Justus-Liebig University Research Articles

High Open-Circuit Voltage Cs2 AgBiBr6 Carbon-Based Perovskite Solar Cells via Green Processing of Ultrasonic Spray-Coated Carbon Electrodes from Waste Tire Sources.

Invited for this month cover is the group of Teresa Gatti at the Justus Liebig University (JLU) in Giessen, Germany, the group of Federico Bella at Politecnico di Torino (POLITO), Italy, and the group of Francesco Lamberti at the University of Padova (UNIPD), also in Italy. The image shows how waste tires can be converted in a conductive carbon powder that undergoes a green processing step to produce carbon electrodes for lead-free perovskite solar cells. Similar devices can be employed to harvest indoor light in order to power the Internet of Things (IoT) ecosystem. The Research Article itself is available at 10.1002/cssc.202201590.

Challenges Faced by Racial Minority Students at Justus-Liebig University, Germany and North-West University, South Africa

Educational institutions are characterised by cultural and institutional racism that is embedded in their structural systems, curriculum and practices that negatively impact the social and academic experiences of racial minority students. Prejudice and discrimination are rooted in hierarchies whereby some cases evidence one directional oppression of a racial group by the dominant or majority group. The study aimed at exploring challenges faced by racial minority students at Justus-Liebig University and North-West University. The study utilized a qualitative research approach in order understand the opinions, experiences and views of racial minority students about their campus realities. Fourteen in-depth interviews were undertaken with racial minority students and findings were analysed through content thematic analysis. The findings revealed that challenges faced by minority racial students from Justus-Lieberg University and North West University were similar. The challenges include but are not limited to; difficulties with interaction with the racial majority group, academic stressors like failure to adapt to high workload, adaptation to the academic climate, language and cultural barriers. This study calls for the development of new policies that pursue a restructuring of the campus environment to make it beneficial to all students. There is a need for universities to establish and maintain inclusive educational programs and policies that can assist minority students to be integrated into the academic systems.

Assessment of renal glomerulosclerosis and thickness of the carotid intima-media complex as a means of age estimation in Western European bodies

IntroductionThe estimation of age-at-death of unidentified cadavers is a central aspect of the identification process. With increasing age, the incidence of glomerulosclerosis and the thickness of the carotid wall have been observed to also increase. This correlation has been demonstrated in various international histological studies. The aim of our study was to assess whether these correlations also apply to a Western European population.MethodologyIn this retrospective observational study, kidney and common carotid artery samples from 216 cases autopsied at the Institute of Legal Medicine at the Justus-Liebig University in Giessen, Germany, were examined. Only cases with available tissue samples from both body sides were included. Exclusion criteria were poor sample quality and an age younger than 21 years. After histological processing, the tissue samples were assessed and digitally evaluated. Regression and classification analyses were used to investigate the correlation between age-at-death and intima-media thickness and age-at-death and the incidence of renal glomerular sclerosis.ResultsOf the 216 autopsy cases, 183 were included for evaluation. Analysis of the carotid artery segments showed a strong correlation (Pearson correlation coefficient r = 0.887) between the intima-media-complex thickness and chronological age. Classification of the glomerulosclerotic incidence showed a correlation of 37.7–43.1% with the predicted age group.DiscussionBoth the intima-media thickness and the proportion of sclerotic glomeruli can be used to estimate age in Western European cadavers. On the basis of these results, both methods are suited to supplement other already established methods for age-at-death estimation in the identification of an unknown cadaver.

Effect of inflammation-mediated endothelial metabolic shift on endothelial barrier function

Abstract Background The integrity of the endothelial cell barrier of the microvasculature is compromised by inflammation. The increased vascular permeability leads to tissue injury and organ dysfunction. In recent years, considerable advances have been made in the understanding of signalling mechanisms regulating the endothelial barrier integrity. The role of endothelial metabolism as a modulator of endothelial barrier integrity is not yet well-studied. The aim of the present study was to investigate the effect of inflammation on endothelial metabolism and its role in the maintenance of endothelial barrier integrity. Methods The study was carried out on cultured human umbilical vein endothelial cells and rat coronary microvascular endothelial cells. Inflammatory condition was simulated by treating cells with low concentrations (1 ng/mL) of TNFα for 24h. Endothelial barrier function was analysed by measuring the flux of albumen through endothelial monolayers cultured on filter membranes. Gene expression was analysed by qPCR-based assays. The capacity of endothelial cells for maximal ATP synthesis rate was investigated by the real-time live-cell imaging using FRET-based ATP-biosensor (live cell FRET). Total cellular ATP concentration was measured using luminescence-based commercial kit (ATPLite, PerkinElmer). Mitochondrial mass was analysed by the ratio of mitochondrial DNA (mtDNA) to nuclear DNA (nDNA). The cellular glucose uptake was measured by fluorescent microscopy using a fluorescent analogue of glucose (2-NBDG). Results Treatment of human endothelial cells with TNFα resulted in significant suppression of mitochondrial and upregulation of glycolytic ATP synthesis rate, suggesting a metabolic switch. This was accompanied by a reduction in mitochondrial content (mtDNA/nDNA), reduction in total cellular ATP levels, an enhanced expression of glycolytic enzymes 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) and phosphofructokinase 1 (PFK1), and enhanced glucose uptake by endothelial cells (n=5; p<0.05 for all parameters tested). Moreover, TNFα caused a 3-fold increase in endothelial permeability. Pharmacological inhibition of glycolysis either by partial replacement of glucose with 2-deoxy glucose (2DG) or an inhibition of PFKFB3 resulted in further worsening (a 5-fold increase in permeability) of TNFα-induced endothelial barrier failure. On the other hand pharmacological activation of AMPK, a potent inducer of mitochondrial biogenesis, could attenuate TNFα-induced but not 2DG-induced endothelial hyperpermeability. Conclusion The study demonstrates that TNFα induces metabolic switch towards glycolysis in endothelial cells. Moreover, the data suggest that upregulation of glycolysis may serve as an endogenous metabolic adaptation to the TNFα-induced suppression of mitochondrial ATP synthesis, which protects endothelial barrier integrity. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Justus-Liebig University GiessenDZHK (German Centre for Cardiovascular Research), partner site Rhein-Main, Bad Nauheim, Germany

Influencing factors on stress management in medical students-with special consideration of depression

Due to high levels of stress, apractical course on stress management in medical school was offered to preclinical medical students at the Justus-Liebig University in Giessen up to 2019. In addition to autogenic training with specific resolution formulas, learning strategies, examination anxiety, and stress management were taught. The aim was to determine the factors influencing the efficacy of the course as well as predictive factors favoring the success of preventive strategies for medical students. A total of 81medical students with an average age of M = 25.4years participated in this study, with 32.1%being male. The pre-post surveys were conducted anonymously with PSQ, BDI, PHQ‑9, HADS, SF-12 and the STQL‑S. With respect to satisfaction, stress, anxiety, and depression, asignificant improvement was achieved at high effect levels (Cohen's d > 1). Initially, 35% of the students suffered from clinically relevant depression; these also showed asignificantly higher stress level at the end of the course. This also applies to students with low study or life satisfaction. There were significant interactions of stress reduction depending on the existence of adequate learning techniques as well as anxiety symptoms but less often due to the existence of adequate stress management strategies. As predictive factors against ahigh stress level in medical students, ahigh study satisfaction and ahigh life satisfaction as well as low depression values could be confirmed. Relevant factors contributing to the efficacy of the course are learning strategies and coping with examination phobia. Theoretical information concerning stress management was found to be less helpful.

Reply by Authors.

No AccessJournal of UrologyAdult Urology1 Mar 2021Reply by Authorsis a reply to letterEditorial Comment Steven Rosenberg, Marc Bonten, Wouter Haazen, Bart Spiessens, Darren Abbanat, Oscar Go, Florian Wagenlehner, Neal Shore, Yosuke Hagiwara, Patricia Ibarra de Palacios, Jeroen Geurtsen, Peter Hermans, and Jan Poolman Steven RosenbergSteven Rosenberg The Iowa Clinic, West Des Moines, Iowa More articles by this author , Marc BontenMarc Bonten Julius Center, UMC Utrecht, Utrecht, Netherlands Financial and/or other relationship with Janssen Pharmaceuticals. Financial and/or other relationship with Janssen Vaccines & Prevention. More articles by this author , Wouter HaazenWouter Haazen Janssen Research & Development, Beerse, Belgium More articles by this author , Bart SpiessensBart Spiessens Janssen Research & Development, Beerse, Belgium More articles by this author , Darren AbbanatDarren Abbanat Janssen Research & Development LLC, Raritan, New Jersey More articles by this author , Oscar GoOscar Go Janssen Research & Development LLC, Raritan, New Jersey More articles by this author , Florian WagenlehnerFlorian Wagenlehner Clinic for Urology, Pediatric Urology and Andrology, Justus-Liebig University, Giessen, Germany Financial and/or other relationship with Janssen Pharmaceuticals. More articles by this author , Neal ShoreNeal Shore Carolina Urologic Research Center, Atlantic Urology Clinics, Myrtle Beach, South Carolina Financial and/or other relationship with Janssen Pharmaceuticals. More articles by this author , Yosuke HagiwaraYosuke Hagiwara Janssen Pharmaceutical K.K., Tokyo, Japan More articles by this author , Patricia Ibarra de PalaciosPatricia Ibarra de Palacios Janssen Vaccines, Bern, Switzerland More articles by this author , Jeroen GeurtsenJeroen Geurtsen Janssen Vaccines & Prevention B.V., Leiden, Netherlands More articles by this author , Peter HermansPeter Hermans Julius Center, UMC Utrecht, Utrecht, Netherlands More articles by this author , and Jan PoolmanJan Poolman ‡Correspondence: Janssen Vaccines & Prevention B.V., Archimedesweg 4-6, 2333 CN, Leiden , The Netherlands telephone: +31 715197626; mobile: +31 631917392; E-mail Address: [email protected] Janssen Vaccines & Prevention B.V., Leiden, Netherlands More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001425.02AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Reply by Authors." The Journal of Urology, 205(3), p. 832 Reference 1. : Antimicrobial-resistant pathogens associated with adult healthcare-associated infections: summary of data reported to the National Healthcare Safety Network, 2015–2017. Infect Control Hosp Epidemiol 2020; 41: 1. Google Scholar This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.FiguresReferencesRelatedDetailsRelated articlesJournal of Urology5 Jan 2021Editorial Comment Volume 205Issue 3March 2021Page: 832-832 Advertisement Copyright & PermissionsCopyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.MetricsAuthor Information Steven Rosenberg The Iowa Clinic, West Des Moines, Iowa More articles by this author Marc Bonten Julius Center, UMC Utrecht, Utrecht, Netherlands Financial and/or other relationship with Janssen Pharmaceuticals. Financial and/or other relationship with Janssen Vaccines & Prevention. More articles by this author Wouter Haazen Janssen Research & Development, Beerse, Belgium More articles by this author Bart Spiessens Janssen Research & Development, Beerse, Belgium More articles by this author Darren Abbanat Janssen Research & Development LLC, Raritan, New Jersey More articles by this author Oscar Go Janssen Research & Development LLC, Raritan, New Jersey More articles by this author Florian Wagenlehner Clinic for Urology, Pediatric Urology and Andrology, Justus-Liebig University, Giessen, Germany Financial and/or other relationship with Janssen Pharmaceuticals. More articles by this author Neal Shore Carolina Urologic Research Center, Atlantic Urology Clinics, Myrtle Beach, South Carolina Financial and/or other relationship with Janssen Pharmaceuticals. More articles by this author Yosuke Hagiwara Janssen Pharmaceutical K.K., Tokyo, Japan More articles by this author Patricia Ibarra de Palacios Janssen Vaccines, Bern, Switzerland More articles by this author Jeroen Geurtsen Janssen Vaccines & Prevention B.V., Leiden, Netherlands More articles by this author Peter Hermans Julius Center, UMC Utrecht, Utrecht, Netherlands More articles by this author Jan Poolman Janssen Vaccines & Prevention B.V., Leiden, Netherlands ‡Correspondence: Janssen Vaccines & Prevention B.V., Archimedesweg 4-6, 2333 CN, Leiden , The Netherlands telephone: +31 715197626; mobile: +31 631917392; E-mail Address: [email protected] More articles by this author Expand All Advertisement PDF downloadLoading ...

Dexamethasone improves therapeutic outcomes in a preclinical bacterial epididymitis mouse model.

Can dexamethasone improve infertility-related cauda epididymidal tissue damage caused by bacterial epididymitis? Dexamethasone in addition to anti-microbial treatment effectively reduces long-term deleterious epididymal tissue damage by dampening the host's adaptive immune response. Despite effective anti-microbial treatment, ~40% of patients with epididymitis experience subsequent sub- or infertility. An epididymitis mouse model has shown that the host immune response is mainly responsible for the magnitude of epididymal tissue damage that is fundamentally causative of the subsequent fertility issues. Bacterial epididymitis was induced in male mice by using uropathogenic Escherichia coli (UPEC). From Day 3 after infection onwards, mice were treated with daily doses of levofloxacin (20mg/kg, total n= 12 mice), dexamethasone (0.5mg/kg, total n= 9) or both in combination (total n= 11) for seven consecutive days. Control animals were left untreated, i.e. given no interventional treatment following UPEC infection (total n= 11). Half of the animals from each group were killed either at 10 or 31days post-infection. A mouse model of induced bacterial epididymitis was applied to adult male C57BL/6J mice. At the respective endpoints (10 or 31days post-infection), epididymides were collected. Effectiveness of antibiotic treatment was assessed by plating of epididymal homogenates onto lysogeny broth agar plates. Overall tissue morphology and the degree and nature of tissue damage were assessed histologically. Quantitative RT-PCR was used to assess local cytokine transcript levels. Blood was drawn and serum analysed for systemic IgG and IgM levels by ELISA. In addition, correlation analyses of clinical data and serum-analyses of IgG and IgM levels in patients with epididymitis were performed. The addition of dexamethasone to the standard anti-microbial treatment did not further worsen epididymal tissue integrity. In fact, an obviously dampened immune response and reduced tissue reaction/damage was observed at both 10 and 31days post-infection following combined treatment. More specifically, epididymal duct continuity was preserved, enabling sperm transit. In contrast, in untreated or antibiotic-treated animals, damage of the epididymal duct and duct constrictions were observed, associated with a lack of cauda spermatozoa. In line with the bacteriostatic/bactericidal effect of levofloxacin (alone as well as in combination), local cytokine transcript levels were significantly and similarly reduced in animals treated with levofloxacin alone (P< 0.01) or in combination with dexamethasone (P< 0.05) compared to UPEC-infected untreated animals. Interestingly, the addition of dexamethasone to the anti-microbial treatment induced a unique dampening effect on adaptive immunity, since systemic IgG and IgM levels as well as the pan-T cell marker CD3 were reduced at both 10 and 31days post-infection. Breeding studies to address the fertility-protecting effect of the combined treatment were not possible in the experimental animals because the vas deferens was ligated (model specific). Whereas innate immunity is necessary and involved in acute bacterial clearance, adaptive immunity seems to be responsible for long-term, subclinical immunological activities that may negatively affect the pathogenesis of bacterial epididymitis even after effective bacterial eradication. These effects can be reduced in mice by the additional treatment with dexamethasone. This immunological characteristic of bacterial epididymitis shows similarities to the Jarisch-Herxheimer reaction known from other types of bacterial infection. The study was supported by grants from the Deutsche Forschungsgemeinschaft, Monash University and the Medical Faculty of Justus-Liebig University to the International Research Training Group on 'Molecular pathogenesis of male reproductive disorders' (GRK 1871). R.W., K.L.L. and M.P.H. were supported by grants from the National Health and Medical Research Council of Australia (ID1079646, ID1081987, ID1020269 and ID1063843) and by the Victorian Government's Operational Infrastructure Support Program. The authors have no conflicts of interest to declare. No clinical trial involved.

Autophagy in Amiodarone induced Lung Fibrosis: A Close Look

Poornima Mahavadi*1,2 Author Affiliations 1Department of Internal Medicine, Justus-Liebig University, Giessen, Germany 2Universities of Giessen and Marburg Lung Centre (UGMLC), Member of the German Centre for Lung Research (DZL), Giessen, Germany Received: May 27, 2019 | Published: June 06, 2019 Corresponding author: Poornima Mahavadi, Department of Internal Medicine, Germany DOI: 10.26717/BJSTR.2019.18.003182 Also View In:

The Phenotypic Spectrum of Ophthalmic Changes in CEP290 Mutations

Inherited retinal diseases (IRDs) may be caused by variations in genes affecting the connecting cilium of photoreceptor cells and intraflagellar transport, manifested as ciliopathies. CEP290 is frequently mutated in non-syndromic, but also syndromic IRDs. In preparation for clinical treatment trials, detailed phenotypic work-up including longitudinal follow-up is mandatory. We performed genotype-phenotype correlations in 30 patients with biallelic mutations in CEP290. The study was approved by the IRB of the medical faculty of the Justus-Liebig University Giessen. The patients received a comprehensive clinical examination, including spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF) recording, and electrophysiology whenever possible. Thirty patients aged 1 month to 84 years (median at first visit 0.6 y) were followed between 5 months and 25.7 years (median 4.8 y). Twenty-three of these patients carried the c.2991+1655A>G mutation (30/60 allele 2, 7 homozygous). The second most frequent mutation was p.K1575* (9/60 alleles). The full-field electroretinogram showed residual response in a few patients only. After progression, electrophysiological responses were below threshold in all patients. Severely reduced visual acuity persisted from birth. Eight patients had quantifiable best corrected visual acuity (BCVA, logMAR 2 - 0.3), in one case up to the age of 84 y. Absent fixation of targets was noted in 15 patients during the first months of life. Ten of these patients did not improve during follow-up past the second year of life. The other patients developed at least light perception (LP, n = 7) or hand movement (HM, n = 3). Better BCVA was not restricted to the c.2991+1655A>G mutation. Fundus photography documented degenerative changes throughout the retina with macular degeneration and circular increased fundus autofluorescence signals (9/30 patients) in the perimacular ring and in the rod ring, and spotty changes in the periphery. SD-OCT (6/30 patients) disclosed reduced photoreceptor layer (OPL to OS) thickness and preserved inner retinal thickness (RNFL to INL). Better BCVA did not correlate to genotype or central photoreceptor layer thickness. As reported earlier, CEP290 variations are one of the most frequent causes of IRDs with infancy onset. In our patient cohort of 30 patients, only 33% had no LP, 67% at least LP, and among these 26% logMAR 2 to 0.3. Together with preserved ganglion cell and nerve fibre cell layers, success with gene therapeutic approaches appears possible.

Pregnancy-associated Death - Clarifying the Cause of Death and Medico-legal Assessments in Accusations of Malpractice.

Background Pregnancy-associated deaths are extremely rare in Germany. Most deaths are from natural causes, and a range of causes are possible. Method The deaths of 22 women who died of pregnancy-associated causes and who were autopsied in the Institute of Forensic Medicine of Justus-Liebig University Gießen between 1992 and 2016 were analyzed. Results The autopsy results and histological examinations for the majority of women who died of pregnancy-associated causes between 1992 and 2016 showed that they had died of natural causes, although complications of pregnancy were a leading cause of death. Conclusion The death of a pregnant woman should not automatically raise the suspicion of malpractice, although the question does arise in cases of bleeding complications only detected at very late stages. Experts must prove that a real mistake was made during treatment and provide evidence of the causality between malpractice and patient death. Particularly when well-known complications of pregnancy were present, this is only the case if poor monitoring resulted in the complication being detected too late or if treatment was not in accordance with accepted standards of care. The majority of pregnancy-associated deaths are from natural causes and the death of a pregnant woman does not mean that medical malpractice was involved, although this accusation is often levelled in cases where rupture was not immediately diagnosed or in cases of fatal postpartum hemorrhage.

Resistance to apoptosis and autophagy leads to enhanced survival in Sertoli cells.

What is the underlying mechanism of Sertoli cell (SC) resistance to cell death? High expression of prosurvival B-cell lymphoma-2 (BCL2) proteins and inhibition of apoptosis and autophagy prolongs SC survival upon exposure to stress stimuli. In human and in experimental models of orchitis, tolerogenic SC survive stress conditions, while germ cells undergo massive apoptosis. In general, non-dividing highly differentiated cells tend to resist stress conditions for a longer time by favoring activation of prosurvival mechanisms and inhibition of cell death pathways. In this cross sectional study, conditions stimulating apoptosis and autophagy were used to induce cell death in primary rat SC. Primary rat peritubular cells (PTC) and immortalized rat 93RS2 SC were used as controls. Each cell isolation was counted as one experiment (n = 1), and each experiment was repeated three to six times. Testis biopsy samples from infertile or subfertile patients and testis samples from rats with experimental autoimmune orchitis were used for immunohistological analysis. Primary SC were isolated from 19-day-old male Wistar rats. To maintain cell purity, cells were cultured in serum-free medium for apoptosis experiments and in medium supplemented with 1% serum for autophagy analyses. To induce apoptosis, cells were stimulated with staurosporine, borrelidin, cisplatin and etoposide for 4 or 24 h. Caspase three activation was examined by immunoblotting and enzymatic activity assay. Mitochondrial membrane potential was measured using tetramethylrhodamine methyl ester followed by flow cytometric analysis. Cytochrome c release was monitored by immunofluorescence. Cell viability was determined using the methylthiazole tetrazolium assay. To monitor autophagy flux, cells were deprived of nutrients using Hank's balanced salt solution for 1, 2 and 3 h. Formation of autophagosomes was analyzed by using immunoblotting, immunofluorescence labeling and ultrastructural analyses. Relative mRNA levels of genes involved in the regulation of apoptosis and autophagy were evaluated. Extracellular high mobility group box protein one was measured as a marker of necrosis using ELISA. SC survive the inflammatory conditions in vivo in human testis and in experimental autoimmune orchitis. Treatment with apoptosis inducing chemotherapeutics did not cause caspase three activation in isolated rat SC. Moreover, mitochondrial membrane potential and mitochondrial localization of cytochrome c were not changed by treatment with staurosporine, suggesting a premitochondrial blockade of apoptosis in SC. Expression levels of prosurvival BCL2 family members were significantly higher in SC compared to PTC at both mRNA and protein levels. Furthermore, after nutrient starvation, autophagy signaling was initiated in SC as observed by decreased levels of phosphorylated UNC- 51-like kinase -1 (ULK1). However, levels of light chain 3 II (LC3 II) and sequestosome1 (SQSTM1) remained unchanged, indicating blockade of the autophagy flux. Lysosomal activity was intact in SC as shown by accumulation of LC3 II following administration of lysosomal protease inhibitors, indicating that inhibition of autophagy flux occurs at a preceding stage. N/A. In this study, we have used primary SC from prepubertal rats. Caution should be taken when translating our results to adult animals, where crosstalk with other testicular cells and hormonal factors may also play a role in regulating survival of SC. Our results suggest that inhibition of autophagy and apoptosis following exposure to extrinsic stress stimuli promotes SC survival, and is a possible mechanism to explain the robustness of SC in response to stress. Cell death resistance in SC is crucial for the recovery of spermatogenesis after chemotherapy treatment in cancer patients. Additionally, understanding the molecular mechanisms of SC survival unravels valuable target proteins, such as BCL2, that may be manipulated therapeutically to control cell viability depending on the context of the disease. This study was funded by the Deutsche Forschungsgemeinschaft (DFG) Grant BH93/1-1, and by the International Research Training Group between Justus Liebig University of Giessen and Monash University, Melbourne (GRK 1871/1) funded by the DFG and Monash University. The support of the Medical Faculty of Justus-Liebig University of Giessen is gratefully acknowledged. The authors declare no conflict of interest.

Writing Centres as the Driving Force of Programme Development: From Add-on Writing Courses to Content and Literacy Integrated Teaching

Academic writing courses and subject-matter courses have been taught independently to a large extent at many European universities following a ‘study skills model’ (Lea and Street 1998). An integrated approach, however, both in students’ L1 (or their language of instruction) and in English (if this is not their L1), in accordance with Lea and Street’s ‘academic literacies model’ has a number of advantages. Introducing an academic literacies model, however, is difficult to implement since it requires the joint effort of both subject-domain teachers and language teachers and involves deviating from familiar teaching methods. To implement the changes required, a three-level approach has been developed at Justus Liebig University (JLU), Giessen/Germany, as one of several measures in a university-wide project. In this approach, the university’s writing centre and teaching centre take over the role of ‘motors’ of literacy development in all disciplines. The macro-level of this three-level approach encompasses central services provided by these centres as well as university-wide literacy development policies. The meso-level addresses programme development, and the micro-level, curriculum and syllabus adaptations for individual courses. The article provides insight into the measures to be taken at each of these levels based on a review of prior research on Integrating Content and Language in Higher Education (ICLHE) (Gustafsson 2011, Gustafsson and Jacobs 2013 and Wilkinson and Walsh 2015) and the central role that writing centres and teaching centres can play in this process.

Simulation of drug release and mobility in healthy and osteoporotic bone

Simulation of drug release and mobility in healthy and osteoporotic bone

Proposal of a Genetic Classifier for Risk Group Stratification in Pediatric T-Cell Lymphoblastic Lymphoma Reveals Significant Differences to T-Cell Lymphoblastic Leukemia

IntroductionT-cell lymphoblastic lymphoma (T-LBL) represent the second most common subtype of Non-Hodgkin lymphoma (NHL) in children and adolescents. In contrast to other pediatric NHL-subtypes and acute lymphoblastic leukemia (ALL) criteria for the stratification of treatment intensity are lacking in T-LBL. Consequently all patients receive identical treatment intensity resulting in over- and under-treatment of a relevant but not yet characterized subgroup of patients. Recently a genetic classifier for adult T-ALL patients was reported. Whether T-ALL and T-LBL represent one or two diseases remains an ongoing discussion. Whole exome sequencing data of pediatric T-LBL cases now support the hypothesis that T-ALL and T-LBL, despite pathogenic similarities are biologically different. Here we used our large dataset of well defined and uniformly treated pediatric patients with T-LBL to define molecular risk factors of the disease.MethodsAll pediatric T-LBL patients of the NHL-BFM group with sufficient material available were sequenced for abnormalities in the genes: NOTCH1, FBXW7, NRAS, KRAS, PTEN, PIK3R1, PIK3CA using Sanger sequencing of known mutational hotspots and loss of heterozygosity of chromosome 6q using fragment length analyses. Patients were treated uniformly according to NHL-BFM protocols for T-LBL. Clinical data were available from the data base of the NHL-BFM study center. Accompanying molecular research for the trials NHL-BFM 95 and EURO-LB 02, in which these patients were recruited, has been approved by the ethical committees of the Hannover Medical School and Justus-Liebig University Giessen, Germany.ResultsThe observed frequencies of somatic mutations with 95% confidence intervals were: NOTCH1 61% (51-70%), FBXW7 18% (12-27%), PTEN 15% (9-23%) in 114 analyzed patients, N-RAS + K-RAS 10% (5-18%) in 99 analyzed patients, PIK3R1+PIK3CA in 8% (4-15%) in 107 analyzed patients, and LOH6q 12% (8-17%) in 217 analyzed patients. Detailed evaluation of potential associations of distinct mutation status and clinical characteristics revealed a statistically significant association of NOTCH1 mutations (p=0.006) and FBXW7 mutations (p=0.034) with age below 10 years compared to patients with germline status. All other analyses evaluated for each gene separately taking into account age, gender, stage of disease, CNS disease, bone marrow involvement, mediastinal tumor, and general condition at diagnosis did not identify any statistically significant association.Concerning the concurrence or exclusion of the analyzed alterations, NOTCH1 mutations were significantly associated with FBXW7 mutations (p=0.03). LOH6q positive patients presented significantly more often in cases with NOTCH1 wildtype status (p=0.03) and PTEN mutations and FBXW7 mutations turned out to present mutually exclusive (p=0.03).The analyses concerning patients outcome allowed the proposal of an new genetic classifier defining three risk groups:1) Good risk group (GR) comprising 39% (35/91) of patients defined by NOTCH1 mutation and no RAS or PIK3 mutation with a cumulative incidence of relapse of 11+5%.2) Intermediate risk group (IR) with all non-GR and non-HR patients including 46% (42/91) of patients with a cumulative incidence of relapse of 20+6%.3) High-risk group (HR) of 15% (14/91) of patients defined by NOTCH1 wildtype in combination with PTEN mutation and/or LOH6q positivity associated with a cumulative incidence of relapse of 64+14%.Except for an overrepresentation of patients 10 to 15 years of age in the HR arm, none of tested patients’ characteristic parameters of was associated with risk group.ConclusionDetailed analyses of genetic alterations in pediatric T-LBL revealed relevant somatic mutation frequencies for gene loci of the PTEN/PI3K pathway and the RAS pathway. Together with earlier published results on the prognostic relevance of NOTCH1 mutations and chromosome 6q alterations the analyzed cohort of about 100 uniformly treated pediatric T-LBL patients allowed the definition of a genetic classifier for risk group stratification. This proposed classifier requires prospective validation. The here proposed genetic classifier for T-LBL might be worth to be analyzed in pediatric T-ALL. Interestingly our proposed T-LBL classifier includes some aspects in parallel, but overall differed significantly from the earlier published classifier for adult T-ALL. DisclosuresNo relevant conflicts of interest to declare.

Editorial introductions

Editorial introductions

Medicus Europaeus: Prof. Pavel Schmidt, MD, PhD (25 November 1933-11 March 1994).

The 80th birthday anniversary of Pavel Schmidt is an opportunity to recognize and celebrate his accomplishments in the fields of hygiene, environmental medicine, medical microbiology, and infectious epidemiology at the national and European level. He is remembered for his extraordinary commitment and contribution to the transformation process of health system in the Czech Republic (CR) after the velvet revolution.Pavel Schmidt was bom in Prague. He started his medical education at Charles University in Prague in 1954. He obtained his PhD from the same University and in 1968 he obtained habilitation in hygiene and epidemiology. In addition, he worked for the Prague Institute for Hygiene and at the Faculty of Hygiene at the Institute for Doctoral Training. He was elected a member of the New York Academy of Science in 1970. Schmidt was granted research fellowship at the Alexander von Humboldt Foundation in Dusseldorf with Prof. Hans-Werner Schlipkoter, M.D., between 1967-1973. Thanks to his commitment, Charles University in Prague established official bilateral relation with Heinrich Heine University in Dusseldorf. He organized an exchange programme for the interns of both universities. His name is also associated with the discovery of methemoglobinemia in infants related to nutrition. In 1962, he was honored by the Czech Medical Association of J. E. Purkyne, Czechoslovakia, for work in this field. Schmidt was responsible for multi-center studies about the effect of air pollution caused by leaded gasoline on damages in children. His actions were aimed at promotion and protection of the environment that children could enjoy. His thinking was influenced by his friend Prof. Josef Svejcar, the pioneer of the Czech paediatrics. Nevertheless, recognition of his achievements could not prevent him and his family from fleeing Czechoslovakia in 1976. He received political asylum in the Federal Republic of Germany and came first to Dusseldorf and then to Giessen, where he accepted the position of Professor at the Hygiene Institute of Justus Liebig University (JLU) in 1978. He coordinated all activities as the director until his death. Schmidt was involved in numerous activities at the Faculty for Hygiene and Environmental Medicine of JLU as well as in the State Chamber of Physicians of Hesse (SCPH). Renowned for his work in different committees of the German Medical Association (GMA), Schmidt assumed various voluntarily functions within the self-administration system of the State Chamber of Physicians in Germany. He published more than 150 scientific essays and other educational materials, books and articles on hygiene. Only due to the long term strategically well planned work of Schmidt, it was possible to build on the existing bilateral relationship between East and West after the fall of communism. Multi-center-studies on topics such as environmental damages in Bitterfeld, Ruhr and the North Bohemian coal mining area were extended through research in the Rhine-Main area and Freiburg etc. …

Nuclear factor of activated T-cells c1 integrates STAT3 signals to link chronic inflammation and carcinogenesis in the pancreas

s / Pancreatology 13 (2013) S2–S98 S16 Conclusion: Our study uncovers an cell-autonomous EGFR-NFATc1 signaling loop which is required for pancreatic cancer initiation. O-42 Abstract id: 318. Nuclear factor of activated T-cells c1 integrates STAT3 signals to link chronic inflammation and carcinogenesis in the pancreas Sandra Baumgart , Nai-ming Chen , Marius Brunner , Reinecke Johanna , Julius Nikorowitsch , Shiv Singh , Alexander K€ onig , Jinsan Zhang , Elmar Wolf , Marek Bartkuhn , Jens Siveke , Irene Esposito , Elisabeth Glesel , Bettina Geisel , Kristina Reutlinger , Garima Singh , Martin Eilers , Thomas Gress , Daniel Billadeau , Volker Ellenrieder . 1 Philipps University of Marburg, Germany Mayo Clinic, United States University of W€ urzburg, Germany 4 Justus-Liebig University of Giessen, Germany 5 Technical University of Munich, Germany Introduction: Chronic pancreatitis along with activating mutations of the oncogene Kras is a central risk factor for pancreatic cancer development. Inflammation-induced signaling involves nuclear factor of activated T cells (NFAT) pathways. NFATc1 is overexpressed and activated in Krasmutated human pancreatic cancers where it mediates cancer growth stimulation. Aims: This study aims to determine the in vivo role of NFATc1 in KrasG12D-dependent carcinogenesis. Materials & methods: Transgenic mice expressing KrasG12D and NFATc1 in the pancreas and NFATc1 knockout mice were engineered and analyzed in terms of (inflammation-induced) carcinogenesis. Immunohistochemistry, Western blot, qPCR analyses, chromatin studies, ChIP-Seq and genome-wide expression profiling were performed to investigate the mechanisms of NFATc1-KrasG12D cooperation in murine and human tissues and tumor cells. Results: Activation of NFATc1 upon inflammation and in KrasG12D;NFATc1 mice dramatically accelerated carcinogenesis and reduced survival. Mechanistically, nuclear NFATc1 activated expression of oncogenic STAT3 transcription factor. Accordingly, high correlative nuclear expression levels of NFATc1 and active STAT3 were detected in the majority of human and murine cancer tissues. In turn, NFATc1/STAT3 complexes, which regulated genome-wide NFATc1 binding to distal chromatin enhancer sites and subsequently enforced recruitment of transcriptional co-activators, were identified. Likewise, corresponding enhancer-promoter communications that stimulated NFATc1-dependent transcription of newly-identified target genes were epigenetically promoted. Pharmacologic and genetic depletion of the NFATc1/STAT3-axis significantly arrested carcinogenesis in mouse models and confirmed the requirement of NFATc1 in Kras-driven pancreatic carcinogenesis. Conclusion: We identified a previously unknown NFATc1-STAT3 complex formation as a driving epigenetic regulatory force in inflammation-linked pancreatic carcinogenesis, which defines this novel pathway a possible point of therapeutic intervention. O-43 Abstract id: 236. Therapeutic interest to target the Phosphoinositide-3-Kinase (PI3K) – mTOR pathway in pancreatic Cancer-Associated Fibroblasts Camille Duluc , Siham Moatassim-Billah , Herbert Schmid , MarieBernadette Delisle , Barbara Garmy-Susini , St ephane Pyronnet , Julie Guillermet-Guibert , Corinne Bousquet . 1 INSERM U1037, France 2 Faculty of Sciences Rabat, University Mohammed V Agdal, Morocco Novartis, Bales, Switzerland 4 Pathology Toulouse Hospital, France Introduction: Pancreatic ductal adenocarcinoma (PDAC) is one of the most stroma-rich cancers. Cancer-associated fibroblasts (CAFs), the most abundant cells in this stroma, orchestrate the secretion of growth factors that engage, in cancer and other stromal cells, survival and angiogenic signals redundant to those targeted by therapies, and of fibrillar components that constitute a barrier to drug delivery. Aims: Therapeutic pitfalls observed in PDAC may in part be explained by the under-estimation of the influences exerted by the microenvironment on cancer cells. Targeting CAFs may therefore constitute a promising strategy. Patients &methods: Primary cultures of CAFs have been isolated from human pancreatic tumor resections and used for in vitro and in vivo studies. Results: Isolated CAFs present, and maintain during the in vitro passages (< 10), an activated phenotype ( aSMA-positive). CAFs promote survival, invasion and chemoprotection (against gemcitabine) of pancreatic cancer cells, either in co-cultures or using CAF conditioned media. Interestingly, CAFs present a high intrinsic activation of the PI3K-mTOR pathway. It results in elevated protein synthesis and secretion specifically of pro-tumoral factors and extracellular matrix proteins. Strikingly, drugs that inhibit the PI3K-mTOR pathway abrogate CAF pro-tumoral and chemoprotective effects on cancer cells both in vitro and in vivo, in co-xenografted mice with CAF and pancreatic cancer cells. Conclusion: Because CAFs are present both in the tumor and in the periphery where drug delivery is still feasible, therapeutic targeting of CAFs using inhibitors of protein synthesis may be of utmost interest for PDAC. O-44 Abstract id: 187. Neural invasion in pancreatic cancer is characterized by beta-1-Integrinand L1-CAM-dependent heterotypic cell adhesion between pancreatic cancer cells and neural Schwann cells Ihsan Ekin Demir, Natascha Klose, Eva Brunner, Helmut Friess, G€ uralp O.

Lebensqualität, Stressbewältigung und Gesundheitsförderung bei Studierenden der Human- und Zahnmedizin

Which are the differences in health-related quality of life and stress management in medical and dental students? 101 dental and 237 medical students from different years of Justus-Liebig University Giessen were examined during winter term 2008/09 and summer term 2009 using the specific Questionnaire on Health Promotion, Life Satisfaction, and Stress Management in Dental or Medical Students (addressing work satisfaction and choice of subject, private life, relaxation behavior and stress management, and health behavior), Beck Depression Inventory (BDI) and SF-36 Health Survey. For statistical analysis, Mann-Whitney-U-Test, analysis of variance (ANOVA), Pearson correlation and Chi2-Tests were primarily used. Dental and medical students showed considerable mental impairment in SF-36. Every fifth dental student suffered from slight to moderate depression. Though averaging more hours per week, medical students were more satisfied with their studies. More than half of the dental and medical students did not have appropriate strategies of coping with stress. Concerning the mental impairment in both groups and regarding a higher health-related quality of life, specific prevention courses or mentoring programs should already be offered at the beginning of medical training in order to cope with strains of medical school and future job strains in the medical or dental profession.

What in Fact Is the Role of Stylized Facts in Fundamental Research of Business and Information Systems Engineering?

In the discussion initiated by Winter on “What in fact is fundamental research in business and information systems engineering?” in issue 2/2009, Zelewski submitted the interesting proposal to use the concept of stylized facts as developed in economics in business and information systems engineering (BISE) in order to promote theory building within our discipline (Winter et al. 2009). Stylized facts constitute elements of knowledge in the form of generalized statements that describe the important characteristics and relationships in the context of a studied phenomenon and are widely supported empirically. For example, the empirically proven relationship between the longterm abstention from changing the employer in Japanese companies and a much larger salary increase compared to U.S. companies is a typical stylized fact in economics. When using stylized facts in the context of BISE, a number of interesting questions arise: What are the typical stylized facts within BISE? How can stylized facts be obtained systematically? What is the importance of stylized facts in design-oriented disciplines? Which role do stylized facts play in practice? What is the difference between technological rules and stylized facts? To what extent can we consider stylized facts to be “technological” knowledge about cause-effect-relationships that can be utilized for the construction of artifacts of information and communication technology? Which role do stylized facts play in empirical research? Which contribution can stylized facts make for building theories in BISE if a multiperspective research approach is assumed? Currently, only scattered experience exists in the application of stylized facts in BISE (Fettke et al. 2010; Houy et al. 2009, 2011). In order to achieve a broad perspective on the issue in the course of this discussion, well-known representatives from the field of business administration, the German-speaking BISE as well as from Information Systems Research were invited to comment on the topic. The following authors accepted our invitation to this discussion (in alphabetical order): Prof. Dr. Ulrich Frank, Chair of Information Systems and Enterprise Modelling, University of Duisburg-Essen, Germany; Prof. Dr. Armin Heinzl, Chair of General Management and Information Systems, Mannheim University, Germany; Prof. Dr. Juhani Iivari, Department of Information Processing Science, Oulu University, Finland; Prof. Dr. Barbara E. Weisenberger, Chair of Controlling and Business Accounting, Justus-Liebig University of Giesen, Germany; Prof. Dr. Stephan Zelewski, Institute of Production and Industrial Information Management, University of Duisburg-Essen, Germany. Within their contributions the authors highlight different facets of the generation and application of stylized facts that appear relevant and important for BISE. Barbara E. Weisenberger outlines the concept and the derivation of stylized facts based on a case study in the field of IT-based controlling systems. Thus, several empirical studies have shown that the “increasing flexibility of IT systems in accounting and control has a positive impact on management accounting and control”. The author argues that the concept contributes to aggregate and structure fragmented knowledge in a research area, with particular emphasis on revealing research gaps. At the same time she points out that the derivation of stylized facts is the result of comprehensive research endeavors. The contribution by Stephan Zelewski considers the concept of stylized facts in the tension between the more designoriented German-speaking BISE on the one hand and the more behavioristic Anglo-Saxon Information Systems Research on the other. He argues that stylized facts are not directly but indirectly fruitful for the design-oriented BISE: Accordingly, stylized facts form a “seed of crystallization” for the development and testing of theories with causal explanatory power, making it possible to “explain and verify prognoses regarding alleged effects of the recommended design measures”. Despite the attractiveness of the concept, the author also points to difficulties in the implementation in current science. Armin Heinzl identifies application areas for stylized facts in BISE, especially

Employability of German Geography Graduates: The Mismatch between Knowledge Acquired and Competences Required

The employability of university graduates is a concern in higher education as labour markets change more and more rapidly. This is of particular relevance for multi-faceted subjects such as geography. Studies on employability have to consider to what degree a university education helps graduates start a career. The results of a survey of 257 geography graduates of JLU (Justus Liebig University) Giessen, Germany, indicate that the traditional curricula did not necessarily prepare German geographers adequately for their jobs. The graduates possess more knowledge than required but lack important competences and transferable skills that the job market demands. This may be partly remedied by the introduction of project-oriented classes.