An integrated approach for the systematic identification and characterization of heart-enriched genes with unknown functions

<p>Abstract</p> <p>Background</p> <p>High throughput techniques have generated a huge set of biological data, which are deposited in various databases. Efficient exploitation of these databases is often hampered by a lack of appropriate tools, which allow easy and reliable identification of genes that miss functional characterization but are correlated with specific biological conditions (e.g. organotypic expression).</p> <p>Results</p> <p>We have developed a simple algorithm (DGSA = Database-dependent Gene Selection and Analysis) to identify genes with unknown functions involved in organ development concentrating on the heart. Using our approach, we identified a large number of yet uncharacterized genes, which are expressed during heart development. An initial functional characterization of genes by loss-of-function analysis employing morpholino injections into zebrafish embryos disclosed severe developmental defects indicating a decisive function of selected genes for developmental processes.</p> <p>Conclusion</p> <p>We conclude that DGSA is a versatile tool for database mining allowing efficient selection of uncharacterized genes for functional analysis.</p

Metabolite analysis distinguishes between mice with epidermolysis bullosa acquisita and healthy mice

Abstract Background Epidermolysis bullosa acquisita (EBA) is a rare skin blistering disease with a prevalence of 0.2/ million people. EBA is characterized by autoantibodies against type VII collagen. Type VII collagen builds anchoring fibrils that are essential for the dermal-epidermal junction. The pathogenic relevance of antibodies against type VII collagen subdomains has been demonstrated both in vitro and in vivo. Despite the multitude of clinical and immunological data, no information on metabolic changes exists. Methods We used an animal model of EBA to obtain insights into metabolomic changes during EBA. Sera from mice with immunization-induced EBA and control mice were obtained and metabolites were isolated by filtration. Proton nuclear magnetic resonance (NMR) spectra were recorded and analyzed by principal component analysis (PCA), partial least squares discrimination analysis (PLS-DA) and random forest. Results The metabolic pattern of immunized mice and control mice could be clearly distinguished with PCA and PLS-DA. Metabolites that contribute to the discrimination could be identified via random forest. The observed changes in the metabolic pattern of EBA sera, i.e. increased levels of amino acid, point toward an increased energy demand in EBA. Conclusions Knowledge about metabolic changes due to EBA could help in future to assess the disease status during treatment. Confirming the metabolic changes in patients needs probably large cohorts. </jats:sec

Morphologic and Clinical Outcome of Intracranial Aneurysms after Treatment Using Flow Diverter Devices: Mid-Term Follow-Up

Flow diverters (FDs) are designed for the endovascular treatment of complex intracranial aneurysm configurations. From February 2009 to March 2013 28 patients (22 females, 6 males) were treated with FD; mean age was 57 years. Data, including aneurysm features, clinical presentation, history of previous bleeding, treatment, and follow-up results, are presented. Early postinterventional neurological deficits (transient: n=3/enduring: n=1) appeared in 4/28 patients (14%), and early improvement of neurological symptoms was observed in 7 patients with previous restriction of cranial nerve function. The overall occlusion rate was 20/26 (77%; 59% after 3 months). 77% achieved best results according to O’Kelly-Marotta score grade D with no contrast material filling (70% of those after 3 months). In 4/6 patients who did not achieve grade D, proximal and/or distal stent overlapping ≥5 mm was not guaranteed sufficiently. During follow-up we did not detect any aneurysm recurrence or haemorrhage. In-stent stenosis emerged as the most frequent complication (4/27; 15%) followed by 2 cases of vascular obliteration (AICA/VA). In conclusion endovascular reconstruction using a FD represents a modern and effective treatment in those aneurysms that are not suitable for conventional interventional or surgical treatment. The appearance of severe complications was rare

Regulatorische Rahmenbedingungen in der Medizintechnik: Herausforderungen für einen Kontinuierlichen Verbesserungsprozess

Die Herstellung von Medizinprodukten stellt nicht nur hohe technische Anforderungen, sondern birgt auch viele organisatorische Herausforderungen, welche sich aus umfangreichen regulatorischen Anforderungen ergeben. Durch diese soll die Sicherheit der Produkte gewährleistet werden, jedoch stehen die Regularien den Anforderungen an eine moderne, wandlungsfähige Produktion mit etablierten kontinuierlichen Verbesserungsprozessen in vielen Fällen entgegen. Im Rahmen dieses Beitrags werden die regulatorischen Anforderungen an die Produktion zusammengefasst und Ansätze aufgezeigt, wie auch bei der Herstellung von Medizinprodukten ein Kontinuierlicher Verbesserungsprozess gelebt werden kann