Botulinum Toxin as Preventive Treatment for Migraine: A Randomized Double-Blind Study

Aim: To determine if botulinum toxin type A (BoNT-A) injections can reduce the frequency and severity of migraines. Methods: Patients (n = 127) were randomized to receive placebo or two doses of BoNT-A (Dysport (R)). The primary endpoint was reduction in number of migraine attacks up to week 8 and between weeks 8 and 12 after injection. Patient diaries were used to record secondary endpoints, including frequency, severity and duration of migraine attacks. Results: There was a mean reduction of 0.54 and 0.94 attacks/month with placebo and BoNT-A, respectively, and absolute attack count was less in the verum group (3.6 vs. 4.2 attacks/month), but this was not statistically significant. The patients' global assessment of efficacy was significantly better than placebo in the high-dose group (p = 0.02) but no effects were seen for the other secondary efficacy parameters. Conclusion: Our study showed a trend towards a reduced attack rate with verum but did not show any statistically significant efficacy of BoNT-A in the prophylactic treatment of migraine. Copyright (C) 2009 S. Karger AG, Base

Barrierefreiheit, Partizipation und Empowerment –Wege zur digitalen Teilhabe

Barrierefreiheit ist eine grundlegende Voraussetzung für die gleichberechtigte Teilhabe von Menschen mit Beeinträchtigungen. Auf europäischer und nationaler Ebene werden seit 2016 wichtige gesetzliche Voraussetzungen für die digitale Barrierefreiheit implementiert. Neben den notwendigen strukturellen Verbesserungen spielen weitere Aspekte im Kontext digitaler Teilhabe eine wichtige Rolle. Zunehmend werden zentrale sozialpolitische und behindertenpädagogische Leitideen wie Partizipation und Empowerment im Kontext der Digitalisierung diskutiert. Trotz dieser Bestrebungen gibt es immer noch Defizite bei der Barrierefreiheit digitaler Angebote. Gleichzeitig muss die Frage beantwortet werden, wie man Menschen mit Beeinträchtigungen noch besser in die Prozesse zur Herstellung digitaler Barrierefreiheit einbinden kann, da diese sie selbst betreffen. Im folgenden Beitrag werden die wichtigsten Richtlinien, Gesetze und Verordnungen zur digitalen Barrierefreiheit vorgestellt und die Relevanz der Partizipation und des Empowerments für die digitale Teilhabe von Menschen mit Beeinträchtigungen näher beleuchtet. Abschließend werden einige der relevantesten Projekte mit Beteiligung des Fachgebiets Rehabilitationstechnologie der TU Dortmund beschrieben und die gewonnenen Erkenntnisse diskutiert.Accessibility is a fundamental prerequisite for the equal participation of people with disabilities. Important legal conditions for digital accessibility have been already implemented at European and national level in Germany. However, in addition to the necessary structural improvements, other aspects also play an important role in the context of digital participation. Increasingly, concepts such as participation and empowerment, are being discussed in the context of digitalisation. Despite all these efforts, most digital resources are still not accessible. Furthermore, it is necessary to develop methods to improve the inclusion of people with disabilities in the processes of achieving digital accessibility. The article presents the most important guidelines, laws and regulations on digital accessibility and highlights the relevance of participation and empowerment for the digital participation of people with disabilities. Finally, important projects in this context under participation of the Department of Rehabilitation Technology at TU Dortmund University are described and discussed

Macitentan attenuates cardiovascular remodelling in infant rats with chronic lung disease

Background Cardiovascular impairment contributes to increased mortality in preterm infants with chronic lung disease. Macitentan, an endothelin-1 receptor antagonist, has the potential to attenuate pulmonary and cardiovascular remodelling. Methods In a prospective randomized placebo-controlled intervention trial, Sprague–Dawley rats were exposed to 0.21 or 1.0 fraction of inspired oxygen (FiO2) for 19 postnatal days. Rats were treated via gavage with placebo or macitentan from days of life 5 to 19. Alveoli, pulmonary vessels, α-smooth muscle actin content in pulmonary arterioles, size of cardiomyocytes, right to left ventricular wall diameter ratio, and endothelin-1 plasma concentrations were assessed. Results FiO2 1.0 induced typical features of chronic lung disease with significant alveolar enlargement (p = 0.012), alveolar (p = 0.048) and pulmonary vessel rarefaction (p = 0.024), higher α-smooth muscle actin content in pulmonary arterioles (p = 0.009), higher right to left ventricular wall diameter ratio (p = 0.02), and larger cardiomyocyte cross-sectional area (p  0.05). Conclusion The endothelin-1 receptor antagonist macitentan attenuated cardiovascular remodelling in an infant rat model for preterm chronic lung disease. This study underscores the potential of macitentan to reduce cardiovascular morbidity in preterm infants with chronic lung disease

Lung-borne systemic inflammation in mechanically ventilated infant rats due to high PEEP, oxygen, and hypocapnia

Background: Intensive care practice calls for ventilator adjustments due to fast-changing clinical conditions in ventilated critically ill children. These adaptations include positive end-expiratory pressure (PEEP), fraction of inspired oxygen (FiO2), and respiratory rate (RR). It is unclear which alterations in ventilator settings trigger a significant systemic inflammatory response. Methods: Fourteen-day old Wistar rat pups were randomized to the following groups: (a) “control” with tidal volume ~8 mL/kg, PEEP 5 cmH2O, FiO2 0.4, RR 90 min-1, (b) “PEEP 1”, (c) “PEEP 9” (d) “FiO2 0.21”, (e) “FiO2 1.0”, (f) “hypocapnia” with RR of 180 min-1, and (g) “hypercapnia” with RR of 60 min-1. Following 120 min of mechanical ventilation, plasma for inflammatory biomarker analyses was obtained by direct cardiac puncture at the end of the experiment. Results: Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were driven by FiO2 0.4 and 1.0 (P=0.02, P<0.01, respectively), tissue plasminogen activator inhibitor type-1 (tPAI-1) was increased by high PEEP (9 cmH2O, P<0.05) and hypocapnia (P<0.05), and TNF-α was significantly lower in hypercapnia (P<0.01). Tissue inhibitor of metalloproteinase-1 (TIMP-1), cytokine-induced neutrophil chemoattractant 1 (CINC-1), connective tissue growth factor (CTGF), and monocyte chemoattractant protein-1 (MCP-1) remained unaffected. Conclusion: Alterations of PEEP, FiO2, and respiratory frequency induced a significant systemic inflammatory response in plasma of infant rats. These findings underscore the importance of lung-protective ventilation strategies. However, future studies are needed to clarify whether ventilation induced systemic inflammation in animal models is pathophysiologically relevant to human infants

SFRP-4 abrogates Wnt-3a-induced β-catenin and Akt/PKB signalling and reverses a Wnt-3a-imposed inhibition of in vitro mammary differentiation

ABSTRACT: BACKGROUND: Conserved Wnt ligands are critical for signalling during development; however, various factors modulate their activity. Among these factors are the Secreted Frizzled-Related Proteins (SFRP). We previously isolated the SFRP-4 gene from an involuting rat mammary gland and later showed that transgenic mice inappropriately expressing SFRP-4 during lactation exhibited a high level of apoptosis with reduced survival of progeny. RESULTS: In order to address the questions related to the mechanism of Wnt signalling and its inhibition by SFRP-4 which we report here, we employed partially-purified Wnt-3a in a co-culture model system. Ectopic expression of SFRP-4 was accomplished by infection with a pBabepuro construct. The co-cultures comprised Line 31E mouse mammary secretory epithelial cells and Line 30F, undifferentiated, fibroblast-like mouse mammary cells. In vitro differentiation of such co-cultures can be demonstrated by induction of the beta-casein gene in response to lactogenic hormones.We show here that treatment of cells with partially-purified Wnt-3a initiates Dvl-3, Akt/PKB and GSK-3beta hyperphosphorylation and beta-catenin activation. Furthermore, while up-regulating the cyclin D1 and connexin-43 genes and elevating transepithelial resistance of Line 31E cell monolayers, Wnt-3a treatment abrogates differentiation of co-cultures in response to the lactogenic hormones prolactin, insulin and glucocorticoid. Cells which express SFRP-4, however, are largely unaffected by Wnt-3a stimulation. Since a physical association between Wnt-3a and SFRP-4 could be demonstrated with immunoprecipitation/Western blotting experiments, this interaction, presumably owing to the Frizzled homology region typical of all SFRPs, explains the refractory response to Wnt-3a which was observed. CONCLUSION: This study demonstrates that Wnt-3a treatment activates the Wnt signalling pathway and interferes with in vitro differentiation of mammary co-cultures to beta-casein production in response to lactogenic hormones. Similarly, in another measure of differentiation, following Wnt-3a treatment mammary epithelial cells could be shown to up-regulate the cyclin D1 and connexin-43 genes while phenotypically they show increased transepithelial resistance across the cell monolayer. All these behavioural changes can be blocked in mammary epithelial cells expressing SFRP-4. Thus, our data illustrate in an in vitro model a mechanism by which SFRP-4 can modulate a differentiation response to Wnt-3a

Technologieakzeptanz als Analyserahmen zum Einsatz von Rehabilitationstechnologien

Rehabilitationstechnologien können die Teilhabe von Menschen mit Behinderung in verschiedenen Lebensbereichen stärken. Trotzdem werden diese häufig nicht genutzt, obwohl sie eigentlich verfügbar wären. Anhand von verschiedenen Technologieakzeptanzmodellen (z. B. TAM, TAM2, UTAUT, TAM3, UTAUT2 oder CAN-Modell) können Faktoren untersucht werden, die die tatsächliche Nutzung einer spezifischen Technologie beeinflussen. Dieser Beitrag gibt einen Überblick darüber, welche Faktoren eine Rolle bei der Nutzung von Rehabilitationstechnologien spielen, die sich an verschiedene Zielgruppen der Rehabilitationswissenschaften richten. Zudem wird eine Übersicht über einschlägige Studienergebnisse von der TU Dortmund gegeben. Es zeigt sich, dass neben den Faktoren der etablierten Technologieakzeptanzmodelle (v. a. Wahrgenommene Einfachheit der Nutzung und Wahrgenommene Nützlichkeit) je nach untersuchter Technologie und Nutzendengruppe eine Vielzahl weiterer Faktoren berücksichtigt werden muss, wenn etwa neue Technologien entwickelt, angeschafft oder in Anwendungskontexte eingeführt werden sollen.Rehabilitation technologies can strengthen the participation of people with disability in various areas of life. Nevertheless, they are often abandoned, although they would actually be available. Different technology acceptance models (e.g., TAM, TAM2, UTAUT, TAM3, UTAUT2, or CAN model) can be used to investigate factors that influence the actual use of a specific technology. This paper provides an overview of different factors that play a role in the use of rehabilitation technologies by different target groups of rehabilitation sciences. Relevant study results from TU Dortmund University are outlined. It is shown that, in addition to the factors of the established technology acceptance models (especially perceived ease of use and perceived usefulness), a variety of other factors must be taken into account depending on the technology and user group studied, for example, when new technologies are to be developed, purchased, or introduced into application contexts

Acetylcholine content and viability of cholinergic neurons are influenced by the activity of protein histidine phosphatase

Background: The first mammalian protein histidine phosphatase (PHP) was discovered in the late 90s of the last century. One of the known substrates of PHP is ATP-citrate lyase (ACL), which is responsible - amongst other functions - for providing acetyl-CoA for acetylcholine synthesis in neuronal tissues. It has been shown in previous studies that PHP downregulates the activity of ACL by dephosphorylation. According to this our present work focused on the influence of PHP activity on the acetylcholine level in cholinergic neurons. Results: The amount of PHP in SN56 cholinergic neuroblastoma cells was increased after overexpression of PHP by using pIRES2-AcGFP1-PHP as a vector. We demonstrated that PHP overexpression reduced the acetylcholine level and induced cell death. The acetylcholine content of SN56 cells was measured by fast liquid chromatographytandem mass spectrometry method. Overexpression of the inactive H53A-PHP mutant also induced cell damage, but in a significantly reduced manner. However, this overexpression of the inactive PHP mutant did not change the acetylcholine content of SN56 cells significantly. In contrast, PHP downregulation, performed by RNAitechnique, did not induce cell death, but significantly increased the acetylcholine content in SN56 cells. Conclusions: We could show for the first time that PHP downregulation increased the acetylcholine level in SN56 cells. This might be a potential therapeutic strategy for diseases involving cholinergic deficits like Alzheimer’s disease

On the Reactivity of NHCtBuAuCl towards Rb6Cs6Si17: The First Gold‐Silicon Cluster [(NHCtBuAu)6(η2‐Si4)]Cl2·7NH3 and an Imide Capped Gold Triangle (NHCtBuAu)3NHCl

Crystals of the two new compounds ((NHCAu)-Au-tBu)(3)NHCl and [((NHCAu)-Au-tBu)(6)(eta(2)-Si-4)]Cl-2 center dot 7NH(3)could be isolated from the reaction of Rb(6)Cs(6)Si(17)with (NHCAuCl)-Au-tBu in the presence of [2.2.2]-cryptand in liquid ammonia. Both compounds were characterized by single-crystal X-ray diffraction and crystallize trigonally without any alkali metals or chelating ligands. Additionally, the crystal of [((NHCAu)-Au-tBu)(6)(eta(2)-Si-4)]Cl-2 center dot 7NH(3)was further interpreted by means of ELF and NBO calculations. In the case of ((NHCAu)-Au-tBu)(3)NHCl, NMR experiments provided an exceptional insight into the reaction processes in solution and allowed for the detection of sequential precursors. In the class of capped gold triangles ((NHCAu)-Au-tBu)(3)NHCl impresses with its unique characteristics of being capped by an imide and bound toN-heterocyclic carbenes as ligands instead of the ubiquitously employed phosphines. The gold capped silicon tetrahedron [((NHCAu)-Au-tBu)(6)(eta(2)-Si-4)]Cl-2 center dot 7NH(3)represents the first known silicide-gold compound, as well as the first known functionalized Zintl anion, crystallized with a cationic central moiety

Influence of Encapsulation Process Temperature on the Performance of Perovskite Mini Modules

Perovskite-on-silicon tandem solar cells are a promising candidate to significantly increase the efficiency of PV modules. Despite the fast research progress on material and solar cells aspects, there is still a lack of processes for an industrial module integration of these devices. One aspect hereby is the adaption of encapsulation materials and processes to the requirements of perovskite materials. Process temperatures of about 150 °C are necessary to use well proven, in silicon PV commonly applied encapsulation materials with a high reliability. However, perovskites start to decompose into their components at high temperatures. This limits the encapsulation process temperature, which in turn constraints the choice of encapsulation materials. This work presents an encapsulation process for methylammonium lead iodide (MAPhb) single junction perovskite solar cells (PSCs) with conventional production tools in glass-glass modules that serves as a model system for perovskite tandem applications. We evaluate the influence of the encapsulation process temperature between 120 °C and 160 °C on the performance of mini modules. The UV-absorbing encapsulation material is processable over the whole investigated temperature regime. We observe a difference in the IV-characteristics between the PSCs encapsulated in the temperature range of 120 °C - 140 °C to those processed at 160 °C. At lower encapsulation temperatures the IV-curves taken 1 h after encapsulation show a pronounced S-shape and no degradation of Foe. In contrast, the PSCs encapsulated at 160 °C exhibit a Foe decrease of up to 29% compared to the initial measurement shortly after PSC fabrication and no significant S-shape. Both, the S-shape that occurs at low encapsulation temperatures and the Foe loss after encapsulation at 160 °C, are no longer significant after one week of module storage under dark conditions. The presented encapsulation process therefore does not permanently damage the MAPbb PSCs even at a standard encapsulation temperature of 160 °C. To ensure long-term operation, we test the fabricated mini modules in a damp heat test at 85 °C and a relative humidity of 85%. We find no significant additional degradation caused by damp heat in 1250 h test duration compared to a reference module stored in ambient air