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Brain ventricle and choroid plexus morphology as predictor of treatment response in major depression: Findings from the EMBARC study
No full textRecent observations suggest a role of the volume of the cerebral ventricle volume, corpus callosum (CC) segment volume, in particular that of the central-anterior part, and choroid plexus (CP) volume for treatment resistance of major depressive disorder (MDD). An increased CP volume has been associated with increased inflammatory activity and changes in the structure of the ventricles and corpus callosum. We attempt to replicate and confirm that these imaging markers are associated with clinical outcome in subjects from the EMBARC study, as implied by a recent pilot study. The EMBARC study is a placebo controlled randomized study comparing sertraline vs. placebo in patients with MDD to identify biological markers of therapy resistance. Association of baseline volumes of the lateral ventricles (LVV), choroid plexus volume (CPV) and volume of segments of the CC with treatment response after 4 weeks treatment was evaluated. 171 subjects (61 male, 110 female) completed the 4 week assessments; gender and age were taken into account for this analyses. As previously reported, no treatment effect of sertraline vs. placebo was observed, therefore the study characterized prognostic markers of response in the pooled population. Change in depression severity was identified by the ratio of the Hamilton-Depression rating scale 17 (HAMD-17) at week 4 divided by the HAMD-17 at baseline (HAMD-17 ratio). Volumes of the lateral ventricles and choroid plexi were positively correlated with the HAMD-17 ratio, indication worse outcome with larger ventricles and choroid plexus volumes, whereas the volume of the central-anterior corpus callosum was negatively correlated with the HAMD-17 ratio. Responders (n = 54) had significantly smaller volumes of the lateral ventricles and CP compared to non-responders (n = 117), whereas the volume of mid-anterior CC was significantly larger compared to non-responders (n = 117), confirming our previous findings. In an exploratory way associations between enlarged LVV and CPV and signs of lipid dysregulation were observed. In conclusion, we confirmed that volumes of lateral ventricles, choroid plexi and the mid-anterior corpus callosum are associated with clinical improvement of depression and may be indicators of metabolic/inflammatory activity.Gefördert durch den Open-Access-Publikationsfonds der UB Marburg
Kinking of GaP Nanowires Grown in an In Situ (S)TEM Gas Cell Holder
No full textNanowires are a promising structure to create new defect-free heterostruc-tures and optoelectronic devices. GaP nanowires grown via the VLS mecha-nism using tertiary-butyl phosphine (TBP) and trimethylgallium (TMGa) as precursors in an in situ closed gas cell heating holder are shown. This holder is a model system to investigate the processes in metal-organic vapour phase epitaxy (MOVPE). GaP nanowires change their growth direction after random distances by producing kinks. Statistics of these kink angles show dominant values of around 70.5°, 109.5°, and 123.7°. A custom holder tip capable of holding a single heating chip is used to perform scanning precession electron diffraction (SPED) measurements on the nanowire kinks. The results show that the predominant kink angles result from micro twins of first and second order. Understanding the defect formation and resulting geometry changes in GaP nanowires can lead to increased control over their shape during growth and mark a huge step toward applicable nanowire devices.Gefördert durch den Open-Access-Publikationsfonds der UB Marburg
Untersuchungen über den Ursprung des 3,4 Dihydroxyphenylmilchsäureteils der Rosmarinsäure in Anthoceros agrestis
No full textPlant terrestrialisation is closely linked to the evolution of phenolic secondary metabolites, which conferred a survival advantage in the presence of new environmental factors, e.g. UV-B radiation, drought, pathogens and herbivores. Besides the incorporation of phenolic components into structural elements (cuticle, spore wall, cell wall), the esters of caffeic acid are of importance (Weng and Chapple 2010). Rosmarinic acid, formally an ester of caffeic acid and 3,4-dihydroxyphenyllactic acid, has been shown to have anti-inflammatory, antimicrobial, antitumour and antioxidant effects, among others (Amoah et al. 2016; Hitl et al. 2021). Besides being abundant in Lamiaceae (Nepetoideae) and Boraginaceae, the component is widespread in the plant kingdom, with hornworts, e.g. Anthoceros agrestis, as the most basal representatives (Petersen 2013). Within the scope of this work, the two enzymes tyrosine aminotransferase (TAT) and hydroxyphenylpyruvate reductase (H(P)PR) were identified, heterologously expressed in E. coli and enzymatically characterised.
TAT revealed a molecular mass of about 50 kDa, with the active enzyme being expected as homodimer. The highest enzyme activity was measured at a pH value of 7.9-8.4 at 60 °C. The most probable substrate/co-substrate pair was determined to be L-tyrosine/2-oxoglutarate. Depending on the actual substrate concentrations, phenylpyruvate could also be considered. Oxaloacetate and pyruvate, on the other hand, were only poorly accepted. In addition, several aromatic and aliphatic amino acids were accepted, as well as the keto acid prephenate. For the identification of these substrates, a rapid and reliable method via thin-layer chromatography with detection by ninhydrin staining verified through HPLC and derivatisation with o-phthalaldehyde was introduced.
HPPR revealed a molecular mass of about 35 kDa and is as well expected as homodimer. The highest enzyme activities were measured at a pH of 7.0-7.5 at a temperature of 44 °C. Contrary to early expectations, hydroxypyruvate was determined as the primary substrate with NADPH as favoured co-substrate and not 4-hydroxyphenylpyruvate. According to the enzyme family, only the D-enantiomer of 4-hydroxyphenyllactate was formed during the reaction. The results correspond to observations on heterologously expressed H(P)PR from Coleus blumei. In addition, the 3-hydroxylated and methoxylated derivative of 4-hydroxyphenylpyruvate as well as phenylpyruvate and pyruvate were accepted.
While no further isoforms could be found for TAT in Anthoceros agrestis, HPPR2 as well as the related HPR1, the photorespiratory isoenzyme, could be amplified and heterologously expressed in E. coli. HPPR2 showed comparable activity with hydroxypyruvate and 4-hydroxyphenylpyruvate, while HPR1 did not accept the latter and favoured NADH.
The investigated enzymes TAT, HPPR as well as HPPR2 could be involved in the biosynthesis of the 3,4-dihydroxyphenyllactic acid moiety analogous to Coleus blumei. Expression analysis over a 14-day culture period revealed a parallel progression of TAT and HPPR2 transcript abundance and rosmarinic acid content, which was different from previous observations in different suspension cultures of Anthoceros agrestis. A definite statement about the involvement of the enzymes mentioned cannot be made based on these data. However, the identification of the potential core enzymes has laid a solid foundation for future work focusing on in vivo analyses.Die Terrestrialisierung der Pflanzen ist eng mit der Entwicklung phenolischer Sekundärmetabolite verbunden, die einen Überlebensvorteil gegenüber neuen Umweltfaktoren wie UV-B-Strahlung, Trockenheit, Krankheitserregern und Herbivoren verschaffen. Neben dem Einbau von phenolischen Komponenten in Strukturelemente (Cutikula, Sporenwand, Zellwand) sind Kaffeesäureester von Bedeutung. Rosmarinsäure, formal ein Ester aus Kaffeesäure und 3,4-Dihydroxyphenylmilchsäure, hat nachweislich unter anderem entzündungshemmende, antimikrobielle, antitumorale und antioxidative Wirkungen. Sie kommt nicht nur in Lamiaceae (Nepetoideae) und Boraginaceae vor, sondern ist im Pflanzenreich weit verbreitet, wobei Hornmoose, z.B. Anthoceros agrestis, die basalsten Vertreter sind. Im Rahmen dieser Arbeit wurden die beiden Enzyme Tyrosin Aminotransferase (TAT) und Hydroxyphenylpyruvat Reduktase (H(P)PR) identifiziert, heterolog in E. coli exprimiert und enzymatisch charakterisiert.
TAT wies eine Molekularmasse von etwa 50 kDa auf, wobei das aktive Enzym als Homodimer auftritt. Die höchste Enzymaktivität wurde bei einem pH-Wert von 7,9-8,4 bei 60 °C gemessen. Als wahrscheinlichstes Substrat/Co-Substrat-Paar wurde L-Tyrosin/2-Oxoglutarat ermittelt. Je nach den tatsächlichen Substratkonzentrationen könnte auch Phenylpyruvat in Betracht gezogen werden. Oxalacetat und Pyruvat hingegen wurden nur schlecht akzeptiert. Darüber hinaus wurden mehrere aromatische und aliphatische Aminosäuren sowie die Ketosäure Prephenat akzeptiert. Für die Identifizierung dieser Substrate wurde eine schnelle und zuverlässige Methode über Dünnschichtchromatographie mit Nachweis durch Ninhydrinfärbung, verifiziert durch HPLC und Derivatisierung mit o-Phthalaldehyd, eingeführt.
Die HPPR hat eine Molekülmasse von etwa 35 kDa, auch dieses Enzym tritt aktiv als Homodimer auf. Die höchste Enzymaktivität wurde bei einem pH-Wert von 7,0-7,5 und einer Temperatur von 44 °C gemessen. Entgegen früheren Erwartungen wurde 4-Hydroxypyruvat als bestes Substrat mit NADPH als bevorzugtem Co-Substrat bestimmt und nicht 4-Hydroxyphenylpyruvat. Entsprechend der Enzymfamilie wurde bei der Reaktion nur das D-Enantiomer von 4-Hydroxyphenyllactat gebildet. Die Ergebnisse stimmen weitgehend mit Beobachtungen an heterolog exprimierter H(P)PR aus Coleus blumei überein. Darüber hinaus wurden das 3-hydroxylierte und methoxylierte Derivat von 4-Hydroxyphenylpyruvat sowie Phenylpyruvat und Pyruvat akzeptiert.
Während für TAT in Anthoceros agrestis keine weiteren Isoformen gefunden werden konnten, ließen sich HPPR2 sowie das verwandte HPR1, das photorespiratorische Isoenzym, amplifizieren und heterolog in E. coli exprimieren. HPPR2 zeigte eine vergleichbare Aktivität mit Hydroxypyruvat und 4-Hydroxyphenylpyruvat, während HPR1 letzteres nicht akzeptierte und NADH bevorzugte.
Die untersuchten Enzyme TAT, HPPR sowie HPPR2 könnten aufgrund ihrer enzymatischen Eigenschaften an der Biosynthese der 3,4-Dihydroxyphenylmilchsäureeinheit analog zu Coleus blumei beteiligt sein. Die Expressionsanalyse über eine 14-tägige Kulturperiode zeigte einen parallelen Verlauf der TAT- und HPPR2-Transkriptabundanz und des Rosmarinsäuregehalts, der sich von einer früheren Beobachtung bei anderen Suspensionskulturen von Anthoceros agrestis unterschied. Eine eindeutige Aussage über die Beteiligung der genannten Enzyme kann auf Grundlage dieser Daten nicht getroffen werden. Die Identifizierung der potenziellen Schlüsselenzyme hat jedoch eine solide Grundlage für künftige Arbeiten geschaffen, die sich auf in-vivo-Analysen konzentrieren sollten
Delayed perforation of an atrial pacemaker electrode: Lifelong risk for a rare but serious complication
No full textWe report the successful percutaneous management of a 77-year-
old
woman who
had a dual-chamber
pacemaker implanted more than 1 year ago and presented
with pericarditis pain and compensated pericardial hemorrhagic tamponade. The
symptoms were due to very late acute perforation of the atrial lead. This report is
intended to raise awareness of procedure-related
complications in the large group
of cardiovascular implantable electronic device patients. Pleuritic or pericardial
pain in these patients should raise suspicion of electrode perforation, as the risk
of perforation is not restricted to the period immediately after implantation and a
lifelong risk cannot apparently be excluded.Gefördert durch den Open-Access-Publikationsfonds der UB Marburg
On the relevance of psychological motives, values, and norms for socially responsible investments: An econometric analysis
No full textBased on unique data from a representative computer-based survey among financial decision makers in Germany, this paper empirically examines the determinants of socially responsible investments (SRI). Our econometric analysis implies that the perceived financial performance of SRI matters for the shares of investments in SRI among all investments. However, our main result is that psychological motives, values, and norms like warm glow motives and ex-pectations of the social environment are even more relevant and thus have strong significant effects on SRI. This suggests that SRI investors gain strong non-financial utility from sustain-able investments. While the membership in Christian churches and the strength of Christian religiosity also seem to be positively correlated with SRI, these correlations become insignifi-cant if other psychological motives, values, and norms are included in the econometric analy-sis. Furthermore, a left-wing political orientation rather has significant negative effects on SRI. An explanation for this surprising result is the general aversion of a left-wing identifica-tion to the participation in stock markets, which is dominant in SRI
Physical and mental health comorbidities of patients with epilepsy in Germany - A retrospective cohort study
No full textZusammenfassung
Ziele:
Ziel dieser Studie war es, die Prävalenz von physischen und psychischen Komorbiditäten bei Patienten mit Epilepsie in Deutschland abzuschätzen, um das komplexe Krankheitsbild und seine Folgen besser zu verstehen.
Methoden:
Diese retrospektive Kohortenstudie umfasste erwachsene Personen mit einer Epilepsiediagnose zwischen Januar 2018 und Dezember 2018 (Indexdatum). Patienten mit Epilepsie wurden 1:1 mit Patienten ohne Epilepsie nach Alter, Geschlecht und Arzt gematcht. Zu den Studienergebnissen gehörten die Assoziationen zwischen Epilepsie und verschiedenen körperlichen und psychischen Störungen, die innerhalb von 365 Tagen nach dem Indexdatum dokumentiert wurden, sowie Multimorbidität, definiert als mindestens zwei, drei, vier und fünf verschiedene Diagnosen. In der vorliegenden Studie wurden multivariate logistische Regessionsmodelle verwendet, bei denen alle Erkrankungen der Studie als abhängige Variablen und Epilepsie als Einflussvariable verwendet wurden.
Ergebnisse:
Nach einem 1:1-Matching umfasste die vorliegende Studie 7942 Patienten mit und 7942 Patienten ohne Epilepsie (Durchschnittsalter: 58,0 Jahre; 49,7 % weiblich). Epilepsie war signifikant positiv mit neun Erkrankungen assoziiert, wobei die stärksten Assoziationen mit geistiger Retardierung (Odds Ratio (OR): 21,11 (95% Konfidenzintervalle (CI): 12,52-35,59)), zerebrovaskulären Erkrankungen (OR: 3,14 (95% CI: 2,80-3,55)) und Demenz (OR: 1,72 (95% CI: 1,47-2,01)) bestanden. Epilepsie war mit einem signifikant erhöhten Risiko für Multimorbidität verbunden.
Schlussfolgerung:
Zusammenfassend lässt sich sagen, dass Personen mit Epilepsie eine erhöhte Prävalenz von Komorbiditäten aufweisen, die mit dem Alter zunehmen. In diesem Bereich sollten weitere Forschungsarbeiten durchgeführt werden, auch zur Ätiologie der Komorbiditäten.Abstract
Aims: The aim of this study was to estimate the prevalence of physical and psychological comorbidities in patients with epilepsy in Germany in order to better understand the complex clinical picture and its consequences.
Methods: This retrospective cohort study included adult individuals with a diagnosis of epilepsy between January 2018 and December 2018 (index date). Patients with epilepsy were matched 1:1 with patients without epilepsy by age, sex, and physician. The study outcomes included the associations between epilepsy and different physical and mental disorders documented within 365 days after the index date as well as multimorbidity defined as at least two, three, four, and five different diagnoses. The present study used multivariate logistic regression models with all study disorders as dependent variables and epilepsy as an impact variable.
Results: After 1:1 matching, the present study included 7942 patients with and 7942 patients without epilepsy (mean age: 58.0 years; 49.7% female). Epilepsy was significantly positively associated with nine disorders, and the strongest associations were with mental retardation (Odds Ratio (OR): 21.11 (95% Confidence Intervals (CI): 12.52-35.59)), cerebrovascular diseases (OR: 3.14 (95% CI: 2.80-3.55)), and dementia (OR: 1.72 (95% CI: 1.47-2.01)). Epilepsy was associated with significantly increased odds of multimorbidity.
Conclusion: In summary, individuals with epilepsy have an increased prevalence of comorbidities that increase with age. Further research should be undertaken in this area, including the etiology of comorbidities
Anti-Proliferative Effect of Radiotherapy and Implication of Immunotherapy in Anaplastic Thyroid Cancer Cells
No full textRadiotherapy and immunotherapy have shown promising efficacy for the treatment of solid
malignancies. Here, we aim to clarify the potential of a combined application of radiotherapy and
programmed cell death-ligand 1 (PD-L1) monoclonal antibody atezolizumab in primary anaplastic
thyroid cancer (ATC) cells. The radiation caused a significant reduction in cell proliferation, measured
by luminescence, and of the number of colonies. The addition of atezolizumab caused a further reduction
in cell proliferation of the irradiated ATC cells. However, the combined treatment did not cause
either the exposure of the phosphatidylserine or the necrosis, assessed by luminescence/fluorescence.
Additionally, a reduction in both uncleaved and cleaved forms of caspases 8 and 3 proteins was
detectable in radiated cells. The DNA damage evidenced the over-expression of TP53, CDKN1A
and CDKN1B transcripts detected by RT-qPCR and the increase in the protein level of P-
H2AX
and the DNA repair deputed kinases. PD-L1 protein level increased in ATC cells after radiation.
Radiotherapy caused the reduction in cell viability and an increase of PD-L1-expression, but not
apoptotic cell death in ATC cells. The further combination with the immunotherapeutic atezolizumab
could increase the efficacy of radiotherapy in terms of reduction in cell proliferation. Further analysis
of the involvement of alternative cell death mechanisms is necessary to clarify their cell demise
mechanism of action. Their efficacy represents a promising therapy for patients affected by ATC.Gefördert durch den Open-Access-Publikationsfonds der UB Marburg
Cemented Sacroiliac Screw Fixation versus Conservative Therapy in Fragility Fractures of the Posterior Pelvic Ring: A Matched-Pair Analysis of a Prospective Observational Study
No full textThe aim of this study was to compare the outcome of cemented sacroiliac screw fixation to
that of conservative treatment in nondisplaced fragility fractures of the sacrum during a 12-month
follow-up. Therefore, matched-pair analysis including 40 patients from a previously performed
prospective observational study was conducted. Pain was assessed using the visual analogue scale
(VAS), functional capabilities and mobility were assessed using the Barthel index, and health-related
quality of life (HRQL) was assessed using the EQ-5D questionnaire at 6 weeks, 6 months, and
12 months after the fracture, respectively. No significant differences between the two groups were
seen regarding pain. In the operative group, a significantly improved Barthel index was observed
after 6 months. A significantly higher HRQL was identified after 6 weeks in the operative group.
Their mobility was comparable between the two groups before the fracture; after 6 weeks, mobility
was significantly improved in the operative group. After 12 months, no significant differences were
found regarding the functional outcome, HRQL or mobility. The 1-year mortality rate was 25% in the
conservative group versus 5% in the operative group (not statistically significant). The present study
revealed favorable short-term outcomes concerning the functional outcome, HRQL and mobility
after sacroiliac screw fixation. After 12 months, the outcomes were similar to those of the patients
managed conservatively.Gefördert durch den Open-Access-Publikationsfonds der UB Marburg
Which Green Nudge Helps to Save Energy? Experimental Evidence
No full textWhich behavioral interventions are more appropriate to induce energy saving: energy saving goals with or without monetary incentives, environmentally related information, social comparison, or a competition to save energy? We try to answer this question in a comprehensive study. First, we designed energy bills with different behavioral interventions. Second, we evaluated their appropriateness in an empirical survey with 457 participants. Third, we tested behavioral consequences in a “real effort” lab experiment with 550 subjects in 11 treatments and one baseline. Finally, we tested two interventions in a small field experiment with 36 test-households. Our results indicate that monetary incentives to save energy foster the intention to invest effort in energy saving but may backfire if real effort is required. Instead, self-set goals – without monetary incentives – and providing social comparison induced substantial effort in our lab experiment. Extending the social comparison to a competition – without monetary incentives – provided the best results. In our field experiment, however, we find no support that goals and social comparison change every-day behavior in energy consumption. Our study concludes with implications for practical policy design and possible future research
COVID-19 Outbreak and Air Pollution in Iran: A Panel VAR Analysis
No full textThe new Coronavirus pandemic has extensive negative socioeconomic impacts. However, its effects on climate change and in particular air pollution, at least at the beginning of the outbreak, is not clear. Fear of getting the Coronavirus in crowded public spaces increased the use of personal cars, while prevention policies that seek to decrease population movement reduced their usage. This paper investigates the relationship between the outbreak of COVID-19, measured by the number of infected cases, and air pollution, measured by PM2.5, in 31 Iranian provinces over the 19 February 2020 to 11 March 2020 period. We employ a panel vector autoregressive (PVAR) approach along with impulse response functions (IRFs), variance decomposition, and Granger causality tests. The analysis shows negative responses of the PM pollution to positive shock in COVID-19 cases in Iran