Spectrum of Cav1.4 dysfunction in congenital stationary night blindness type 2.

Defective retinal synaptic transmission in patients affected with congenital stationary night blindness type 2 (CSNB2) can result from different dysfunction phenotypes in Cav1.4 L-type calcium channels. Here we investigated two prototypical Cav1.4 variants from either end of the functional spectrum. Using whole-cell and single-channel patch-clamp techniques, we provide analysis of the biophysical characteristics of the point mutation L860P and the C-terminal truncating mutation R1827X. L860P showed a typical loss-of-function phenotype attributed to a reduced number of functional channels expressed at the plasma membrane as implied by gating current and non-stationary noise analyses. This phenotype can be rationalized, because the inserted proline is predicted to break an amphipatic helix close to the transmembrane segment IIIS1 and thus to reduce channel stability and promote misfolding. In fact, L860P was subject to an increased turnover. In contrast, R1827X displayed an apparent gain-of-function phenotype, i.e., due to a hyperpolarizing shift of the IV-curve and increased single-channel activity. However, truncation also resulted in the loss of functional C-terminal modulation and thus unmasked calcium-dependent inactivation. Thus R1827X failed to support continuous calcium influx. Current inactivation curtails the dynamic range of photoreceptors (e.g., when adapting to variation in illumination). Taken together, the analysis of two representative mutations that occur in CSNB2 patients revealed fundamental differences in the underlying defect. These may explain subtle variations in the clinical manifestation and must be taken into account, if channel function is to be restored by pharmacochaperones or related approaches.

Development of a Protocol for Automated Glucose Measurement Transmission Used in Clinical Decision Support Systems Based on the Continua Design Guidelines.

BACKGROUND: A fast and accurate data transmission from glucose meter to clinical decision support systems (CDSSs) is crucial for the management of type 2 diabetes mellitus since almost all therapeutic interventions are derived from glucose measurements. OBJECTIVES: Aim was to develop a prototype of an automated glucose measurement transmission protocol based on the Continua Design Guidelines and to embed the protocol into a CDSS used by healthcare professionals. METHODS: A literature and market research was performed to analyze the state-of-the-art and thereupon develop, integrate and validate an automated glucose measurement transmission protocol in an iterative process. RESULTS: Findings from literature and market research guided towards the development of a standardized glucose measurement transmission protocol using a middleware. The interface description to communicate with the glucose meter was illustrated and embedded into a CDSS. CONCLUSION: A prototype of an interoperable transmission of glucose measurements was developed and implemented in a CDSS presenting a promising way to reduce medication errors and improve user satisfaction.

Biosignals, Standards and FHIR - The Way to Go?

BACKGROUND: Standards have become available to share semantically encoded vital parameters from medical devices, as required for example by personal healthcare records. Standardised sharing of biosignal data largely remains open. OBJECTIVES: The goal of this work is to explore available biosignal file format and data exchange standards and profiles, and to conceptualise end-to-end solutions. METHODS: The authors reviewed and discussed available biosignal file format standards with other members of international standards development organisations (SDOs). RESULTS: A raw concept for standards based acquisition, storage, archiving and sharing of biosignals was developed. The GDF format may serve for storing biosignals. Signals can then be shared using FHIR resources and may be stored on FHIR servers or in DICOM archives, with DICOM waveforms as one possible format. CONCLUSION: Currently a group of international SDOs (e.g. HL7, IHE, DICOM, IEEE) is engaged in intensive discussions. This discussion extends existing work that already was adopted by large implementer communities. The concept presented here only reports the current status of the discussion in Austria. The discussion will continue internationally, with results to be expected over the coming years.

Applicability of IHE/Continua components for PHR systems: learning from experiences.

Capturing personal health data using smartphones, PCs or other devices, and the reuse of the data in personal health records (PHR) is becoming more and more attractive for modern health-conscious populations. This paper analyses interoperability specifications targeting standards-based communication of computer systems and personal health devices (e.g. blood pressure monitor) in healthcare from initiatives like Integrating the Healthcare Enterprise (IHE) and Continua Health Alliance driven by industry and healthcare professionals. Furthermore it identifies certain contradictions and gaps in the specifications and suggests possible solutions. Despite these shortcomings, the specifications allow fully functional implementations of PHR systems. Henceforth, both big business and small and medium-sized enterprises (SMEs) can actively contribute to the widespread use of large-scale interoperable PHR systems.

Certification programs for eHealth--status quo.

The skills of the workforce are a core factor for the quality of healthcare systems. On top of the basic education, postgraduate training is an important factor for continuously maintaining as well as improving the workforce qualification level. Advanced training often provides certification of the acquired skills. This paper analyses the status quo of international certification programs in the sector of eHealth (EU, US, Global). It uses available literature and observations from international educational expert's workgroups. It identifies gaps regarding certifications in eHealth and suggests steps for solutions. Despite little attention to legal and financial eHealth related content in certification programs in the EU as well as a low degree of harmonization of international certifications in general, there are strong activities especially in the international scope towards personal certification programs in eHealth. Major changes are to be expected within the coming years.

Education for eHealth--a status analysis.

eHealth is not only a growing market, but also an important factor for new healthcare systems. National and European initiatives implicitly demand a higher level of knowledge in the areas of healthcare, engineering and management. As part of the eLearning4eHealth project an initial web based study was performed concentrating on European and global eHealth related educational programs. The results show that eHealth related courses do not evenly exist for the identified professions. 43% of the offered programs are focused on the engineering sector, whereas only 21% are available for the management sector. In order to offer compatible and comparable state of knowledge in the identified fields of profession and knowledge, further educational programs may be necessary. Despite the found shortcomings, results have shown that international activities have started in order to close the gaps and improve the quality of knowledge in the interdisciplinary field of eHealth.

Differences in receptor binding affinity of several phytocannabinoids do not explain their effects on neural cell cultures.

Phytocannabinoids are potential candidates for neurodegenerative disease treatment. Nonetheless, the exact mode of action of major phytocannabinoids has to be elucidated, but both, receptor and non-receptor mediated effects are discussed. Focusing on the often presumed structure-affinity-relationship, Ki values of phytocannabinoids cannabidiol (CBD), cannabidivarin (CBDV), cannabichromene (CBC), cannabigerol (CBG), cannabinol (CBN), THC acid (THCA) and THC to human CB1 and CB2 receptors were detected by using competitive inhibition between radioligand [(3)H]CP-55,940 and the phytocannabinoids. The resulting Ki values to CB1 range from 23.5 nM (THCA) to 14711 nM (CBDV), whereas Ki values to CB2 range from 8.5 nM (THC) to 574.2 nM (CBDV). To study the relationship between binding affinity and effects on neurons, we investigated possible CB1 related cytotoxic properties in murine mesencephalic primary cell cultures and N18TG2 neuroblastoma cell line. Most of the phytocannabinoids did not affect the number of dopaminergic neurons in primary cultures, whereas propidium iodide and resazurin formation assays revealed cytotoxic properties of CBN, CBDV and CBG. However, THC showed positive effects on N18TG2 cell viability at a concentration of 10 µM, whereas CBC and THCA also displayed slightly positive activities. These findings are not linked to the receptor binding affinity therewith pointing to another mechanism than a receptor mediated one. [Corrected]