β1-Class Integrins Regulate the Development of Laminae and Folia in the Cerebral and Cerebellar Cortex

Mice that lack all beta1-class integrins in neurons and glia die prematurely after birth with severe brain malformations. Cortical hemispheres and cerebellar folia fuse, and cortical laminae are perturbed. These defects result from disorganization of the cortical marginal zone, where beta1-class integrins regulate glial endfeet anchorage, meningeal basement membrane remodeling, and formation of the Cajal-Retzius cell layer. Surprisingly, beta1-class integrins are not essential for neuron-glia interactions and neuronal migration during corticogenesis. The phenotype of the beta1-deficient mice resembles pathological changes observed in human cortical dysplasias, suggesting that defective integrin-mediated signal transduction contributes to the development of some of these diseases.

Infraspinatus Kontraktur beim Cavalier King Charles

Ein 6,5 Jahre alter Cavalier King Charles Spaniel wurde mit einer seit 6 Wochen bestehenden Lahmheit der linken Vorderextremität vorgestellt. In der klinischen Untersuchung wurden eine Abduktion der linken Vordergliedmaße, eine Atrophie des M. infraspinatus, M. supraspinatus und M. deltoideus, eine Dolenz bei Palpation bzw. Flexion des Schultergelenks sowie eine mittelgradige Hangbeinlahmheit mit charakteristischer Aussenrotation der Schulter festgestellt. Als Diagnose wurde eine Kontraktur des M. infraspinatus gestellt, und die komplette Tenektomie seiner Ansatzsehne führte zur Wiederherstellung der normalen Gliedmaßenfunktion.

The impact of neural invasion severity in gastrointestinal malignancies: a clinicopathological study.

OBJECTIVES Because neural invasion (NI) is still inconsistently reported and not well characterized within gastrointestinal malignancies (GIMs), our aim was to determine the exact prevalence and severity of NI and to elucidate the true impact of NI on patient's prognosis. BACKGROUND The union internationale contre le cancer (UICC) recently added NI as a novel parameter in the current TNM classification. However, there are only a few existing studies with specific focus on NI, so that the distinct role of NI in GIMs is still uncertain. MATERIALS AND METHODS NI was characterized in approximately 16,000 hematoxylin and eosin tissue sections from 2050 patients with adenocarcinoma of the esophagogastric junction (AEG)-I-III, squamous cell carcinoma (SCC) of the esophagus, gastric cancer (GC), colon cancer (CC), rectal cancer (RC), cholangiocellular cancer (CCC), hepatocellular cancer (HCC), and pancreatic cancer (PC). NI prevalence and severity was determined and related to patient's prognosis and survival. RESULTS NI prevalence largely varied between HCC/6%, CC/28%, RC/34%, AEG-I/36% and AEG-II/36%, SCC/37%, GC/38%, CCC/58%, and AEG-III/65% to PC/100%. NI severity score was uppermost in PC (24.9±1.9) and lowest in AEG-I (0.8±0.3). Multivariable analyses including age, sex, TNM stage, and grading revealed that the prevalence of NI was significantly associated with diminished survival in AEG-II/III, GC, and RC. However, increasing NI severity impaired survival in AEG-II/III and PC only. CONCLUSIONS NI prevalence and NI severity strongly vary within GIMs. Determination of NI severity in GIMs is a more precise tool than solely recording the presence of NI and revealed dismal prognostic impact on patients with AEG-II/III and PC. Evidently, NI is not a concomitant side feature in GIMs and, therefore, deserves special attention for improved patient stratification and individualized therapy after surgery.

Die Unfähigkeit zu schreiben: Eine Verarbeitungsgeschichte des Nationalsozialismus anhand der Briefe von Maria Gleit an Ernst Kreuder

Mit dem 8. Mai 1945 ist das Exil der aus dem nationalsozialistischen Deutschland und Österreich Geflohenen und Vertriebenen nicht beendet. Aber Versuche, Kontakt aufzunehmen und an alte Beziehungen anzuknüpfen, setzen ein, um Lebensumstände, Positionen, Stimmungen und aktuelle Entwicklungen zu klären. In den Beiträgen des Sammelbandes geht es um Briefe von Frauen unterschiedlicher sozialer Herkunft und Lage, politischer Überzeugung und beruflicher Ausbildung und Perspektive: Ella Bergmann- Michel, Ilse Bing, Erna Blencke, Erna Döblin, Maria Gleit, Gabriele Kätzler, Hildegard Kramer, Vera Lachmann, Luise von Leyden, Johanna Marum, Lili Pollatz, Anna Siemsen, Minna Specht, Hilde Spiel, Grete Weil und Alma S. Wittlin schreiben über traumatische Erfahrungen, über die NS-Verbrechen, die Entfremdung und auch über ihre Akkulturation im Exilland sowie über ihre Pläne und die Vorbereitung einer möglichen Rückkehr, sofern diese nicht kategorisch abgelehnt wird, und über ihre Hoffnungen und Enttäuschungen nach der Remigration.

Motivational profiles of sport event volunteers.

Aim of the study Due to the valuable contribution made by volunteers to sporting events, a better understanding of volunteers’ motivation is imperative for event managers in order to develop effective volunteer re-cruitment and retention strategies. The adoption of working conditions and task domains to the mo-tives and needs of volunteers is one of the key challenges in volunteer management. Conversely, an ignorance of the motives and needs of volunteers could negatively affect their performance and attitude, which will have negative consequences for the execution of events (Strigas & Jackson, 2003). In general, the motives of volunteers are located on a continuum between selflessness (e.g. helping others), and self-interest (e.g. pursuing one’s own interests). Furthermore, it should take into account that volunteers may be motivated by more than one need or goal, and therefore, configure different bundles of motives, resulting in heterogeneous types of motives for voluntary engagement (Dolnicar & Randle, 2007). Despite the extensive number of studies on the motives of sport event volunteers, only few studies focus on the analysis of individual motive profiles concerning volun-teering. Accordingly, we will take a closer look at the following questions: To what extent do volun-teers at sporting events differ in the motives of their engagement, and how can the volunteers be ade-quately classified? Theoretical Background According to the functional approach, relevant subjective motives are related to the outcomes and consequences that volunteering is supposed to lead to and to produce. This means, individuals’ mo-tives determine which incentives are anticipated in return for volunteering (e.g. increase in social contacts), and are important for engaging in volunteering, e.g. the choice between different oppor-tunities for voluntary activity, or different tasks (Stukas et al., 2009). Additionally, inter-individual differences of motive structures as well as matching motives in the reflections of voluntary activities will be considered by using a person-oriented approach. In the person-oriented approach, it is not the specific variables that are made the entities of investigation, but rather persons with a certain combination of characteristic features (Bergmann et al., 2003). Person-orientation in the field of sports event volunteers, it is therefore essential to implement an orientation towards people as a unit of analysis. Accordingly, individual motive profiles become the object of investigation. The individ-ual motive profiles permit a glimpse of intra-individual differences in the evaluation of different motive areas, and thus represent the real subjective perspective. Hence, a person will compare the importance of individual motives for his behaviour primarily in relation to other motives (e.g. social contacts are more important to me than material incentives), and make fewer comparisons with the assessments of other people. Methodology, research design and data analysis The motives of sports event volunteers were analysed in the context of the European Athletics Championships 2014 in Zürich. After data cleaning, the study sample contained a total of 1,169 volunteers, surveyed by an online questionnaire. The VMS-ISA scale developed by Bang and Chel-ladurai (2009) was used and replicated successfully by a confirmatory factor analysis. Accordingly, all seven factors of the scale were included in the subsequent cluster analysis to determine typical motive profiles of volunteers. Before proceeding with the cluster analysis, an intra-individual stand-ardization procedure (according to Spiel, 1998) was applied to take advantage of the intra-individual relationships between the motives of the volunteers. Intra-individual standardization means that every value of each motive dimension was related to the average individual level of ex-pectations. In the final step, motive profiles were determined using a hierarchic cluster analysis based on Ward’s method with squared Euclidean distances. Results, discussion and implications The results reveal that motivational processes differ among sports event volunteers, and that volunteers sometimes combine contradictory bundles of motives. In our study, four different volunteer motive profiles were identified and described by their positive levels on the individual motive dimension: the community supporters, the material incentive seekers, the social networkers, and the career and personal growth pursuers. To describe the four identified motive profiles in more detail and to externally validate them, the clusters were analysed in relation to socio-economic, sport-related, and voluntary work characteristics. This motive-based typology of sports event volunteers can provide valuable guidance for event managers in order to create distinctive and designable working conditions and tasks at sporting events that should, in relation to a person-oriented approach, be tailored to a wide range of individ-ual prerequisites. Furthermore, specific recruitment procedures and appropriate communication measures can be defined in order to approach certain groups of potential volunteers more effectively. References Bang, H., & Chelladurai, P. (2009). Development and validation of the volunteer motivations scale for international sporting events (VMS-ISE). International Journal Sport Management and Market-ing, 6, 332-350. Bergmann, L. R., Magnusson, D., & El-Khouri, B. M. (2003). Studying individual development in an interindividual context. Mahwah, NJ: Erlbaum. Dolnicar, S., & Randle, M. (2007). What motivates which volunteers? Psychographic heterogeneity among volunteers in Australia. Voluntas, 18, 135-155. Spiel, C. (1998). Four methodological approaches to the study of stability and change in develop-ment. Methods of Psychological Research Online, 3, 8-22. Stukas, A. A., Worth, K. A., Clary, E. G., & Snyder, M. (2009). The matching of motivations to affordances in the volunteer environment: an index for assessing the impact of multiple matches on volunteer outcomes. Nonprofit and Voluntary Sector Quarterly, 38, 5-28.

Structural Insight into Multivalent Galactoside Binding to Pseudomonas aeroginosa lectin LecA

Multivalent galactosides inhibiting Pseudomonas aeruginosa biofilms may help control this problematic pathogen. To understand the binding mode of tetravalent glycopeptide dendrimer GalAG2 [(Gal-β-OC6H4CO-Lys-Pro-Leu)4(Lys-Phe-Lys-Ile)2Lys-His-Ile-NH2] to its target lectin LecA, crystal structures of LecA complexes with divalent analog GalAG1 [(Gal-β-OC6H4CO-Lys-Pro-Leu)2Lys-Phe-Lys-Ile-NH2] and related glucose-triazole linked bis-galactosides 3u3 [Gal-β-O(CH2)n-(C2HN3)-4-Glc-β-(C2HN3)-[β-Glc-4-(N3HC2)]2-(CH2)n-O-β-Gal (n = 1)] and 5u3 (n = 3) were obtained, revealing a chelate bound 3u3, cross-linked 5u3, and monovalently bound GalAG1. Nevertheless, a chelate bound model better explaining their strong LecA binding and the absence of lectin aggregation was obtained by modeling for all three ligands. A model of the chelate bound GalAG2·LecA complex was also obtained rationalizing its unusually tight LecA binding (KD = 2.5 nM) and aggregation by lectin cross-linking. The very weak biofilm inhibition with divalent LecA inhibitors suggests that lectin aggregation is necessary for biofilm inhibition by GalAG2, pointing to multivalent glycoclusters as a unique opportunity to control P. aeruginosa biofilms.

Multivalency effects in Pseudomonas aeruginosa biofilm inhibition and dispersal by glycopeptide dendrimers targeting lectin LecA

The galactose specific lectin LecA partly mediates the formation of antibiotic resistant biofilms by Pseudomonas aeruginosa, an opportunistic pathogen causing lethal airways infections in immunocompromised and cystic fibrosis patients, suggesting that preventing LecA binding to natural saccharides might provide new opportunities for treatment. Here 8-fold (G3) and 16-fold (G4) galactosylated analogs of GalAG2, a tetravalent G2 glycopeptide dendrimer LecA ligand and P. aeruginosa biofilm inhibitor, were obtained by convergent chloroacetyl thioether (ClAc) ligation between 4-fold or 8-fold chloroacetylated dendrimer cores and digalactosylated dendritic arms. Hemagglutination inhibition, isothermal titration calorimetry and biofilm inhibition assays showed that G3 dendrimers bind LecA slightly better than their parent G2 dendrimers and induce complete biofilm inhibition and dispersal of P. aeruginosa biofilms, while G4 dendrimers show reduced binding and no biofilm inhibition. A binding model accounting for the observed saturation of glycopeptide dendrimer galactosyl groups and LecA binding sites is proposed based on the crystal structure of a G3 dendrimer LecA complex.

Interlaboratory variability of MIB1 staining in well-differentiated pancreatic neuroendocrine tumors

Neuroendocrine tumors (NET) are routinely graded and staged to judge prognosis. Proliferation index using MIB1 staining has been introduced to assess grading. There are vivid discussions on cutoff definitions, automated counting, and interobserver variability. However, no data exist regarding interlaboratory reproducibility for low proliferation indices which are of importance to discriminate between G1 and G2 NET. We performed MIB1 staining in three different university hospital-based pathology laboratories on a tissue micro array (TMA) of a well-characterized patient cohort, containing pancreatic NET of 61 patients. To calculate the proliferation index, number of positive tumor nuclei was divided by the total number of tumor nuclei. Labeling index was compared to mitotic counts in whole tissue sections and to clinical outcome. Linear regression analysis, intraclass comparison, and log-rank analysis were performed. Intraclass correlation showed moderate-to-fair agreement. Especially low proliferating tumors were affected by interlaboratory differences. Log-rank analysis was performed for each lab and resulted in three different cutoffs (5.0, 3.0, and 0.5 %). Every calculated cutoff stratified the patient cohort to a significant extent for the underlying stain (p < 0.001, <0.001, and <0.001) but showed no or lesser significance when applied to the other stains. Significant and relevant interlab differences for MIB1 exist. Since the MIB1 proliferation index influences grading, local cutoffs or external standardization should urgently be introduced to achieve reliability and reproducibility.

Assessment of the Breakaway Torque at the Posterior Pelvic Ring in Human Cadavers

PURPOSE To enhance the diminished screw purchase in cancellous, osteoporotic bone following the fixation of posterior pelvic ring injuries by iliosacral screws an increased bone-implant contact area using modificated screws, techniques or bone cement may become necessary. The aim of the study was to identify sites within the pathway of iliosacral screws requiring modifications of the local bone or the design of instrumentations placed at this site. MATERIALS AND METHODS The breakaway torque was measured mechanically at the iliosacral joint ("ISJ"), the sacral lateral mass ("SLM") and the center of the S1 ("CS1"), at a superior and an inferior site under fluoroscopic control on five human cadaveric specimens (3 female; mean age 87 years, range: 76-99) using the DensiProbe™Spine device. RESULTS The measured median (range) breakaway torque was 0.63 Nm (0.31-2.52) at the "iliosacral joint", 0.14 Nm (0.05-1.22) at the "sacral lateral mass", 0.57 Nm (0.05-1.42) at the "S1 center." The "sacral lateral mass" breakaway torque was lower than compared to that at the "iliosacral joint" (p < .001) or "S1 center" (p < .001). The median (range) breakaway torque measured at all superior measurement points was 0.52 Nm (0.10-2.52), and 0.48 Nm (0.05-1.18) at all inferior sites. The observed difference was statistically significant (p < .05). CONCLUSIONS The lateral mass of the sacrum provides the lowest bone quality for implant anchorage. Iliosacral screws should be placed as superior as safely possible, should bridge the iliosacral joint and may allow for cement application at the lateral mass of the sacrum through perforations.

Genome-wide Association Studies Identify Genetic Loci Associated with Albuminuria in Diabetes

Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and associate with increased risk for end-stage renal disease and cardiovascular events. To gain insight into the pathophysiological mechanisms underlying albuminuria, we conducted meta-analyses of genome-wide association studies and independent replication in up to 5,825 individuals of European ancestry with diabetes mellitus and up to 46,061 without diabetes, followed by functional studies. Known associations of variants in CUBN, encoding cubilin, with the urinary albumin-to-creatinine ratio (UACR) were confirmed in the overall sample (p=2.4*10(-10)). Gene-by-diabetes interactions were detected and confirmed for variants in HS6ST1 and near RAB38/CTSC. SNPs at these loci demonstrated a genetic effect on UACR in individuals with but not without diabetes. The change in average UACR per minor allele was 21% for HS6ST1 and 13% for RAB38/CTSC (p=6.3*10(-7) and 5.8*10(-7), respectively). Experiments using streptozotocin-treated diabetic Rab38 knockout and control rats showed higher urinary albumin concentrations and reduced amounts of megalin and cubilin at the proximal tubule cell surface in Rab38 knockout vs. control rats. Relative expression of RAB38 was higher in tubuli of patients with diabetic kidney disease compared to controls. The loci identified here confirm known and highlight novel pathways influencing albuminuria.