Optimiertes Hands-on-Trainingsphantom für die ERCP | Evaluation und Vermeidung von Strahlenbelastung

Die inzwischen meist mit therapeutischer Intention durchgeführte ERCP, die „Königsdisziplin“ der flexiblen Endoskopie, stellt aufgrund ihrer klinischen und technischen Komplexität nach wie vor eine sehr große Herausforderung für die endoskopische Ausbildung dar. Exzellente anatomische, physiologische, klinische und apparative Kenntnisse sowie ausgeprägtes manuelles Geschick sind nötig, um im klinischen Betrieb mit limitierten Fallzahlen eine ausreichende Kompetenz auf diesem Gebiet zu entwickeln. Die immer noch weit verbreitete endoskopische Ausbildung am Patienten als „humanem Versuchskaninchen“ ist inzwischen als eindeutig unethisch zu betrachten, da Trainingsalternativen existieren. Die Voraussetzungen für ein effektives Training, nämlich eine patientenanaloge Anatomie mit realistischen Pathologien, didaktische Konzepte mit beliebiger Wiederholbarkeit der Interventionen, die Verwendung von Endoskopen und Instrumentarium aus dem klinischen Alltagsbetrieb und das Vermeiden von Ethik- und Hygieneproblemen – wie bei Tierversuchen und Biomodellen – waren bislang unzulänglich oder überhaupt nicht gelöst. Mechanische Trainingsmodelle eignen sich aufgrund anatomischer und haptischer Defizite nur für absolute Anfänger. Die weit verbreiteten Biomodelle – prinzipiell geeignet für Anfänger und Fortgeschrittene – korrelieren nicht mit der humanen Anatomie, zudem sind sie in der Wiederholbarkeit der Interventionen eingeschränkt und bieten erhebliche Probleme mit Logistik und Hygiene. Virtuelle Simulatoren (sehr kostspielig, aufwendig und kaum verfügbar) sind in ihrem Trainingsspektrum limitiert und bieten unzureichendes haptisches Feedback. Im Rahmen dieser Arbeit wurden Prototypen des Tübinger hands-on ERCP-Trainingsphantoms Biliphant in allen wesentlichen Punkten überarbeitet und durch zusätzliche Module ergänzt, die nach anatomischen, klinischen und didaktischen Erfordernissen neu entwickelt und modellbautechnisch realisiert wurden. Dabei wurden viele Modellelemente verbessert bzw. neu konzipiert und für eine Kleinserienreife vorbereitet. Als Durchbruch für den Modellbau hat sich hier die Einführung der 3D-Druck Technologie erwiesen, für die modernste Hardware und Software genutzt wurden. Das auf dieser Grundlage realisierte, neue Hands-on-Phantom für die ERCP erfüllt auch anspruchsvolle Anforderungen: - Exakte Nachbildung der menschlichen Anatomie des oberen Gastrointestinaltraktes inklusive des bilio-pankreatischen Systems - Modular auswechselbare Gangsysteme (Gallengänge bis zur 4. Ordnung, Pankreasgang) auf der Grundlage klinischer Bildgebung (3D-Rekonstruktionen) realisiert - Interventionsfähige pathologische Strukturen (Tumore, Stenosen, Steine) ausnahmslos aus künstlichem Gewebe, keine tierischen Organe oder Materialien - Realistische Optik und Haptik - Ethische und hygienische Unbedenklichkeit - Verwendung von Klinik-analogem Equipment und Instrumentarium, keine speziellen Tier-Endoskope/-instrumente erforderlich - Alle denkbaren ERCP-Interventionen möglich (Biopsie, alle HF- und APC-Applikationen an der Papille, alle Arten von Stenosetherapie, Stenting, Steintherapie inkl. mechanische Lithotripsie und EHL, Cholangioskopie, etc.) - Beliebige Wiederholbarkeit aller Interventionen - Modularer Aufbau für verschiedene Trainingslevel, individuelle Phantomgestaltung (z. B. Nachbildung realer Patientenfälle) durch die Nutzung des 3D-Drucks - Virtuelles Röntgen-Simulations-Modul (RöSIM) für zeitlich unbegrenztes, ERCP-Training in Echtzeit ohne jede Strahlenbelastung In der ausführlichen Evaluation des Modells konnte gezeigt werden, dass Anfänger und Experten das Phantom gleichermaßen als sehr gut bewerten. Das betrifft vor allem die Bereiche Anatomie, Röntgendarstellung, Papillenanatomie und die Realistik der verschiedenen Interventionen (explizit die verschiedenen Möglichkeiten der Papillotomie). In der Gesamtbewertung der diagnostischen und therapeutischen Möglichkeiten wurde eine herausragend gute Bewertung des Modells erreicht, auch die sehr positiven individuellen Rückmeldungen der Teilnehmer aus zahlreichen Kursen belegen dies. Erstmals wurde anhand von individuellen Lernkurven zwischen Anfängern und Experten klar unterschieden und die Validität des Phantoms damit bestätigt. Insbesondere zeigte sich ein deutlicher Lernfortschritt bei den supervidierten Anfängern. Das alles zeigt die bedeutende Rolle dieses Tübinger Trainingsmodells für die ERCP-Ausbildung. Insgesamt konnte mit dem in dieser Arbeit entwickelten Hands-on-Phantom Biliphant eine neue Dimension von Trainingsmodellen für die ERCP erreicht werden, die zweifellos der Aus- und Weiterbildung sowie der Kompetenz von Endoskopikern zugutekommt. Des Weiteren bieten sich vielerlei Möglichkeiten für andere Zielgruppen, wie z. B. Studenten, Assistenzpersonal und vor allem auch für die Forschung und für die Entwicklung im Bereich der medizintechnischen Industrie.ERCP continues to be the supreme discipline of flexible endoscopy. Due to its clinical and technical complexity and mostly performed with therapeutic intent, ERCP training remains a major challenge in endoscopic education. Excellent anatomical, physiological, clinical, and instrumental knowledge as well as distinct manual skills are necessary to develop sufficient competence in this field of limited case numbers. Common practice of endoscopic training on patients as "human guinea pigs" – still widely used – is clearly considered to be unethical as training alternatives do exist. The preconditions for effective training, namely patient-analog anatomy with realistic pathologies, didactic concepts with random repeatability of interventions, the use of endoscopes and instruments from everyday clinical practice, and the absence of ethics and hygiene problems – as in animal- and biomodels – have so far been inadequately solved or not solved at all. Mechanical training models are only appropriate for beginners due to their anatomical and tactile deficits. The widely used biomodels – generally suitable for beginners and experienced clinicians – do not correlate with human anatomy, and they are also limited in the repetitiveness of interventions. In addition, they offer significant logistical and hygienical problems. Virtual simulators (highly expensive, elaborate and barely available) are limited in their training spectrum, and offer insufficient haptic feedback. Within the scope of this thesis, prototypes of the Tübingen hands-on ERCP training phantom Biliphant were revised in all essential points and supplemented by additional modules, which were redesigned according to anatomical, clinical, and didactic requirements. In the process, many model elements were implemented, improved, or re-engineered and prepared for series production. A breakthrough for modeling has been the introduction of 3D printing technology, using the latest hardware and software. The new hands-on ERCP phantom, which has been further optimized in this thesis, also fulfills all demanding requirements: - Exact replication of the human anatomy of the upper gastrointestinal tract including the biliary and pancreatic system - Modular exchangeable ducts systems (bile ducts up to 4th order, pancreatic duct) based on clinical imaging (3D reconstructions) - Treatable pathological structures (tumors, stenoses, stones) from artificial tissue without exception, no animal organs or biomaterials - Realistic optics and haptics - Ethical and hygienic safety - Use of clinic-analog equipment and instruments, no special animal endoscopes/instruments required - All possible ERCP interventions can be performed (biopsy, all HF- and APC applications to the papilla, all types of stenosis therapy, stenting, stone therapy incl. mechanical lithotripsy and EHL, cholangioscopy, etc.). - Repetitiveness of all procedures - Modular setup for different training levels, individual phantom design (e.g. replication of real patient cases) by the use of 3D printing - Virtual X-ray simulation module (X-SIM) for unlimited real-time ERCP training without any radiation exposure The intense evaluation of the model showed that beginners and experts alike rated the phantom as very good. This especially relates to the aspects of anatomy, X-ray display, anatomy of the papilla and the realism of various interventions (explicitly the multiple options of papillotomy). The overall evaluation of the diagnostic and therapeutic features resulted in an outstandingly good rating of the model, and the very positive individual feedback of the participants from numerous courses also proves this. For the first time, individual learning curves were created, so that a significant distinction between beginners and experts could be made, thus confirming the validity of the phantom. Especially the learning progress of supervised beginners was clearly demonstrated. All of this indicates the significant role of the Tübingen training model for ERCP education. Altogether, the hands-on phantom Biliphant created in this thesis has reached a new dimension in ERCP training models, which will undoubtedly benefit the education and training as well as the competence of endoscopists. Moreover, there are many opportunities for other groups, such as students, assistants and, above all, for research and development in the field of medical technology

The accumulation of plutonium isotopes (239+240) in the components of the natural environment in the territory of the Karaganda region adjacent to the Semipalatinsk test site

Presents the results of a radiological survey of the territory of the Karaganda region. The data obtained on contamination of isotopes of plutonium (239+240), assessed the impact of nuclear testing on Semipalatinsk testing nuclear polygon. Currently, the pollution of the examined areas of technogenic radionuclides in most places, does not exceed the background level of global fallout, and only at some points noted in the reading background of global fallout. However, there are local areas of contamination, which could be formed as a result of testing of BRV, or other atmospheric fallout from nuclear testing

Conditional gene ablation of Stat3 reveals differential signaling requirements for survival of motoneurons during development and after nerve injury in the adult

Members of the ciliary neurotrophic factor (CNTF)/leukemia inhibitory factor (LIF)/cardiotrophin gene family are potent survival factors for embryonic and lesioned motoneurons. These factors act via receptor complexes involving gp130 and LIFR-β and ligand binding leads to activation of various signaling pathways, including phosphorylation of Stat3. The role of Stat3 in neuronal survival was investigated in mice by Cre-mediated gene ablation in motoneurons. Cre is expressed under the neurofilament light chain (NF-L) promoter, starting around E12 when these neurons become dependent on neurotrophic support. Loss of motoneurons during the embryonic period of naturally occurring cell death is not enhanced in NF-L–Cre; Stat3flox/KO mice although motoneurons isolated from these mice need higher concentrations of CNTF for maximal survival in culture. In contrast, motoneuron survival is significantly reduced after facial nerve lesion in the adult. These neurons, however, can be rescued by the addition of neurotrophic factors, including CNTF. Stat3 is essential for upregulation of Reg-2 and Bcl-xl expression in lesioned motoneurons. Our data show that Stat3 activation plays an essential role for motoneuron survival after nerve lesion in postnatal life but not during embryonic development, indicating that signaling requirements for motoneuron survival change during maturation

Comparative Analysis of Selenocysteine Machinery and Selenoproteome Gene Expression in Mouse Brain Identifies Neurons as Key Functional Sites of Selenium in Mammals

Although dietary selenium (Se) deficiency results in phenotypes associated with selenoprotein depletion in various organs, the brain is protected from Se loss. To address the basis for the critical role of Se in brain function, we carried out comparative gene expression analyses for the complete selenoproteome and associated biosynthetic factors. Using the Allen Brain Atlas, we evaluated 159 regions of adult mouse brain and provided experimental analyses of selected selenoproteins. All 24 selenoprotein mRNAs were expressed in the mouse brain. Most strikingly, neurons in olfactory bulb, hippocampus, cerebral cortex, and cerebellar cortex were exceptionally rich in selenoprotein gene expression, in particular in GPx4, SelK, SelM, SelW, and Sep15. Over half of the selenoprotein genes were also expressed in the choroid plexus. A unique expression pattern was observed for one of the highly expressed selenoprotein genes, SelP, which we suggest to provide neurons with Se. Cluster analysis of the expression data linked certain selenoproteins and selenocysteine machinery genes and suggested functional linkages among selenoproteins, such as that between SelM and Sep15. Overall, this study suggests that the main functions of selenium in mammals are confined to certain neurons in the brain

Comparative Analysis of Selenocysteine Machinery and Selenoproteome Gene Expression in Mouse Brain Identifies Neurons as Key Functional Sites of Selenium in Mammals

Although dietary selenium (Se) deficiency results in phenotypes associated with selenoprotein depletion in various organs, the brain is protected from Se loss. To address the basis for the critical role of Se in brain function, we carried out comparative gene expression analyses for the complete selenoproteome and associated biosynthetic factors. Using the Allen Brain Atlas, we evaluated 159 regions of adult mouse brain and provided experimental analyses of selected selenoproteins. All 24 selenoprotein mRNAs were expressed in the mouse brain. Most strikingly, neurons in olfactory bulb, hippocampus, cerebral cortex, and cerebellar cortex were exceptionally rich in selenoprotein gene expression, in particular in GPx4, SelK, SelM, SelW, and Sep15. Over half of the selenoprotein genes were also expressed in the choroid plexus. A unique expression pattern was observed for one of the highly expressed selenoprotein genes, SelP, which we suggest to provide neurons with Se. Cluster analysis of the expression data linked certain selenoproteins and selenocysteine machinery genes and suggested functional linkages among selenoproteins, such as that between SelM and Sep15. Overall, this study suggests that the main functions of selenium in mammals are confined to certain neurons in the brain

Bariatric Surgery—from the Non-surgical Approach to the Post-Surgery Individual Care: Role of Endoscopy in Bariatric Therapy

Obesity is the underlying constant for the development of the most common modern diseases such as insulin resistance, high blood pressure, lipid metabolism disorders, non-alcoholic steatohepatitis (fatty liver), joint problems and various malignancies. The role of endoscopic diagnostic and therapy in obese patients is highlighted in this chapter. In this chapter all devices and methods used in flexible endoscopy for diagnostic and treatment in obese patients are introduced. Role of endoscopy is presented in three parts: in preoperative setting, in post-operative complication management and instead of surgery as endoscopic bariatric therapy. If possible presentation of the effectiveness is compiled with study data. Finally, the interaction between endoscopy and surgery in the treatment of obesity is complex, essential and promising. Endoscopy is indispensable in preoperative preparation, as a primary therapeutic approach, and also in the detection and treatment of acute complications and long-term complications of obesity surgery

Enhancement of the Kapitza conductance at 0.32 meV phonon energy

Using quasimonochromatic relaxation phonons emitted by superconducting tunneling functions, the phonon transfer through real solid-liquid helium interfaces was tested. We found an enhancement of the energy transmission if the incident phonons exceed the threshold energy Eo = 0.32 meV. This sharp threshold energy shifts to 0.42 meV if the lighter isotope 3 He is used

iGentifier: indexing and large-scale profiling of unknown transcriptomes

Development and refinement of methods to analyse differential gene expression has been essential in the progress of molecular biology. A novel approach called iGentifier is presented for profiling known and unknown transcriptomes, thus bypassing a major limitation in microarray analysis. The iGentifier technology combines elements of fragment display (e.g. Differential Display or RMDD) and tag sequencing (e.g. SAGE, MPSS) and allows for analysis of samples in high throughput using current capillary electrophoresis equipment. Application to epidermal tissue of wild-type and mlo5 barley (Hordeum vulgare) plants, infected with powdery mildew [Blumeria graminis (DC.) E.O. Speer f.sp.hordei], led to the identification of several 100 genes induced or repressed upon infection with many well known for their response to fungal pathogens or other stressors. Ten of these genes are suggested to be classified as marker genes for durable resistance mediated by the mlo5 resistance gene