Validity of LupusQoL-China for the Assessment of Health Related Quality of Life in Chinese Patients with Systemic Lupus Erythematosus

<div><p>Objectives</p><p>To adapt and assess the validity and reliability of LupusQoL for use in Chinese patients with systemic lupus erythematosus (SLE).</p><p>Methods</p><p>Debriefing interviews of subjects with SLE guided the language modifications of the tool. The process of adaptation proceeded according to the guideline and pre-testing results of LupusQoL-China. 220 SLE patients completed LupusQoL-China and a generic preference-based measurement of health EuroQoL scale (EQ-5D), and 20 patients repeated them after 2 weeks. Internal consistency (ICR) and test-retest (TRT) reliability, convergent and discriminant validity were examined. Factor analysis and Rasch analysis were performed.</p><p>Results</p><p>The mean (SD) age of the 208 subjects with SLE was 33.93 (±9.19) years. ICR and TRT of the eight domains ranged from 0.811 to 0.965 and 0.836 to 0.974, respectively. The LupusQoL-China domains demonstrated substantial evidence of construct validity when compared with equivalent domains on the EQ-5D (physical health and usual activities r = −0.63, pain and pain/discomfort r = −0.778, emotional health and anxiety/depression r = −0.761, planning and usual activities r = −0.560). Most LupusQoL-China domains could discriminate patients with varied disease activities and end-organ damage (according to SELENA-SLEDAI and SLICC-DI). The principal component analysis revealed six factors, and confirmatory factor analysis result of which is similar to eight factors model.</p><p>Conclusions</p><p>These results provide evidence that the LupusQoL-China is valid as a disease-specific HRQoL assessment tool for Chinese patients with SLE.</p></div

Structural and Kinetic Analyses of Macrophage Migration Inhibitory Factor Active Site Interactions

Macrophage migration inhibitory factor (MIF) is a secreted protein expressed in numerous cell types that counters the antiinflammatory effects of glucocorticoids and has been implicated in sepsis, cancer, and certain autoimmune diseases. Interestingly, the structure of MIF contains a catalytic site resembling the tautomerase/isomerase sites of microbial enzymes. While bona fide physiological substrates remain unknown, model substrates have been identified. Selected compounds that bind in the tautomerase active site also inhibit biological functions of MIF. It had previously been shown that the acetaminophen metabolite, N-acetyl-p-benzoquinone imine (NAPQI), covalently binds to the active site of MIF. In this study, kinetic data indicate that NAPQI inhibits MIF both covalently and noncovalently. The structure of MIF cocrystallized with NAPQI reveals that the NAPQI has undergone a chemical alteration forming an acetaminophen dimer (bi-APAP) and binds noncovalently to MIF at the mouth of the active site. We also find that the commonly used protease inhibitor, phenylmethylsulfonyl fluoride (PMSF), forms a covalent complex with MIF and inhibits the tautomerase activity. Crystallographic analysis reveals the formation of a stable, novel covalent bond for PMSF between the catalytic nitrogen of the N-terminal proline and the sulfur of PMSF with complete, well-defined electron density in all three active sites of the MIF homotrimer. Conclusions are drawn from the structures of these two MIF−inhibitor complexes regarding the design of novel compounds that may provide more potent reversible and irreversible inhibition of MIF

Discovery of Human Macrophage Migration Inhibitory Factor (MIF)-CD74 Antagonists via Virtual Screening

Macrophage migration inhibitory factor (MIF) is a cytokine that is involved in the regulation of inflammation as well as cell proliferation and differentiation. Deactivation of MIF by antibodies or inhibition of MIF binding to its receptor, CD74, attenuates tumor growth and angiogenesis. To discover small-molecule inhibitors of MIF’s biological activity, virtual screening was performed by docking 2.1 million compounds into the MIF tautomerase active site. After visual inspection of 1200 top-ranked MIF-ligand complexes, 26 possible inhibitors were selected and purchased and 23 of them were assayed. The in vitro binding assay for MIF with CD74 revealed that 11 of the compounds have inhibitory activity in the micromolar regime, including four compounds with IC50 values below 5 μM. Inhibition of MIF tautomerase activity was also established for many of the compounds with IC50 values as low as 0.5 μM; Michaelis−Menten analysis was performed for two cases and confirmed the competitive inhibition

Boundaries of intra-retinal layers in OCT macular images.

<p>As seen in this image taken by UHR-OCT in the horizontal meridian, nine boundaries of intra-retinal layers were visualized. Images taken in the vertical meridian by UHR-OCT and in both meridians by the RTVue100 were similar to this.</p

The detailed sequence in the boundary segmentation process.

<p>(a) Original image. (b) Image smoothing. (c) Gradient image. (d) The ILM and the boundary between the RPE and choroid layers were first segmented. (e) Limiting detection area and search the minimum-weighted path. (f) Segmented image.</p

Bland-Altman plots of thickness measurements determined with the automated segmentation algorithm on UHR-OCT and RTVue100 images.

<p>Only the images along the horizontal meridian were analyzed. The horizontal full lines represent the mean of thickness differences, and the horizontal dashed lines represent the mean differences ±1.96 standard deviation.</p

Multi-Dimensional Health Assessment Questionnaire in China: Reliability, Validity and Clinical Value in Patients with Rheumatoid Arthritis

<div><p>Objective</p><p>To evaluate the psychometric properties and clinical utility of Chinese Multidimensional Health Assessment Questionnaire (MDHAQ-C) in patients with rheumatoid arthritis (RA) in China.</p><p>Methods</p><p>162 RA patients were recruited in the evaluation process. The reliability of the questionnaire was tested by internal consistency and item analysis. Convergent validity was assessed by correlations of MDHAQ-C with Health Assessment Questionnaire (HAQ), the 36-item Short-Form Health Survey (SF-36) and the Hospital anxiety and depression scales (HAD). Discriminant validity was tested in groups of patients with varied disease activities and functional classes. To evaluate the clinical values, correlations were calculated between MDHAQ-C and indices of clinical relevance and disease activity. Agreement with the Disease Activity Score (DAS28) and Clinical Disease Activity Index (CDAI) was estimated.</p><p>Results</p><p>The Cronbach's alpha was 0.944 in the Function scale (FN) and 0.768 in the scale of psychological status (PS). The item analysis indicated all the items of FN and PS are correlated at an acceptable level. MDHAQ-C correlated with the questionnaires significantly in most scales and scores of scales differed significantly in groups of different disease activity and functional status. MDHAQ-C has moderate to high correlation with most clinical indices and high correlation with a spearman coefficient of 0.701 for DAS 28 and 0.843 for CDAI. The overall agreement of categories was satisfying.</p><p>Conclusion</p><p>MDHAQ-C is a reliable, valid instrument for functional measurement and a feasible, informative quantitative index for busy clinical settings in Chinese RA patients.</p></div

Configuration of the two OCT instruments.

<p>Configuration of the two OCT instruments.</p

profiles of eight intra-retinal layers determined from the UHR-OCT and RTVue100 images in the horizontal meridian.

<p>Thickness profiles of eight intra-retinal layers along the horizontal meridian were averaged for 20 normal healthy eyes. Error bars represent standard deviation.</p

Scatter plots of correlation between RAPID3 and DAS28 in 156 patients with Rheumatoid Arthritis (spearman's method).

<p>Scatter plots of correlation between RAPID3 and DAS28 in 156 patients with Rheumatoid Arthritis (spearman's method).</p