Autoimmune antibody profiling plays a prominent role in both classification and prognosis of systemic sclerosis (SSc). In the last years novel autoantibodies have been discovered and have become available in diagnostic assays. However, standardization in autoimmune serology is lacking, which may have a negative impact on the added value of autoantibodies in diagnosis and prognosis of SSc. In this paper we describe the comparison of commercially available diagnostic assays for the detection of SSc-associated autoantibodies and explored the coexistence of multiple SSc-associated autoantibodies within patients.
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AIM: To systematically review the available literature on the diagnostic accuracy of questionnaires and measurement instruments for headaches associated with musculoskeletal symptoms.DESIGN: Articles were eligible for inclusion when the diagnostic accuracy (sensitivity/specificity) was established for measurement instruments for headaches associated with musculoskeletal symptoms in an adult population. The databases searched were PubMed (1966-2018), Cochrane (1898-2018) and Cinahl (1988-2018). Methodological quality was assessed with the Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2) and COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist for criterion validity. When possible, a meta-analysis was performed. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) recommendations were applied to establish the level of evidence per measurement instrument.RESULTS: From 3450 articles identified, 31 articles were included in this review. Eleven measurement instruments for migraine were identified, of which the ID-Migraine is recommended with a moderate level of evidence and a pooled sensitivity of 0.87 (95% CI: 0.85-0.89) and specificity of 0.75 (95% CI: 0.72-0.78). Six measurement instruments examined both migraine and tension-type headache and only the Headache Screening Questionnaire - Dutch version has a moderate level of evidence with a sensitivity of 0.69 (95% CI 0.55-0.80) and specificity of 0.90 (95% CI 0.77-0.96) for migraine, and a sensitivity of 0.36 (95% CI 0.21-0.54) and specificity of 0.86 (95% CI 0.74-0.92) for tension-type headache. For cervicogenic headache, only the cervical flexion rotation test was identified and had a very low level of evidence with a pooled sensitivity of 0.83 (95% CI 0.72-0.94) and specificity of 0.82 (95% CI 0.73-0.91).DISCUSSION: The current review is the first to establish an overview of the diagnostic accuracy of measurement instruments for headaches associated with musculoskeletal factors. However, as most measurement instruments were validated in one study, pooling was not always possible. Risk of bias was a serious problem for most studies, decreasing the level of evidence. More research is needed to enhance the level of evidence for existing measurement instruments for multiple headaches.
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OBJECTIVES: Patients with hip or knee osteoarthritis (OA) may experience functional limitations in work settings. In the Cohort Hip and Cohort Knee study (CHECK) physical function was both self-reported and measured performance-based, using Functional Capacity Evaluation (FCE). Relations between self-reported scores on SF-36 and WOMAC (Western Ontario and McMaster Arthritis Index, function scales) and FCE performance were studied, and their diagnostic value for clinicians in predicting observed physical work limitations was assessed.METHODS: Ninety-two subjects scored physical function on SF-36 (scale 0-100, 100 indicating the best health level) and WOMAC (scale 0-68, 68 indicates maximum restriction) and performed the FCE. Correlations were calculated between all scores. Cross-tables were constructed using both questionnaires as diagnostic tests to identify work limitations. Subjects lifting <22.5 kg on the FCE-test 'lifting-low' were labeled as having physical work limitations. Diagnostic aspects at different cut-off scores for both questionnaires were analysed.RESULTS: Statistically significant correlations (Spearman's rho 0.34-0.49) were found between questionnaire scores and lifting and carrying tests. Results of a diagnostic cross-table with cut-off point <60 on SF-36 'physical functioning' were: sensitivity 0.34, specificity 0.97 and positive predictive value (PV+) 0.95. Cut-off point > or =21 on WOMAC 'function' resulted in sensitivity 0.51, specificity 0.88 and PV+ 0.88.CONCLUSION: Low self-reported function scores on SF-36 and WOMAC diagnosed subjects with limitations on the FCE. However, high scores did not guarantee performance without physical work limitations. These results are specific to the tested persons with early OA, in populations with a different prevalence of limitations, different diagnostic values will be found. FCE may be indicated to help clinicians to assess actual work capacity.
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Structural colour (SC) is created by light interacting with regular nanostructures in angle-dependent ways resulting in vivid hues. This form of intense colouration offers commercial and industrial benefits over dyes and other pigments. Advantages include durability, efficient use of light, anti-fade properties and the potential to be created from low cost materials (e.g. cellulose fibres). SC is widely found in nature, examples include butterflies, squid, beetles, plants and even bacteria. Flavobacterium IR1 is a Gram-negative, gliding bacterium isolated from Rotterdam harbour. IR1 is able to rapidly self-assemble into a 2D photonic crystal (a form of SC) on hydrated surfaces. Colonies of IR1 are able to display intense, angle-dependent colours when illuminated with white light. The process of assembly from a disordered structure to intense hues, that reflect the ordering of the cells, is possible within 10-20 minutes. This bacterium can be stored long-term by freeze drying and then rapidly activated by hydration. We see these properties as suiting a cellular reporter system quite distinct from those on the market, SC is intended to be “the new Green Fluorescent Protein”. The ability to understand the genomics and genetics of SC is the unique selling point to be exploited in product development. We propose exploiting SC in IR1 to create microbial biosensors to detect, in the first instance, volatile compounds that are damaging to health and the environment over the long term. Examples include petroleum or plastic derivatives that cause cancer, birth defects and allergies, indicate explosives or other insidious hazards. Hoekmine, working with staff and students within the Hogeschool Utrecht and iLab, has developed the tools to do these tasks. We intend to create a freeze-dried disposable product (disposables) that, when rehydrated, allow IR1 strains to sense and report multiple hazardous vapours alerting industries and individuals to threats. The data, visible as brightly coloured patches of bacteria, will be captured and quantified by mobile phone creating a system that can be used in any location by any user without prior training. Access to advice, assay results and other information will be via a custom designed APP. This work will be performed in parallel with the creation of a business plan and market/IP investigation to prepare the ground for seed investment. The vision is to make a widely usable series of tests to allow robust environmental monitoring for all to improve the quality of life. In the future, this technology will be applied to other areas of diagnostics.
Pre-eclampsia (PE) is a common and severe pregnancy complication and is associated with substantial perinatal morbidity and mortality in mothers and infants. The disease is often characterized by a non-specific presentation which makes it challenging for physician to diagnose PE during regular pregnancy check-ups. To date, there are no diagnostic tests on the market for detection of PE early in pregnancy (first trimester). In this project, we will develop a platform to sensitively analyse calcium-binding proteins (CBPs) which will unlock the full potential of CBPs as predictive PE markers. The technology will also be applicable for other diseases (e.g., dementia and cancer) where CBPs are also known to play a key role in disease pathophysiology. We will develop with phage display antibodies that can recognize calcium binding to specific motifs in proteins. To this end we will synthesize peptide motifs with and without calcium to select antibodies that are specific for calcium bound proteins. These antibodies will be validated for their clinical use. For this goal we will use serum samples from the Improved studie (EU subsidised study) to determine if we can recognize pre-eclampsia in a very early stage. This knowledge can lead to a better treatment of pregnant women suffering from this disease and also will probably increase the well-being for the baby born and the development further in life.
The missing link in diagnostic testing for rheumatoid arthritis (RA) is an agglutination assay, easy to perform and dedicated to decentralized testing. Approximately 75% of RA patients produce autoantibodies to citrullinated proteins (ACPA), which can be detected using an agglutination-based diagnostic test. Such a diagnostic test will be cheaper, less laborious and faster than current tests and does not require sophisticated equipment. Novio Catalpa is developing this alternative test for ACPA in collaboration with Radboud University. To develop this test, specifically tagged and citrullinated nanobodies are needed, but the production is still challenging. Current methods for the production of ACPA diagnostics involve chemical synthesis, in which a variety of toxic chemicals are used in each step. The alternative assay involves nanobodies fused with RA-biomarker target entities, which can be completely produced by ‘green synthesis’ in the yeast Pichia pastoris using the expertise of HAN BioCentre. The yeast P. pastoris has proven to be able to produce nanobodies and is a fast and cost-effective platform that often results in high protein yields. Goal of the project is therefore to determine the feasibility and best green route to produce purified nanobodies tagged with citrullinated ACPA targets that can be used for developing an agglutination assay for RA. P. pastoris does not produce endogenous PAD enzymes which are needed for citrullination of the nanobodies in order to be able to use it in a RA agglutination test. Therefore, PAD enzymes from other sources need to be tested and applied. The project results will be directly used by Novio Catalpa to further develop the innovative test for RA. This project will contribute to and finally result in a single-step agglutination assay suitable for both point-of-care testing and automation in clinical laboratories.
