Talin-KANK1 interaction controls the recruitment of cortical microtubule stabilizing complexes to focal adhesions

The cross-talk between dynamic microtubules and integrin-based adhesions to the extracellular matrix plays a crucial role in cell polarity and migration. Microtubules regulate the turnover of adhesion sites, and, in turn, focal adhesions promote cortical microtubule capture and stabilization in their vicinity, but the underlying mechanism is unknown. Here, we show that cortical microtubule stabilization sites containing CLASPs, KIF21A, LL5 beta and liprins are recruited to focal adhesions by the adaptor protein KANK1, which directly interacts with the major adhesion component, talin. Structural studies showed that the conserved KN domain in KANK1 binds to the talin rod domain R7. Perturbation of this interaction, including a single point mutation in talin, which disrupts KANK1 binding but not the talin function in adhesion, abrogates the association of microtubule- stabilizing complexes with focal adhesions. We propose that the talin-KANK1 interaction links the two macromolecular assemblies that control cortical attachment of actin fibers and microtubules

Using Rasch analysis to form plausible health states amenable to valuation: the development of CORE-6D from CORE-OM in order to elicit preferences for common mental health problems

Purpose: To describe a new approach for deriving a preference-based index from a condition specific measure that uses Rasch analysis to develop health states. Methods: CORE-OM is a 34-item instrument monitoring clinical outcomes of people with common mental health problems. CORE-OM is characterised by high correlation across its domains. Rasch analysis was used to reduce the number of items and response levels in order to produce a set of unidimensionally-behaving items, and to generate a credible set of health states corresponding to different levels of symptom severity using the Rasch item threshold map. Results: The proposed methodology resulted in the development of CORE-6D, a 2-dimensional health state description system consisting of a unidimensionally-behaving 5-item emotional component and a physical symptom item. Inspection of the Rasch item threshold map of the emotional component helped identify a set of 11 plausible health states, which, combined with the physical symptom item levels, will be used for the valuation of the instrument, resulting in the development of a preference-based index. Conclusions: This is a useful new approach to develop preference-based measures where the domains of a measure are characterised by high correlation. The CORE-6D preference-based index will enable calculation of Quality Adjusted Life Years in people with common mental health problems

Quantification of the level descriptors for the standard EQ-5D three-level system and a five-level version according to two methods

Objectives: Our aim was to compare the quantitative position of the level descriptors of the standard EQ-5D three-level system (3L) and a newly developed, experimental five-level version (5L) using a direct and a vignette-based indirect method. Methods: Eighty-two respondents took part in the study. The direct method represented a visual analog scale (VAS) rating of the nonextreme level descriptors for each dimension and each instrument separately. The indirect method required respondents to score 15 health scenarios with 3L, 5L and a VAS scale. Investigated were: (1) equidistance (Are 3L and 5L level descriptors distributed evenly over the VAS continuum?); (2) isoformity (Do the identical level descriptors on 3L and 5L yield similar results?); and (3) consistency between dimensions (Do the positions of similar level descriptors differ across dimensions within instruments?). Results: Equidistance without transformation was rejected for all dimensions for both 3L and 5L but satisfied for 5L after transformation. Isoformity gave mixed results. Consistency between dimensions was satisfied for both instruments and both methods. Discussion: The level descriptors have similar distributions across comparable dimensions within each system, but the pattern differs between 3L and 5L. This methodological study provides evidence of increased descriptive power and a broadened measurement continuum that encourages the further development of an official five-level EQ-5D

Fibrinogen beta variants confer protection against coronary artery disease in a Greek case-control study

<p>Abstract</p> <p>Background</p> <p>Although plasma fibrinogen levels are related to cardiovascular risk, data regarding the role of fibrinogen genetic variation in myocardial infarction (MI) or coronary artery disease (CAD) etiology remain inconsistent. The purpose of the present study was to investigate the effect of <it>fibrinogen A (FGA)</it>, <it>fibrinogen B (FGB) </it>and <it>fibrinogen G (FGG) </it>gene SNPs and haplotypes on susceptibility to CAD in a homogeneous Greek population.</p> <p>Methods</p> <p>We genotyped for rs2070022, rs2070016, rs2070006 in <it>FGA </it>gene, the rs7673587, rs1800789, rs1800790, rs1800788, rs1800787, rs4681 and rs4220 in <it>FGB </it>gene and for the rs1118823, rs1800792 and rs2066865 SNPs in <it>FGG </it>gene applying an arrayed primer extension-based genotyping method (APEX-2) in a sample of CAD patients (n = 305) and controls (n = 305). Logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), before and after adjustment for potential confounders.</p> <p>Results</p> <p>None of the <it>FGA </it>and <it>FGG </it>SNPs and <it>FGA, FGB, FGG </it>and <it>FGA-FGG </it>haplotypes was associated with disease occurrence after adjustment. Nevertheless, rs1800787 and rs1800789 SNPs in <it>FGB </it>gene seem to decrease the risk of CAD, even after adjustment for potential confounders (OR = 0.42, 95%CI: 0.19-0.90, p = 0.026 and OR = 0.44, 95%CI:0.21-0.94, p = 0.039, respectively).</p> <p>Conclusions</p> <p><it>FGA </it>and <it>FGG </it>SNPs as well as <it>FGA, FGB, FGG </it>and <it>FGA-FGG </it>haplotypes do not seem to be important contributors to CAD occurrence in our sample. On the contrary, <it>FGB </it>rs1800787 and rs1800789 SNPs seem to confer protection to disease onset lowering the risk by about 50% in homozygotes for the minor alleles.</p

Analysis on the situation of subjective well-being and its influencing factors in patients with ankylosing spondylitis

BACKGROUND: To examine the subjective well-being (SWB) in patients with ankylosing spondylitis (AS) compared with the healthy controls, and to explore the associations between SWB and demographic characteristics, disease-specific variables in AS patients. METHODS: SWB was assessed with General Well-Being Schedule (GWBS) in 200 AS patients and 210 healthy controls. Comparisons among subgroups were performed to investigate how certain aspects operate as favorable or adverse factors in influencing SWB in the patients with AS. RESULTS: Both men and women with AS reported significantly impaired SWB on all scales of the GWBS except for the Control (O) scale. The results revealed that better sleep, lower disease activity and more family care predicted higher SWB. In AS patients, positive attitude towards therapy prospect was significantly associated with higher SWB. Therapy prospect refers to the hope of patients about the disease treatment. CONCLUSIONS: Compared with general population, SWB might be affected by the onset of AS. There are significant associations between SWB and sleep quality, BASDAI, APGAR, therapy prospect