035— Working Memory and Locomotor Activity in Old and Young Mice Fed a Ketogenic Diet

The ketogenic diet (KD), a high-fat, low-carb diet, has recently been used to treat disorders associated with an inflexibility of cognitive and behavioral routines, such as dementia and autism spectrum disorder. However, there has been little investigation into how KD’s beneficial effects on cognitive behavior may change with age. Here, we show the effects of KD on performance in a working memory task and locomotor activity in young and old C57BL6/J mice. In Experiment 1, we used a Barnes Maze to assess working memory. In the Barnes Maze, mice locate an escape box under a target hole by using spatial cues. Each day the target hole is moved to a new location. We found that mice on KD performed better, indicated by shorter latencies to find the target hole. However, only the young mice on KD made fewer errors. To check for differences in activity between mice on KD and mice fed a normal diet, Experiment 2 employed a 1h locomotor test. KD increased horizontal activity in young and old mice. Thus, regardless of age, mice fed KD performed better in a working memory task and were more active. Findings may be useful for using KD as a therapy

Hemodynamic evaluation of anesthetized baboons and piglets by transpulmonary thermodilution: Normal values and interspecies differences with respect to xenotransplantation

Background Transpulmonary thermodilution is well established as a tool for in-depth hemodynamic monitoring of critically ill patients during surgical procedures and intensive care. It permits easy assessment of graft function following cardiac transplantation and guides post-operative volume and catecholamine therapy. Since no pulmonary catheter is needed, transpulmonary thermodilution could be useful in experimental cardiac pig-to-baboon xenotransplantation. However, normal values for healthy animals have not yet been reported. Here, we present data from piglets and baboons before xenotransplantation experiments and highlight differences between the two species and human reference values. Methods Transpulmonary thermodilution from baboons (body weight 10-34 kg) and piglets (body weight 10-38kg) were analyzed. Measurements were taken in steady state after induction of general anesthesia before surgical procedures commenced. Cardiac index (CI), mean arterial pressure (MAP), systemic vascular resistance index (SVRI), parameters quantifying cardiac filling (global end-diastolic volume index, GEDI), and pulmonary edema (extravascular lung water, ELWI) were assessed. Results Preload, afterload, and contractility parameters clearly correlated with total body weight or body surface area. Baboons had lower CI values than weight-matched piglets (4.2 +/- 0.9l/min/m(2) vs 5.3 +/- 1.0/min/m(2), P < .01). MAP and SVRI were higher in baboons than piglets (MAP: 99 +/- 22 mm Hg vs 62 +/- 11 mm Hg, P < .01;SVRI: 1823 +/- 581 dyn*s/cm(5)*m(2) vs 827 +/- 204 dyn*s/cm(5)*m(2), P < .01). GEDI and ELWI did differ significantly between both species, but measurements were within similar ranges (GEDI: 523 +/- 103 mL/m(2) vs 433 +/- 78 mL/m(2), P < .01;ELWI: 10 +/- 3 mL/kg vs 11 +/- 2 mL/kg, P < .01). Regarding adult human reference values, CI was similar to both baboons and piglets, but all other parameters were different. Conclusions Parameters of preload, afterload, and contractility differ between baboons and piglets. In particular, baboons have a much higher afterload than piglets, which might be instrumental in causing perioperative xenograft dysfunction and post-operative myocardial hypertrophy after orthotopic pig-to-baboon cardiac xenotransplantation. Most transpulmonary thermodilution-derived parameters obtained from healthy piglets and baboons lie outside the reference ranges for humans, so human normal values should not be used to guide treatment in those animals. Our data provide reference values as a basis for developing algorithms for perioperative hemodynamic management in pig-to-baboon cardiac xenotransplantation

Identification of Ocular Autoantigens Associated With Juvenile Idiopathic Arthritis-Associated Uveitis

The purpose of the current study was to analyze the binding patterns of serum autoantibodies from juvenile idiopathic arthritis (JIA) and JIA-associated uveitis (JIAU) patients to proteomes from different ocular tissues and to identify potential ocular autoantigens in JIAU. Proteomes from porcine iris, ciliary body, or retina tissue were isolated, separated using 2D-gel electrophoresis, and transferred to a blotting membrane. The binding pattern of serum antibodies from JIA or JIAU patients or healthy controls to ocular proteins was visualized by using anti-human IgG secondary antibodies and chemiluminescence reaction. Selected protein spots were excised from silver-stained 2D gels and subjected to mass spectrometry. Serum antibodies binding to ocular proteins were detected in all patient groups and healthy controls. Irrespective of the patient groups, serum antibodies bound to 49 different protein spots of the retina proteome, to 53 of the ciliary body proteome, and to 44 of the iris proteome. The relative binding frequency of sera to these iris protein spots was significantly higher in JIAU than in JIA patients or healthy controls. Particularly in JIAU patients, cluster analyses indicated a broad range of serum antibodies directed against ocular antigens, mostly in the iris proteome. Iris proteins frequently bound by serum antibodies in all groups were identified as tubulin beta chain, vimentin, ATP synthase subunit beta, actin, and L-lactate dehydrogenase B chain. Iris proteins exclusively bound by JIAU serum antibodies were heat shock cognate 71 kDa protein and keratin. Although serum autoantibody binding to ocular antigens was not disease-specific, a significant diversity of autoantibodies against a broad range of antigens, particularly from the iris tissue, was detected in JIAU patients. As the iris is a major site of inflammation in JIAU, the present data give further evidence that autoantibodies may be involved in JIAU immunopathology

Long-term effects of preeclampsia on maternal cardiovascular health and postpartum utilization of primary care: an observational claims data study

Purpose: Preeclampsia occurs in up to 15% of pregnancies and constitutes a major risk factor for cardiovascular disease. This observational cohort study aimed to examine the association between preeclamptic pregnancies and cardiovascular outcomes as well as primary and specialized care utilization after delivery. Methods: Using statutory claims data we identified women with singleton live births between 2010 and 2017. Main outcomes included the occurrence of either hypertension or cardiovascular disease after one or more preeclamptic pregnancies, number of contacts to a general practitioner or cardiologist after delivery and prescribed antihypertensive medication. Data were analyzed using Cox proportional hazard regression models adjusted for maternal age, diabetes, dyslipidemia, and obesity. Results: The study cohort consisted of 181,574 women with 240,698 births. Women who experienced preeclampsia once had an increased risk for cardiovascular (hazard ratio, HR = 1.29) or hypertensive (HR = 4.13) events. In women affected by recurrent preeclampsia, risks were even higher to develop cardiovascular disease (HR = 1.53) or hypertension (HR = 6.01). In the following years after delivery, general practitioners were seen frequently, whereas cardiologists were consulted rarely (0.3 and 2.4%). Conclusion: Women affected by preeclampsia experience an increased risk of developing chronic hypertension and cardiovascular disease, especially those with recurrent preeclampsia. Future medical guidelines should take this potential risk into account

The NMDA agonist D-cycloserine facilitates fear memory consolidation in humans

Animal research suggests that the consolidation of fear and extinction memories depends on N-methyl D-aspartate (NMDA)- type glutamate receptors. Using a fear conditioning and extinction paradigm in healthy normal volunteers, we show that postlearning administration of the NMDA partial agonist D-cycloserine (DCS) facilitates fear memory consolidation, evidenced behaviorally by enhanced skin conductance responses, relative to placebo, for presentations of a conditioned stimulus (CS) at a memory test performed 72 h later. DCS also enhanced CS-evoked neural responses in a posterior hippocampus/collateral sulcus region and in the medial prefrontal cortex at test. Our data suggest a role for NMDA receptors in regulating fear memory consolidation in humans

Hemodynamics in pig‐to‐baboon heterotopic thoracic cardiac xenotransplantation: Recovery from perioperative cardiac xenograft dysfunction and impairment by cardiac overgrowth

Introduction Orthotopic cardiac xenotransplantation has seen notable improvement, leading to the first compassionate use in 2022. However, it remains challenging to define the clinical application of cardiac xenotransplantation, including the back-up strategy in case of xenograft failure. In this regard, the heterotopic thoracic technique could be an alternative to the orthotopic procedure. We present hemodynamic data of heterotopic thoracic pig-to-baboon transplantation experiments, focusing on perioperative xenograft dysfunction and xenograft overgrowth. Methods We used 17 genetically modified piglets as donors for heterotopic thoracic xenogeneic cardiac transplantation into captive-bred baboons. In all animals, pressure probes were implanted in the graft's left ventricle and the recipient's ascending aorta and hemodynamic data (graft pressure, aortic pressure and recipient's heart rate) were recorded continuously. Results Aortic pressures and heart rates of the recipients’ hearts were postoperatively stable in all experiments. After reperfusion, three grafts presented with low left ventricular pressure indicating perioperative cardiac dysfunction (PCXD). These animals recovered from PCXD within 48 h under support of the recipient's heart and there was no difference in survival compared to the other 14 ones. After 48 h, graft pressure increased up to 200 mmHg in all 17 animals with two different time-patterns. This led to a progressive gradient between graft and aortic pressure. With increasing gradient, the grafts stopped contributing to cardiac output. Grafts showed a marked weight increase from implantation to explantation. Conclusion The heterotopic thoracic cardiac xenotransplantation technique is a possible method to overcome PCXD in early clinical trials and an experimental tool to get a better understanding of PCXD. The peculiar hemodynamic situation of increasing graft pressure but missing graft's output indicates outflow tract obstruction due to cardiac overgrowth. The heterotopic thoracic technique should be successful when using current strategies of immunosuppression, organ preservation and donor pigs with smaller body and organ size

Building in Quatar - Field excursion of the Faculty of Civil Engineering of the HTWG Konstanz

Die große Exkursion 2010 der Fakultät Bauingenieurwesen führte in das Emirat Qatar am persischen Golf. Qatar verfügt über 15% der weltweiten Reserven anErdgas und investiert u.a. in Infrastruktur- und Bau¬maßnahmen. Deutsche Firmen sind an diesem Aufbau beteiligt. Bei der Exkursion wurden verschiedene Hoch- und Tiefbaustellen, „Mega-Projekte“ deutscher Unternehmen, aber auch eines arabischen Baukonzerns besucht. Auch das Ausstellungszentrum der Deutschen Bahn stand auf dem Programm. Der Bericht gibt die Eindrücke beim Besuch der Projekte wie auch die Reiseerlebnisse wieder.The student excursion of the University of Applied Sciences, Konstanz, Germany, lead to the Emirat of Qatar at the Persian Gulf. The country possesses 15% of the reserves of natural gas and is investing in building and infrastructures measures. German companies are part of this development. During the excursion different structural sites of “mega-projects” of German and Arabic Companies as well as the exposition Center of the “Deutsche Bahn” have been visited

Human alveolar progenitors generate dual lineage bronchioalveolar organoids

Mechanisms of epithelial renewal in the alveolar compartment remain incompletely understood. To this end, we aimed to characterize alveolar progenitors. Single-cell RNA-sequencing (scRNA-seq) analysis of the HTII-280+/EpCAM+ population from adult human lung revealed subclusters enriched for adult stem cell signature (ASCS) genes. We found that alveolar progenitors in organoid culture in vitro show phenotypic lineage plasticity as they can yield alveolar or bronchial cell-type progeny. The direction of the differentiation is dependent on the presence of the GSK-3β inhibitor, CHIR99021. By RNA-seq profiling of GSK-3β knockdown organoids we identified additional candidate target genes of the inhibitor, among others FOXM1 and EGF. This gives evidence of Wnt pathway independent regulatory mechanisms of alveolar specification. Following influenza A virus (IAV) infection organoids showed a similar response as lung tissue explants which confirms their suitability for studies of sequelae of pathogen-host interaction

Did aid promote democracy in Africa?: the role of technical assistance in Africa’s transitions

Did foreign aid impede or catalyze democratization in Africa in the 1990s? We argue that after the Cold War, donors increased their use of technical assistance in aid packages, improving their monitoring capacity and thus reducing autocrats’ ability to use aid for patronage. To remain in power, autocrats responded by conceding political rights to their opponents—from legalizing opposition parties to staging elections. We test our theory with panel data for all sub-Saharan African countries. While other factors played pivotal roles in Africa’s political liberalization, we find technical assistance helps to explain the timing and extent of Africa’s democratization

Abschlussbericht des Forschungsprojekts "Broker für Dynamische Produktionsnetzwerke"

Der Broker für dynamische Produktionsnetzwerke (DPNB) ist ein vom Bundesministerium für Bildung und Forschung (BMBF) gefördertes und durch den Projektträger Karlsruhe (PTKA) betreutes Forschungsprojekt zwischen sieben Partnern aus Wissenschaft und Wirtschaft mit einer Laufzeit von Januar 2019 bis einschließlich Dezember 2021. Über den Einsatz von Cloud Manufacturing sowie Hard- und Software-Komponenten bei den teilnehmenden Unternehmen, sollen Kapazitätsanbieter mit Kapazitätsnachfrager verbunden werden. Handelbare Kapazitäten sind in diesem Falle Maschinen-, sowie Transport- und Montagekapazitäten, um Supply Chains anhand des Anwendungsfalls der Blechindustrie möglichst umfassend abzubilden. Der vorliegende Abschlussbericht fasst den Stand der Technik sowie die Erkenntnisse aus dem Projekt zusammen. Außerdem wird ein Überblick über die Projektstruktur sowie die Projektpartner gegeben