Evolving neural network optimization of cholesteryl ester separation by reversed-phase HPLC

Cholesteryl esters have antimicrobial activity and likely contribute to the innate immunity system. Improved separation techniques are needed to characterize these compounds. In this study, optimization of the reversed-phase high-performance liquid chromatography separation of six analyte standards (four cholesteryl esters plus cholesterol and tri-palmitin) was accomplished by modeling with an artificial neural network–genetic algorithm (ANN-GA) approach. A fractional factorial design was employed to examine the significance of four experimental factors: organic component in the mobile phase (ethanol and methanol), column temperature, and flow rate. Three separation parameters were then merged into geometric means using Derringer’s desirability function and used as input sources for model training and testing. The use of genetic operators proved valuable for the determination of an effective neural network structure. Implementation of the optimized method resulted in complete separation of all six analytes, including the resolution of two previously co-eluting peaks. Model validation was performed with experimental responses in good agreement with model-predicted responses. Improved separation was also realized in a complex biological fluid, human milk. Thus, the first known use of ANN-GA modeling for improving the chromatographic separation of cholesteryl esters in biological fluids is presented and will likely prove valuable for future investigators involved in studying complex biological samples

Genome-wide scan reveals association of psoriasis with IL-23 and NF-κB pathways

Psoriasis is a common immune-mediated disorder that affects the skin, nails and joints. To identify psoriasis susceptibility loci, we genotyped 438,670 SNPs in 1,409 psoriasis cases and 1,436 controls of European ancestry. We followed up 21 promising SNPs in 5,048 psoriasis cases and 5,041 controls. Our results provide strong support for the association of at least seven genetic loci and psoriasis (each with combined P less than 5 × 10−8). Loci with confirmed association include HLA-C, three genes involved in IL-23 signaling (IL23A, IL23R, IL12B), two genes that act downstream of TNF-α and regulate NF-κB signaling (TNIP1, TNFAIP3) and two genes involved in the modulation of Th2 immune responses (IL4, IL13). Although the proteins encoded in these loci are known to interact biologically, we found no evidence for epistasis between associated SNPs. Our results expand the catalog of genetic loci implicated in psoriasis susceptibility and suggest priority targets for study in other auto-immune disorders

Non-invasive accurate measurement of arterial PCO2 in a pediatric animal model

<p>The PCO2 in arterial blood (PaCO2) is a good parameter for monitoring ventilation and acid-base changes in ventilated patients, but its measurement is invasive and difficult to obtain in small children. Attempts have been made to use the partial pressure of CO2 in end-tidal gas (PetCO(2)), as a noninvasive surrogate for PaCO2. Studies have revealed that, unfortunately, the differences between PetCO(2) and PaCO2 are too variable to be clinically useful. We hypothesized that end-inspiratory rebreathing, previously shown to equalize PetCO(2) and PaCO2 in spontaneously breathing humans, would also be effective with positive pressure ventilation. Eight newborn Yorkshire pigs were mechanically ventilated via a partial rebreathing circuit to implement end-inspiratory rebreathing. Arterial blood was sampled and tested for PaCO2. A variety of alveolar ventilations resulting in different combinations of end-tidal PCO2 (30-50 mmHg) and PO2 (35-500 mmHg) were tested for differences between PetCO(2) and PaCO2 (Pet-aCO(2)). The Pet-aCO(2) of all samples was (mean +/- 1.96 SD) 0.4 +/- 2.7 mmHg. Our study demonstrates that, in ventilated juvenile animals, end-inspiratory rebreathing maintains Pet-aCO(2) to what would be a clinically useful range. If verified clinically, this approach could open the way for non-invasive monitoring of arterial PCO2 in critically ill patients.</p>