The Vasodilatory Response to CGRP of the Anterior and Posterior Cerebral Circulation in Migraine

IntroductionMigraine aura can be associated with headache or it may occur without one, which suggests an independent mechanism for the aura and for migraine headache. The role of CGRP in migraine headache is well established, but the connection between CGRP and the aura is still lacking an explanation. Exogenous CGRP can induce CGRP headaches and migraine auras in patients with migraine. The results of our recent study suggest differences in the vascular response to CGRP stimulation between migraine without aura and migraine with aura. Therefore, we hypothesized that the magnitude of the posterior cerebral circulation response in migraine with aura is greater than in migraine without aura and that CGRP stimulation has different effects on the anterior and posterior circulation in migraine with aura and migraine without aura.MethodsBy using transcranial doppler, we studied the hemodynamic effects of CGRP intravenous infusion at a rate of 1.5 mcg/min in 20 min on the mean arterial velocity in the middle cerebral artery and in the posterior cerebral artery in twenty patients with migraine and in a control group of twenty healthy subjects. The same CGRP effects on cerebral hemodynamics were analyzed separately for the group of patients with migraine with aura and the group of patients with migraine without aura. Fifteen patients with migraine (75%) had migraine without aura and 5 patients (25%) had migraine with aura.ResultsWe found that migraine has a significant impact on the vasodilatory response of the anterior (B = 4,249, SE = 1.023, r = 0.363, p < 0.001) and posterior cerebral circulation (B = 3.634, SE = 1.461, r = 0.227, p = 0.014). Migraine with aura was significantly associated with changes in the anterior (B = 2.558, SE = 0.880, r = 0.275, p = 0.005) and posterior cerebral circulation (B = 7.565, SE = 2,368, r = 0.359, p = 0.002), while migraine without aura was only significantly associated with changes in the anterior circulation. In addition, we established a significant impact of migraine with aura on VR PCA (B = 5.901, SE = 2,546, r = 0.291, p = 0.024).ConclusionWe conclude that TVR in the posterior cerebral circulation might be enhanced in MA and that aura might be a consequence of TVR enhancement

Enhanced Hemodynamic and Clinical Response to αCGRP in Migraine Patients—A TCD Study

Introduction: Sensitisation of the nervous system in a patient with migraine is supposed to be associated with calcitonin gene-related peptide (CGRP) activity. Therefore, the vascular response to human αCGRP (hαCGRP) could be a surrogate marker for the sensitization. We hypothesize that vascular response to hαCGRP is augmented in a patient with migraine.Methods: Twenty healthy subjects and 20 patients with migraine participated in our study. TCD was used to monitor mean arterial velocity in the middle cerebral artery (vm MCA). Simultaneously, end-tidal CO2 (Et-CO2), mean arterial pressure (MAP), and heart rate (HR) were measured. The reconstruction of the signals was made for basal conditions, during and after CGRP infusion which were compared using statistics.Results: In both groups, we found significant decrease between measurement points of vm MCA and Et-CO2 during and after hαCGRP infusion. MAP did not show significant trends during the infusion, but it was significantly increased after the infusion in migraine patients only. Responses to hαCGRP, defined as differences between two measurement points, were significantly higher for vm MCA and Et-CO2 in patients with migraine. A significant difference between groups was found in MAP response. Significant relationships were found between migraine and vm MCA, Et-CO2, and MAP.Conclusion: In patients with migraine, vm MCA responses to hαCGRP are significantly higher and are associated with CGRP-induced headache which indicates that patients with migraine are more prone to sensitization

αCGRP-Induced Changes in Cerebral and Systemic Circulation; A TCD Study

It is known that perivascular application of CGRP induces cerebral vasodilatation. However, it is unclear whether intravenous alfa CGRP (αCGRP) induces changes in cerebral and systemic hemodynamics. Therefore, we studied the influence of an αCGRP intravenous infusion at a rate of 1.5 mcg/min in 20 min on mean arterial velocity in the middle cerebral artery (vm MCA) and in the posterior cerebral artery (vm PCA) in twenty healthy subjects using transcranial Doppler (TCD). We found out that αCGRP decreased vm MCA (p < 0.001), vm PCA (p < 0.001), mean arterial pressure (MAP) (p < 0.001) and end-tidal CO2 (Et-CO2) (p = 0.030). The heart rate (HR) increased during αCGRP infusion (p < 0.001). In addition, we found a positive relationship between Et-CO2 and vm MCA (p = 0.001) as well as vm PCA (p = 0.043). In our view, αCGRP induces changes in cerebral and systemic circulation in healthy volunteers. It might cause vasodilatation of MCA and PCA and a compensatory decrease of Et-CO2 to αCGRP related hemodynamic changes

Marked space

My diploma explores architectural habitat and its historicizing. The area of exploring is the space in which I live, and also in which I cherishes the experience of visual art interventions. In my diploma I have attempted to interpret the conceptual bases already mentioned beyond the concept of land art and historicizing through the mountain pass Ljubelj and stories of my grandmother who lives in that area. Documentation and artistic design for the selected (open) area connects my task to all that gives meaning to the concept of mountain pass Ljubelj, which is one of the first Alpine links between North and South (East) Europe. The location of this place is also important because I and my family are part of this area. This place is a study room where I run art workshops for children and at the same time realize our artistic leanings that are associated with the understanding of ground handling art. The location of this area is placed in the side of the sky as the narrow passage that is overgrown with pine trees to low scree. Above that area are mighty rock walls on both sides. I live at the edge of the forest where I can find countless creative possibilities. I conceptually understand mountain pass or passage as the power of overcoming distances and as closeness and my shelter. Home means the opportunity for survival and shelter to me. I understand home conceptually through self-selected and documentary texts in parallel with the drawing and photography. I have chosen a form of intervention in an open area where additional natural and artificial media such as paper are used for the project as "Frogs", then "Shearwaters or Storm trees", "Mirrors", "Nest".... . The research area is at the same time reflected on the didactic field in the learning process of the high school programmes as an understanding of ground handling art

Understanding colours through the land art amongst pupils of 1st, 2nd and 3rd grade

In my thesis, I investigate the ability of understanding colour mixing through a so-called Land art at 1st, 2nd and 3rd graders. Colour mixing is usually based and on prepared industrial tube colours bought at usual shops. However, nature is an immense source of dyes and colours that offer colour mixing in the art. In the past the artists prepared pigments from natural substances by themselves. Nowadays various artists in landscape art exploit the potential of natural materials in mixing colours. I have explored this issue through the theoretical and empirical research approach. In the theoretical part, I have analysed the problem of colour mixing in conjunction with the appearance of colours in nature (natural pigments, various colour phenomena in nature, the natural materials of different colours, etc.) considering descriptive methods and field literature to establish the advantage of mixing colours in the visual arts. I take into account the analysis of the various contemporary artists who exploit the colours of nature in its landscape art. In the empirical part, I investigated the ability of pupils’ understanding the colour mixing through the Landscape Art in action survey in three steps. The first step was to present the colour mixing on an established way of industrial tube paints to students. In a second step, I included the teacher of chemistry; we conducted a cross-curricular link, on the subject of colour mixing and extraction of natural dyes by extraction. In the third step, students mixed colours using substances found in nature near their school, and this leads to certain characteristics of landscape art. Students created a variety of natural materials available in near school location (the school, where I conducted research is located in the countryside). The study will contribute to art didactics innovative methods of teaching colour mixing in conjunction with the nature and landscape art. Emphasis was on an open and creative functioning of students in a wide range of materials and ideas. This will help the students to strengthen environmental awareness and awareness of coexistence with nature

Multi-Attribute Decision Model for Evaluating Public Health Officials\u27 Work Efficiency for Promotion Purposes

Napredovanje javnih zdravstvenih uslužbencev je povezano z ocenjevanjem strokovnih in delovnih kvalitet zaposlenega. Namen procesa ocenjevanja delovne uspešnosti je dodatno motiviranje zaposlenih za doseganje še boljših in vidnejših delovnih rezultatov. Čeprav je sistem napredovanja v javnem zdravstvenem sektorju zakonsko predpisan, še ni v celoti dorečen in praktično opredeljen. Pri izvajanju so se pokazale določene pomanjkljivosti, ki jih bo v prihodnosti potrebno odpraviti. Glavna cilja študije sta bila izdelava in validacija večparametrskega hierarhičnega modela za ocenjevanje delovne uspešnosti javnih zdravstveni uslužbencev. Model sloni na večparametrskih odločitvenih modelih in je podprt z računalniškim programom za večparametrsko odločanje DEXi. Računalniško podprto ocenjevanje delovne uspešnosti javnih zdravstvenih uslužbencev se je izkazalo kot primerno. Z zagotavljanjem enakih kriterijev za vse omogoča bolje organizirano, sistematično in objektivno ocenjevanje delovne uspešnosti zaposlenih ter transparentno razlago ocene. To pripomore k pravičnejšemu sistemu napredovanj zaposlenih v javnem zdravstvenem sektorju, kar poveča zadovoljstvo in predstavlja dodatno motivacijo za nadaljnje kakovostno opravljanje dela. Zgrajeni model smo preizkusili in kritično ovrednotili na praktičnem primeru javnega zdravstvenega zavoda. Nadaljnja praktična uporaba bo pokazala, v kolikšni meri je mogoče ta model za ocenjevanje delovne uspešnosti za potrebe napredovanja še izboljšati.Promotion of the public health staff is associated with the evaluation of professional and working qualities of the employee. The purpose of the process of performance appraisal of public health staff is to motivate employees to achieve even better and more visible business results. Although the system of promotion in the public health sector is a legal requirement, however, not yet fully agreed on and practically defined. The implementation has revealed some weaknesses that are left to be solved in the future. The main objectives of the study were to develop and validate a multi-attribute evaluation model for performance appraisal of public health officials. The model is based on a multi-attribute evaluation model and is supported by a computer program for multi-attribute decision making DEXi. The model tested as appropriate. By applying the same criteria across the sector it allows for a more organized, systematic and objective performance evaluation of employees and enables a transparent explanation of the estimation. This makes the system of employee promotions in the public health sector fairer, increases satisfaction and represents an additional incentive for further quality work. The constructed model was tested and critically evaluated on a case study in a selected public health institution. Further practical applications will show in what ways the existing evaluation model for performance appraisal can further be improved

Enhanced Hemodynamic and Clinical Response to αCGRP in Migraine Patients-A TCD Study.

Introduction: Sensitisation of the nervous system in a patient with migraine is supposed to be associated with calcitonin gene-related peptide (CGRP) activity. Therefore, the vascular response to human αCGRP (hαCGRP) could be a surrogate marker for the sensitization. We hypothesize that vascular response to hαCGRP is augmented in a patient with migraine. Methods: Twenty healthy subjects and 20 patients with migraine participated in our study. TCD was used to monitor mean arterial velocity in the middle cerebral artery (vm MCA). Simultaneously, end-tidal CO2 (Et-CO2), mean arterial pressure (MAP), and heart rate (HR) were measured. The reconstruction of the signals was made for basal conditions, during and after CGRP infusion which were compared using statistics. Results: In both groups, we found significant decrease between measurement points of vm MCA and Et-CO2 during and after hαCGRP infusion. MAP did not show significant trends during the infusion, but it was significantly increased after the infusion in migraine patients only. Responses to hαCGRP, defined as differences between two measurement points, were significantly higher for vm MCA and Et-CO2 in patients with migraine. A significant difference between groups was found in MAP response. Significant relationships were found between migraine and vm MCA, Et-CO2, and MAP. Conclusion: In patients with migraine, vm MCA responses to hαCGRP are significantly higher and are associated with CGRP-induced headache which indicates that patients with migraine are more prone to sensitization

Dataset of normalised Slovene text KonvNormSl 1.0

Data used in the experiments described in: Nikola Ljubešić, Katja Zupan, Darja Fišer and Tomaž Erjavec: Normalising Slovene data: historical texts vs. user-generated content. Proceedings of KONVENS 2016, September 19–21, 2016, Bochum, Germany. https://www.linguistics.rub.de/konvens16/pub/19_konvensproc.pdf (https://www.linguistics.rub.de/konvens16/) Data are split into the "token" folder (experiment on normalising individual tokens) and "segment" folder (experiment on normalising whole segments of text, i.e. sentences or tweets). Each experiment folder contains the "train", "dev" and "test" subfolders. Each subfolder contains two files for each sample, the original data (*.orig.txt) and the data with hand-normalised words (*.norm.txt). The files are aligned by lines. There are four datasets: - goo300k-bohoric: historical Slovene, hard case (<1850) - goo300k-gaj: historical Slovene, easy case (1850 - 1900) - tweet-L3: Slovene tweets, hard case (non-standard language) - tweet-L1: Slovene tweets, easy case (mostly standard language) The goo300k data come from http://hdl.handle.net/11356/1025, while the tweet data originate from the JANES project (http://nl.ijs.si/janes/english/). The text in the files has been split by inserting spaces between characters, with underscore (_) substituting the space character. Tokens not relevant for normalisation (e.g. URLs, hashtags) have been substituted by the inverted question mark '¿' character

The Influence of Calcitonin Gene-Related Peptide on Cerebral Hemodynamics in Nonmigraine Subjects with Calcitonin Gene-Related Peptide-Induced Headaches

Background. Calcitonin gene-related peptide (CGRP) is regarded as an important molecule in trigeminovascular sensitization (TVS). CGRP-induced headaches (CGRP-IH) are evoked by intravascular administration of CGRP in nonmigraine and migraine subjects. CGRP might be associated with vasodilatation of the middle cerebral artery (MCA). It is unclear whether CGRP-induced hemodynamic changes relate to CGRP-IH in nonmigraine subjects. Methods. Twenty healthy subjects participated in our study. Polymodal recording of mean arterial velocity in MCA (vm MCA), end-tidal carbon dioxide partial pressure (Et-CO2), mean arterial pressure (MAP), and heart rate (HR) was employed using transcranial Doppler (TCD) sonography. During the experiment, we administered intravenous infusion of CGRP at a rate of 1.5 mcg/min. The vm MCA, Et-CO2, HR, and MAP were determined at time points T0, T1, T2, and T3. We calculated the responses at different time points and combined them into a single response vm MCAtot, Et-CO2tot, HRtot, and MAPtot. Results. We found significant differences along the time points in vm MCA (p=<0.001), Et-CO2 (p=0.003), MAP (p<0.001), and HR (p<0.001). The relationship between vm MCAtot and Et-CO2tot was significant and positive (p=0.005). The t-test showed significant differences between CGRP-IH and non-CGRP-IH subjects in vm MCAtot (p=0.021) but not in Et-CO2tot (p=0.838), MAPtot (p=0.839), and HRtot (p=0.198). Only vm MCAtot showed a significant relationship with CGRP-IH (p=0.028). Conclusions. Our study provides evidence for vasodilatation of MCA in relation to CGRP-IH due to intravascular CGRP detected by multimodal TCD. In the context of TVS induced by CGRP, MCA vasodilatation seems to represent an epiphenomenon of the underlying TVS