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Symptoms, the GerdQ score and patients’ characteristics do not predict gastroesophageal reflux disease in patients with proton-pump-inhibitor-refractory reflux symptoms : results from a large prospective database
No full textThe number of patients with proton pump inhibitor (PPI)-refractory reflux symptoms is underestimated since many patients resign after an unsuccessful therapy attempt. Thus, it would be useful having a non-invasive tool that can help identify true gastroesophageal reflux disease (GERD) patients in order to manage them early and properly. The GerdQ is a validated tool developed for this purpose but its applicability in PPI-refractory patients has not yet been investigated. Our aim was to investigate if reflux symptoms per se, the GerdQ and patients characteristics are suitable for non-invasive diagnosis of GERD in patients with PPI refractory reflux symptoms.
A total of 500 patients from a prospectively recorded data base with PPI-refractory reflux symptoms were retrospectively analyzed. All patients received comprehensive diagnostic workup including EGD, pH-impedance measurement and manometry. GERD was diagnosed according to the recent Lyon consensus.
Of all patients enrolled in the study, 280 (56%) finally fulfilled the criteria for objectively verified GERD according to the Lyon consensus. There were no significant differences in age and gender between the patients with and without GERD, whereas the body mass index was significantly higher in the group with verified GERD, but the discriminative value was low (Welch-Test, p < .001, Cohen’s d = 0.39). Furthermore, there were no significant differences in the GerdQ values between the two groups. A GerdQ cutoff value ≥ 9 resulted in a sensitivity of 43% and specificity of 57% with a positive predictive value of 56% and a negative predictive value of 44%.
Based on our study, neither symptoms and the GerdQ score nor patients’ characteristics are appropriate tools to distinguish between GERD and other causes for reflux symptoms in patients with PPI-refractory reflux symptoms.Gefördert durch den Open-Access-Publikationsfonds der UB Marburg
Verfolgte, Widerständige, Mitläuferinnen und Täterinnen: Marburger Frauen im Nationalsozialismus
No full textAusstellungskatalog zur Ausstellung “Verfolgte, Widerständige, Mitläuferinnen und Täterinnen: Marburger Frauen im Nationalsozialismus”
Die Ausstellung „Marburger Frauen im Nationalsozialismus“ ist aus einem Seminar der Soziologin Randi Becker am Marburger Zentrum für Gender Studies und feministische Zukunftsforschung hervorgegangen: Studierende haben darin die Geschichten von 22 Marburger Frauen im Nationalsozialismus erforscht, darunter Verfolgte, Widerständige aber auch Täterinnern. Ihre Geschichten werden in der Ausstellung vorgestellt.
Der Druck der Ausstellung wurde durch die freundliche Förderung des Fachbereichs Gleichstellung der Stadt Marburg unter der Leitung von Christine Amend-Wegmann, sowie der Frauen- und Gleichstellungsbeauftragten der Universität Marburg Dr. Nina Schumacher ermöglicht.
Die Erstellung des Ausstellungskatalogs wurde durch die freundliche Förderung des Projekt-Fonds zur Antisemitismusprävention der Stabsstelle Antidiskriminierung und Diversität der Universität Marburg ermöglicht
Working with patients’ treatment expectations – what we can learn from homeopathy
No full textThe usual homeopathic remedy, “globules,” does not contain any
pharmacologically active ingredient. However, many patients and practitioners
report beneficial effects of homeopathic treatment on various health outcomes.
Experimental and clinical research of the last two decades analyzing the
underlying mechanisms of the placebo effect could explain this phenomenon,
with patients’ treatment expectations as the predominant mechanism.
Treatment expectations can be optimized through various factors, such as
prior information, communication, and treatment context. This narrative review
analyses how homeopathy successfully utilizes these factors. Subsequently,
it is discussed what evidence-based medicine could learn from homeopathic
practice to optimize treatment expectations (e.g., using an empathic, patientcentered
communication style, deliberately selecting objects in practice rooms,
or using clear treatment rituals and salient contextual stimuli) and thereby
treatment effectiveness. Homeopathic remedy does not work beyond the
placebo effect but is recommended or prescribed as an active treatment by
those who believe in it. Thus, practitioners need to understand the manner in
which homeopathy (as an example of inert treatment) works and are advised to
reintegrate its underlying effective placebo mechanisms into evidence-based
medicine. This promises to increase treatment efficacy, tolerability, satisfaction,
and compliance with evidence-based treatments, and addresses the desires
patients are trying to satisfy in homeopathy in an ethical, fully informed way that
is grounded in evidence-based medicine.Gefördert durch den Open-Access-Publikationsfonds der UB Marburg
Unconventional Monetary Policy and Bank Risk-Taking in the Euro Area
No full textThis paper studies risk-taking by European banks. After an overview about the banking landscape in the euro area, we construct a measure of risk-taking which relates changes in three month ahead expected credit standards for several non-financial private sector categories to the risk of the macroeconomic environment banks operate in. With this approach we want to tackle the question if credit standards react disproportionately strong to changes in the monetary policy stance. We use an estimated bond market based measure to assess the overall riskiness prevailing in the economy. With this approach we want to shed some light on whether banks act excessively risky and provide new evidence as well as an alternative assessment on the amplifying nature of the risk-taking channel of monetary policy. We put our measure into a VAR model in which structural innovations are identified with sign restrictions. The key outcomes of this paper are the following: expansionary monetary policy shocks decrease our measure of risk-taking. Decreases in our measure are caused by disproportionately strong reactions in credit standards compared to the overall macroeconomic risk, especially during the recent financial crisis. Disproportionately in the sense that our macroeconomic risk measure is less affected by expansionary monetary policy shocks than credit standards. The credit granting reaction depends on the category: In general, loans to non-financial corporations are less sensitive to monetary policy shocks while mortgages seem to be affected more. We conclude that expansionary monetary policy shifts the portfolio of banks to overall riskier asset holdings
Die Rolle des Tumorsupressors p53 in the Biogenese und Funktion extrazellulärer Vesikel.
No full textThe progression and metastasis of ovarian cancer (OC) relies on the intricate interplay between cancer cells and their surrounding tumor microenvironment (TME). Within this complex ecosystem, various cell types, particularly fibroblasts, play a significant role in facilitating OC invasion and metastasis. The TME also encompasses diverse soluble components, including cytokines or extracellular matrix (ECM) and, notably, extracellular vesicles (EVs). EVs have emerged as critical mediators of cellular communication by transporting and presenting their cargo, including proteins, lipids, and nucleic acids. The complex biogenesis of EVs involves different mechanisms and factors, with recent attention focusing on the tumor protein p53. In the majority of ovarian cancer cases, p53 is mutated, but its potential role as a facilitator of EV biogenesis remains elusive. Therefore, this study aims to further unravel the role of p53 in EV biogenesis and its impact on the TME, with a specific focus on cancer-associated fibroblasts (CAFs).
To address this, I genetically engineered ovarian cancer cell lines (OVCAR8) with a defined p53 status, including lines with a p53 knockout (KO), a p53 wildtype (WT), and two specific hot spot mutations (mutp53; R175H or R273H). The characterization of the secreted EVs revealed no significant differences in particle size and EV marker expression between knockout and mutated cells. Of note, transcriptomic analysis demonstrated higher expression of genes involved in exosome biogenesis, such as ESCRT components, in p53 WT cells, which also released elevated amounts of EVs. Moreover, EVs preferentially transferred WTp53 compared to mutp53 to recipient cells, although it was lower expressed in the respective cells. Treatment of human fibroblast with EVs from p53 wildtype cells and, to a remarkably lesser extent, from p53KO/mutp53 cells induced an inflammatory phenotype. This was shown to be at least partially mediated by NFκB and STAT3 activity. Secretome analysis further confirmed the inflammatory phenotype of wildtype EV-treated fibroblast with the secretion of cytokines and chemokines, such as IL6, CXCL1, and CXCL8. In contrast, EVs from p53KO cells induced a phenotype associated with ECM remodeling, including secretion of COMP, POSTN, and TGFB1. Notably, EV from mutp53 cells did not cause a specific phenotype in fibroblasts.
In conclusion, our findings indicate that EVs from OC cells expressing p53 wildtype influence the phenotype of human fibroblasts, indicating that p53 directs specific EV cargo loading. These findings provide the basis to further investigate p53 as an essential mediator of EV biogenesis and potentially develop innovative strategies to educate the TME and, specifically, fibroblasts to an anti-tumorigenic phenotype by utilizing p53 wildtype-derived EVs.Die Progression und Metastasierung von Eierstockkrebs werden maßgeblich durch das komplexe Zusammenspiel von Krebszellen mit ihrer umgebenden Tumormikroumgebung beeinflusst. Innerhalb dieses hochkomplexen Ökosystems spielen verschiedene Zelltypen, insbesondere Fibroblasten, eine entscheidende Rolle. Die Tumormikroumgebung setzt sich außerdem aus verschiedenen löslichen Bestandteilen zusammen, darunter Zytokine, extrazelluläre Matrix (ECM) und extrazelluläre Vesikel (EVs). EVs die als innovative Vermittler der zellulären Kommunikation hervorstechen, haben die einzigartige Fähigkeit, eine breite Palette von Molekülen, darunter Proteine, Lipide und Nukleinsäuren, zu transportieren und zu präsentieren. Die Biogenese von EVs ist komplex und involviert verschiedene Mechanismen und Faktoren. In den letzten Jahren hat sich das Tumorprotein p53, welches in fast allen Fällen von Eierstockkrebs mutiert ist, als potentiell wichtiger Faktor in der Biogenese von EVs herauskristallisiert. Allerdings ist die genaue Rolle von p53 nach wie vor unklar, weshalb diese Studie das Ziel hat, diese Funktionen und dessen Auswirkungen auf die Tumormikroumgebung, insbesondere im Zusammenhang mit krebsassoziierten Fibroblasten weiter zu erforschen.
Um dies zu untersuchen, haben wir Eierstockkrebszelllinien (OVCAR8) mit einem bestimmten p53-Status genetisch erzeugt, sodass sie entweder, einen p53-Knockout (KO), ein p53-Wildtyp (WT) oder eine von zwei spezifischen Hotspot-Mutationen (mutp53, R175H oder R273H) exprimieren. Bei der Charakterisierung der sekretierten EVs wurden keine signifikanten Unterschiede in Partikelgröße und EV Marker Expression zwischen Knockout- und mutierten Zellen beobachtet. Die transkriptomische Analyse zeigte jedoch eine höhere Expression von Genen in p53WT-Zellen, die an der Exosom-Biogenese, wie z.B. verschiedene ESCRT-Komponenten, beteiligt sind. Außerdem sekretierten diese Zellen erhöhte Mengen an EVs. Es konnte weiterhin gezeigt werden, dass WTp53 bevorzugt in EVs geladen wird, und diese von Zielzellen, wie z.B. Krebszellen oder Fibroblasten, aufgenommen werden können. Die Behandlung von humanen Fibroblasten mit EVs von p53WT Zellen resultierte in einen entzündlichen Phänotyp, welcher zumindest teilweise durch NFκB und STAT3 Aktivität vermittelt wird. Eine Sekretome-Analyse zeigte außerdem eine erhöhte Ausschüttung von Zytokinen und Chemokinen wie z.B. IL6, CXCL1 und CXCL8 durch die mit WT-EVs behandelten Fibroblasten was somit die Ergebnisse in den Transkriptomanalysen bestärken. Im Gegensatz dazu zeigten p53KO EV-behandelte Fibroblasten einen Phänotyp der mit der Modellierung der extrazellulären Matrix assoziiert ist, wie zum Beispiel durch Sekretion von COMP, POSTN oder TGFB1. Interessanterweise, zeigten Fibroblasten die mit EVs von mutierten p53 Zellen behandelt wurden keinen gesonderten Phänotyp.
Zusammenfassend zeigen unsere Ergebnisse, dass EVs von Eierstockkrebszellen, die WTp53 exprimieren, den Phänotyp von humanen Fibroblasten beeinflussen, was darauf hindeutet, dass p53 an einer spezifische EV Biogenese beteiligt ist. Diese Erkenntnisse bilden eine Grundlage für weitere Untersuchungen von p53 als einen wichtigen Vermittler der EV-Biogenese
Design of Chiral-at-Ruthenium and Chiral-at-Iron Complexes for Asymmetric Catalysis
No full textThis thesis is deals with the development of new types of octahedral chiral-at-ruthenium and chiral- at-iron complexes. The chiral-at-iron complexes were investigated for applications in asymmetric catalysis.
In the first section, we introduce a new type of racemic and non-racemic octahedral ruthenium complexes where the metal center is cyclometalated by two 7-alkyl-1,7-phenanthrolium ions, giving chelating pyridylidene remote N-heterocyclic carbene ligands. The octahedral coordination sphere is incorporating two additional acetonitriles and the dicationic complexes are complemented by two hexafluorophosphate counterions. The racemic complexes are synthesized in a C 2 -symmetric geometry. Resolution of racemic complexes with a chiral sulfinamide auxiliary, followed by treating with TFA, results in non-C 2 -symmetric chiral-at-ruthenium complexes. Single crystal X-ray analysis showed that one of the bidentate ligands underwent a reorganization within the ligand sphere. Depending on the helical twist of the bidentate ligands, the metal center can adopt either a Λ or Δ metal-centered configuration. These chiral-at-ruthenium complexes are stable and enantiomeric enriched as confirmed by 1 H NMR and CD spectroscopy. Furthermore, the trans-effect of the pyridylidenes in this family of ruthenium complexes is investigated by crystallographic analysis, indicating the stronger electron-donating ability of pyridylidenes in comparison to pyridyl donors, as well as imidazol-2-ylidenes in related complexes.
In the second section, the first example of a chiral-at-iron complex for asymmetric catalysis is described, which is exclusively constructed with achiral bidentate and monodentate ligands and the iron ion serves as the stereogenic center. The cis-geometric coordination consists of two N-(2-pyridyl) imidazol-2-ylidene ligands and two acetonitrile ligands. Two acetonitrile ligands are labilized due to a strong electron donating imidazolylidene ligand in trans-position and hence promotes asymmetric transition metal catalysis. This is demonstrated with an enantioselective Cannizzaro reaction (96% yield, 89% ee) and an asymmetric Nazarov cyclization (89% yield, >20:1 d.r., 83% ee). A highly enantioselective and diastereoselective transformation catalyzed by this new class of chiral-at-iron catalysts is developed by introduction of high steric crowding around the catalytic site. An iron complex bearing bulky 2,6-diisopropylphenyl moieties at the imidazolylidene ligands, proved to be the best catalyst for inverse electron demand hetero-Diels-Alder cycloadditions of b,r-unsaturated a-ketoester with enol ethers, providing 3,4-dihydro-2H-pyrans in high yields with excellent diastereoselectivities (up to 99:1 dr) and excellent enantioselectivities (up to 99:1 er). An electron rich vinyl azide is also cyclized to the corresponding product with excellent diastereoselectivity (95:5 d.r.) and enantioselectivity (95% ee).Der Fokus dieser Arbeit bestand hauptsächlich aus der Synthese und Charakterisierung von neuartigen oktaedrischen Ruthenium- und Eisenkomplexen mit ausschließlich metallzentrierter Chiralität (chiral-at-metal-Komplexe). Die Eisenkomplexe wurden auf Anwendungen in der asymmetrischen Katalyse untersucht. Im ersten Abschnitt wird eine neue Art von racemischen und nicht-racemischen oktaedrischen Rutheniumkomplexen vorgestellt, bei denen das Metallzentrum von zwei 7-Alkyl-1,7-Phenanthrolium-Liganden koordiniert ist, wodurch chelatisierende Pyridyliden-N-heterocyclische Carbenliganden erhalten wurden. Die oktaedrische Koordinationssphäre besteht zudem aus zwei Acetonitril-Liganden und der dikationischen Komplex ist mit zwei Hexafluorophosphat-Gegenionen ergänzt. Die racemischen Komplexe wurden in einer C2 -symmetrischen Geometrie synthetisiert, wohingegen die Trennung der Enantiomere mit einem chiralen Sulfinamid-Auxiliar und die anschließende Behandlung mit TFA zu nicht C2 -symmetrischen chiralen Rutheniumkomplexen führte. Einkristall-Röntgenanalyse zeigte, dass es zu einer Isomerisierung kam. Abhängig von der helikalen Verdrehung der zweizähnigen Liganden kann das Metallzentrum entweder eine - oder -Konfiguration annehmen. Diese chiralen Rutheniumkomplexe waren stabil und enantiomerenangereichert, was durch 1 H-NMR- und CD-Spektroskopie bestätigt wurde. Darüber hinaus wurde der trans-Effekt der Pyridyliden-Liganden in diesen Komplexen durch kristallographische Analyse untersucht, die die stärkeren elektronenschiebenden Eigenschaften von Pyridylidenen im Vergleich zu Pyridyl-Donoren sowie zu Imidazol-2-yliden in analogen Komplexen bestätigen. Im zweiten Abschnitt dieser Arbeit wird das erste Beispiel eines chiralen chiral-at-metal Katalysators beschrieben, der ausschließlich aus achiralen bidentaten und monodentaten Liganden aufgebaut ist und dessen Eisenatom als Stereozentrum dient. Die cis-Anordnung der bidentation Liganden besteht aus zwei N-(2 Pyridyl)imidazol-2-yliden-Liganden und zwei Acetonitril-Liganden, die aufgrund der stark elektronenschiebenden Imidazolyliden-Liganden in trans-Position eine hohe Labilität aufweisen, was asymmetrische Lewissäurekatalyse an diesen Stellen erleichtert. Dies wurde mit einer enantioselektiven Cannizzaro-Reaktion (96% Ausbeute, 89% ee) und einer asymmetrischen Nazarov-Cyclisierung (89% Ausbeute, >20:1 d.r.,
83% ee) gezeigt. Weiterhin wurde erstmalig eine hochgradig enantio- und diastereoselektive Transformation gezeigt, die durch einen chiral-at-iron Komplex katalysiert wurde, der keine chiralen Liganden enthält. Der Vorteil dieses neuen chiral-at-iron Katalysator-Designs besteht aus der Einführung sterisch anspruchsvoller Gruppen in der Nähe des katalytisch aktiven Zentrums, was für eine verbesserte Stereoselektivität von entscheidender Bedeutung ist. Ein Eisen-Komplex, der große 2,6-Diisopropylphenyl-Reste an den Imidazolyliden-Liganden trägt, erwies sich als bester Katalysator für eine Hetero-Diels-Alder-Cycloaddition mit inversem Elektronenbedarf von b,r-ungesättigten a-Ketoestern mit Enolethern. Die dabei gebildeten 3,4-Diyhydro-2H-Pyrane konnten in hohen Ausbeuten mit hervorragenden Diastereoselektivitäten (bis zu 99:1 d.r.) und hervorragenden Enantioselektivitäten (bis zu 99:1 e.r.) erhalten werden. Ein elektronenreiches Vinylazid wurde ebenfalls zu dem entsprechenden Produkt mit ausgezeichneter Diastereoselektivität (95:5 d.r.) und Enantioselektivität (95% ee) cyclisiert
Determinants of FDI Location in Egypt—Empirical Analysis Using Governorate Panel Data
No full textWe empirically analyse the determinants of inward foreign direct investment (FDI) in Egypt employing a novel panel dataset of 26 Egyptian governorates for the period 1992–2008. Using the case of Arab FDI to Egypt, we also investigate whether FDI location determinants are different depending on similarity of culture and language between FDI source and host region. Our results indicate that domestic private investment, well-functioning Free Zones, and labour abundance positively affect FDI location. In contrast to results for other countries, we find no significant effect of concentration of previous FDI stocks on the location of inward FDI. Moreover, regional investment preferential policies in Egypt—with the exception of Free Zones—do not affect the unequal spatial FDI distribution. Finally, we find that the location of Arab FDI inflows to Egypt is not sensitive to the usual determinants. Arab investors are more willing to invest in less investment-agglomerated areas and are less affected by economic considerations and incentives
Who Is Successful in Foreign Exchange Margin Trading? New Survey Evidence from Japan
No full textWe use a 2018 survey of FX margin traders in Japan to investigate which key factors influence their performance: socio-demographic and economic situation, investment strategy and trading behaviour, and/or financial literacy. First, the data show that variables from all three groups are significant predictors of traders’ performance. Second, we find that older traders and those without a specific trading strategy demonstrate lower performance. Performance is higher for those who trade greater amounts, rely more on fundamental analysis, and report having profitable FX trade skills. Third, respondents’ subjectively stated claim of having FX trade skills is based on a more advanced understanding of FX trading and a reliance on professional advice. Neither objective financial knowledge nor over/underconfidence play a noteworthy role in the performance of margin traders
Does Educational Status Influence Parents’ Response to Bad News in the NICU?
No full textCommunication in neonatal intensive care units and the relationship between families
and staff have been reported to influence parental mental well-being. Research has also shown an
impact of parental educational level on their well-being. However, whether different educational
levels result in different reactions to breaking bad news (BBN) by physicians remains unanswered
so far. We therefore examined the impact of parental level of education on their mental state after a
BBN conversation and their relation to physicians. A prospective quantitative survey was conducted
amongst 54 parents whose preterm or term infants were hospitalized in three German neonatal
units. Parental education was classified as low (lower secondary/less (1), n: 23) or high (higher
secondary/more (2), n: 31). Parents answered questions about certain aspects of and their mental
state after BBN and their trust in physicians. The two groups did not differ significantly in their
mental condition after BBN, with both reporting high levels of exhaustion and worries, each (median
(min;max): (1): 16 (6;20) vs. (2): 14 (5;20), (scaling: 5–20)). However, lower-educated parents reported
a lower trust in physicians (median (min;max): (1): 2 (0;9) vs. (2): 1 (0;6), p < 0.05 (scaling: 0–10))
and felt less safe during BBN (median (min;max): (1): 15 (9;35) vs. (2): 13 (9;33), p < 0.05). Only
among higher-educated parents was trust in physicians significantly correlated with the safety and
orientation provided during BBN (r: 0.583, p < 0.05, r: 0.584, p < 0.01). Concurrently, only among
less-educated parents was safety correlated with the hope conveyed during BBN (r: 0.763, p < 0.01).
Therefore, in BBN discussions with less-educated parents, physicians should focus more on giving
them hope to promote safety.Gefördert durch den Open-Access-Publikationsfonds der UB Marburg
Explaining Central Bank Trust in an Inflation Targeting Country: The Case of the Reserve Bank of New Zealand
No full textEmploying data from a representative population survey conducted in New Zealand in 2016, this paper examines factors that influence, or are at least associated with, public trust in the Reserve Bank of New Zealand (RBNZ). The large number of specifically designed questions allows studying the relationship between six dimensions and RBNZ trust: (i) economic situation, (ii) monetary policy knowledge, (iii) nonspecific trust, (iv) interest and information search, (v) politicians and government, and (vi) socio-demographic indicators. Using ordered logit models, we find that at least one indicator from each of these six dimensions has a statistically significant conditional correlation with individuals’ trust in RBNZ. Satisfaction with own financial situation, objective knowledge about the RBNZ’s main policy objective, responsibility for interest rate setting, subjective knowledge about inflation, trust in government institutions, desire to be informed about RBNZ, age, and full-time selfemployment have a positive relationship with RBNZ trust. The reverse is found for respondents who do not keep up with RBNZ and believe that politicians are long-term oriented. In terms of economic relevance, institutional trust has the largest single impact on RBNZ trust and the subjective and objective knowledge indicators show a strong combined influence