"Museum Ramboux"

Die Sammlung ist in der Forschung bislang nur ausschnitthaft und vor allem in Bezug auf die Geschichte der abgebildeten Kunstwerke untersucht worden. Angesichts der in diesem Rahmen festgestellten, herausragenden Bedeutung der Blätter analysiert und katalogisiert die Arbeit im Vergleich mit den Vorlagen in ihrem dokumentierten und heutigen Zustand erstmals die gesamte Sammlung und erfüllt damit ein Desiderat der Forschung. Um die Kopien angemessen zu interpretieren geht sie darüber hinaus der Fragen nach, welche Ursachen zu der Erstellung und Zusammensetzung der Sammlung führten, die Qualität der Wiedergabe der Vorlagen bestimmten und welche Funktion die Sammlung hatte. Die Kopien entstanden aus der erlebten Notwendigkeit heraus, Bildquellen für die zeitgenössische Kunstrezeption sowohl durch Künstler als auch Kunsthistoriker zu sammeln und über die Zerstörung dieser Kunstwerke hinaus für diese zu bewahren. Als selten konkreter Ausdruck der nazarenischen Rezeption historischer Kunst spiegelt sie in ihrer Zusammensetzung das praktische Interesse der Nazarener, die christliche Kunst von ihren Wurzeln her zu begreifen und zu erneuern. Die Sammlung stellt damit sowohl eine Art „nazarenischer Vorbilderkanon“ als auch eine „Kunstgeschichte in Kopien“ dar. Diese zeigt sich zwar konkret beeinflusst von zeitgenössischen kunsthistorischen Schriften, erweitert und aktualisiert die Geschichte der christlichen Kunst Italiens aber durch eine Reihe bis dato noch relativ unbekannter Kunstwerke, die Ramboux mitunter zufällig entdeckte. Die romantisch-nazarenische Kunstbetrachtung öffnete den Blick auch für bislang unbeachtete Details: Die Aufwertung, die das formal-stilistische Erscheinungsbild der historischen Kunstwerke ist auf den Blättern ablesbar – sofern man die auf allen Blättern erkennbare, gleichförmige nazarenische und mediale Interpretation ausblendet. Seit 1841 war die Sammlung in der Königlichen Kunstakademie Düsseldorf als „Museum Ramboux“ allen Interessierten zugänglich, bildete als Teil der akademischen Lehrsammlung bis 1921 geschätzte Grundlage für die Lehre der christlichen Kunstgeschichte und war historische Quellensammlung für Historienmaler. Sie hinterließ – direkt oder indirekt – mehr oder weniger deutliche Spuren in der Malerei des 19. Jahrhunderts, wie im Rahmen der Planungen für die Ausmalung der Remagener Apollinariskirche. Die fehlende druckgrafische Vervielfältigung sowie organisatorische Umstände verhinderten weitgehend eine kunsthistorische Rezeption, obwohl das Desiderat nach Abbildungen besonders frühmittelalterlicher Gemälde noch bis weit in die zweite Hälfte des 19. Jahrhunderts bestand. Bei der Untersuchung der einzelnen Blätter wurde deutlich, dass die Aquarelle in vielen Fällen die frühesten detaillierten Farbabbildungen der Malereien darstellen. Doch sind es keine „fotografischen“ Wiedergaben in unserem Sinne. Ramboux befand sich in dem für seine Zeit üblichen Zwiespalt, die Forderungen der Ästhetik und dem Interesse am ursprünglichen Erscheinungsbild des Kunstwerks mit den Forderungen der dokumentarischen Abbildung überein zu bringen. Dieses Nebeneinander auf einem Blatt macht die Hauptproblematik bei der Beurteilung der Kopien hinsichtlich ihres Dokumentarwerts aus und führte in der Forschung mitunter zu Fehlinterpretationen der Wiedergaben, die nun teilweise korrigiert werden konnten. Im Rahmen der Möglichkeiten ergab sich, dass bewusste Veränderungen beim Kopieren nur in sehr begrenzten Ausnahmefällen vorgenommen wurden und Ergänzungen höchstwahrscheinlich auf erhaltenen Darstellungsresten fußen. So kann der begrenzten Anzahl von Blättern, die der kunsthistorischen Forschung bislang bekannt ist und der eine große Bedeutung für die Erforschung der abgebildeten Kunstwerke zugebilligt wird, nun eine lange Reihe weiterer Blätter hinzugefügt werden, die u.a. wichtige Erkenntnisse über das Erscheinungsbild heute überrestau-rierter, beschädigter oder gar zerstörter Kunstwerke gibt. Auch wenn in anderen Fällen nicht eindeutig beantwortet werden konnte, ob Ramboux Teile ergänzend oder wahrheitsgemäß abgebildet hat, spricht angesichts der Ergebnisse bei der Analyse anderer Kopien der Sammlung vieles dafür, diese Abweichungen nicht als freie Erfindungen Ramboux’ abzutun, sondern als konkrete Hinweise auf bislang nicht dokumentierte Eingriffe an den Vorlagen zu interpretieren.The collection has only partly been investigated especially regarding what kind of significance the copies have for the history of the works of art they depict. Considering both the copies’ exceptional relevance which has been stated so far and the existing research gap, the present dissertation analyses and catalogues for the first time the complete collection by comparing the copies with the originals in their documented and present appearance. Essential for interpretating the copies appropriately, the dissertation investigates why and under which circumstances the collection was created, which aspects the quality of the copies was determined by, and which function the collection had. The copies were created to collect and to preserve pictoral sources for art reception by artists as well as art historians. As a rare concrete expression of Nazarene reception of historic art, the collection structure reflects the practical interest the Nazarenes had in understanding and reviving Christian art from its roots. In this respect, the collection represents a kind of a „canon of Nazarene reference works of art“ as well as an „art history in copies“. This art history is partly influenced by actual art historical publications but comprises on the other hand works of art which were widely (visually) unknown and accidentially discovered by Ramboux. The Romantic-Nazarene art perception also opened the eyes for details which had not been perceived so far: the upvaluation of stylistic features left its mark on the sheets – apart from the uniform Nazarene and technical interpretations. In 1841 the collection was included in the academic teaching collection of the Düsseldorf Art Academy. Partly displayed for public in the academy building, the collection was soon well known under the name „Museum Ramboux“ and served as illustrative material for art history lessons as well as source for history painters. It left – directly or indirectly – its marks on 19th century painting, as for instance on the monumental mural program for the Remagen church St. Apollinaris. Although illustrations after especially early medieval paintings were still sought-after in the second half of the 19th century, the sheets were only rarely used by art historians because of organzising conditions and the fact that the sheets were not published in reproduction prints. Many watercolours are the earliest detailed (colour) illustrations of the paintings to date, thus they are no „photographic“ images of the originals in our sense – Ramboux was determined by the conflict between both aesthetic demands and the interest in the original appearance of the work of art as well as the demands of documenting the actual appearance of the work of art. Many copies are characterised by this coincidence which make interpretations difficult and caused in some cases wrong interpretations which could now be partly corrected. Within the realms of possibilities it turned out that only a very few copies contain deliberate modifications as additions were very likely based on remains of the original depiction. So there is a large number of sheets to be added to the few amount of sheets already known, containing important indications of the appearance paintings had before they were (over-)restored, damaged or even destroyed. In most cases, however, the more or less significant differences the copies show in comparison with the originals in both their documented and present appearance could not clearly be identified either as modifications by Ramboux or as authentic reproductions of the appearance the originals had back then. Yet the results of the analysis of most of the sheets do suggest that these differences should not automatically be considered as fictional inventions by Ramboux but may be understood as indications of features which are not preserved and have not been documented

A tissue-based approach to selection of reference genes for quantitative real-time PCR in a sheep osteoporosis model

Background: In order to better understand the multifactorial nature of osteoporosis, animal models are utilized and compared to healthy controls. Female sheep are well established as a model for osteoporosis induced by ovariectomy, calcium and vitamin D low diet, application of steroids, or a combination of these treatments. Transcriptional studies can be performed by applying quantitative real time PCR (RT-qPCR). RT-qPCR estimates mRNA-levels of target genes in relation to reference genes. A chosen set of reference genes should not show variation under experimental conditions. Currently, no standard reference genes are accepted for all tissue types and experimental conditions. Studies examining reference genes for sheep are rare and only one study described stable reference in mandibular bone. However, this type of bone differs from trabecular bone where most osteoporotic fractures occur. The present study aimed at identifying a set of reference genes for relative quantification of transcriptional activity of ovine spine bone and ovine in vitro differentiated mesenchymal stromal cells (MSC) for reliable comparability. Methods: Twelve candidate reference genes belonging to different functional classes were selected and their expression was measured from cultured ovMSCs (n = 18) and ovine bone samples (n = 16), respectively. RefFinder was used to rank the candidate genes. Results: We identified B2M, GAPDH, RPL19 and YWHAZ as the best combination of reference genes for normalization of RT-qPCR results for transcriptional analyses of these ovine samples. Conclusion: This study demonstrates the importance of applying a set of reference genes for RT-qPCR analysis in sheep. Based on our data we recommend using four identified reference genes for relative quantification of gene expression studies in ovine bone or for in vitro experiments with osteogenically differentiated ovine MSCs

It’s About Time: The Circadian Network as Time-Keeper for Cognitive Functioning, Locomotor Activity and Mental Health

A variety of organisms including mammals have evolved a 24h, self-sustained timekeeping machinery known as the circadian clock (biological clock), which enables to anticipate, respond, and adapt to environmental influences such as the daily light and dark cycles. Proper functioning of the clock plays a pivotal role in the temporal regulation of a wide range of cellular, physiological, and behavioural processes. The disruption of circadian rhythms was found to be associated with the onset and progression of several pathologies including sleep and mental disorders, cancer, and neurodegeneration. Thus, the role of the circadian clock in health and disease, and its clinical applications, have gained increasing attention, but the exact mechanisms underlying temporal regulation require further work and the integration of evidence from different research fields. In this review, we address the current knowledge regarding the functioning of molecular circuits as generators of circadian rhythms and the essential role of circadian synchrony in a healthy organism. In particular, we discuss the role of circadian regulation in the context of behaviour and cognitive functioning, delineating how the loss of this tight interplay is linked to pathological development with a focus on mental disorders and neurodegeneration. We further describe emerging new aspects on the link between the circadian clock and physical exercise-induced cognitive functioning, and its current usage as circadian activator with a positive impact in delaying the progression of certain pathologies including neurodegeneration and brain-related disorders. Finally, we discuss recent epidemiological evidence pointing to an important role of the circadian clock in mental health.Peer Reviewe

Evidence-based guideline of the German Nutrition Society: fat intake and prevention of selected nutrition-related diseases

As nutrition-related chronic diseases have become more and more frequent, the importance of dietary prevention has also increased. Dietary fat plays a major role in human nutrition, and modification of fat and/or fatty acid intake could have a preventive potential. The aim of the guideline of the German Nutrition Society (DGE) was to systematically evaluate the evidence for the prevention of the widespread diseases obesity, type 2 diabetes mellitus, dyslipoproteinaemia, hypertension, metabolic syndrome, coronary heart disease (CHD), stroke, and cancer through the intake of fat or fatty acids. The main results can be summarized as follows: it was concluded with convincing evidence that a reduced intake of total and saturated fat as well as a larger intake of polyunsaturated fatty acids (PUFA) at the expense of saturated fatty acids (SFA) reduces the concentration of total and low-density lipoprotein cholesterol in plasma. Furthermore, there is convincing evidence that a high intake of trans fatty acids increases risk of dyslipoproteinaemia and that a high intake of long-chain polyunsaturated n-3 fatty acids reduces the triglyceride concentration in plasma. A high fat intake increases the risk of obesity with probable evidence when total energy intake is not controlled for (ad libitum diet). When energy intake is controlled for, there is probable evidence for no association between fat intake and risk of obesity. A larger intake of PUFA at the expense of SFA reduces risk of CHD with probable evidence. Furthermore, there is probable evidence that a high intake of long-chain polyunsaturated n-3 fatty acids reduces risk of hypertension and CHD. With probable evidence, a high trans fatty acid intake increases risk of CHD. The practical consequences for current dietary recommendations are described at the end of this article

An optimized whole blood assay measuring expression and activity of NLRP3, NLRC4 and AIM2 inflammasomes

The proinflammatory protease caspase-1 plays pivotal roles in central pathways of innate immunity, thereby contributing to pathogen clearance. Beside its physiological role, dysregulated activity of caspase-1 is known to contribute to an increasing number of diseases. In this study, we optimized and validated a low-volume human whole blood assay facilitating the measurement of caspase-1 activation and inflammasome-related gene expression upon stimulation of the NLRP3, NLRC4 or AIM2 inflammasome. Using the NLRP3 inflammasome specific inhibitor MCC950, we were able to measure the activity of canonical or alternative NLRP3 pathways, AIM2 and NLRC4 inflammasomes in whole blood. Based on our data we assume a superposition of NLRP3 and NLRC4 inflammasome activities in human whole blood following stimulation with S. typhimurium. The optimized whole blood assay may be suitable for diagnostic and research purposes for pediatric patients who can only donate small amounts of blood

Regular breakfast consumption and type 2 diabetes risk markers in 9- to 10-year-old children in the child heart and health study in England (CHASE): a cross-sectional analysis.

BACKGROUND: Regular breakfast consumption may protect against type 2 diabetes risk in adults but little is known about its influence on type 2 diabetes risk markers in children. We investigated the associations between breakfast consumption (frequency and content) and risk markers for type 2 diabetes (particularly insulin resistance and glycaemia) and cardiovascular disease in children. METHODS AND FINDINGS: We conducted a cross-sectional study of 4,116 UK primary school children aged 9-10 years. Participants provided information on breakfast frequency, had measurements of body composition, and gave fasting blood samples for measurements of blood lipids, insulin, glucose, and glycated haemoglobin (HbA1c). A subgroup of 2,004 children also completed a 24-hour dietary recall. Among 4,116 children studied, 3,056 (74%) ate breakfast daily, 450 (11%) most days, 372 (9%) some days, and 238 (6%) not usually. Graded associations between breakfast frequency and risk markers were observed; children who reported not usually having breakfast had higher fasting insulin (percent difference 26.4%, 95% CI 16.6%-37.0%), insulin resistance (percent difference 26.7%, 95% CI 17.0%-37.2%), HbA1c (percent difference 1.2%, 95% CI 0.4%-2.0%), glucose (percent difference 1.0%, 95% CI 0.0%-2.0%), and urate (percent difference 6%, 95% CI 3%-10%) than those who reported having breakfast daily; these differences were little affected by adjustment for adiposity, socioeconomic status, and physical activity levels. When the higher levels of triglyceride, systolic blood pressure, and C-reactive protein for those who usually did not eat breakfast relative to those who ate breakfast daily were adjusted for adiposity, the differences were no longer significant. Children eating a high fibre cereal breakfast had lower insulin resistance than those eating other breakfast types (p for heterogeneity <0.01). Differences in nutrient intakes between breakfast frequency groups did not account for the differences in type 2 diabetes markers. CONCLUSIONS: Children who ate breakfast daily, particularly a high fibre cereal breakfast, had a more favourable type 2 diabetes risk profile. Trials are needed to quantify the protective effect of breakfast on emerging type 2 diabetes risk. Please see later in the article for the Editors' Summary

ATP synthase deficiency due to TMEM70 mutation leads to ultrastructural mitochondrial degeneration and is amenable to treatment.

TMEM70 is involved in the biogenesis of mitochondrial ATP synthase and mutations in the TMEM70 gene impair oxidative phosphorylation. Herein, we report on pathology and treatment of ATP synthase deficiency in four siblings. A consanguineous family of Roma (Gipsy) ethnic origin gave birth to 6 children of which 4 were affected presenting with dysmorphic features, failure to thrive, cardiomyopathy, metabolic crises, and 3-methylglutaconic aciduria as clinical symptoms. Genetic testing revealed a homozygous mutation (c.317-2A>G) in the TMEM70 gene. While light microscopy was unremarkable, ultrastructural investigation of muscle tissue revealed accumulation of swollen degenerated mitochondria with lipid crystalloid inclusions, cristae aggregation, and exocytosis of mitochondrial material. Biochemical analysis of mitochondrial complexes showed an almost complete ATP synthase deficiency. Despite harbouring the same mutation, the clinical outcome in the four siblings was different. Two children died within 60 h after birth; the other two had recurrent life-threatening metabolic crises but were successfully managed with supplementation of anaplerotic amino acids, lipids, and symptomatic treatment during metabolic crisis. In summary, TMEM70 mutations can cause distinct ultrastructural mitochondrial degeneration and almost complete deficiency of ATP synthase but are still amenable to treatment

Incidence of anogenital warts in Germany: a population-based cohort study

<p>Abstract</p> <p>Background</p> <p>Human papilloma virus (HPV) types 6 and 11 account for 90 percent of anogenital warts (AGW). Assessment of a potential reduction of the incidence of AGW following introduction of HPV vaccines requires population-based incidence rates. The aim of this study was to estimate incidence rates of AGW in Germany, stratified by age, sex, and region. Additionally, the medical practitioner (gynaecologist, dermatologist, urologist etc.) who made the initial diagnosis of AGW was assessed.</p> <p>Methods</p> <p>Retrospective cohort study in a population aged 10 to 79 years in a population-based healthcare insurance database. The database included more than 14 million insurance members from all over Germany during the years 2004-2006. A case of AGW was considered incident if a disease-free period of twelve months preceded the diagnosis. To assess regional variation, analyses were performed by federal state.</p> <p>Results</p> <p>The estimated incidence rate was 169.5/100,000 person-years for the German population aged 10 to 79 years. Most cases occurred in the 15 to 40 years age group. The incidence rate was higher and showed a peak at younger ages in females than in males. The highest incidence rates for both sexes were observed in the city-states Berlin, Hamburg and Bremen. In females, initial diagnosis of AGW was most frequently made by a gynaecologist (71.7%), whereas in males, AGW were most frequently diagnosed by a dermatologist (44.8%) or urologist (25.1%).</p> <p>Conclusions</p> <p>Incidence of AGW in Germany is comparable with findings for other countries. As expected, most cases occurred in the younger age groups. The frequency of diagnoses of AGW differs between sexes and women and men receive treatment by doctors of different specialties.</p

Efficacy and safety of immune checkpoint inhibitor rechallenge in individuals with hepatocellular carcinoma

BACKGROUND & AIMS: We investigated the efficacy and safety of immune checkpoint inhibitor (ICI) rechallenge in patients with hepatocellular carcinoma (HCC) who received ICI-based therapies in a previous systemic line. METHODS: In this international, retrospective multicenter study, patients with HCC who received at least two lines of ICI-based therapies (ICI-1, ICI-2) at 14 institutions were eligible. The main outcomes included best overall response and treatment-related adverse events. RESULTS: Of 994 ICI-treated patients screened, a total of 58 patients (male, n = 41; 71%) with a mean age of 65.0±9.0 years were included. Median systemic treatment lines of ICI-1 and ICI-2 were 1 (range, 1-4) and 3 (range, 2-9), respectively. ICI-based therapies used at ICI-1 and ICI-2 included ICI alone (ICI-1, n = 26, 45%; ICI-2, n = 4, 7%), dual ICI regimens (n = 1, 2%; n = 12, 21%), or ICI combined with targeted therapies/anti-VEGF (n = 31, 53%; n = 42, 72%). Most patients discontinued ICI-1 due to progression (n = 52, 90%). Objective response rate was 22% at ICI-1 and 26% at ICI-2. Responses at ICI-2 were also seen in patients who had progressive disease as best overall response at ICI-1 (n = 11/21; 52%). Median time-to-progression at ICI-1 and ICI-2 was 5.4 (95% CI 3.0-7.7) months and 5.2 (95% CI 3.3-7.0) months, respectively. Treatment-related adverse events of grade 3-4 at ICI-1 and ICI-2 were observed in 9 (16%) and 10 (17%) patients, respectively. CONCLUSIONS: ICI rechallenge was safe and resulted in a treatment benefit in a meaningful proportion of patients with HCC. These data provide a rationale for investigating ICI-based regimens in patients who progressed on first-line immunotherapy in prospective trials. IMPACT AND IMPLICATIONS: Therapeutic sequencing after first-line immune checkpoint inhibitor (ICI)-based therapy for advanced hepatocellular carcinoma (HCC) remains a challenge as no available second-line treatment options have been studied in immunotherapy-pretreated patients. Particularly, the role of ICI rechallenge in patients with HCC is unclear, as data from prospective trials are lacking. We investigated the efficacy and safety of ICI-based regimens in patients with HCC pretreated with immunotherapy in a retrospective, international, multicenter study. Our data provide the rationale for prospective trials investigating the role of ICI-based regimens in patients who have progressed on first-line immunotherapy