SALUS-A Study on Self-Tonometry for Glaucoma Patients: Design and Implementation of the Electronic Case File.

BACKGROUND: In times of omnipresent digitization and big data, telemedicine and electronic case files (ECFs) are gaining ground for networking between players in the health care sector. In the context of the SALUS study, this approach is applied in practice in the form of electronic platforms to display and process disease-relevant data of glaucoma patients. OBJECTIVES: The SALUS ECF is designed and implemented to support data acquisition and presentation, monitoring, and outcome control for patients suffering from glaucoma in a clinical setting. Its main aim is to provide a means for out- and inpatient exchange of information between various stakeholders with an intuitive user interface in ophthalmologic care. Instrument data, anamnestic data, and diagnostic assessments need to be accessible and historic data stored for patient monitoring. Quality control of the data is ensured by a reading center. METHODS: Based on an intensive requirement analysis, we implemented the ECF as a web-based application in React with a Datomic back-end exposing REST and GraphQL APIs for data access and import. A flexible role management was developed, which addresses the various tasks of multiple stakeholders in the SALUS study. Data security is ensured by a comprehensive encryption concept. We evaluated the usability and efficiency of the ECF by measuring the durations medical doctors need to enter and work with the data. RESULTS: The evaluation showed that the ECF is time-saving in comparison to paper-based assessments and offers supportive monitoring and outcome control for numerical and imaging-related data. By allowing patients and physicians to access the digital ECF, data connectivity as well as patient autonomy were enhanced. CONCLUSION: ECFs have a great potential to efficiently support all patients and stakeholders involved in the care of glaucoma patients. They benefit from the efficient management and view of the data tailored to their specific role.

Effectiveness of simulator-based echocardiography training of noncardiologists in congenital heart diseases.

BACKGROUND: Congenital heart diseases (CHD) are responsible for substantial morbidity and mortality in neonates. The preliminary diagnosis often is made by noncardiologists. For this reason, there is a huge demand of training in echocardiography of CHD. This is difficult to achieve due to limited resources of specialized centers. OBJECTIVE: The goal of this study was to investigate the training effect of the echocardiography simulator EchoCom on trainee's ability to diagnose CHD. DESIGN/METHODS: We enrolled 10 residents for simulator-based training in echocardiography of CHD. All participants were instructed on the simulator's basic handling and had one hour to scan the first 9 datasets information (ventricular septal defect, atrial septal defect, atrioventricular septal defect, Tetralogy of Fallot, transposition of great arteries, congenital corrected transposition of great arteries, common arterial trunk, hypoplastic left heart syndrome, normal anatomy) and establish a diagnosis. No help was given except for support regarding simulator related issues. Afterward, 2 rounds of structured simulator based echocardiography training focused on echocardiographic anatomy, spatial orientation, standard views, and echocardiographic anatomy of different CHD followed. All participants completed a standardized questionnaire containing 10 multiple-choice (MC) questions focusing on basic theoretical knowledge in echocardiographic anatomy and common CHD. RESULTS: Almost all of the residents invited from the affiliated children's hospital had little (20%) or no experience (80%) in echocardiography of CHD. Their Pretest and Posttest scores showed significant improvement for both, MC test and performance test, respectively. CONCLUSIONS: Our study showed that simulator-based training in echocardiography in CHD could be very effective and may assist with training outside the scope of CHD.

Short-term feedback regulation of bile salt uptake by bile salts in rodent liver.

UNLABELLED: The sodium taurocholate cotransporting polypeptide (Ntcp) is the major bile salt uptake transporter at the sinusoidal membrane of hepatocytes. Short-term feedback regulation of Ntcp by primary bile salts has not yet been investigated in vivo. Subcellular localization of Ntcp was analyzed in Ntcp-transfected HepG2-cells by flow cytometry and in immunofluorescence images from tissue sections by a new automated image analysis method. Net bile salt uptake was investigated in perfused rat liver by a pulse chase technique. In Flag-Ntcp-EGFP (enhanced green fluorescent protein) expressing HepG2-cells, taurochenodeoxycholate (TCDC), but not taurocholate (TC), induced endocytosis of Ntcp. TCDC, but not TC, caused significant internalization of Ntcp in perfused rat livers, as shown by an increase in intracellular Ntcp immunoreactivity, whereas Bsep distribution remained unchanged. These results correlate with functional studies. Rat livers were continuously perfused with 100 µmol/L of TC. 25 µmol/L of TCDC, taurodeoxycholate (TDC), tauroursodeoxycholate (TUDC), or TC were added for 30 minutes, washed out, followed by a pulse of (3) [H]-TC. TCDC, but not TDC, TUDC, or TC significantly increased the amount of (3) [H]-TC in the effluent, indicating a reduced sinusoidal net TC uptake. This effect was sensitive to chelerythrine (protein kinase C inhibitor) and cypermethrin (protein phosphatase 2B inhibitor). Phosphoinositide 3-kinase (PI3K) inhibitors had an additive effect, whereas Erk1/2 (extracellular signal activated kinase 1/2), p38MAPK, protein phosphatase 1/2A (PP1/2A), and reactive oxygen species (ROS) were not involved. CONCLUSION: TCDC regulates bile salt transport at the sinusoidal membrane by protein kinase C- and protein phosphatase 2B-mediated retrieval of Ntcp from the plasma membrane. During increased portal bile salt load this mechanism may adjust bile salt uptake along the acinus and protect periportal hepatocytes from harmful bile salt concentrations.

Toponomics method for the automated quantification of membrane protein translocation.

BACKGROUND: Intra-cellular and inter-cellular protein translocation can be observed by microscopic imaging of tissue sections prepared immunohistochemically. A manual densitometric analysis is time-consuming, subjective and error-prone. An automated quantification is faster, more reproducible, and should yield results comparable to manual evaluation. The automated method presented here was developed on rat liver tissue sections to study the translocation of bile salt transport proteins in hepatocytes. For validation, the cholestatic liver state was compared to the normal biological state. RESULTS: An automated quantification method was developed to analyze the translocation of membrane proteins and evaluated in comparison to an established manual method. Firstly, regions of interest (membrane fragments) are identified in confocal microscopy images. Further, densitometric intensity profiles are extracted orthogonally to membrane fragments, following the direction from the plasma membrane to cytoplasm. Finally, several different quantitative descriptors were derived from the densitometric profiles and were compared regarding their statistical significance with respect to the transport protein distribution. Stable performance, robustness and reproducibility were tested using several independent experimental datasets. A fully automated workflow for the information extraction and statistical evaluation has been developed and produces robust results. CONCLUSIONS: New descriptors for the intensity distribution profiles were found to be more discriminative, i.e. more significant, than those used in previous research publications for the translocation quantification. The slow manual calculation can be substituted by the fast and unbiased automated method.

Qualification of a new and precise automatic tool for the assessment of hair diameters in phototrichograms.

BACKGROUND/PURPOSE: To automatically assess hair growth during cosmetic trials, incorporating parameters such as anagen-to-telogen rate, growth rate, and especially hair diameter. METHODS: We designed and qualified a new and automatic phototrichogram system based on a high-resolution DSLR camera system (theoretical resolution of 2.557 µm/pixel) and modular macrolens system with fixed focus, combined with a trainable pattern recognition software for automated analysis. RESULTS: We improved the standard routine for dermatological phototrichogram technique to overcome inaccuracy in thickness measurements due to hair swelling by using an alternative immersion fluid, and increased the effective resolution for hair size and thickness measurement to <4 µm. After having qualified manual measurements as gold standard for the determination of hair diameters, we established a new trainable automatic picture analysis software able to locate and measure individual hairs in length and thickness even in picture series taken from the same skin area at different time points. Comparisons between manual and automatic measurements of the same hairs showed a >90% correlation, and by comparing the automatic results with manual measurements of the same images without individual hair annotation, we could find a correlation of at least 80%. CONCLUSION: According to the results and findings generated in this qualification study, we have a reliable tool now that enables us to test cosmetic products for hair treatment in a highly automated way with a sufficient degree of precision and accuracy to detect even small changes in hair diameter during cosmetic trials.

Evaluating descriptors for the lateral translocation of membrane proteins.

Microscopic images of tissue sections are used for diagnosis and monitoring of therapy, by analysis of protein patterns correlating to disease states. Spatial protein distribution is influenced by protein translocation between different membrane compartments and quantified by comparison of microscopic images of biological samples. Cholestatic liver diseases are characterized by translocation of transport proteins, and quantification of their dislocation offers new diagnostic options. However, reliable and unbiased tools are lacking. The nowadays used manual method is slow, subjective and error-prone. We have developed a new workflow based on automated image analysis and improved it by the introduction of scale-free descriptors for the translocation quantification. This fast and unbiased method can substitute the manual analysis, and the suggested descriptors perform better than the earlier used statistical variance.

Analyzing and mining automated imaging experiments.

Image mining is the application of computer-based techniques that extract and exploit information from large image sets to support human users in generating knowledge from these sources. This review focuses on biomedical applications of this technique, in particular automated imaging at the cellular level. Due to increasing automation and the availability of integrated instruments, biomedical users are becoming increasingly confronted with the problem of analyzing such data. Image database applications need to combine data management, image analysis and visual data mining. The main point of such a system is a software layer that represents objects within an image and the ability to use a large spectrum of quantitative and symbolic object features. Image analysis needs to be adapted to each particular experiment; therefore, 'end user programming' will be desired to make the technology more widely applicable.

Analyzing and mining image databases.

Image mining is the application of computer-based techniques that extract and exploit information from large image sets to support human users in generating knowledge from these sources. This review focuses on biomedical applications, in particular automated imaging at the cellular level. An image database is an interactive software application that combines data management, image analysis and visual data mining. The main characteristic of such a system is a layer that represents objects within an image, and that represents a large spectrum of quantitative and semantic object features. The image analysis needs to be adapted to each particular experiment, so 'end-user programming' will be desirable to make the technology more widely applicable.

Computer-based training in two-dimensional echocardiography using an echocardiography simulator.

Two-dimensional (2D) echocardiography is a user-dependent technique that poses some inherent problems to the beginner. The first problem for beginners is spatial orientation, especially the orientation of the scan plane in reference to the 3-dimensional (3D) geometry of the heart. The second problem for beginners is steering of the ultrasound probe. We have designed a simulator to teach these skills. On a computer screen a side-by-side presentation of a 3D virtual reality scene on the right side and a 2D echocardiographic view on the left side is given. The virtual scene consists of a 3D heart and an ultrasound probe with scan plane. The 2D echocardiographic image is calculated from 3D echocardiographic data sets that are registered with the heart model to achieve spatial and temporal congruency. The displayed 2D echocardiographic image is defined and controlled by the orientation of the virtual scan plane. To teach hand-eye coordination we equipped a dummy transducer with a 3D tracking system and placed it on a dummy torso. We have evaluated the usability of the simulator in an introductory course for final-year medical students. The simulator was graded realistic and easy to use. According to a subjective self-assessment by a standardized questionnaire the aforementioned skills were imparted effectively.

Three-Dimensional Echocardiography: The Gateway to Virtual Reality!

Virtual reality (VR) is one of the latest developments in cardiac three-dimensional (3-D) ultrasound. A VR heart model linked to 3-D echocardiographic image datasets provides the observers spatial information regarding a 3-D image dataset and prevents the "lost in space effect" in difficult and relevant coupled diseases when integrated into 3-D reconstruction software. Standardized echocardiographic views can be selected within the integrated developed VR heart model, and this is the first step to automatic 3-D computations with minimal operator interaction. VR heart models open exciting opportunities in the field of teaching echocardiographic cardiology, diagnosis, and examinable states.