Der Einfluss von Omega-3-Fettsäuren auf die Ausbreitung der Entzündungsreaktion in der Cerulein-induzierten akuten Pankreatitis im Mausmodell

Die akute Pankreatitis ist eine ernst zu nehmende Erkrankung mit hoher Morbidität und Mortalität, die bisher rein symptomatisch behandelt wird. Eine entzündungshemmende Therapie existiert bislang nicht. Für die Zufuhr von Omega-3 Fettsäuren (n-3 Fettsäuren) konnten im Rahmen unterschiedlicher Erkrankungen (z. B. Rheumatoide Arthritis, chronisch entzündliche Darmerkrankungen, Hepatitis) entzündungshemmende Wirkungen nachgewiesen werden. Das Ziel dieser Arbeit war, den Einfluss eines zugunsten von n-3 Fettsäuren veränderten Lipidprofils im Gewebe auf die Entzündungsausbreitung einer akuten Pankreatitis unter kontrollierten Bedingungen zu untersuchen. Dafür wurde erstmalig das Fat-1 Mausmodell genutzt, das durch endogen erhöhte n-3 Fettsäuren im Gewebe der Mäuse gekennzeichnet ist. Die akute Pankreatitis wurde durch das gut steuerbare Überstimulationsmodell mit Cerulein induziert. Die Ausprägung der Erkrankung wurde anschließend auf histopathologischer und molekularer Ebene verglichen. Es konnte gezeigt werden, dass Fat-1 Mäuse geringere Gewebeschäden im Rahmen einer akuten Pankreatitis ausbilden, verglichen mit Wildtyp Mäusen. Zusätzlich war das pro-inflammatorisch wirkende Zytokin IL-1β signifikant reduziert im Pankreasgewebe der transgenen Tiere. Als Hinweis auf eine Reduktion der systemischen Entzündungsausbreitung waren das IL-6 im Serum der Fat-1 Mäuse sowie die Migration von neutrophilen Granulozyten in das Lungengewebe dieser Tiere signifikant reduziert. Die Arbeit belegt eine Reduktion der Gewebeschädigung und der systemischen Entzündungsausbreitung bei der akuten Pankreatitis durch ein verändertes n-3 Fettsäureprofil in dem Gewebe der Fat-1 Mäuse. Insbesondere scheint die Zytokinproduktion dadurch beeinflusst zu werden. Diese Beobachtungen könnten Hinweise auf eine mögliche Behandlung oder Prävention der akuten Pankreatitis liefernAcute Pancreatitis is a severe debilitating disease with high morbidity and significant mortality. Treatment is mostly supportive, and until now there are no clinically useful strategies for anti-inflammatory therapy. Although omega-3 polyunsaturated fatty acids (n-3 PUFA) are known to have anti-inflammatory effects, the utility of these fatty acids in the alleviation of acute pancreatitis remained to be investigated. The aim of this study was to examine the effect of n-3 PUFA on acute pancreatitis in a well-controlled experimental system. Therefore we used the fat-1 transgenic mouse model with endogenously increased tissue levels of n-3 PUFA and their wild-type littermates to examine their effect on cerulein-induced acute pancreatitis. Disease activity and inflammatory status was assessed by histology and biochemical methods. There was significantly lower pancreatic tissue necrosis, accompanied by a significantly reduced IL-1β level in the pancreatic tissue of the fat-1 mice, both representing an alleviation of the local damage. As evidence for a reduction of systemic inflammation there were reduced levels of plasma IL-6 as well as reduced neutrophil infiltration in the lung of the fat-1 mice. Our data provide evidence for a reduction of pancreatic tissue damage and systemic inflammation by increasing the tissue content of omega-3 polyunsaturated fatty acids. These results suggest a therapeutic potential for n-3 PUFA supplementation for the reduction of acute pancreatitis

Curve classes on conic bundle threefolds and applications to rationality

We undertake a study of conic bundle threefolds $\pi\colon X\to W$ over geometrically rational surfaces whose associated discriminant covers $\tilde{\Delta}\to\Delta\subset W$ are smooth and geometrically irreducible. First, we determine the structure of the group $\mathrm{CH}^2 X_{\overline{k}}$ of rational equivalence classes of curves. Precisely, we construct a Galois-equivariant group homomorphism from $\mathrm{CH}^2X_{\overline{k}}$ to a group scheme associated to the discriminant cover $\tilde{\Delta}\to \Delta$ of $X$. The target group scheme is a generalization of the Prym variety of $\tilde{\Delta}\to\Delta$ and so our result can be viewed as a generalization of Beauville's result that the algebraically trivial curve classes on $X_{\overline{k}}$ are parametrized by the Prym variety. Next, we use our structural result on curve classes to study rationality obstructions, in particular the refined intermediate Jacobian torsor (IJT) obstruction recently introduced by Hassett--Tschinkel and Benoist--Wittenberg. We show that for conic bundle threefolds there is no strongest (known) rationality obstruction. Precisely, we construct a geometrically rational irrational conic bundle threefold where the IJT obstruction cannot witness irrationality (irrationality is detected through the real topology) and a geometrically rational irrational conic bundle threefold where all classical rationality obstructions vanish and the IJT obstruction is needed to prove irrationality.Comment: 28 pages. Comments welcome! v2: Updated introductio

University Libraries and the Open Research Knowledge Graph

The transfer of knowledge has not changed fundamentally for many hundreds of years: It is usually document-based - formerly printed on paper as a classic essay and nowadays as PDF. With around 2.5 million new research contributions every year, researchers drown in a flood of pseudo-digitized PDF publications. As a result research is seriously weakened. In this article, we argue for representing scholarly contributions in a structured and semantic way as a knowledge graph. The advantage is that information represented in a knowledge graph is readable by machines and humans. As an example, we give an overview on the Open Research Knowledge Graph (ORKG), a service implementing this approach. For creating the knowledge graph representation, we rely on a mixture of manual (crowd/expert sourcing) and (semi-)automated techniques. Only with such a combination of human and machine intelligence, we can achieve the required quality of the representation to allow for novel exploration and assistance services for researchers. As a result, a scholarly knowledge graph such as the ORKG can be used to give a condensed overview on the state-of-the-art addressing a particular research quest, for example as a tabular comparison of contributions according to various characteristics of the approaches. Further possible intuitive access interfaces to such scholarly knowledge graphs include domain-specific (chart) visualizations or answering of natural language questions

4D Biofabrication of fibrous artificial nerve graft for neuron regeneration

In this paper, we describe the application of the 4D biofabrication approach for the fabrication of artificial nerve graft. Bilayer scaffolds consisting of uniaxially aligned polycaprolactone-poly(glycerol sebacate) (PCL-PGS) and randomly aligned methacrylated hyaluronic acid (HA-MA) fibers were fabricated using electrospinning and further used for the culture of PC-12 neuron cells. Tubular structures form instantly after immersion of fibrous bilayer in an aqueous buffer and the diameter of obtained tubes can be controlled by changing bilayer parameters such as the thickness of each layer, overall bilayer thickness, and medium counterion concentration. Designed scaffolds showed a self-folded scroll-like structure with high stability after four weeks of real-time degradation. The significance of this research is in the fabrication of tuneable tubular nerve guide conduits that can simplify the current existing clinical treatment of neural injuries. © 2020 The Author(s). Published by IOP Publishing Ltd

Outcome of Communication Training in Veterinary Studies: Influence on the Perception of the Relevance of Veterinary Competencies and Self-Assessment of Communication Skills

Since communication skills contribute significantly to professional success among veterinarians, there is a particular focus on developing communication classes in veterinary curricula. At Freie Universität Berlin, an e-learning course covering the basics of communication and a practical communication course based on role plays with and without simulation persons have been established. The outcome of these communication courses on the assessment of the relevance of several veterinary competencies and on the self-assessment of communication skills using the SE-12 questionnaire was investigated. For this purpose, students were surveyed before and after the e-learning course as well as before and after the practical course. Veterinarians were also surveyed on the relevance of veterinary competencies. The relevance of communicative competencies for professional success was rated significantly higher by the students after completing the practical course than by the other students and the veterinarians. Self-assessment of communication skills showed little increase after the e-learning course, but a significant increase after the practical course. Thus, an effective outcome of the communication classes was observed mainly after the practical course. However, the effect of the e-learning course cannot be ruled out since the students participating in the practical course have also completed the e-learning course beforehand

Integration and potential of teaching communication skills in the study of veterinary medicine in Germany

Goal: Presentation of the current range of courses regarding communication at the five German educational institutions for veterinary medicine. In addition to learning objectives and individual solutions, possible potential for future developments are presented. Methods: Interviews with communication educators at the five German education institutions and subsequent synopsis. Results: To date, there are no binding education guidelines regarding communication in veterinary medicine. Nevertheless, communication education has been introduced at all five education institutions, albeit depth and formats vary considerably. The learning objectives are largely consistent and based on the recommendations for day-one-skills made by the European Association of Establishments for Veterinary Education. Communication is not recognized as a fully-fledged subject in the curricula of any of the education institutions. All education institutions clearly fall short of teaching the recommended 150 lecture hours. Conclusion: To ensure communication skills in veterinary medicine graduates, binding education guidelines should be agreed upon. Communication education should be integrated into all veterinary curricula as a fully-fledged subject with longitudinally increasing depth

Teaching small animal reproduction via virtual patients

Virtual patients have become an interesting alternative in medical education. Due to increasing demands regarding theoretical and clinical teaching and to improve an interdisciplinary approach, a new blended learning concept including virtual patients was developed and implemented in the veterinary curriculum of the Freie Universität Berlin. In the presented project, three virtual patients from the field of canine reproduction were developed. They focus on pregnancy diagnosis with suspected luteal insufficiency, pyometra and benign prostatic hyperplasia, respectively. The results of an evaluation by veterinary students of the 7th semester showed a high acceptance of virtual patients in a blended learning reproduction module in the interdisciplinary lectures. Students especially preferred videos, such as video lectures, hands‐on videos and animations as well as a glossary for background information, to successfully and autonomously work on a virtual case. The content covered by the new modules that were developed in the context of this project is part of a spiral curriculum; they will be revised and enhanced during the clinical year

Korruption: ein ungerechtfertigter Eingriff in internationale Menschenrechte? Chancen und Grenzen einer opferbezogenen Korruptionsperspektive

<p><b>Daily carbohydrate (A) and sugar (B) intake by groups and subgroups.</b> Carbohydrate (A) and sugar intake (B) as illustrated in percent. The boxes cover the first quartile on the bottom and the third quartile on the top. Whiskers reach from the minimum to the maximum value excluding outliers (illustrated by dots). Shift-working group and shift-working nursing-staff subgroup cover identical cohorts. NG, non-shift-working group; SG, shift-working group; SN, shift-working nursing-staff subgroup; NO, non-shift-working office-staff subgroup; NN, non-shift-working nursing-staff subgroup *p<0.05.</p

Neural origins of human sickness in interoceptive responses to inflammation

BACKGROUND: Inflammation is associated with psychological, emotional, and behavioral disturbance, known as sickness behavior. Inflammatory cytokines are implicated in coordinating this central motivational reorientation accompanying peripheral immunologic responses to pathogens. Studies in rodents suggest an afferent interoceptive neural mechanism, although comparable data in humans are lacking. METHODS: In a double-blind, randomized crossover study, 16 healthy male volunteers received typhoid vaccination or saline (placebo) injection in two experimental sessions. Profile of Mood State questionnaires were completed at baseline and at 2 and 3 hours. Two hours after injection, participants performed a high-demand color word Stroop task during functional magnetic resonance imaging. Blood samples were performed at baseline and immediately after scanning. RESULTS: Typhoid but not placebo injection produced a robust inflammatory response indexed by increased circulating interleukin-6 accompanied by a significant increase in fatigue, confusion, and impaired concentration at 3 hours. Performance of the Stroop task under inflammation activated brain regions encoding representations of internal bodily state. Spatial and temporal characteristics of this response are consistent with interoceptive information flow via afferent autonomic fibers. During performance of this task, activity within interoceptive brain regions also predicted individual differences in inflammation-associated but not placebo-associated fatigue and confusion. Maintenance of cognitive performance, despite inflammation-associated fatigue, led to recruitment of additional prefrontal cortical regions. CONCLUSIONS: These findings suggest that peripheral infection selectively influences central nervous system function to generate core symptoms of sickness and reorient basic motivational states. PMID:19409533[PubMed - indexed for MEDLINE] PMCID: PMC2885492Free PMC Articl

Relevance of Minor Neuropsychological Deficits in Patients With Subjective Cognitive Decline

peer reviewed[en] BACKGROUND AND OBJECTIVES: To determine the relevance of minor neuropsychological deficits (MNPD) in patients with subjective cognitive decline (SCD) with regard to CSF levels of Alzheimer disease (AD) biomarkers, cognitive decline, and clinical progression to mild cognitive impairment (MCI). METHODS: This study included patients with clinical SCD and SCD-free, healthy control (HC) participants with available baseline CSF and/or longitudinal cognitive data from the observational DZNE Longitudinal Cognitive Impairment and Dementia study. We defined MNPD as a performance of at least 0.5SD below the mean on a demographically adjusted total score derived from the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological assessment battery. We compared SCD patients with MNPD and those without MNPD with regard to CSF amyloid-β (Aβ)42/Aβ40, phosphorylated tau (p-tau181), total tau and Aβ42/p-tau181 levels, longitudinal cognitive composite trajectories, and risk of clinical progression to incident MCI (follow-up M ± SD: 40.6 ± 23.7 months). In addition, we explored group differences between SCD and HC in those without MNPD. RESULTS: In our sample (N = 672, mean age: 70.7 ± 5.9 years, 50% female), SCD patients with MNPD (n = 55, 12.5% of SCD group) showed significantly more abnormal CSF biomarker levels, increased cognitive decline, and a higher risk of progression to incident MCI (HR: 4.07, 95% CI 2.46-6.74) compared with SCD patients without MNPD (n = 384). MNPD had a positive predictive value of 57.0% (95% CI 38.5-75.4) and a negative predictive value of 86.0% (95% CI 81.9-90.1) for the progression of SCD to MCI within 3 years. SCD patients without MNPD showed increased cognitive decline and a higher risk of incident MCI compared with HC participants without MNPD (n = 215; HR: 4.09, 95% CI 2.07-8.09), while AD biomarker levels did not differ significantly between these groups. DISCUSSION: Our results suggest that MNPD are a risk factor for AD-related clinical progression in cognitively normal patients seeking medical counseling because of SCD. As such, the assessment of MNPD could be useful for individual clinical prediction and for AD risk stratification in clinical trials. However, SCD remains a risk factor for future cognitive decline even in the absence of MNPD