Exploring cut-off values for large waist circumference in older adults: a new methodological approach

BACKGROUND: There is an ongoing debate about the applicability of current criteria for large waist circumference (WC) in older adults. OBJECTIVES: Our aim was to explore cut-off values for large WC in adults aged 70 years and older, using previously used and new methods. DESIGN: Prospective cohort study. PARTICIPANTS: Data of 1049 participants of the Longitudinal Aging Study Amsterdam (LASA) (1995-1996), aged 70-88y, were used. MEASUREMENTS: Measured BMI and WC, and self-reported mobility limitations. RESULTS: Linear regression analyses showed that the values of WC corresponding to BMI of 25kg/m2 and 30kg/m2 were higher than the current cut-offs. Cut-offs found in men were 97 and 110cm, whereas 88 and 98cm represented the cut-offs in women. Areas under the Receiver Operating Characteristic (ROC) curves showed that the accuracy to predict mobility limitations improved when the higher cut-offs were applied. Spline regression curves showed that the relationship of WC with mobility limitations was U-shaped in men, while in women, the risk for mobility limitations increased gradually with increasing WC. However, at the level of current cut-off values for WC the odds for mobility limitations were not increased. CONCLUSION: Based on results of extensive analyses, this study suggests that the cut-offs for large WC should be higher when applied to older adults. The association of WC with other negative health outcomes needs to be investigated to establish the final cut-points

The Discovery and Mass Measurement of a New Ultra-Short-Period Planet: K2-131b

FWN – Publicaties zonder aanstelling Universiteit LeidenStars and planetary system

Vitreal IgM autoantibodies target neurofilament medium in a spontaneous model of autoimmune uveitis.

PURPOSE. Although the presence of IgG autoantibodies in the vitreous of spontaneous cases of equine recurrent uveitis (ERU) has been demonstrated, the potential role of IgM reactivities during ERU pathogenesis remains unexplored. The purpose of this study was to examine the presence of IgM autoantibodies in vitreous specimens of ERU-affected horses and to test their binding specificity to intraocularly expressed proteins. METHODS. To test IgM autoantibody responses to retinal tissue, vitreous samples of eye-healthy controls and ERU patients were analyzed via two-dimensional Western blot analysis with equine retinal tissue as an antigen source. A candidate protein, the peptide neurofilament medium (NF-M), was identified via mass spectrometry and validated via enzyme-linked immunosorbent assay. Immunohistochemistry for NF-M expression was performed on healthy and ERU-affected retinal sections. RESULTS. Whereas autoreactivity was never detected in the healthy vitreous samples, NF-M was specifically targeted by vitreal IgM autoantibodies in 44% of the ERU cases. Vitreal anti-NF-M IgG was detected in only 8% of the ERU samples, pointing to a persistent IgM response. In healthy horse retina, NF-M was located in the retinal ganglion cells and their processes, with additional staining in the outer plexiform layer. NF-M expression in ERU-affected retinas decreased considerably, and the remaining expression was limited to the nerve fiber layer. CONCLUSIONS. Intraocular anti NF-M IgM autoantibodies occur with high prevalence in vitreous of spontaneous autoimmune uveitis cases. The IgM dominated response may indicate a thymus-independent response to NF-M and merits further investigation in ERU, as well as in its human counterpart, autoimmune uveitis. ( Invest Ophthalmol Vis Sci. 2012; 53:294-300) DOI:10.1167/iovs.11-873

Identification of autoantigens in body fluids by combining pull-downs and organic precipitations of intact immune complexes with quantitative label-free mass spectrometry.

Most autoimmune diseases are multifactorial diseases and are caused by the immunological reaction against a number of autoantigens. Key for understanding autoimmune pathologies is the knowledge of the targeted autoantigens, both initially and during disease progression. We present an approach for autoantigen identification based on isolation of intact autoantibody-antigen complexes from body fluids. After organic precipitation of high molecular weight proteins and free immunoglobulins, released autoantigens were identified by quantitative label-free liquid chromatography mass spectrometry. We confirmed feasibility of target enrichment and identification from highly complex body fluid proteomes by spiking of a pre-defined antigen-antibody complex at low level of abundance. As a proof of principle we studied the blinding disease autoimmune uveitis, which is caused by autoreactive T-cells attacking the inner eye and is accompanied by autoantibodies. We identified three novel autoantigens in the spontaneous animal model equine recurrent uveitis (secreted acidic phosphoprotein osteopontin, extracellular matrix protein 1 and metalloproteinase inhibitor 2) and confirmed presence of the corresponding autoantibodies in 15 - 25% of patient samples by enzyme-linked immunosorbent assay. Thus, this workflow led to the identification of novel autoantigens in autoimmune uveitis and may provide a versatile and useful tool to identify autoantigens in other autoimmune diseases in future

How to determine an impaired health status in COPD: Results from a population-based study

Background: Chronic obstructive pulmonary disease (COPD) is associated with a significantly impaired health status and lost work productivity across all degrees of airflow limitation. The current study investigated whether an impaired health status is better represented by the recommended COPD Assessment Test (CAT) cut-point of 10 points, or the 95th percentile of the CAT score in a non-COPD population. Additionally, the impact of COPD on health status in a Dutch population, after stratification for work status, was measured. Methods: Demographics, clinical characteristics, post-bronchodilator spirometry, and CAT were assessed in subjects from the Longitudinal Aging Study Amsterdam (LASA), a large Dutch population-based study. Normative values for the CAT score were described by percentiles using the mean, standard deviation, median and range. Results: In total, 810 COPD and non-COPD subjects (50.4% male, mean age 60.5 ± 2.9 years) were analysed. Significant differences were observed in CAT scores between non-COPD and COPD subjects (6.7 ± 5.2 vs. 9.5 ± 5.9, p 18 cut-point; 7.6%). Higher CAT scores were seen in working COPD patients compared with working non-COPD subjects (9.3 ± 5.2 vs. 6.0 ± 4.6, p 18 points to indicate an impaired health status in COPD. This would imply an adaptation of the current GOLD classification of the disease

Label-free LC-MSMS analysis of vitreous from autoimmune uveitis reveals a significant decrease in secreted Wnt signalling inhibitors DKK3 and SFRP2.

Equine recurrent uveitis is a severe and frequent blinding disease in horses which presents with auto-reactive invading T-cells, resulting in the destruction of the inner eye. Infiltration of inflammatory cells into the retina and vitreous is driven by currently unknown guidance cues, however surgical removal of the vitreous (vitrectomy) has proven therapeutically successful. Therefore, proteomic analyses of vitrectomy samples are likely to result in detection of proteins contributing to disease pathogenesis. Vitreous from healthy and ERU diseased horses were directly compared by quantitative mass spectrometry based on label-free quantification of peak intensities across samples. We found a significant upregulation of complement and coagulation cascades and downregulation of negative paracrine regulators of canonical Wnt signalling including the Wnt signalling inhibitors DKK3 and SFRP2. Based on immunohistochemistry, both proteins are expressed in equine retina and suggest localisation to retinal Muller glial cells (RMG), which may be the source cells for these proteins. Furthermore, retinal expression levels and patterns of DKK3 change in response to ERU. Since many other regulated proteins identified here are associated with RMG cells, these cells qualify as the prime responders to autoimmune triggers. This article is part of a Special Issue entitled: "Farm animal proteomics"

Do disease specific characteristics add to the explanation of mobility limitations in patients with different chronic diseases? A study in The Netherlands.

STUDY OBJECTIVES: To determine whether disease specific characteristics, reflecting clinical disease severity, add to the explanation of mobility limitations in patients with specific chronic diseases. DESIGN AND SETTING: Cross sectional study of survey data from community dwelling elderly people, aged 55-85 years, in the Netherlands. PARTICIPANTS AND METHODS: The additional explanation of mobility limitations by disease specific characteristics was examined by logistic regression analyses on data from 2830 community dwelling elderly people. MAIN RESULTS: In the total sample, chronic non-specific lung disease, cardiac disease, peripheral atherosclerosis, diabetes mellitus, stroke, arthritis and cancer (the index diseases), were all independently associated with mobility limitations. Adjusted for age, sex, comorbidity, and medical treatment disease specific characteristics that explain the association between disease and mobility mostly reflect decreased endurance capacity (shortness of breath and disturbed night rest in chronic non-specific lung disease, angina pectoris and congestive heart failure in cardiac disease), or are directly related to mobility function (stiffness and lower body complaints in arthritis). For atherosclerosis and diabetes mellitus, disease specific characteristics did not add to the explanation of mobility limitations. CONCLUSIONS: The results provide evidence that, to obtain more detailed information about the differential impact of chronic diseases on mobility, disease specific characteristics are important to take into account