desirable than the iterative method.     

An application of CIFAP for predicting the binding affinity of Chk1 inhibitors derived from 2‐aminothiazole‐4‐carboxamide

Investigation of protein‐ligand interactions obtained from experiments has a crucial part in the design of newly discovered and effective drugs. Analyzing the data extracted from known interactions could help scientists to predict the binding affinities of promising ligands before conducting experiments. The objective of this study is to advance the CIFAP (compressed images for affinity prediction) method, which is relevant to a protein‐ligand model, identifying 2D electrostatic potential images by separating the binding site of protein‐ligand complexes and using the images for predicting the computational affinity information represented by pIC₅₀ values. The CIFAP method has 2 phases, namely, data modeling and prediction. In data modeling phase, the separated 3D structure of the binding pocket with the ligand inside is fitted into an electrostatic potential grid box, which is then compressed through 3 orthogonal directions into three 2D images for each protein‐ligand complex. Sequential floating forward selection technique is performed for acquiring prediction patterns from the images. In the prediction phase, support vector regression (SVR) and partial least squares regression are used for testing the quality of the CIFAP method for predicting the binding affinity of 45 CHK1 inhibitors derived from 2‐aminothiazole‐4‐carboxamide. The results show that the CIFAP method using both support vector regression and partial least squares regression is very effective for predicting the binding affinities of CHK1‐ligand complexes with low‐error values and high correlation. As a future work, the results could be improved by working on the pose of the ligands inside the grid.     

The impact of hybrids between genetically modified crop plants and their related species: introgression and weediness

Assessing the impact of hybrids between transgenic plants and nontarget wild species involves answering several questions such as: (i) what are the hybridization and introgression rates; (ii) what is the behaviour of a transgene in a wild population; and (iii) what will be the consequences of the expression of a transgene in a wild population? These issues are discussed using results from experiments on oilseed rape and wild related Brassiceae. Evidence is given of large variations in the estimates of cross-fertilization probabilities. The first stage of introgression into wild populations is demonstrated to occur spontaneously through back-crossing. Population analysis may also be valuable to detect traces of past introgression. Data from the literature on weed biology, and especially herbicide resistance, are used to illustrate the behaviour of a new gene in weed populations. The need for computer models simulating the introgression process is stressed.