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Advancing information theory for distributed computation - with applications to biological networks and Artificial Intelligence
No full textBiological brains and artificial neural networks alike derive their impressive
information processing abilities from the complex interplay of individual
neurons. While the function of an individual neuron is comparatively simple to
understand, how they organize into distributed computation systems capable of
solving difficult tasks remains mostly elusive. Understanding this organization
requires an interpretable and implementation-independent framework for
information processing. Such a framework can be found in Information Theory,
which quantifies how well one variable can be predicted from another. In
distributed computation, however, the more relevant question is how one variable
can be predicted from multiple sources, e.g., how information from individual
neurons is integrated in a neuron’s activity. Disentangling the different ways in
which these sources can contribute to the overall prediction in unique, redundant
and synergistic ways is the subject of Partial Information Decomposition (PID).
Through this decomposition, PID provides a powerful tool to understand how
information is represented and transformed in distributed computation systems.
This thesis advances information theory and PID for analyzing and
constructing distributed computation systems. Key contributions include the
definition of a novel analytical definition and estimator for a continuous PID,
computationally efficient and interpretable PID-based summary structures
revealing that representations in deep neural networks become more accessible
and robust with training and throughout the network architecture, and the
introduction of novel locally-learning neurons optimizing an abstract PID-based
goal function. Furthermore, the thesis introduces a two-step framework for
identifying spatial information flows through biological tissue, marking a first
step towards understanding spatial computation in living tissue. Collectively,
these efforts provide novel concepts, tools and insights for understanding and
constructing distributed computation systems.2025-10-2
Investigation of Surface Dynamics on Oxidized Metal Surfaces Using Ion Imaging Techniques
No full textHeterogeneous catalysis plays a pivotal role in modern life, with applications ranging from the Haber-Bosch process over ethylene epoxidation to exhaust conversion in modern three-way catalysts in automobiles. While these reactions are well understood on the macroscopic level, the microscopic details are often unclear. This knowledge gap is where surface science experiments can provide valuable insights, enabling a deeper understanding of reactions at the nanoscopic level.
In this work, surface reaction products which desorb from oxidized rhodium and silver surfaces were examined. The oxidized metal surfaces were characterized, and typical reactions on these surfaces were studied with a special emphasis on the effects of subsurface oxygen (Osub)
formation on reaction dynamics. For that, the velocity distributions () of desorbing surface reaction products were chosen as a fingerprint of the dynamics.
Recombinative desorption of oxygen from oxidized metal surfaces was studied on Rh(111) and on Ag(111). The experimental method of choice was a combination of temperature-programmed desorption (TPD) and velocity map imaging (VMI). By combining these two
methods, the velocity distributions () deduced by VMI were assigned to distinct desorption features in TPD experiments. Additionally, molecular beam surface scattering experiments were conducted to study two different model reactions: styrene epoxidation on silver and CO
oxidation on rhodium.
The results from in total four experimental series are presented in this thesis. Chapters 4 and 5 report the velocity and angular distributions for recombinative desorption of oxygen atoms from Rh(111) and Ag(111), as well as the impact of Osub formation on Rh(111). The recombinatively-desorbing oxygen atoms display hyperthermal velocity distributions, and the angular flux distribution is narrower than predicted by a thermal cos() distribution. Application of detailed balance provides a framework for interpreting these deviations.
Chapter 6 presents the results for styrene epoxidation on Ag(111). Molecular beam surface scattering experiments demonstrate that an electrophilic oxygen (Oelec) phase, coexisting with Osub, exclusively produces styrene oxide. Once Oelec is depleted, only styrene combustion by nucleophilic oxygen (Onuc) occurs in titration experiments.
Chapter 7 focuses on the dynamics of CO oxidation on a bifaceted Rh(111)/Rh(332) crystal. Velocity-resolved kinetics (VRK) measurements reveal that without Osub, only hyperthermal CO2 forms on both facets. Upon Osub formation, however, a thermal reaction channel emerges, whose contribution increases with the amount of Osub until exclusively thermal CO2 is observed. This behavior indicates that Osub does not simply act as an oxygen atom reservoir but also modifies the underlying potential energy surface (PES). First experimental findings
on the reaction kinetics are presented, and preliminary theoretical models are shown which explain the observed velocity shift of CO2 induced by Osub incorporation.
The findings of this dissertation have significant implications for our understanding of heterogeneous catalysis and the role of Osub in reaction dynamics. The results also provide a foundation for further experiments in the future and allow for the development and refinement
of improved theoretical models. This could lead to a deeper understanding of oxidized metal surfaces.2025-11-1
Der Einfluss von kontinuierlichen Nierenersatzverfahren auf die Bestimmung des Herzzeitvolumens mittels Thermodilutions-Technik
No full textThis study examines the effects of continuous renal replacement therapy (CRRT) on cardiac output (CO) measurement using both transpulmonary and pulmonary artery thermodilution techniques. As CRRT is commonly applied continuously in critically ill patients, understanding its potential impact on hemodynamic monitoring is of clinical relevance. At the initiation of this research, it was uncertain whether CRRT needed to be paused to obtain accurate CO values.
Our findings indicate that CO measurements are significantly elevated during CRRT interruption, consistent with previous results. Any modification in CRRT operation particularly the cessation or resumption of filtration results in immediate and pronounced fluctuations in CO readings, most likely due to rapid temperature changes within the extracorporeal circuit. Even during stable CRRT operation, a modest but statistically significant temperature-related effect persists, though its clinical relevance appears limited. A novel aspect of this study is the assessment of return-flow temperature, which offers additional mechanistic insight.
From a clinical standpoint, CO measurements should only be performed after thermal equilibrium has been re-established following any change in CRRT operation.2025-12-2
OH NO! - Investigating the microsolvation of aminoxyl radicals via FTIR spectroscopy
No full textThis work investigates complexes of stable organic radicals with halogenated alcohols using FTIR jet spectroscopy combined with quantum chemical calculations. Due to the formation of a hydrogen bond, the OH stretching vibration of the alcohol serves as a sensitive probe for the presence of a specific heterodimer (1:1) conformation in the supersonic expansion. The TEMPO (2,2,6,6-tetramethylpiperidinyloxyl) radical is combined with benzyl alcohol and its halogenated derivatives, which are investigated separately beforehand. Two main conformer types are identified, differing in the orientation of the alcohol relative to the radical. The preferred conformer can be controlled in subtle ways by introducing halogens of different sizes (F, Cl, Br, I) and at different positions to the aromatic system of benzyl alcohol. This variation of the alcohol reveals how the interplay between hydrogen bonding and dispersion forces affects the complex stability. The amount of dispersion interaction is quantified using local energy decomposition. Switching to the TEMPO derivative TEMPONE (4-oxo-TEMPO) shows that the additional carbonyl group can act as a hydrogen bond acceptor, competing with the radical NO side. Due to the chiral nature of TEMPONE, relative chirality becomes relevant for the complexes with the transiently chiral benzyl alcohol.2025-12-0
Untersuchung der intra- und postoperativen Komplikationen der ölbasierten Vitrektomie bei rhegmatogener Ablatio retinae
No full textDie rhegmatogene Ablatio retinae stellt durch ihre Epidemiologie und Ätiologie eine für alle
Altersgruppen relevante Erkrankung dar, welche den Visus potenziell bedroht.
Die Silikonöl-Endotamponade bietet in der Regel eine hervorragende Therapieoption bei
komplexen Situationen, was sich auch anhand der vorliegenden Ergebnisse bestätigt. Die
Patienten der Kontrollgruppe (n = 201) erfuhren im Durchschnitt eine Verbesserung ihrer
präoperativen Sehschärfe um 4,5 Zeilen nach 80 Tagen. Andererseits wiesen 7,4 % der
UMG-Patienten (n = 16) einen signifikanten Visusverlust (> - 0,1) auf, welcher nicht durch
sekundäre Ursachen erklärt werden konnte. Durchschnittlich verloren die 16 Patienten 5,1
Visuszeilen nach 80 Tagen. Die Sehschärfe erholte sich im Verlauf nicht.
Insgesamt waren signifikant mehr Patienten mit initial anliegender Makula (24,4 %) und
weniger mit abgelöster Makula (2,4 %) betroffen, was den Makulastatus als Einflussfaktor
unserer sekundären Fragestellung vermuten ließ. Aufgrund der deutlich besseren
Ausgangssituation von Patienten mit Makula-on-RRDs wurden relevante Visusverluste in
dieser Gruppe jedoch möglicherweise überschätzt. Der präoperativ gute Visus fiel nach der
Operation rapide um insgesamt 6,5 Zeilen ab und war auch nach 3 Jahren anhaltend
gesunken (- 7,7 Zeilen). Diese Patienten hatten „mehr zu verlieren“, während Patienten mit
Makula-off-RRDs bei niedrigem präoperativem Visus vergleichsweise geringe Einbußen
verzeichneten (- 1,2 Zeilen nach 80 Tagen und insgesamt - 5,2 Zeilen nach 3 Jahren). Als
eindeutige Einflussfaktoren eines unklaren Visusverlustes unter Öl konnten morphologische
Variablen wie große Netzhautlöcher oder ein Riesenriss detektiert werden, während keine
verdächtigen Chargen gefunden werden konnten. Die Ausdehnung der Netzhautablösung
hatte keinen Einfluss. Auch ophthalmologische Komorbiditäten und operative
Komplikationen zeigten keinen signifikanten Zusammenhang zur Fragestellung.
Auf der Suche nach einer pathogenetischen Erklärung des untersuchten Phänomens bot die
Literatur viele Ansätze. In Zusammenschau der Ergebnisse erscheint zum aktuellen
Zeitpunkt eine retrograde synaptische Degeneration der retinalen Neuronen des papillomakulären Bündels durch eine Optikopathie am wahrscheinlichsten. Dieser Prozess könnte durch einen
komorbiden Riesenriss mit vermehrter Zirkulation von Flüssigkeiten zwischen prä- und subretinalem Raum verstärkt werden und sich bildgebend als mikrozystisches Makulaödem in der INL äußern.
Letztlich bleibt die Ursache der Sehminderung im Rahmen einer Netzhautoperation mit
Ölendotamponade unklar. Als klinische Konsequenz ergibt sich aus der vorliegenden Arbeit
die Empfehlung, engmaschige postoperative Kontrolle von Patienten mit Silikonöl-
Endotamponade durchzuführen, insbesondere bei Patienten mit einem Riesenriss. Eine
weitere Empfehlung ist der restriktive Einsatz von Silikonöl bei moderaten Netzhautablösungen.Due to its epidemiology and etiology, rhegmatogenous retinal detachment is a disease that is relevant for all age groups and potentially threatens vision. Silicone oil endotamponade is generally an excellent treatment option in complex situations, which is also confirmed by the present results. The patients in the control group (n = 201) experienced an average improvement in their preoperative visual acuity of 4.5 lines after 80 days. On the other hand, 7.4% of the UMG patients (n = 16) had a significant loss of visual acuity (> - 0.1) that could not be explained by secondary causes. On average, the 16 patients lost 5.1 visual acuity lines after 80 days. Visual acuity did not recover over time. Overall, significantly more patients with an initially attached macula (24.4%) and fewer with a detached macula (2.4%) were affected, which suggested that macular status was an influencing factor in our secondary question. However, due to the significantly better initial situation of patients with macular-on RRDs, relevant visual acuity losses in this group may have been overestimated. The preoperatively good visual acuity fell rapidly by a total of 6.5 lines after the operation and continued to fall after 3 years (-7.7 lines). These patients had "more to lose", while patients with macular-off RRDs with low preoperative visual acuity experienced comparatively small losses (-1.2 lines after 80 days and a total of -5.2 lines after 3 years). Morphological variables such as large retinal holes or a giant tear were identified as clear influencing factors of unclear visual loss under oil, while no suspicious batches were found. The extent of the retinal detachment had no influence. Ophthalmological comorbidities and surgical complications also showed no significant connection to the question. In the search for a pathogenetic explanation of the phenomenon under investigation, the literature offered many approaches. In summary, the results currently appear to be a retrograde synaptic degeneration of the retinal neurons of the papillomacular bundle due to opticopathy. This process could be exacerbated by a comorbid giant tear with increased circulation of fluids between the pre- and subretinal space and manifest itself in imaging as microcystic macular edema in the INL. Ultimately, the cause of the visual impairment during retinal surgery with oil endotamponade remains unclear. As a clinical consequence, the present study recommends that patients with silicone oil endotamponade be closely monitored postoperatively, especially in patients with a giant tear. Another recommendation is the restrictive use of silicone oil in cases of moderate retinal detachments.2025-02-2
Characterization of the synapse-specific distribution of the protein Mover during the differentiation of neuronal primary cultures
No full textDas Protein Mover wurde in einem Hefe-Zwei-Hybrid-System als Bindungspartner des
präsynaptischen Gerüstproteins Bassoon entdeckt. Es wurde biochemisch gezeigt, dass das
Protein mit synaptischen Vesikeln assoziiert vorkommt. Elektrophysiologische
Untersuchungen ergaben Hinweise darauf, dass Mover die Freisetzungswahrscheinlichkeit
von Neurotransmittern aus synaptischen Vesikeln regulieren könnte, wobei eine Studie eine
fördernde Rolle, die andere Studie eine hemmende Rolle von Mover nahelegt. Bisherige
Studien an Hirnschnitten der Maus ergaben ein komplexes Verteilungsmuster von Mover an
den verschiedenen Synapsentypen, innerhalb einzelner Hirnbereiche wie beispielsweise dem
Hippocampus sowie über das gesamte Gehirn verteilt. Eine erhöhte Menge des Proteins
wurde im anterioren cingulären Cortex von Schizophrenie-Patient*innen entdeckt.
In dieser Arbeit wurde eine systematische Charakterisierung der Verteilung von Mover in
Primärkulturen in verschiedenen Entwicklungsstadien mittels Fluoreszenzmikroskopie
vorgenommen. Dafür wurden in hippocampalen Sandwichkulturen (in denen Glia und
Neurone in zwei verschiedenen Kompartimenten einer Petrischale kultiviert werden),
cortikalen Cokulturen (in denen Neurone und Glia auf demselben Deckglas zusammen
kultiviert werden) und astrozytären Monokulturen Immunfärbungen durchgeführt.
Die Ergebnisse zeigten, dass Mover mit synaptischen Vesikelmarkern colokalisiert, aber nur
an einem Teil der Synapsen vorkommt. Weitere Untersuchungen zeigten, dass Mover an
nahezu allen inhibitorischen Synapsen nachzuweisen ist, aber nur an einem Teil der
exzitatorischen Synapsen. Außerdem konnte gezeigt werden, dass Mover mit Synaptoporin
colokalisiert, einem Marker für Moosfaserterminalien des Hippocampus, und dass Mover in
afferenten Nervenendigungen an inhibitorischen Interneuronen des Cortex vorkommt.
Neben seinem Vorkommen an Synapsen kann Mover bereits in sehr jungen Astrozyten
detektiert werden. In älteren Kulturen colokalisiert es mit Markern für Lipidtröpfchen.
Insgesamt bestätigen die Ergebnisse dieser Zellkulturstudien die Hypothese, dass Mover an
Synapsen angereichert vorkommen kann und dass die Lokalisation von Mover an Synapsen
ein heterogenes Verteilungsmuster aufweist. Darüberhinaus zeigen sie, dass Mover an
exzitatorischen Synapsen heterogener verteilt ist als an inhibitorischen Synapsen. Zukünftige
Studien können nun klären, wie sich Mover-negative und Mover-positive glutamaterge
Synapsen funktionell voneinander unterscheiden und welche Bedeutung erhöhte
Konzentrationen von Mover im Kontext mit Schizophrenie haben.The protein Mover was identified as a binding partner of the presynaptic scaffolding protein Bassoon using a yeast two-hybrid system. Biochemical studies have shown that Mover is associated with synaptic vesicles. Electrophysiological investigations provided evidence suggesting that Mover may regulate the release probability of neurotransmitters from synaptic vesicles. While one study indicated a promoting role for Mover, another suggested an inhibitory role. Previous studies using mouse brain slices revealed a complex distribution pattern of Mover across different types of synapses, within individual brain regions such as the hippocampus, and throughout the entire brain. An increased amount of the protein was detected in the anterior cingulate cortex of patients with schizophrenia.
In this study, a systematic characterization of Mover's distribution in primary cultures at various developmental stages was conducted using fluorescence microscopy. Immunostainings were performed in hippocampal sandwich cultures (where glia and neurons are cultured in two separate compartments of a Petri dish), cortical co-cultures (where neurons and glia are cultured together on the same coverslip), and astrocyte monocultures.
The results showed that Mover colocalizes with synaptic vesicle markers but is present only at a subset of synapses. Further analyses revealed that Mover is detectable at nearly all inhibitory synapses but only at a subset of excitatory synapses. Additionally, it was shown that Mover colocalizes with synaptoporin, a marker for mossy fiber terminals in the hippocampus, and is present in afferent nerve endings at inhibitory interneurons in the cortex.
Beyond its presence at synapses, Mover can already be detected in very young astrocytes. In older cultures, it colocalizes with markers for lipid droplets.
Overall, the findings of these cell culture studies support the hypothesis that Mover is enriched at synapses and that its localization shows a heterogeneous distribution pattern at synapses. Furthermore, they show that Mover is more heterogeneously distributed at excitatory synapses than at inhibitory synapses. Future studies can now investigate how Mover-negative and Mover-positive glutamatergic synapses functionally differ and the significance of increased Mover concentrations in the context of schizophrenia.2026-01-1
Incidence of arrhythmias after liver surgery: risk factors for the occurrence of postoperative cardiac arrhythmias and their influence on the postoperative course of patients
No full textNicht nur nach kardialen bzw. thorakalen Operationen, sondern auch nach abdominellen Operationen, bspw. im Bereich der Leber, treten Arrhythmien als postoperative Komplikation regelmäßig noch während des stationären Verlaufs auf. Dabei handelt es sich meist um tachykardes Vorhofflimmern, seltener auch um andere Formen von HRST. Studien zur Inzidenz und zur prognostischen Relevanz von neuaufgetretenen HRST nach Leberoperationen liegen in der Literatur bislang nicht vor. Insofern werden in dieser Arbeit erstmals entsprechende Ergebnisse vorgestellt.
Nach Prüfung der Ausschlusskriterien konnten n = 460 Patienten, die zwischen Januar 2012 und April 2020 in der Klinik für Allgemein-, Viszeral- und Kinderchirurgie der UMG eine Leberoperation erhielten, in der retrospektiven Datenanalyse berücksichtigt werden.
Zusammenfassend lag die Inzidenz von neuaufgetretenen HRST nach Leberoperationen bei 5,4% (n = 25) und war damit vergleichsweise niedrig. Unter den zwölf durchgeführten Leberoperationsarten variierte die Inzidenz von postoperativen HRST zwischen maximal 50% bei der Trisegmentektomie links, 20% bei der Multiviszeralresektion inkl. HIPEC und unter 10% bei allen weiteren Resektionsarten.
Im Rahmen einer multiplen logistischen Regressionsanalyse konnten vier assoziierte Faktoren eruiert werden, die signifikant mit dem Auftreten von HRST nach Leberoperationen (postoperativen Arrhythmien, PA) korrelierten: der Fibrosegrad der Leber, chirurgische intraoperative Komplikationen, eine postoperative Gallefistel, -leckage oder ein Biliom und postoperatives Organversagen. Auch war das durchschnittliche Alter von Patienten mit PA (M = 65,34 Jahre; SD = 9,9) signifikant höher als das von Patienten ohne PA (M = 60,66 Jahre; SD = 13,8; p < 0,05).
Die Inzidenz von postoperativen HRST war mit einer verlängerten medianen Aufenthaltsdauer auf der Intensivstation verbunden (19 Tage für Patienten mit PA vs. 5 Tage für Patienten ohne PA; p < 0,01).
Während des postoperativen stationären Aufenthalts verstarben n = 20 Patienten (4,3%). Im Regressionsmodell statistisch signifikant mit der intrahospitalen Mortalität assoziierte Faktoren waren CHA2DS2-VASc-Score, Aszites, Infektionen und Organversagen. Das Neuauftreten von HRST bzw. die Variable „postoperative Arrhythmie“ korrelierte nur in der Einzelanalyse mit der intrahospitalen Mortalität, war in Zusammenschau mit den genannten Variablen im schrittweisen logistischen Regressionsmodell jedoch nicht mehr signifikant.
Im weiteren postoperativen Verlauf nach Entlassung verstarben die Patienten mit PA signifikant früher als Patienten ohne PA (Md = 11,3 vs. 56,8 Monate).
Obwohl die Inzidenz von neuaufgetretenen HRST nach Leberoperationen im Vergleich zu anderen nicht-kardialen Operationen eher niedrig erscheint, zeigen die Ergebnisse dieser Studie, dass ihre Bedeutung für den postoperativen Verlauf nicht unerheblich ist: Postoperative HRST sind beispielsweise mit einem längeren intensivstationären Aufenthalt und mit einem kürzeren Überleben assoziiert. Inwiefern perioperative Faktoren kausal die Auftretenswahrscheinlichkeit von HRST und das Mortalitätsrisiko im weiteren Verlauf nach Leberoperationen beeinflussen, bleibt als Frage an eine künftige prospektive Studie offen.Not only after cardiac or thoracic operations, but also after abdominal operations such as liver resections, cardiac arrhythmias (CA) regularly occur as a postoperative complication during the inpatient course. This is usually tachycardic atrial fibrillation, and more rarely other forms of CA. Studies on the incidence and prognostic relevance of newly occurring CA after liver surgery are not yet available in the literature. In this respect, corresponding results are presented for the first time in this work.
All together n = 460 patients who underwent liver surgery in the UMG Clinic for General, Visceral and Pediatric Surgery between January 2012 and April 2020 were included in the retrospective data analysis.
In summary, the incidence of new CA after liver surgery was 5.4% (n = 25) and was therefore comparatively low. Among the twelve types of liver surgery performed, the incidence of postoperative CA varied between a maximum of 50% for left trisegmentectomy, 20% for multivisceral resection including HIPEC and less than 10% for all other types of resections.
Using a multiple logistic regression analysis, four associated factors were identified being significantly correlated with the occurrence of CA after liver surgery (postoperative arrhythmia, PA): the degree of fibrosis of the liver, surgical intraoperative complications, a postoperative bile fistula, leak or bilioma, and postoperative organ failure. Also, the average age of patients with PA (m = 65.34 years; sd = 9.9) was significantly higher than that of patients without PA (m = 60.66 years; sd = 13.8; p < 0 .05). The incidence of PA was associated with an increased median length of ICU stay (19 days for patients with PA vs. 5 days for patients without PA; p < 0.01).
During the postoperative hospital stay, n = 20 patients (4.3%) died. CHA2DS2-VASc score, ascites, infections and organ failure were statistically significantly associated with intrahospital mortality in the regression model. PA only correlated with intrahospital mortality in the individual analysis but was no longer significant when viewed together with the variables mentioned in the stepwise logistic regression model.
In the further postoperative course after discharge, the patients with PA died significantly earlier than patients without PA (md = 11.3 vs. 56.8 months).
Although the incidence of newly occurring CA after liver surgery appears to be rather low compared to other non-cardiac operations, the results of this study show that their importance for the postoperative course is not insignificant: PA, for example, is associated with a longer intensive care unit stay and with a shorter one associated with survival. The extent to which perioperative factors causally influence the probability of occurrence of PA and the risk of mortality further after liver surgery remains an open question for a future prospective study.2025-02-1
Impact of Triple Cryoablation on Ablation Lesion Formation and Coronary Perfusion in the Developing Myocardium
No full textSupraventricular tachycardias (SVT) are the most common tachyarrhythmias in pediatric patients. The estimated incidence ranges between 0.1% and 0.4% (Albinni et al., 2010). Given the significant impact these rhythm disorders can have on the quality of life of affected children and their families, advancing the analysis and optimization of SVT therapy in this patient population is of utmost importance.
Currently, two ablation techniques are available for the treatment of SVT in children and adolescents: radiofrequency (RF) ablation and cryoablation (Collins et al., 2006; Santangeli et al., 2014). While cryoablation has been shown to be somewhat less effective in the long term compared to RF ablation, it is a gentler method associated with fewer complications. The recurrence rate following cryoablation ranges from approximately 7–29%, with reported success rates between 62–92% (Brugada et al., 2013). In contrast, RF ablation demonstrates a lower recurrence rate of 5–10% and an acute success rate exceeding 90% (Brugada et al., 2013). Overall, cryoablation has a superior safety profile compared to RF ablation, albeit with the trade-off of lower success rates and higher recurrence rates (Andrade et al., 2013).
Determining the optimal number of freezing and thawing sequences that maximize long-term efficacy while minimizing complications remains an ongoing challenge. It is hypothesized that additional freezing and thawing cycles may enlarge the lesions created, thereby increasing both the acute success rate and long-term efficacy. Previous studies conducted by our research group have supported this hypothesis with findings on double cryoablation (Schneider et al., 2013; Schneider et al., 2019). Consequently, this study explored a further modified approach employing triple cryoablation, involving three freeze-thaw cycles, with follow-up analysis performed six months later.
The study cohort consisted of five pigs. A total of 31 lesions were detected in the five pig hearts after paraffin embedding and were examined macroscopically and microscopically. Neither intracardiac ultrasound (ICUS), coronary angiography, nor macroscopic assessments revealed any significant complications, such as thromboses, hemorrhages, or coronary vessel involvement. Detailed histological analysis of the lesions corroborated these findings. Volumetric analysis of the lesions allowed comparison with data from previous studies by our group.
Compared to RF ablation (Paul et al., 1997), single cryoablation (Kriebel et al., 2005; Kriebel et al., 2010), and early results from double cryoablation (Schneider et al., 2013), significantly larger lesion volumes were observed in this study. While the lesion volumes at six months post-triple cryoablation were larger than those observed 48 hours after triple cryoablation (Krause et al., 2017), this difference did not reach statistical significance. Lesion volumes at six months post-triple cryoablation were comparable to those observed six months post-double cryoablation (Schneider et al., 2019).
This study demonstrated that triple cryoablation did not lead to a significant further increase in lesion volumes compared to double cryoablation after six months. Future studies involving larger cohorts and direct comparisons between the different methods are necessary to further validate these findings.2025-02-1
Mechanism of glucocorticoids in the regulation of immunometabolism in human T cells
No full textGlukokortikoide werden zur Behandlung zahlreicher entzündlicher Erkrankungen eingesetzt. Doch trotz jahrzehntelanger Forschung sind die exakten Wirkmechanismen bis heute nicht gänzlich verstanden. Glukokortikoide beeinflussen die Aktivität und Effektor-Funktionen von T-Zellen auf vielfältige Weise. Wenig untersucht ist jedoch die Bedeutung des Energiemetabolismus von T-Zellen als Regelstelle von Glukokortikoiden. Nachdem Voruntersuchungen nachweisen konnten, dass eine in vitro Gabe von Glukokortikoiden die Expression metabolischer Gene, die während der T-Zell-Aktivierung hochreguliert werden, in murinen und humanen T-Zellen hemmt, sollten im Rahmen dieser Dissertation die zugrunde liegenden molekularen Mechanismen untersucht werden. Darüber hinaus sollte überprüft werden, ob auch eine in vivo Gabe von Glukokortikoiden eine hemmende Wirkung auf den Energiemetabolismus von T-Zellen hat.
Im ersten Schritt wurden T-Zellen von gesunden Blutspender*innen in vitro in Gegenwart von Dexamethason stimuliert. Anschließend wurde betrachtet, ob eine pharmakologische Blockade der Transkriptionsfaktoren STAT1 und mTOR die Fähigkeit der Glukokortikoide zur Hemmung metabolischer Gene in T-Zellen einschränkt. Mit mTOR konnte dabei eine wichtige Regelstelle ermittelt werden, mittels derer Glukokortikoide möglicherweise ihren hemmenden Effekt auf den Energiemetabolismus von T-Zellen erzielen. STAT1 war für die hemmende Wirkung von Glukokortikoiden auf den Energiemetabolismus hingegen zu vernachlässigen. Zur Überprüfung, ob auch eine in vivo Gabe von Glukokortikoiden den Energiemetabolismus hemmt, wurden T-Zellen aus dem Blut von Multiple Sklerose Patient*innen mit progredienter Verlaufsform untersucht, die Glukokortikoide in Form einer intravenösen Methylprednisolon-Pulstherapie erhalten. Die Ergebnisse bestätigen, dass es auch hier zu einer Hemmung der Expression metabolischer Gene in T-Zellen kommt. Darüber hinaus konnte gezeigt werden, dass Veränderungen in der metabolischen Genexpression von Patient*innen mit einer sekundär progredienten Multiplen Sklerose mit einer Verbesserung klinischer Symptome korrelieren.
Zusammenfassend zeigen die Ergebnisse dieser Dissertation, dass der Energiemetabolismus von T-Zellen ein bislang unbekanntes Ziel von Glukokortikoiden im Rahmen ihrer hemmenden Wirkung auf die Aktivität und Effektor-Funktionen von T-Zellen darstellt. Dieser neue Mechanismus von Glukokortikoiden könnte somit für die Weiterentwicklung von anti-entzündlichen Therapien von Bedeutung sein.Glucocorticoids are used to treat numerous inflammatory diseases. But despite decades of research, their exact mechanisms of action remain incompletely understood. Glucocorticoids influence the activity and effector functions of T cells in various ways. However, little is known about their impact on T cell energy metabolism, although it is widely accepted that this process is a critical rheostat of T cell activity. Previous investigations demonstrated that in vitro administration of glucocorticoids represses the expression of metabolic genes, which are upregulated during T cell activation, in murine and human T cells. This dissertation aimed to investigate the underlying molecular mechanisms of this effect. Furthermore, it sought to determine whether in vivo administration of glucocorticoids also exerts an inhibitory effect on the energy metabolism of T cells.
In the first step, T cells from healthy blood donors were stimulated in vitro in the presence of dexamethasone. Subsequently, the effect of pharmacological blockade of the transcription factors STAT1 and mTOR on the ability of glucocorticoids to inhibit metabolic genes in T cells was examined. mTOR was identified as a critical target through which glucocorticoids may exert their inhibitory effect on T cell energy metabolism. In contrast, STAT1 was found to be negligible in mediating the inhibitory effect of glucocorticoids on energy metabolism. To investigate whether in vivo administration of glucocorticoids also represses energy metabolism, T cells were analysed from the blood of patients with progressive forms of multiple sclerosis undergoing intravenous methylprednisolone pulse therapy. The results confirmed that glucocorticoids also suppress the expression of metabolic genes in T cells in vivo. Moreover, it was demonstrated that changes in metabolic gene expression in patients with secondary progressive multiple sclerosis correlated with improvements in clinical symptoms. In summary, the findings of this dissertation reveal that the energy metabolism of T cells represents a previously unknown target of glucocorticoids in their inhibitory effects on T cell activity and effector functions. This newly identified mechanism of glucocorticoids may therefore have implications on the development of improved anti-inflammatory therapies
Serum 25-hydroxyvitamin D as a predictor of quality of life in adolescents with allergic rhinoconjunctivitis
No full textZahlreiche Studien haben Zusammenhänge zwischen der Serumkonzentration von 25-Hydroxyvitamin D und Parametern der gesundheitsbezogenen Lebensqualität, der Erythropoese und des Krebsrisikos untersucht. Das Ziel der vorliegenden Post-hoc-Auswertung aus der repräsentativen, bundesweiten KiGGS-Studie war es, im Serum gemessene Vitamin-D-Konzentrationen bei Kindern und Jugendlichen im Alter von 11 bis 17 Jahren mit allergischer Rhinokonjunktivitis und Asthma bronchiale zu erfassen. Hierfür lagen Daten aus einer Stichprobe von insgesamt 7.697 Teilnehmer/innen der KiGGS-Studie ohne bzw. mit der Diagnose einer allergischen Rhinokonjunktivitis oder eines Asthma bronchiale vor. Für diese Auswertung verwendet wurden Angaben zur Medikation mit Glukokortikoiden, zum körperlichen und psychischen Wohlbefinden sowie zu Verhaltensauffälligkeiten. Die 25-Hydroxy-Vitamin-D-Messung erfolgte mithilfe des automatisierten LIAISON Lumineszenz-Immunoassays (DiaSorin). Verhaltensauffälligkeiten wurden anhand der deutschsprachigen Version des Strengths and Difficulties Questionnaire (SDQ) erhoben und der gut validierte KINDL-R-Fragebogen diente der Bestimmung der gesundheitsbezogenen Lebensqualität, wobei von beiden Fragebögen sowohl Einschätzungen aus der Eigen- als auch aus der Elternperspektive vorlagen. Die statistischen Analysen wurde mithilfe des SPSS-Programms unter Verwendung eines Gewichtungsfaktors für die Vitamin-D-Bestimmung berechnet.
Eine Serie von logistischen Regressionsmodelle adjustiert auf Geschlecht, Alter, Body-Mass-Index und sozioökonomischem Status sowie einzelnen hämatologischen Parametern zeigte bei den Kindern und Jugendlichen zwischen 11 und 17 Jahren signifikante Assoziationen zwischen dem Serum-Vitamin-D-Spiegel und dem Vorliegen einer allergischer Rhinokonjunktivitis. Zusätzlich ergaben sich in dieser Studie eine signifikante positive Korrelation zwischen den Serum-Vitamin-D-Werten und der gesundheitsbezogenen Lebensqualität bzw. eine inverse Assoziation mit Verhaltensauffälligkeiten. Dieser Zusammenhänge sollten durch weitere epidemiologische Untersuchungen überprüft werden, auch um die gegebenenfalls zugrundeliegenden psychophysiologischen Mechanismen zu klären.Summary
Numerous studies have investigated associations between serum concentrations of 25-hydroxyvitamin D and parameters of health-related quality of life, erythropoiesis and cancer risk. The aim of the present post-hoc analysis from the representative, nationwide KiGGS study was to record serum vitamin D concentrations measured in children and adolescents aged 11 to 17 years with allergic rhinoconjunctivitis and bronchial asthma. Data from a sample of 7,697 participants in the KiGGS study with or without a diagnosis of allergic rhinoconjunctivitis or bronchial asthma were available for this purpose. Information on medication with glucocorticoids, physical and mental well-being and behavioral problems was used for this evaluation. The 25-hydroxyvitamin D measurement was carried out using the automated LIAISON luminescence immunoassay (DiaSorin). Behavioral problems were assessed using the German-language version of the Strengths and Difficulties Questionnaire (SDQ) and the well-validated KINDL-R questionnaire was used to determine health-related quality of life, with both questionnaires providing self-assessments and assessments from the parents' perspective. The statistical analyses were calculated using the SPSS program using a weighting factor for the vitamin D determination.
A series of logistic regression models adjusted for gender, age, body mass index and socioeconomic status as well as individual hematological parameters showed significant associations between serum vitamin D levels and the presence of allergic rhinoconjunctivitis in children and adolescents between 11 and 17 years of age. In addition, this study showed a significant positive correlation between serum vitamin D levels and health-related quality of life and an inverse association with behavioral problems. These correlations should be verified by further epidemiological studies, also in order to clarify any underlying psychophysiological mechanisms.2025-02-2