Pragmatic MDR: a metadata repository with bottom-up standardization of medical metadata through reuse.

BACKGROUND: The variety of medical documentation often leads to incompatible data elements that impede data integration between institutions. A common approach to standardize and distribute metadata definitions are ISO/IEC 11179 norm-compliant metadata repositories with top-down standardization. To the best of our knowledge, however, it is not yet common practice to reuse the content of publicly accessible metadata repositories for creation of case report forms or routine documentation. We suggest an alternative concept called pragmatic metadata repository, which enables a community-driven bottom-up approach for agreeing on data collection models. A pragmatic metadata repository collects real-world documentation and considers frequent metadata definitions as high quality with potential for reuse. METHODS: We implemented a pragmatic metadata repository proof of concept application and filled it with medical forms from the Portal of Medical Data Models. We applied this prototype in two use cases to demonstrate its capabilities for reusing metadata: first, integration into a study editor for the suggestion of data elements and, second, metadata synchronization between two institutions. Moreover, we evaluated the emergence of bottom-up standards in the prototype and two medical data managers assessed their quality for 24 medical concepts. RESULTS: The resulting prototype contained 466,569 unique metadata definitions. Integration into the study editor led to a reuse of 1836 items and item groups. During the metadata synchronization, semantic codes of 4608 data elements were transferred. Our evaluation revealed that for less complex medical concepts weak bottom-up standards could be established. However, more diverse disease-related concepts showed no convergence of data elements due to an enormous heterogeneity of metadata. The survey showed fair agreement (Kalpha = 0.50, 95% CI 0.43-0.56) for good item quality of bottom-up standards. CONCLUSIONS: We demonstrated the feasibility of the pragmatic metadata repository concept for medical documentation. Applications of the prototype in two use cases suggest that it facilitates the reuse of data elements. Our evaluation showed that bottom-up standardization based on a large collection of real-world metadata can yield useful results. The proposed concept shall not replace existing top-down approaches, rather it complements them by showing what is commonly used in the community to guide other researchers.

A Case of Severe Anaphylaxis to Polyhexanide: Cross-Reactivity between Biguanide Antiseptics.

We present the case of a 77-year-old female patient who suffered from severe anaphylaxis during wound care. Allergologic evaluation yielded specific IgE antibodies to chlorhexidine, but anaphylaxis to chlorhexidine was not congruent with the patient history and dermal provocation tests. However, skin prick tests provided evidence for a sensitization to polyhexanide that was further supported by the detection of specific IgE antibodies to polyhexanide, the results of basophil activation tests and IgE inhibition analysis. We presume cross-reactive IgE antibodies binding to both biguanide antiseptics and identified polyhexanide as the likely cause of the anaphylactic reaction. We recognize polyhexanide as an emerging allergen that has to be considered as a cause of anaphylaxis.

Occupational sensitization to lactase in the dietary supplement industry.

Aerogen lactase exposure carries a risk for the development of allergic asthma and rhinitis; only a few occupationally affected patients have been reported. The authors report the results of allergy testing with employees of a lactase tablets manufacturing plant. The survey involved 13 workers, including a questionnaire, spirometry, basophil activation test (BAT), and skin prick tests (SPTs) with lactase and a panel of common aeroallergens. Furthermore, lactase-specific immunoglobulin E (IgE) antibodies were analyzed. Sensitization to lactase could be proven for 9 workers by SPT and BAT; specific IgE antibodies could be detected in serum samples of all sensitized. However, IgE levels ≥0.35 kU/L were only found in 4 sera. These data confirm that occupational exposure to lactase can induce IgE-mediated respiratory sensitization resulting in allergic diseases. Protective measures should thus be obligatory when working with lactase.

Allergy--current insights into prevention and diagnostic workup of immediate-type allergy and treatment of allergic rhinoconjunctivitis.

In recent decades, the incidence of allergic diseases has dramatically increased, by now affecting a large percentage of the population. For a long time, allergen avoidance was considered the most crucial measure in primary allergy prevention. However, studies have increasingly shown that exposure to allergens is an essential prerequisite for the development of immunological tolerance. Diagnostic workup is based on patient history, skin tests, and measurement of specific IgE antibodies. The introduction of component-based diagnostic workup offer an option to differentiate between primary sensitization and cross-reactivity caused by sensitization to panallergens or sensitization to cross-reactive carbohydrate epitopes. Symptomatic treatment only leads to temporary relief of allergic symptoms. By contrast, specific immunotherapy (SIT) may have long-lasting therapeutic effects and potentially even result in a complete cure. The selection of allergens for SIT is guided by the principle of major allergens. It is recommended to use those preparations that have been proven safe and effective in controlled clinical studies. With respect to subcutaneous immunotherapy, a host of tested and approved extracts are available for a wide range of different allergens. Large clinical trials have also confirmed the efficacy of sublingual immunotherapy with grass and also birch pollen extracts, which has led to the official approval of some preparations containing these allergens.

Cross-reacting carbohydrate determinants and hymenoptera venom allergy.

PURPOSE OF REVIEW: Insect venom allergy is an important cause of anaphylaxis. Venom immunotherapy assume the clear identification of the culprit insect, but this is impeded by Immunoglobulin E (IgE) antibodies to cross reactive carbohydrate determinant (CCD) epitopes of common glycoproteins. Here we give an overview about inducers, importance, and relevance of anti-N-Glycan CCD IgE antibodies. RECENT FINDINGS: Pollen exposure and insect stings induce anti-CCD IgE antibodies interfering with in-vitro tests for allergy diagnosis due to extensive IgE cross-reactivity. Instead of being biologically active these antibodies are irrelevant for allergic reactions due to hymenoptera stings. The general response of the immune system to the ubiquitous exposure to N-glycan containing glycoproteins is still a matter of debate. CCD specific IgG antibodies in sera of bee keepers suggest tolerance induction due to high-dose exposure. Tolerance induction by pollen and food glycoproteins has not been proved. SUMMARY: Hymenoptera stings and pollen exposure induce anti-CCD IgE. In regard to anaphylaxis due to Hymenoptera stings these antibodies are not clinically relevant, but they are important for the specificity of in-vitro tests proving insect venom allergy. The introduction of component based diagnostic IgE testing improves the specificity of in-vitro tests if proteins devoid of CCD epitopes are used.

The membrane-tethered transcription factor ANAC089 serves as redox-dependent suppressor of stromal ascorbate peroxidase gene expression.

The stromal ascorbate peroxidase (sAPX) functions as central element of the chloroplast antioxidant defense system. Its expression is under retrograde control of chloroplast signals including redox- and reactive oxygen species-linked cues. The sAPX promoter of Arabidopsis thaliana was dissected in transient reporter assays using mesophyll protoplasts. The study revealed regulatory elements up to -1868 upstream of the start codon. By yeast-one-hybrid screening, the transcription factor ANAC089 was identified to bind to the promoter fragment 2 (-1262 to -1646 bp upstream of translational initiation). Upon mutation of the cis-acting element CACG, binding of ANAC089 was abolished. Expression of a fused fluorescent protein version and comparison with known endomembrane markers localized ANAC089 to the trans-Golgi network and the ER. The transcription factor was released upon treatment with reducing agents and targeted to the nucleus. Transactivation assays using wild type and mutated versions of the promoter showed a partial suppression of reporter expression. The data indicate that ANAC089 functions in a negative retrograde loop, lowering sAPX expression if the cell encounters a highly reducing condition. This conclusion was supported by reciprocal transcript accumulation of ANAC089 and sAPX during acclimation to low, normal, and high light conditions.

miR-290 cluster modulates pluripotency by repressing canonical NF-κB signaling.

Embryonic stem cell (ESC)-specific microRNAs (miRNAs) play a critical role in the maintenance of pluripotency and self-renewal but the complete network between these miRNAs and their broad range of target genes still remains elusive. Here we demonstrate that miR-290 cluster, the most abundant miRNA family in ESCs, targets the NF-κB subunit p65 (also known as RelA) by repressing its translation. Forced expression of p65 causes loss of pluripotency, promotes differentiation of ESCs, and leads to an epithelial to mesenchymal transition. These data define p65 as a novel target gene of miR-290 cluster and provide new insight into the function of ESC-specific miRNAs.