SUMMARYTo examine whether differentially expressed proteins are present in the serum of patients with obstructive sleep apnoea (OSA), iTRAQ techniques (isobaric tags for relative and absolute quantification) were employed in a prospective study. Individuals were assigned to either a non-OSA control group (apnoea-hypopnoea index, AHI <5) or an OSA group (AHI ‡5). Blood samples were collected, aliquoted and frozen at )80°C. Protein digestion and tagging with iTRAQ4plex â and mass spectrometry analysis was then performed (MALDI TOF ⁄ TOF). Ten male subjects were included in the control group (age = 45 ± 9.7 years) and 30 male patients in the OSA group (age = 45 ± 10.7 years), the latter being then subdivided into three severity groups. A total of 103 proteins were identified with differential levels between patients with OSA and controls. Of these, 11 proteins were underexpressed and 19 were overexpressed in patients with OSA. C4BPA and thrombospondin were underexpressed in all three OSA severity groups. Among the overexpressed proteins, 13 were overexpressed in the mild OSA group, seven in the moderate group and five in the severe group. Analysis of interactions between the identified proteins revealed that protein alterations in OSA are primarily associated with derangements in lipid and vascular metabolic pathways. This study provides initial evidence that differential protein expression occurs in adults with OSA, and that such proteins change according to disease severity, and appear to primarily involve lipid and vascular metabolic pathways.
Objectives The estimates of biological variation (BV) have traditionally been determined using direct methods, which present limitations. In response to this issue, two papers have been published addressing these limitations by employing indirect methods. Here, we present a new procedure, based on indirect methods that analyses data collected within a multicenter pilot study. Using this method, we obtain CVI estimates and calculate confidence intervals (CI), using the EFLM-BVD CVI estimates as gold standard for comparison. Methods Data were collected over a 18-month period for 7 measurands, from 3 Spanish hospitals; inclusion criteria: patients 18–75 years with more than two determinations. For each measurand, four different strategies were carried out based on the coefficient of variation ratio (rCoeV) and based on the use of the bootstrap method (OS1, RS2 and RS3). RS2 and RS3 use symmetry reference change value (RCV) to clean database. Results RS2 and RS3 had the best correlation for the CVI estimates with respect to EFLM-BVD. RS2 used the symmetric RCV value without eliminating outliers, while RS3 combined RCV and outliers. When using the rCoeV and OS1 strategies, an overestimation of the CVI value was obtained. Conclusions Our study presents a new strategy for obtaining robust CVI estimates using an indirect method together with the value of symmetric RCV to select the target population. The CVI estimates obtained show a good correlation with those published in the EFLM-BVD database. Furthermore, our strategy can resolve some of the limitations encountered when using direct methods such as calculating confidence intervals.
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