Fabry disease (FD) is an X-linked lysosomal disorder caused by α-galactosidase A enzyme activity deficiency. Although glycosphingolipid analogs have been identified in the plasma or urine of patients with FD, there is a limited understanding of altered metabolomics profiles beyond the globotriaosylceramide accumulation in FD. Methods: Metabolomics study was performed for monitoring of biomarker and altered metabolism related with disease progression in serum and urine from male α-galactosidase A knockout mice and age-matched wild-type mice at 20 and 40 weeks. Profiling analysis for metabolites, including organic acids, amino acids, fatty acids, kynurenine pathway metabolites, and nucleosides in the serum and urine was performed using gas chromatography-tandem mass spectrometry and liquid chromatography-tandem mass spectrometry combined with star symbol patterns and partial least squares discriminant analysis (PLS-DA). Results: A total of 27 and 23 metabolites from the serum and urine of FD mice were distinguished from those of wild-type mice, respectively, based on p-value (<0.05) and variable importance in projection scores (>1.0) of PLS-DA. In the serum, metabolites of the glutathione, glutathione disulfide, citrulline, and kynurenine pathways that are related to oxidative stress, nitric oxide biosynthesis, and inflammation were increased, whereas those involved in pyruvate and tyrosine metabolism and the tricarboxylic acid cycle were altered in the 20- and 40-week-old urine of FD model mice. Conclusion: Altered metabolic signatures associated with disease progression by oxidative stress, inflammation, nitric oxide biosynthesis, and immune regulation in the early and late stages of FD.

In order to compare a group of examinees to other group, the tests taken by two groups of examinees should be equivalent. The first step of the equating the test is to make anchor items. In medical schools, the students prepare the examination through the thorough review of the test items of previous year. So it is said that the reuse of the same items could be undesirable. The purpose of this study is to find out response variations to the same items between two consecutive grades when the items are reused. The senior classes of a medical school are sampled and the test items of graduation examination was analysed. On the basis of item difficulty(item's p-value) and discrimination index, we selected 35 items. Next year, we reused those items to the same examination to the senior class of that year, and the result was analysed. Among those 35 items, 14 items were modified slightly. The averages of the item difficulty and discrimination index on the previous examination were 0.49 and 0.20 which were in the desirable ranges. But at the next year these data were worsened to 0.84 and 0.10 respectively. This trends were not different in the slightly modified items. And there was no significant differences among the item groups classified on the basis of the level of knowledge. We could ascertain that if a previously used item used again to a test, the item difficulty will increase(become easy) and discrimination index will decrease even though minor modification is done.
Discrimination (Psychology) ; Humans ; Schools, Medical*