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Dams, Judith ; Rimane, Eline ; Steil, Regina ; Renneberg, Babette ; Rosner, Rita ; König, Hans-Helmut
Background: Posttraumatic stress disorder (PTSD) is one of the psychopathological consequences of sexual and/or physical abuse. The economic burden is assumed to be high, whereas health-related quality of life and education is negatively affected. This study aims to determine health care costs, health-related quality of life, and educational interruption in adolescents and young adults with PTSD after sexual and/or physical abuse in Germany.
Methods: This analysis used data of 87 participants aged 14–21 years of a randomized controlled trial. Health care utilization, health-related quality of life (EQ-5D-5L), sick leave days, productivity, and delay or failure to achieve educational aims were assessed. Health care costs from a payer perspective were calculated using unit costs for the year 2014.
Results: Mean health care costs for a six-month period were 5,243€ (SE 868€). In particular, costs of inpatient stays in psychiatric hospitals, general hospitals and rehabilitation as well as child welfare institutions were high. In addition, health-related quality of life was lower due to anxiety/depression, resulting in a mean EQ-5D index and EQ-VAS score of 0.70 and 61.0, respectively. Furthermore, participants reported on average 27 sick leave days, a productivity loss of 61%, and a delay in education attainment as well as having been unable to achieve educational aims.
Conclusion: PTSD in adolescents and young adults is associated with a high economic burden. Health-related quality of life was substantially reduced. Furthermore, delay and productivity losses in education were observed.
Clinical Trial Registration: German Clinical Trials Register identifier: DRKS00004787; date of registration: 18th March 2013; https://www.drks.de.
Die CXCR4/CXCL12-Achse ist von entscheidender Bedeutung für die Entstehung und Aufrechterhaltung einer gesunden, reifen Hämatopoese. Erstmals beschrieben wurde der später als CXCR4 bezeichnete Rezeptor 1996 allerdings als Co-Rezeptor für den Eintritt humaner HI-Viren in Lymphozyten. Ein großes Interesse bestand daraufhin darin, sowohl natürliche Inhibitoren des G-Protein gekoppelten Rezeptors zu identifizieren, als auch synthetische herzustellen, um einen Eintritt des Virus in den menschlichen Organismus zu verhindern bzw. seine Ausbreitung zu unterbinden. Ein natürlich vorkommender CXCR4-Ligand, der 2015 von Zirafi und Kollegen erstmals beschrieben wurde, fand sich im Hämofiltrat von Dialysepatienten. Der im weiteren Verlauf als EPI-X4 bezeichnete CXCR4-Antagonist wurde als Spaltprodukt von Albumin identifiziert, welches über viele Spezies hochkonserviert ist. Diese Eigenschaft interpretieren wir als Hinweis auf eine relevante physiologische Funktion des Peptids. Da die Halbwertszeit von natürlich vorkommendem EPI-X4 beim Menschen vermutlich sehr kurz ist, sind in vivo- und darauffolgende in vitro-Analysen schwierig durchzuführen. In-vitro-Spike-Analysen von synthetischem EPI-X4 in humanem Plasma ergaben eine Halbwertszeit von nur 17 Minuten. Die geringen auftretenden Konzentrationen erschweren die Problematik zusätzlich. In dieser Arbeit sollen deshalb im Mausmodell in vivo-Analysen durchgeführt werden, um die Effekte von potentiell entstehendem EPI-X4 in verschiedenen experimentellen Ansätzen aufzudecken. Ein probates, hier verwendetes Mittel, ist die Analyse einer Knock-out (KO)-Maus. Die für die Bindung an CXCR4 entscheidende Aminosäure von EPI-X4, das am N-Terminus gelegene Leucin, wurde durch Alanin ersetzt, welches die Entstehung von EPI-X4 unterbindet und zusätzlich dessen Bindung an CXCR4 verhindert. Mit Hilfe zweier Mausmodelle können nun Analysen im EPI-X4-defizienten Modell durchgeführt werden, die im Umkehrschluss Informationen über die organismische Wirkung von EPI-X4 beinhalten. Zunächst wurde in beiden Modellen die physiologisch normale reife und unreife Hämatopoese charakterisiert. Hierbei zeigte sich kein signifikanter systematischer Einfluss von EPI-X4 auf reife Leukozyten (WBC), lediglich eine leichte Lymphozytose in der HR-Ala-Variante. Im weiteren Verlauf der homöostatischen Analyse der Hämatopoese der Ala-EPI-X4-Mäuse zeigten sich keine signifikanten Unterschiede zu wildtypischen Mäusen. Sowohl reife als auch unreife Zellen zeigten, außer in der T- und B-Zelllinie, keine zahlenmäßigen oder funktionalen Auffälligkeiten, weder im Blut, noch in der Milz oder im Knochenmark. Analysen der Zellzyklusaktivität unterschiedlicher Unreifestufen wiesen ebenfalls keine Auffälligkeiten auf. Diese Daten einer normalen, von einer C57Bl/6-Maus zu erwartenden Ergebnisse dienten als Grundlage zur Bewertung und Analyse von durchgeführten hämatopoetischen Stressmodellen. Hierfür wurden
zunächst hämatopoetische Stamm- und Vorläuferzellen (HSPC) mobilisiert. In den angewandten Mobilisierungsmodellen fanden sich lediglich unter G-CSF-Behandlung im Knochenmark eine größere Anzahl Granulozyten, was auf einen Einfluss von EPI-X4 auf HSPC schließen lässt. Um potentielle Auswirkungen von EPI-X4 im Knochenmark weiter zu untersuchen, wurde ein weiteres Stressmodell gewählt, welches ebenfalls mutmaßlich die Bedingungen zur EPI-X4-Generierung schafft: Subletale Bestrahlung der Mäuse sorgt für Schäden an allen Zellarten im Knochenmark, es wird ein steriles entzündliches Milieu kreiert. Unter diesen Umständen wurde die Regeneration von Blutzellen analysiert. Es zeigten sich keine nennenswerten Unterschiede sowohl in der akuten Phase des Schadens als auch in regelmäßigen Blutentnahmen während der Regenerierung.
Die Beschreibung von natürlich vorkommendem EPI-X4 in Vaginal- und Rektalschleimhaut zeigt seine Entstehung an Schleimhautbarrieren auf. Ala-EPI-X4-Muse werden deshalb auf deren Durchlässigkeit untersucht: LPS-Konzentrationen als Marker für eindringende pathogene Bakterien wurden im Plasma untersucht. Hierbei zeigten sich keine Unterschiede zwischen den Gruppen, eine Störung scheint hier nicht vorzuliegen. Zusätzlich wurde die Zusammensetzung des Mikrobioms im Darm untersucht, da beschrieben wurde, dass sich Mikrobiom und die Integrität der Darmschleimhaut gegenseitig beeinflussen. Im Falle der EPI-X4-defizienten Mäuse liegt zwar keine offensichtliche pathologische Veränderung vor, dennoch konnte in männlichen HR-Ala-Mäusen die Abwesenheit des Proteobakteriums Parasutterella nachgewiesen werden. Um eine mögliche Defizienz der Barrierefunktion weiter zu testen, wurden zwei Stressmodelle gewählt: Zunächst wurde den Mäusen eine akute, sterile Peritonitis zugefügt, woraufhin die Anzahl und Zusammensetzung der ins Peritoneum einströmenden Leukozyten analysiert wird. Die Reaktion auf diesen Entzündungsprozess war nicht verändert. Ähnliche Ergebnisse zeigten sich auch in einem akuten Colitis-Stressmodell.
Insgesamt konnte in dieser Arbeit mithilfe zweier KO-Mausmodelle die Rolle von EPI-X4 in der Hämatopoese und der Immunologie von Mäusen beginnend charakterisiert werden. Die homöostatische Hämatopoese scheint kaum von EPI-X4 abhängig zu sein, lediglich die Zahl der B- und T-Zellen, insbesondere der regulatorischen T-Zellen, scheint beeinflusst. Damit einhergehend konnten Veränderungen in Zytokinlevels bei inflammatorischen Ereignissen gezeigt werden. Experimente zur beeinflussten, eventuell gestörten Barrierefunktion von Ala-EPI-X4-Mäusen zeigten vielversprechende Ansätze und sollten in Zukunft weiter analysiert werden.
Erasmus, christlicher Humanismus und Spiritualität in Spanien und Neu-Spanien (16. Jahrhundert)
(2020)
Schriften des Erasmus von Rotterdam (1466/69–1536) entfalteten während des 16. Jahrhunderts eine große Wirkung in Spanien. Auf Grundlage der klassischen wie der jüngeren Historiographie widmet sich der Aufsatz diesem religions- und kulturgeschichtlichen Phänomen – mit Seitenblicken auf Luther – in vier Teilen: Nach einer Skizze zu Leben und Werk des christlichen Humanisten behandelt der zweite Teil den Erasmianismus in Spanien von seiner Erfolgsgeschichte in den 1520er Jahren (etwa bei Hof, an den Universitäten und in Übersetzungen) bis zur Verfolgung seiner Anhänger seit den 1530er Jahren durch die Inquisition. Drittens werden neuere Forschungstendenzen diskutiert, die das klassische, von Marcel Bataillon geprägte Bild korrigieren und weiterentwickeln, auch im Hinblick auf das ambivalente Verhältnis von Scholastik und Humanismus. Der letzte Teil widmet sich dem Einfluss des Erasmus in Neuspanien (Mexiko) am Beispiel von (Erz-) Bischöfen und Mönchen sowie von frühkolonialen Fallstudien.
Endogenous clocks enable organisms to adapt their physiology and behavior to daily variation in environmental conditions. Metabolic processes in cyanobacteria to humans are effected by the circadian clock, and its dysregulation causes metabolic disorders. In mouse and Drosophila were shown that the circadian clock directs translation of factors involved in ribosome biogenesis and synchronizes protein synthesis. However, the role of clocks in Drosophila neurogenesis and the potential impact of clock impairment on neural circuit formation and function is less understood. Here we demonstrate that light stimuli or circadian clock causes a defect in neural stem cell growth and proliferation accompanied by reduced nucleolar size. Further, we define that light and clock independently affect the InR/TOR growth regulatory pathway due to the effect on regulators of protein biosynthesis. Altogether, these data suggest that alterations in growth regulatory pathways induced by light and clock are associated with impaired neural development.
Historiadora do cinema, Miriam Hansen examinou e sistematizou as contribuições de Siegfried Kracauer, Walter Benjamin e Theodor Adorno para a teorização do cinema. Nesta pesquisa bibliográfica, buscamos sintetizar e apresentar aos leitores de língua portuguesa o desenvolvimento de sua investigação sobre o tema. Mostramos como Hansen foi capaz de identificar as principais diferenças entre os teóricos frankfurtianos, bem como evidenciar que eles, em comum, pensaram este fenômeno cultural contemporâneo em relação às condições sociais e econômicas de produção. Em suas reflexões, o cinema aparece como expressão da sociedade urbano-industrial, como um elemento sintomático da cultura de massa.
Dassou, Hospice Gbèwonmèdéa ; Idohou, Rodrigue ; Adomou, Aristide Cossi ; Ouachinou, Jéronime Marie-Ange Sènami ; Yédomonhan, Hounnankpon
Ipomoea beninensis Akoègn., Lisowski & Sinsin (Convolvulaceae) is the only endemic plant known for Benin. To date, no data exist on its usages, distribution, abundance, and threats. An improved understanding of indigenous know- ledge and of local practices can provide insight into how the species could be sustainably conserved. We interviewed 114 local residents for collecting ethnobotanical and ethnoecological data in six sites known to host the species. Data were pro- cessed by calculation of descriptive statistics and variance and multivariate analyses. A total of twelve uses were reported. Among them, treatment of varicella (19%), malaria (18%) and fodder (17%) were the most recurrent. These mainly involve use of the species rootstock. Almost all respondents mentioned decline of the species in natural habitats. None of them was aware about the endemic status of the species. Consequently, negative practices toward the protection of I. beninensis were prevalent among local residents. Several conservation measures are proposed to ensure the longterm survival of I. beninensis.
Central and peripheral fields of view extract information of different quality and serve different roles during visual tasks. Past research has studied this dichotomy on-screen in conditions remote from natural situations where the scene would be omnidirectional and the entire field of view could be of use. In this study, we had participants looking for objects in simulated everyday rooms in virtual reality. By implementing a gaze-contingent protocol we masked central or peripheral vision (masks of 6 deg. of radius) during trials. We analyzed the impact of vision loss on visuo-motor variables related to fixation (duration) and saccades (amplitude and relative directions). An important novelty is that we segregated eye, head and the general gaze movements in our analyses. Additionally, we studied these measures after separating trials into two search phases (scanning and verification). Our results generally replicate past on-screen literature and teach about the role of eye and head movements. We showed that the scanning phase is dominated by short fixations and long saccades to explore, and the verification phase by long fixations and short saccades to analyze. One finding indicates that eye movements are strongly driven by visual stimulation, while head movements serve a higher behavioral goal of exploring omnidirectional scenes. Moreover, losing central vision has a smaller impact than reported on-screen, hinting at the importance of peripheral scene processing for visual search with an extended field of view. Our findings provide more information concerning how knowledge gathered on-screen may transfer to more natural conditions, and attest to the experimental usefulness of eye tracking in virtual reality.
Tigers are indisputably in danger of extinction due to habitat loss and demand for their parts. Tigers are extirpated in the wild from every country bar one in mainland East and Southeast Asia. Although consumption of tiger products is known to be established in China, less is known about demand for tiger products in Southeast Asia. In this study, we investigate tiger product demand in Vietnam, a major illegal wildlife consumer country. There has been little research into consumption, in particular the level of use, the products being consumed, variation in use of products between areas, and the motivations of consuming tiger products. Through a quantitative survey of 1120 individuals, we show that use of tiger products could be as high as ~11% of the sample in both urban centers of Vietnam, Hanoi and Ho Chi Minh City. Tiger bone glue is the predominant product used, for medicinal purposes. In Hanoi, it is generally purchased by the individual for self-use, while in Ho Chi Minh City it is generally purchased as a gift. In both cities, individuals were generally highly satisfied with the product, indicating entrenched belief in efficacy among consumers. Ultimately, our results show that tiger product use is relatively pervasive. We suggest that conservation organizations should focus on behavior change campaigns that are informed by the results here, and that are specific to each area and to the specific use of tiger product glue for medicine. By reducing demand, beleaguered tiger populations will have a greater chance of stabilization and eventual growth.
De Meyer, Sandra ; Bojkova, Denisa ; Cinatl, Jindrich ; Damme, Ellen van ; Buyck, Christophe ; Loock, Marnix van ; Woodfall, Brian ; Ciesek, Sandra
Objectives: Given the high need and the absence of specific antivirals for treatment of COVID-19 (the disease caused by severe acute respiratory syndrome-associated coronavirus-2 [SARS-CoV-2]), human immunodeficiency virus (HIV) protease inhibitors are being considered as therapeutic alternatives. Methods: Prezcobix/Rezolsta is a fixed-dose combination of 800 mg of the HIV protease inhibitor darunavir (DRV) and 150 mg cobicistat, a CYP3A4 inhibitor, which is indicated in combination with other antiretroviral agents for the treatment of HIV infection. There are currently no definitive data on the safety and efficacy of DRV/cobicistat for the treatment of COVID-19. The in vitro antiviral activity of darunavir against a clinical isolate from a patient infected with SARS-CoV-2 was assessed. Results: DRV showed no antiviral activity against SARS-CoV-2 at clinically relevant concentrations (EC50 > 100 μM). Remdesivir, used as a positive control, demonstrated potent antiviral activity (EC50 = 0.38 μM). Conclusions: Overall, the data do not support the use of DRV for the treatment of COVID-19.