Repetitive application of remote ischemic conditioning (RIC) in patients with peripheral arterial occlusive disease (PAOD) as a non-invasive treatment option: study protocol for a randomised controlled clinical trial

Background The best medical treatment (BMT) for most patients with early stage of peripheral arterial occlusive disease (PAOD) is often limited to gait training and pharmacological therapy besides endovascular surgery. The application of remote ischemic conditioning (RIC) has been described as a promising experimental strategy for the improvement of therapeutic outcome in cardiovascular disease but has not proven beneficial effects in clinical practice and treatment of PAOD yet. Methods Here we describe a prospective, randomized trial for the evaluation of possible effects of repeated application of RIC in patients with PAOD. This monocentric study will enrol 200 participants distributed to an intervention group receiving RIC + BMT and a control group only receiving BMT for four weeks. Patients are at least 18 years of age and have diagnosed PAOD Fontaine stage II b. Pain-free and total walking distance will be measured via treadmill test (primary endpoints). In addition, ankle-brachial index (ABI) and quality of life (QoL) will be assessed using the SF-36 and VascuQoL-6 questionnaire. Moreover, evaluation of markers for atherosclerosis, angiogenic profiling and mononuclear cell characterization will be performed using biochemical assays, proteome profiling arrays and flow cytometry (secondary endpoints). Discussion Our prospective, randomized monocentric trial is the first of its kind to analyse the effects of chronic and repetitive treatment with RIC in patients with PAOD and might provide important novel information on the molecular mechanisms associated with RIC in PAOD patients. Trial registration Prospectively registered in the German Clinical Trials Register (Deutsche Register Klinischer Studien) Registration number: DRKS00025735; Date of registration: 01.07.2021

LIFE-SHARE Project: Developing a Digitisation Strategy Toolkit

This poster will outline the Digitisation Strategy Toolkit created as part of the LIFE-SHARE project. The toolkit is based on the lifecycle model created by the LIFE project and explores the creation, acquisition, ingest, preservation (bit-stream and content) and access requirements for a digitisation strategy. This covers the policies and infrastructure required in libraries to establish successful practices. The toolkit also provides both internal and external resources to support the service. This poster will illustrate how the toolkit works effectively to support digitisation with examples from three case studies at the Universities of Leeds, Sheffield and York

Human monocytes subjected to ischaemia/reperfusion inhibit angiogenesis and wound healing in vitro

Objectives The sequence of initial tissue ischaemia and consecutive blood flow restoration leads to ischaemia/reperfusion (I/R) injury, which is typically characterized by a specific inflammatory response. Migrating monocytes seem to mediate the immune response in ischaemic tissues and influence detrimental as well as regenerative effects during I/R injury. Materials and methods To clarify the role of classical monocytes in I/R injury, isolated human monocytes were subjected to I/R in vitro (3 hours ischaemia followed by 24 hours of reperfusion). Cellular resilience, monocyte differentiation, cytokine secretion, as well as influence on endothelial tube formation, migration and cell recovery were investigated. Results We show that I/R supported an enhanced resilience of monocytes and induced intracellular phosphorylation of the prosurvival molecules Erk1/2 and Akt. FACS analysis showed no major alteration in monocyte subtype differentiation and surface marker expression under I/R. Further, our experiments revealed that I/R changes the cytokine secretion pattern, release of angiogenesis associated proteins and MMP-9 activity in supernatants of monocytes exposed to I/R. Supernatants from monocytes subjected to I/R attenuated endothelial tube formation as indicator for angiogenesis as well as endothelial cell migration and recovery. Conclusion In summary, monocytes showed no significant change in cellular integrity and monocyte subtype after I/R. Functionally, monocytes might have a rather detrimental influence during the initial phase of I/R, suppressing endothelial cell migration and neoangiogenesis

Pathogen burden, inflammation, proliferation and apoptosis in human in-stent restenosis - Tissue characteristics compared to primary atherosclerosis

Pathogenic events leading to in-stent restenosis (ISR) are still incompletely understood. Among others, inflammation, immune reactions, deregulated cell death and growth have been suggested. Therefore, atherectomy probes from 21 patients with symptomatic ISR were analyzed by immunohistochemistry for pathogen burden and compared to primary target lesions from 20 stable angina patients. While cytomegalovirus, herpes simplex virus, Epstein-Barr virus and Helicobacter pylori were not found in ISR, acute and/or persistent chlamydial infection were present in 6/21 of these lesions (29%). Expression of human heat shock protein 60 was found in 8/21 of probes (38%). Indicated by distinct signals of CD68, CD40 and CRP, inflammation was present in 5/21 (24%), 3/21 (14%) and 2/21 (10%) of ISR cases. Cell density of ISR was significantly higher than that of primary lesions ( 977 +/- 315 vs. 431 +/- 148 cells/mm(2); p < 0.001). There was no replicating cell as shown by Ki67 or PCNA. TUNEL+ cells indicating apoptosis were seen in 6/21 of ISR specimens (29%). Quantitative analysis revealed lower expression levels for each intimal determinant in ISR compared to primary atheroma (all p < 0.05). In summary, human ISR at the time of clinical presentation is characterized by low frequency of pathogen burden and inflammation, but pronounced hypercellularity, low apoptosis and absence of proliferation. Copyright (C) 2004 S. Karger AG, Basel

Standardized postnatal management of infants with congenital diaphragmatic hernia in Europe: The CDH EURO Consortium Consensus - 2015 Update

In 2010, the congenital diaphragmatic hernia (CDH) EURO Consortium published a standardized neonatal treatment protocol. Five years later, the number of participating centers has been raised from 13 to 22. In this article the relevant literature is updated, and consensus has been reached between the members of the CDH EURO Consortium. Key updated recommendations are: (1) planned delivery after a gestational age of 39 weeks in a high-volume tertiary center; (2) neuromuscular blocking agents to be avoided during initial treatment in the delivery room; (3) adapt treatment to reach a preductal saturation of between 80 and 95% and postductal saturation >70%; (4) target PaCO2 to be between 50 and 70 mm Hg; (5) conventional mechanical ventilation to be the optimal initial ventilation strategy, and (6) intravenous sildenafil to be considered in CDH patients with severe pulmonary hypertension. This article represents the current opinion of all consortium members in Europe for the optimal neonatal treatment of CDH

Influence of a Non-Adiabatic Turbocharger Model on Overall Engine Process Simulation of Turbocharged Passenger Car Diesel Engines

Die Gesamtprozess-Simulation abgasturboaufgeladener Motoren erfolgt unter Zuhilfenahme entsprechender Kennfelder für Verdichter und Turbine. Diese Kennfelder werden im Allgemeinen auf einem Turboladerprüfstand bei definierten Randbedingungen beim Turboladerhersteller gemessen. Die so ermittelten Kennfelder decken jedoch nur einen bestimmten Betriebsbereich des Turboladers ab, der Bereich kleiner Turboladerdrehzahlen, der für den motorischen Teil- und Schwachlastbetrieb relevant ist, wird nicht erfasst. Mathematisch basierte Extrapolationsalgorithmen machen diesen Bereich zwar zugänglich, die Genauigkeit der Ergebnisse ist aber zum Teil unzureichend. Die vorliegende Dissertation befasst sich zunächst mit der Abhängigkeit der allgemein bekannten Verdichter- und Turbinenwirkungsgrade von der Turbineneintrittstemperatur bei derart kleinen Turboladerdrehzahlen. Dazu wurden zu einem Turbolader Versuche auf einem Turboladerprüfstand, insbesondere bei extrem niedrigen Drehzahlen, bei inversen Verdichter-Druckverhältnissen als auch bei verschiedenen Turbineneintrittstemperaturen, durchgeführt. Als wesentliche Ursache der sich ergebenden Abhängigkeiten wurden die inneren Wärmeflüsse des Turboladers identifiziert, so dass zur Berücksichtigung dieser Abhängigkeiten das Diabatverhalten des Turboladers beschrieben werden muss. Die Dissertation greift einen physikalisch basierten, diabaten Modellansatz für den Turbolader auf, der die Turboladeraerodynamik von den Wärmeübertragungseffekten trennt und die bekannten Wirkungsgraddefinitionen für Verdichter und Turbine entsprechend erweitert. Es wird sowohl über die Leistungsfähigkeit einer stand-alone-Version dieser diabaten Turboladermodellierung als auch über das Zusammenwirken mit zwei Programmpaketen zur Motorgesamtprozess-Simulation (THEMOS, PROMO) berichtet. Stationäre Versuche zu einem PKW-Dieselmotor bildeten die Grundlage für eine schrittweise und ausführliche Analyse der Auswirkungen des Diabatansatzes auf die Simulationsergebnisse.Overall process simulation of turbocharged engines presently is based on measured turbocharger performance maps, which are typically determined by the turbocharger manufacturer on turbocharger test rigs under steady state conditions. Usually, these maps cover only a limited turbocharger operating range. The range of low turbocharger speeds, which is relevant for the part load engine operation range, is not included. Mathematically based extrapolation algorithms are able to calculate this range, but the results are partly inadequate. This dissertation deals with the dependency of compressor and turbine efficiencies on the turbine inlet temperature at such low turbocharger speeds. Experimental investigations were conducted on a turbocharger test rig especially at extremely low speeds, inverse compressor pressure ratios and different turbine inlet temperatures. The internal heat flow from the turbine to the compressor was detected to be the main cause of these dependencies. In order to consider these influences the non-adiabatic behaviour of the turbocharger should be described. A physically meaningful, non-adiabatic method of turbocharger performance prediction is picked up in this dissertation. This method takes into account the internal heat flow in turbochargers as well as the aerodynamic performance of the compressor and the turbine, respectively. At first it is referred about the capability of a stand-alone program using the turbocharger model proposed above, extending the performance prediction down to zero turbocharger speed. After integration into two program systems simulating the overall engine process this turbocharger model is subsequently verified by calculation/measurement comparisons. Steady state experiments with a passenger car diesel engine were performed for a stepwise and comprehensive impact study of the non-adiabatic turbocharger model on computational results of both, zero-dimensional (THEMOS) and one-dimensional (PROMO) engine process models

Strategies to Overcome the Barrier of Ischemic Microenvironment in Cell Therapy of Cardiovascular Disease

The transplantation of various immune cell types are promising approaches for the treatment of ischemic cardiovascular disease including myocardial infarction (MI) and peripheral arterial disease (PAD). Major limitation of these so-called Advanced Therapy Medicinal Products (ATMPs) is the ischemic microenvironment affecting cell homeostasis and limiting the demanded effect of the transplanted cell products. Accordingly, different clinical and experimental strategies have been evolved to overcome these obstacles. Here, we give a short review of the different experimental and clinical strategies to solve these issues due to ischemic cardiovascular disease