Lymph Node Transplantation and Its Immunological Significance in Animal Models

Lymph nodes (LNs) are distributed all over the body and whatever the site consists of the same cell populations. However, there are great differences between LN from different draining areas. For example, in mesenteric LN, homing molecules, for example, CCR9 and α4β7 integrin, were induced and cytokines, for example, IL-4, were produced on higher levels compared to peripheral LN. To study the immunological functions of LN, LN transplantation was performed in some specific areas using different animal models. Many groups investigated not only the regeneration of transplanted LN but also the induction of immune responses or tolerance after transplantation. Existing differences between LNs were still detectable after transplantation. Most important, stromal cells of the LN were identified as responsible for these differences. They survive during regeneration and were shown to reconstruct not only the structure of the new LN but also the microenvironment

Stromal mesenteric lymph node cells are essential for the generation of gut-homing T cells in vivo

T cells primed in the gut-draining mesenteric lymph nodes (mLN) are imprinted to express α4β7-integrin and chemokine receptor CCR9, thereby enabling lymphocytes to migrate to the small intestine. In vitro activation by intestinal dendritic cells (DC) or addition of retinoic acid (RA) is sufficient to instruct expression of these gut-homing molecules. We report that in vivo stroma cells, but not DC, allow the mLN to induce the generation of gut tropism. Peripheral LN (pLN) transplanted into the gut mesenteries fail to support the generation of gut-homing T cells, even though gut-derived DC enter the transplants and prime T cells. DC that fail to induce α4β7-integrin and CCR9 in vitro readily induce these factors in vivo upon injection into mLN afferent lymphatics. Moreover, uniquely mesenteric but not pLN stroma cells express high levels of RA-producing enzymes and support induction of CCR9 on activated T cells in vitro. These results demonstrate a hitherto unrecognized contribution of stromal cell delivered signals, including RA, on the imprinting of tissue tropism in vivo

Support Vector Machine Analysis of Functional Magnetic Resonance Imaging of Interoception Does Not Reliably Predict Individual Outcomes of Cognitive Behavioral Therapy in Panic Disorder with Agoraphobia

Background: The approach to apply multivariate pattern analyses based on neuro imaging data for outcome prediction holds out the prospect to improve therapeutic decisions in mental disorders. Patients suffering from panic disorder with agoraphobia (PD/AG) often exhibit an increased perception of bodily sensations. The purpose of this investigation was to assess whether multivariate classification applied to a functional magnetic resonance imaging (fMRI) interoception paradigm can predict individual responses to cognitive behavioral therapy (CBT) in PD/AG. Methods: This analysis is based on pretreatment fMRI data during an interoceptive challenge from a multicenter trial of the German PANIC-NET. Patients with DSM-IV PD/AG were dichotomized as responders (n = 30) or non-responders (n = 29) based on the primary outcome (Hamilton Anxiety Scale Reduction ≥50%) after 6 weeks of CBT (2 h/week). fMRI parametric maps were used as features for response classification with linear support vector machines (SVM) with or without automated feature selection. Predictive accuracies were assessed using cross validation and permutation testing. The influence of methodological parameters and the predictive ability for specific interoception-related symptom reduction were further evaluated. Results: SVM did not reach sufficient overall predictive accuracies (38.0–54.2%) for anxiety reduction in the primary outcome. In the exploratory analyses, better accuracies (66.7%) were achieved for predicting interoception-specific symptom relief as an alternative outcome domain. Subtle information regarding this alternative response criterion but not the primary outcome was revealed by post hoc univariate comparisons. Conclusion: In contrast to reports on other neurofunctional probes, SVM based on an interoception paradigm was not able to reliably predict individual response to CBT. Results speak against the clinical applicability of this technique

Association of perinatal sentinel events, placental pathology and cerebral MRI in neonates with hypoxic-ischemic encephalopathy receiving therapeutic hypothermia

OBJECTIVE: Placental pathology might provide information on the etiology of hypoxic-ischemic encephalopathy (HIE). To evaluate the association of perinatal sentinel events (PSE), placental pathology and cerebral MRI in cooled neonates with moderate/severe HIE. STUDY DESIGN: Retrospective analysis of 52 neonates with HIE registered in the Swiss National Asphyxia and Cooling Register 2011-2019. PSE and Non-PSE groups were tested for association with placental pathology. Placental pathology categories were correlated with MRI scores. RESULTS: In total, 14/52 neonates (27%) had a PSE, 38 neonates (73%) did not have a PSE. There was no evidence for an association of occurrence of PSE and placental pathologies (p = 0.364). Neonates with high MRI scores tended to have more often chronic pathologies in their placentas than acute pathologies or normal placentas (p = 0.067). CONCLUSION: Independent of the occurrence of PSE, chronic placental pathologies might be associated with more severe brain injury and needs further study

Placental findings are not associated with neurodevelopmental outcome in neonates with hypoxic-ischemic encephalopathy - an 11-year single-center experience

OBJECTIVES: Although neonates with moderate to severe hypoxic ischemic encephalopathy (HIE) receive therapeutic hypothermia (TH), 40-50% die or have significant neurological disability. The aim of this study is to analyse the association of placental pathology and neurodevelopmental outcome in cooled neonates with HIE at 18-24 months of age. METHODS: Retrospective analysis of prospectively collected data on 120 neonates registered in the Swiss National Asphyxia and Cooling Register born between 2007 and 2017. This descriptive study examines the frequency and range of pathologic findings in placentas of neonates with HIE. Placenta pathology was available of 69/120 neonates, whose results are summarized as placental findings. As neonates with HIE staged Sarnat score 1 (21/69) did not routinely undergo follow-up assessments and of six neonates staged Sarnat Score 2/3 no follow-up assessments were available, 42/48 (88%) neonates remain to assess the association between placental findings and outcome. RESULTS: Of the 42/48 (88%) neonates with available follow up 29% (12/42) neonates died. Major placenta abnormalities occurred in 48% (20/42). Major placenta abnormality was neither associated with outcome at 18-24 months of age (OR 1.75 [95% CI 0.50-6.36, p=0.381]), nor with death by 2 years of age (OR 1.96 [95% CI 0.53-7.78, p=0.320]). CONCLUSIONS: In this study cohort there could not be shown an association between the placenta findings and the neurodevelopmental outcome at 18-24 months of age

Familie - Generation - Institution. Generationenkonzepte in der Vormoderne

Dieser Band versammelt Beiträge zu Generationenbeziehungen und Generationenkonzepten in der Vormoderne, die auf eine Tagung des DFG-Graduiertenkollegs 'Generationenbewusstsein und Generationenkonflikte in Antike und Mittelalter' in Bamberg zurückgehen. Die behandelten Untersuchungsgegenstände reichen von den antiken Diadochenreichen über die ottonische Königsfamilie des 10. und 11. Jahrhunderts bis zum frühneuzeitlichen Landadel Westfalens. Dabei werden historische, literaturwissenschaftliche und soziologische Fragestellungen aufgegriffen, um den Erkenntniswert des Konzepts 'Generation' interdisziplinär zu diskutieren.This volume brings together contributions on generational relations and concepts of generation in Early Modernity given on the occasion of a conference organized at Bamberg by the Research Training Group of the German Research Foundation (DFG) 'Generational Awareness and Generational Conflicts in Antiquity and the Middle Ages'. The topics ranged from the ancient Diadoch kingdoms to the history of the Ottonian royal family of the 10th and 11th centuries and the early modern landed gentry in Westfalia. Addressing questions from historical, literary and social studies the validity of the concept of 'generation' was discussed among scholars and students from a variety of disciplines

The 'Survivorship Passport' for childhood cancer survivors

Background: Currently, there are between 300,000 and 500,000 childhood cancer survivors (CCSs) in Europe. A significant proportion is at high risk, and at least 60% of them develop adverse health-related outcomes that can appear several years after treatment completion. Many survivors are unaware of their personal risk, and there seems to be a general lack of information among healthcare providers about pathophysiology and natural history of treatment-related complications. This can generate incorrect or delayed diagnosis and treatments. Method: The Survivorship Passport (SurPass) consists of electronic documents, which summarise the clinical history of the childhood or adolescent cancer survivor. It was developed by paediatric oncologists of the PanCare and SIOPE networks and IT experts of Cineca, together with parents, patients, and survivors' organisations within the European Union–funded European Network for Cancer research in Children and Adolescents. It consists of a template of a web-based, simply written document, translatable in all European languages, to be given to each CCS. The SurPass provides a summary of each survivor's clinical history, with detailed information about the original cancer and of treatments received, together with personalised follow-up and screening recommendations based on guidelines published by the International Guidelines Harmonization Group and PanCareSurFup. Results: The SurPass data schema contains a maximum of 168 variables and uses internationally approved nomenclature, except for radiotherapy fields, where a new classification was defined by radiotherapy experts. The survivor-specific screening recommendations are mainly based on treatment received and are automatically suggested, thanks to built-in algorithms. These may be adapted and further individualised by the treating physician in case of special disease and survivor circumstances. The SurPass was tested at the Istituto Giannina Gaslini, Italy, and received positive feedback. It is now being integrated at the institutional, regional and national level. Conclusions: The SurPass is potentially an essential tool for improved and more harmonised follow-up of CCS. It also has the potential to be a useful tool for empowering CCSs to be responsible for their own well-being and preventing adverse events whenever possible. With sufficient commitment on the European level, this solution should increase the capacity to respond more effectively to the needs of European CCS

Websitemarketing deutscher Hochschulen zur Anwerbung internationaler Studierender: eine Evaluation ausgewählter Websites sowie Hinweise zur Gestaltung der Websites im Interesse eines erfolgreichen internationalen Hochschulmarketings

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