Aim To investigate the involvement of the vesicular membrane trafficking regulator Synaptotagmin IV (Syt IV) in Alzheimers disease pathogenesis and to define the cell types containing increased levels of Syt IV in the -amyloid plaque vicinity. Methods Syt IV protein levels in wild type (WT) and Tg2576 mice cortex were determined by Western blot analysis and immunohistochemistry. Co-localization studies using double immunofluorescence staining for Syt IV and markersfor astrocytes (glial fibrillary acidic protein), microglia (major histocompatibility complex class II), neurons (neuronalspecific nuclear protein), and neurites (neurofilaments) were performed in WT and Tg2576 mouse cerebral cortex. Results Western blot analysis showed higher Syt IV levelsin Tg2576 mice cortex than in WT cortex. Syt IV was foundonly in neurons. In plaque vicinity, Syt IV was up-regulatedin dystrophic neurons. The Syt IV signal was not up-regulatedin the neurons of Tg2576 mice cortex without plaques (resembling the pre-symptomatic conditions). Conclusions Syt IV up-regulation within dystrophic neuronsprobably reflects disrupted vesicular transport or/and impaired protein degradation occurring in Alzheimers diseaseand is probably a consequence but not the cause of neuronal degeneration. Hence, Syt IV up-regulation and/or its accumulation in dystrophic neurons may have adverse effects on the survival of the affected neuron.
F.22 Improvement to existing health/diagnostic methods/procedures
COBISS.SI-ID: 30928601Protocols for the assessment of postural tachycardia differ in both type of orthostatic challenge and test duration. We therefore compared heart rate (HR) and blood pressure responses during an active standing test (AST) and a head-up tilt test (HUT) in 34 patients with orthostatic intolerance and 31 asymptomatic subjects. A subset also performed 24-h ambulatory blood pressure monitoring (ABPM). HR responses were similar between AST and HUT both in asymptomatic and in orthostatic intolerant subjects. Specificity of HR increase 30 bpm for orthostatic intolerance was high (above 0.85) with both AST and HUT and was similar at 3 minutes and at 9 minutes. HR changes recorded during self-performed AST (in the context of 24-h ABPM) and circadian HR difference corresponded well to changes recorded during AST in the autonomic laboratory. We conclude that AST and HUT are comparable methods for the assessment of postural tachycardia, that 3-min and 9-min tests are appropriate, and that ABPM is a useful ancillary test in the assessment of orthostatic responses.
F.22 Improvement to existing health/diagnostic methods/procedures
COBISS.SI-ID: 887468Objective: The paper describes the use of expert's knowledge in practice and the efficiency of a recently developed technique called argument-based machine learning (ABML) in the knowledge elicitation process. We are developinga neurological decision support system to help the neurologists differentiate between three types of tremors: Parkinsonian, essential, and mixed tremor (comorbidity). The system is intended to act as a second opinion for the neurologists, and most importantly to help them reduce the number of patients in the "gray area" that require a very costly further examination (DaTSCAN). We strive to elicit comprehensible and medically meaningful knowledge in such a way that it does not come at the cost of diagnostic accuracy. Materials and methods: To alleviate the difficult problem of knowledge elicitation from data and domain experts, we used ABML. ABML guidesthe expert to explain critical special cases which cannot be handled automatically by machine learning. This very efficiently reduces the expert'sworkload, and combines expert's knowledge with learning data. 122 patients were enrolled into the study. Results: The classification accuracy of the final model was 91%. Equally important, the initial and the final models were also evaluated for their comprehensibility by the neurologists. All13 rules of the final model were deemed as appropriate to be able to support its decisions with good explanations. Conclusion: The paper demonstrates ABML's advantage in combining machine learning and expert knowledge. The accuracy of the system is very high with respect to the current state-of-the-art in clinical practice, and the system's knowledge base is assessed to be very consistent from a medical point of view. This opens up the possibility to use the system also as a teaching tool.
F.22 Improvement to existing health/diagnostic methods/procedures
COBISS.SI-ID: 30199257In the past few decades, considerable efforts have been devoted to develop neuroprosthetics that interface selectively with the human nervous system via multi-electrode spiral cuffs, using electronic implantable devices. The objective of this study was to investigate the structural properties of a cold-rolled platinum foil used to manufacture multi-electrode spiral nerve cuffs. To attain this objective, 0.03-mm-thick cold-rolled platinum foil strips with 99.99 wt. % purity were used. For this purpose, the strips were mounted into the sample holder within the furnace of the custom designed setup. The resistivity measurements were made using a 4-point probe technique in which the strips were subjected to dynamic annealing in an argon atmosphere within the tempeature range between room temperature and 900°C. Finally, the microstructure of the strips prepared using standard metallographic techniques, was investigated by the method of optical microscopy. In the resistivity measurements, a small change is observed at ~280 °C. This change could be explained as the partial recovery elicited by the decrease of dislocation density. Above 500 °C, a significant decrease in resistivity was recorded, and the decrease reached a maximum at ~750 °C. These results provide deeper insight into the fabrication of platinum foil to be used in the further development of multi-electrode neural stimulating spiral cuffs. The most important finding is that the results of the resistivity measurements provide one criteria for selecting materials, and that appropriate thermal and mechanical working processes are required to fabricate stimulating electrodes. These results may make cold roled platinum ribbon the best material for the long term applications of multi-electrode spiral cuffs in SNS.
F.14 Improvements to existing production methods and tools or processes
COBISS.SI-ID: 31031001Here we present the relevant data on estimated cost of brain disorders in Slovenia for 2010. The total cost of disorders of the brain for Slovenia is estimated at €2,425 billion in 2010, adjusted for purchasing power parities (€PPP). Direct costs constitute the majority of costs (42.3 % direct healthcare costs and 22.0 % direct non-medical costs) whereas the remaining 35.7 % were indirect costs associated with patients’ production losses. On average, the estimated cost per person with a disorder of the brain in Slovenia ranged between €PPP 178 for headache and €PPP 2,2045 for neuromuscular disorders. The Slovenian per capita cost of disorders of the brain was €PPP 1,185. Even though this review included many disorders, diagnoses, age groups and cost items that were omitted in 2004, there are still remaining disorders that could not be included due to limitations in the available data. The estimate of the total cost of brain disorders in Europe and Slovenia is therefore considered to be conservative. In terms of the health economic burden outlined in the 2010 European Brain Council (EBC) report and here, disorders of the brain likely constitute the number one economic challenge for health care in all European countries, now and in the future. The results are consistent with administrative data on the health care expenditure in Europe, and comparable to previous studies on the cost of specific disorders in Europe, while being lower than analogous estimates from the US. The reported results should be considered by all stakeholders, including policy makers, industry and patient advocacy groups, to reconsider the current science, research and public health agenda and shape a coordinated national action-plan to address the imminent challenges posed by disorders of the brain.
F.22 Improvement to existing health/diagnostic methods/procedures
COBISS.SI-ID: 745388