Den Himmel Erden

In dieser Arbeit soll untersucht werden, welche theologischen Grundlagen in Dorothee Sölles Denken den Anstoß zu politischem Engagement bzw. politischer Praxis der Menschen geben. Dorothee Sölle hat Zeit ihres Lebens um eine Theologie gekämpft, die in einer Zeit nach Katastrophen wie Auschwitz weiterhin Bedeutung haben kann. Ebenso war die Frage nach Identität in postmodernen Zeiten Antrieb ihres Denkens. Ich bin der Ansicht, dass Sölles Denken eine gute Grundlage für eine heutige Spiritualität des politischen Handelns bietet, da sie die Suche nach der richtigen Praxis immer in Verbindung mit der menschlichen Frage nach Identität und Glück verbindet. Ziel der Arbeit ist es, die klassischen theologischen Topoi wie: Sünde, Gnade, Kreuz, Auferstehung, Reich Gottes, Schöpfung, Kirche u.a. auf ihren theologisch-politischen Konnex hin zu untersuchen. Dabei verfolge ich die These, dass Sölle politische Praxis als unumgängliche Glaubenspraxis sieht, ohne die christlicher Glaube nicht zu denken ist. Politische Praxis ist damit nicht ein Imperativ, der aus dem Glauben entsteht, sondern Teil des Glaubens selbst. Sie ist konsequenter Ausdruck von Liebe, die alle Menschen sowie die Schöpfung umfassen muss. Nur durch diese tätige Liebe können wir zu Identität und Glück finden. Dies hat Sölle auch in ihrem eigenen Leben wahrgemacht. Um diese Forderung auszuformulieren, bedient sich Sölle der Befreiungstheologie, der feministischen Theologie, dem historischen Materialismus u.a. In einem umfangreichen Schlusskapitel wird gezeigt, dass Sölle zentrale Themen angedacht hat, die auch heute in der Theologie, speziell aber in der feministischen Theologie, der Theologie der Befreiung und der neuen Politischen Theologie von Bedeutung sind. Damit soll Sölles Denken auch für eine Theologie heute zum Anknüpfungspunkt werden

Speaking up about patient safety concerns: view of nursing students.

BACKGROUND "Speaking up" is considered an important patient safety behaviour. The main idea is to voice patient safety concerns; however, several studies revealed that the organisational culture can be obstructive. In previous studies, we already identified barriers for doctors, nurses and medical students. In the current study, we explore how nursing students use "speaking up" during their internship in an academic teaching hospital. METHODS Between 2019 and 2020, 212 nursing students were invited to take part in the survey. The validated Speaking Up about Patient Safety Questionnaire (SUPS-Q) was used to assess speaking up behaviours in nursing students. The SUPS-Q consisted of three behaviour related scales (11 items), three culture related scales (11 items), a question regarding barriers to speak up as well as a clinical vignette assessing a hypothetical speaking up situation. RESULTS In total, 118 nursing students took part in the survey (response rate: 56%). Most of them noticed specific safety concerns, observed errors or rule violations. The vignette was seen as very realistic and harmful to the patient. However, the majority responded that they did not speak up and remained silent. They reported a rather discouraging environment and high levels of resignation towards speaking up. However, more advanced students were less likely to speak up than less advanced students (p = 0.027). Most relevant barriers were fear of negative reaction (64%), reaction not predictable (62%) and ineffectiveness (42%). CONCLUSIONS Survey results of nursing students imply that speaking-up behaviours and remaining silent are common behaviours and coexist in the same individual. The clinical vignette and barriers to speaking up revealed that a hierarchical system does not support speaking-up behaviours. Organizational development is needed to foster professional teamwork, support attentive listening, encourage critical thinking, and problem-solving skills

Regional and organ-level responses to local lung irradiation in sheep

Lung is a dose-limiting organ in radiotherapy. This may limit tumour control when effort is made in planning to limit the likelihood of radiation-induced lung injury (RILI). Understanding the factors that dictate susceptibility to radiation-induced pulmonary fibrosis will aid in the prevention and management of RILI, and may lead to more effective personalized radiotherapy treatment. As the interaction of regional and organ-level responses may shape the chronic consequences of RILI, we sought to characterise both aspects of the response in an ovine model. A defined volume of left pulmonary parenchyma was prescribed 5 fractions of 6 Gy within 14 days while the contralateral lung dose was constrained. Radiographic changes via computed tomography (CT) were documented to define differences in radio-exposed lung relative to non-exposed lung at d21, d63 and d171 (n = 2), and at d21, d147 and d227 (n = 2). Gross and histologic lung changes were evaluated in samples derived at necropsy examination to define the chronic pulmonary response to radiation. Irradiated lung demonstrated reduced radio-density and increased homogeneity as evidenced from texture based radiomic feature analysis, relative to the control lung. At necropsy, the radiation field was readily defined by pallor on the pleural surface, which was also evident on the cut surface of fixed lung specimens. The degree and homogeneity of pallor reflected the sparse presence of erythrocytes in alveolar septal capillaries of radiation-exposed lung. These changes contrasted with dilated and congested microvasculature in the contralateral control lung. Referencing data to measurements made in control lung volumes of sheep experiencing acute RILI indicated that interstitial collagen continues to deposit in the radio-exposed lung field. Overall lung vascularity increased during the chronic response, as evidenced by increased expression of endothelial cell marker (CD31); however, vascularity was consistently decreased in irradiated lung and was negatively correlated with lung collagen. Other organ-level responses included increased expression of alpha smooth muscle actin (ASMA), increased numbers of proliferating cells (Ki67 positive), and cells expressing the dendritic cell-lysosomal associated membrane protein (DC-LAMP) antigen. The chronic response to RILI in this model is effected at both the whole organ and local lung level. Whilst the long-term consequences of exposure to radiation involved the continued deposition of collagen in the radiation field, organ-level responses also included increased vascularization and increased expression of ASMA, Ki67 and DC-LAMP. Interrupting the interplay between these aspects may influence susceptibility to pulmonary fibrosis after radiotherapy. We advocate for the importance of large animal model systems in pursuing these opportunities to target local, organ-level and systemic mechanisms in parallel within the same subject over time

Distinct roles of nonmuscle myosin ii isoforms for establishing tension and elasticity during cell morphodynamics

Nonmuscle myosin II (NM II) is an integral part of essential cellular processes, including adhesion and migration. Mammalian cells express up to three isoforms termed NM IIA, B, and C. We used U2OS cells to create CRISPR/Cas9-based knockouts of all three isoforms and analyzed the phenotypes on homogenously coated surfaces, in collagen gels, and on micropatterned substrates. In contrast to homogenously coated surfaces, a structured environment supports a cellular phenotype with invaginated actin arcs even in the absence of NM IIA-induced contractility. A quantitative shape analysis of cells on micropatterns combined with a scale-bridging mathematical model reveals that NM IIA is essential to build up cellular tension during initial stages of force generation, while NM IIB is necessary to elastically stabilize NM IIA-generated tension. A dynamic cell stretch/release experiment in a three-dimensional scaffold confirms these conclusions and in addition reveals a novel role for NM IIC, namely the ability to establish tensional homeostasis

Production of biopharmaceuticals in an intensified perfusion process of HEK 293 cells

CHO cells are the workhorses of the biopharmaceutical field with many success stories. However human cell-based systems might bring important advantages. These can provide production systems resulting in proteins with more human-like posttranslational modifications and potentially alleviate the production of difficult-to-produce molecules. HEK 293 cells are well known and used today for the production of two biopharmaceuticals and for viral vectors. The purpose of the present study is to evaluate the potential of this system for its ability to produce biopharmaceuticals, benchmarking against CHO cells. We are currently exploring the possibility to secrete human proteins in CHO cells by systematically addressing all the human proteins naturally secreted in the human body. So far, we have covered around half of the human secretome (N = 3000) with an overall success rate around 65%. To address the need for a host capable of expressing difficult-to-produce proteins, different HEK 293 strains have been investigated for the production of 30 selected proteins in comparison with CHO cells, revealing a higher success rate in HEK 293 system. This expression has been studied in flask system and includes comparative transcriptomics analyses. To evaluate the potential of HEK 293 cells for the production of biopharmaceuticals, a high cell density perfusion process using Alternating Tangential Flow filtration has been developed for the production of EPO. In this process, the cells are stably maintained at a density of 80 to 100 x 106 cells/mL while the EPO cell specific productivity is comparable to low cell density (e.g. 20 x106 cells/ml) in perfusion mode. The cell metabolism is slowed down by lowering the temperature, allowing a reduction of the perfusion rate down to 1 reactor volume per day at this high cell concentration. This process has been developed in our new scale-down perfusion bioreactor of 200 mL working volume. In this system, the effect of shear stress on the HEK 293 cells resulting from their passage in the hollow fibre filter has been characterised by transcriptomics analysis helping to decipher why HEK 293 cells are more sensitive than CHO cells and a systematic feeding strategy for perfusion has been developed. The ability to express difficult-to-produce proteins and to achieve very high cell densities with productivity comparable to low density processes make HEK 293 cells an attractive system for the production of biopharmaceuticals which are challenging for CHO cells

A randomized double-blind placebo-controlled crossover trial of sodium nitrate in patients with stable angina INAS

In an aging western population, a significant number of patients continue to suffer from angina once all revascularization and optimal medical treatment options are exhausted. Under experimental conditions, oral supplementation with inorganic nitrate was shown to exhibit a blood pressure-lowering effect, and has also been shown to promote angiogenesis, improve endothelial dysfunction and mitochondrial efficiency in skeletal muscle. It is unknown whether similar changes occur in cardiac muscle. In the current study, we investigate whether oral sodium nitrate treatment will improve myocardial ischemia in patients with stable angina

Inorganic nitrate in angina study:A randomized double-blind placebo-controlled trial

Background--In this double-blind randomized placebo-controlled crossover trial, we investigated whether oral sodium nitrate, when added to existing background medication, reduces exertional ischemia in patients with angina. Methods and Results--Seventy patients with stable angina, positive electrocardiogram treadmill test, and either angiographic or functional test evidence of significant ischemic heart disease were randomized to receive oral treatment with either placebo or sodium nitrate (600 mg; 7 mmol) for 7 to 10 days, followed by a 2-week washout period before crossing over to the other treatment (n=34 placebo-nitrate, n=36 nitrate-placebo). At baseline and at the end of each treatment, patients underwent modified Bruce electrocardiogram treadmill test, modified Seattle Questionnaire, and subgroups were investigated with dobutamine stress, echocardiogram, and blood tests. The primary outcome was time to 1 mm ST depression on electrocardiogram treadmill test. Compared with placebo, inorganic nitrate treatment tended to increase the primary outcome exercise time to 1 mm ST segment depression (645.6 [603.1, 688.0] seconds versus 661.2 [6183, 704.0] seconds, P=0.10) and significantly increased total exercise time (744.4 [702.4, 786.4] seconds versus 760.9 [719.5, 802.2] seconds, P=0.04; mean [95% confidence interval]). Nitrate treatment robustly increased plasma nitrate (18.3 [15.2, 21.5] versus 297.6 [218.4, 376.8] μmol/L, P < 0.0001) and almost doubled circulating nitrite concentrations (346 [285, 405] versus 552 [398, 706] nmol/L, P=0.003; placebo versus nitrate treatment). Other secondary outcomes were not significantly altered by the intervention. Patients on antacid medication appeared to benefit less from nitrate supplementation. Conclusions--Sodium nitrate treatment may confer a modest exercise capacity benefit in patients with chronic angina who are taking other background medication

A genome-wide library of MADM mice for single-cell genetic mosaic analysis

Mosaic analysis with double markers (MADM) offers one approach to visualize and concomitantly manipulate genetically defined cells in mice with single-cell resolution. MADM applications include the analysis of lineage, single-cell morphology and physiology, genomic imprinting phenotypes, and dissection of cell-autonomous gene functions in vivo in health and disease. Yet, MADM can only be applied to 96% of the entire mouse genome can now be subjected to single-cell genetic mosaic analysis. Beyond a proof of principle, we apply our MADM library to systematically trace sister chromatid segregation in distinct mitotic cell lineages. We find striking chromosome-specific biases in segregation patterns, reflecting a putative mechanism for the asymmetric segregation of genetic determinants in somatic stem cell division

Inorganic nitrate and nitrite supplementation fails to improve skeletal muscle mitochondrial efficiency in mice and humans

Supported by Medical Research Council program grant MRC G1001340 (to M Madhani, M Feelisch, and MP Frenneaux). We thank Lesley Cheyne for their contributions to the present study. The authors’ responsibilities were as follows—VSV, M Madhani, JDH, MF, DD, MPF: designed the research; MN, NEKP, KS, BLL, M Minnion, BOF, DV, DC-T, PGC: conducted the research; DV: provided essential materials; MN, NEKP, M Minnion, BOF, DC-T, MF, PGC: analyzed the data; MN, NEKP, PGC, MPF: wrote the paper; MPF: had primary responsibility for the final manuscript; and all authors: read and approved the final manuscript. None of the authors reported a conflict of interest related to the study.Peer reviewedPublisher PD