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Untersuchung androgener Steroidhormone in Ihrer Metabolisierung sowie deren Einfluss auf die Androgenrezeptor-Aktivität in Genitalhautfibroblasten mit Hilfe des APOD-Assays
No full textTestosteron (T) bewirkt durch Aktivierung des Androgenrezeptors (AR) die Ausbildung der inneren männlichen Geschlechtsorgane. Für die äußere Virilisierung wird T über die 5α-Reduktase Typ II (5α-RD) in Dihydrotestosteron (DHT) umgewandelt. Patienten mit 5α-RD-Mangel können bei hohem T-Anstieg in der Pubertät jedoch auch virilisieren. Ziel war, zu untersuchen, wie T und dessen Vorstufe Androstendion (Andro) in Genitalhautfibroblasten (GF) von männlichen Kontrollen sowie Patienten mit 5α-RD-Mangel metabolisiert werden und ob sie den AR direkt aktivieren können. Der APOD-Assay bietet die Möglichkeit, die AR-Aktivierung endogen in Genitalhautfibroblasten zu untersuchen, indem es die Androgen-abhängige Induktion des AR-Zielgens Apoliprotein D (APOD) misst. Es zeigte sich, dass neben DHT auch T die APOD-Expression hochregulieren und somit den AR aktivieren kann. In den GF ist v.a. der klassische Steroidbiosyntheseweg aktiv, bei dem Andro über die 17ß-Hydroxysteroid-Dehydrogenase III (17ß-HSD III) zu T umgewandelt wird und T über die 5α-RD Typ II zu DHT. Die Kontrollzelllinien haben somit signifikant mehr Andro und T in DHT umgewandelt, während die Zelllinien mit 5α-RD-Mutation oder geringer 5α-RD-Expression T über die 17ß-HSD III zurück zu Andro metabolisiert haben, da T nicht weiter in DHT umgewandelt werden konnte
Risk of weight gain due to the consumption of ultra-processed foods or Cystic Fibrosis Transmembrane Conductance Regulator modulator intake: Studies on the impact of protein content in ultra-processed foods and an inpatient rehabilitation programme in people with Cystic Fibrosis
Full text linkThis doctoral thesis explores two critical risk factors for obesity: the consumption of ultra-processed foods (UPF) and the use of a novel pharmacological therapy in people with Cystic Fibrosis (CF). Strategies to address these risks include protein fortification of UPF and rehabilitation programmes combining exercise and dietary counselling for people with CF, who often have poor diet quality. The low protein content of UPF may contribute to increased energy intake, as humans overconsume low-protein foods to meet protein targets (protein leverage). The first study presents a market analysis of high-protein (HP) UPF in German supermarkets and online shops, assessing nutritional value, additives, and hyper-palatability. HP UPF had an improved nutritional profile with lower energy density, sugar and fat content, higher fibre and protein content, but more additives and higher salt content. The use of flavourings and artificial sweeteners in HP UPF may increase palatability and promote hedonic eating and excessive intake. Thus, protein fortification in UPF may not effectively reduce the risk of weight gain. Long-term studies are needed to assess their impact on energy balance and health. The second study examines the impact of CFTR modulator therapy (ETI: Elexacaftor, Tezacaftor, Ivacaftor) on appetite regulation and energy balance during a 3-week inpatient rehabilitation programme with exercise. ETI patients had higher post-exercise meal intake, but changes in BMI and body composition were comparable to those without ETI, likely due to the higher prevalence of pancreatic insufficiency. These findings imply that rehabilitation programmes with regular exercise may improve body composition in people with CF on ETI therapy without leading to a more positive energy balance. Given links between ETI intake and fat mass gain, rehabilitation programmes should prioritise improving body composition and reduce UPF consumption to support long-term metabolic health
Burden of coeliac disease in Germany: real-world insights from a large retrospective health insurance claims database analysis
Full text linkBackground Coeliac disease (CeD) is a chronic immune-mediated disease triggered by exposure to dietary gluten in genetically predisposed individuals. The burden of CeD on patients and the healthcare system remains poorly evaluated in Germany. Objectives To assess the healthcare resource utilisation (HCRU) and costs of diagnosed CeD patients in a German claims database. Design A retrospective CeD case-control study was conducted using German claims data between 2017 and 2021. Methods CeD diagnosis was defined by at least one inpatient or two outpatient diagnostic codes (International Statistical Classification of Diseases and Related Health Problems, 10th Revision, German Modification (ICD-10-GM) K90.0) within four quarters (irrespective of calendar year) for CeD during the study period. Controls (non-CeD patients) were matched in a ratio of 5:1 by age, Charlson Comorbidity Index, sex and region. HCRU (hospitalisations, outpatient visits, medication use, sick leaves) and healthcare costs (outpatient services, inpatient services, outpatient pharmaceuticals, sick leaves and aids and remedies) were compared between CeD patients and controls. Results From the 3,352,188 patients with continuous enrolment during the study period (2017-2021), 8258 (0.25%) patients were identified as having a CeD diagnosis. The mean number of hospitalisations and outpatient visits within 5 years was 1.8- and 1.5-fold higher among matched CeD patients (n = 8243) compared to their controls (n = 41,215), resulting in an excess healthcare cost of €5251. Inpatient expenses were the main cost driver and accounted for 31.5% of total incremental costs. Conclusion The current study showed that CeD patients have considerably higher HCRU and related costs compared to matched controls. Our findings suggest the need for improved treatment options for CeD patients in addition to a gluten-free diet
Die Bedeutung GABAerger Interneurone für die Ausbildung räumlich präziser Erinnerung
Full text linkInhibitorische Interneurone (IN) im Gyrus dentatus (GD) spielen eine wichtige Rolle bei der räumlichen Erinnerung. Diese Arbeit untersucht, wie sich die Aktivitätsmuster (Engramme) der Hauptneurone (Körnerzellen) im GD ohne den hemmenden Einfluss der SOMI durch laterale Inhibition verändern. Dabei wurde die Differenzierungsfähigkeit auf zellulärer Ebene zwischen zwei ähnlichen Kontexten untersucht. SOMI wurden durch Injektion von Tetanus-toxin-Leichtketten-tragenden Viren (rAAV) in die Hippocampusregion in genmodifizierten SOM-Cre-Mäusen gezielt inaktiviert. Danach wurden die Tiere entweder zweimal im gleichen oder in zwei unterschiedlichen Kontexten exponiert. Die Aktivierung der Körnerzellen wurde mittels Fluoreszenz In-situ Hybridisierung (FISH) anhand des Immediate Early Genes (IEG) Zif268/Egr1 markiert. Das fluorezenzmarkierte IEG im Zytoplasma zeigte die Aktivierung während der ersten Exposition, im Zellkern während der zweiten. Zellen mit beiden Signalen wurden in beiden Expositionen aktiviert, was auf eine Wiedererkennung hindeutet, quantifiziert mittels Reaktivierungsratio als zelluläres Pendant der Wiedererkennung. Der Vergleich der Bedingungen ergab keine signifikanten Unterschiede in der Reaktivierungsrate zwischen den Gruppen oder Bedingungen. Es gab Hinweise, dass die Differenzierung der Engramme bei den Versuchs-Tieren geringer ausfiel als bei den Kontrolltieren. Zudem zeigte sich eine signifikant höhere Zellaktivierung im GD bei inaktivierten SOMI im Vergleich zu den Kontrolltieren und zur basalen Aktivität. Dies stützt die Theorie, der lateralen Inhibition, die nach Aktivierung der Hauptneurone ihre Wirkung entfaltet. Insgesamt deuten die Ergebnisse darauf hin, dass die SOMI für die Mustertrennung sowie die im Vergleich zu anderen Regionen geringe Aktivität der Körnerzellen im GD eine maßgebliche Rolle spielen
Koronararterienverschlüsse nach arterieller Switch-Operation – Stellenwert der Koronarangiographie als Bestandteil der Routinenachsorge von Patienten mit Transposition der großen Arterien
Full text linkDie Transposition der großen Gefäße ist der zweithäufigste zyanotische Herzfehler. Als operatives Korrekturverfahren hat sich die arterielle Switch-Operation etabliert. Hierbei werden die vertauschte Körper- und die Lungenschlagader oberhalb der Klappenebene durchtrennt und umgesetzt. Zusätzlich müssen die Koronararterien explantiert und in der Neo-Aortenwurzel reimplantiert werden. Die arterielle Switch-Operation kann mit niedriger Mortalität durchgeführt werden. Dennoch sind verschiedene Komplikationen, wie u.a. Verschluss oder Stenose der Koronararterien oder Probleme im Bereich der ventrikulären Ausflusstrakte bekannt, die eine lebenslange Nachsorge erfordern. In Kiel erfolgt im Rahmen dieser Nachsorge etwa ein Jahr nach der Operation eine routinemäßige Herzkatheteruntersuchung inklusive Koronarangiographie. In der vorliegenden Arbeit wurde der prognostische Wert und der therapeutische Einfluss dieser routinemäßigen Koronarangiographie ein Jahr postoperativ in einer retrospektiven monozentrischen Kohortenstudie über einen Zeitraum von 20 Jahren anhand eines Kollektives von TGA-Patienten, bei denen eine arterielle Switch-Operation durchgeführt wurde, untersucht. Es wurden u.a. die Anzahl der Todesfälle, Koronararterienverschlüssen, Reoperationen und Katheterinterventionen dokumentiert und ausgewertet. Koronarverschlüsse oder -stenosen waren ein insgesamt seltenes Ereignis. In keinem der Fälle wurde eine therapeutische Konsequenz aus dem Befund gezogen. Eine Beschränkung einer Herzkatheteruntersuchung auf ein definiertes Risikokollektiv scheint daher rational. Patienten mit komplexer Morphologie oder assoziierten Aortenbogenanomalien haben ein erhöhtes Risiko für Reoperationen und Reinterventionen, die zum größten Teil im Bereich des rechtsventrikulären Ausflusstraktes erfolge
Multi-AUV sediment plume estimation using Bayesian optimization
Full text linkSediment plumes created by dredging or mining activities have an impact on the ecosystem in a much larger area than the mining or dredging area itself. It is therefore important and sometimes mandatory to monitor the developing plume to quantify the impact on the ecosystem including its spatial-temporal evolution. To this end, a Bayesian Optimization (BO)-based approach is proposed for plume monitoring using autonomous underwater vehicles (AUVs), which are used as a sensor network. Their paths are updated based on the BO, and additionally, a split-path method and the traveling salesman problem are utilized to account for the distances the AUVs have to travel and to increase the efficiency. To address the time variance of the plume, a sliding-window approach is used in the BO and the dynamics of the plume are modeled by a drift and decay rate of the suspended particulate matter (SPM) concentration measurements. Simulation results with SPM data from a simulation of a dredge experiment in the Pacific Ocean show that the method is able to monitor the plume over space and time with good overall estimation error
Some Combinatorial Games on Hypergraphs: Builder Game and Discrepancy
Full text linkThis thesis explores several graph-theoretical problems and presents three games played on hypergraphs. In Chapter 2, we present theoretical results related to the existence of paths and expanders in hypergraphs. Chapters 3 and 4 discuss properties of random graph processes and an approximation of the number of edges in a k-nearest neighbor graph. In Chapter 5, the Builder game focuses on constructing specific subgraphs in 3-uniform hypergraphs through controlled random graph processes. The player must construct a subgraph that satisfies properties such as minimum degree or includes a perfect matching, a Hamilton path, a k-vertex tree, or a cycle, within a given edge budget. Chapter 6 extends the study of discrepancy games, focusing on the (p:p)-discrepancy game played on hypergraphs. In these games, two players, the Balancer and the Unbalancer, alternately claim vertices of a hypergraph. The Balancer aims to choose approximately half of the vertices in each edge, while the Unbalancer tries to disrupt this. In Chapter 7 we extend the study of Vector balancing games. These are two-player positional games in which one player selects vectors, and the other player assigns signs to minimize the infinity norm of the resulting sum
Subnanometer Tracking of the Oxidation State on Co3O4 Nanoparticles by Identical Location Imaging and Spectroscopy
Full text linkUnderstanding a catalytic reaction requires tools that elucidate the structure of the catalyst surface and subsurface, ideally at atomic resolution and under reaction conditions. Operando electron microscopy meets this requirement in some cases, but fails in others where the required reaction conditions cannot be reached or lead to an unwanted influence of the electron beam on the reactant and catalyst. We introduce ILIAS (identical location imaging and spectroscopy) in combination with a quasi in situ approach to disentangle the effect of heat and gas on the surface of nanoparticles from the effect of the electron beam. With this approach we allow high temperatures and pressures in any gaseous environment on the one hand, and atomic resolution imaging and spectroscopy on the other. As a proof of concept, we resolve the structural evolution of a Co3O4 spinel catalyst using ILIAS and track the oxidation state across the surface before and after heating in a reductive or oxidative environment. We then titrate the surface of the catalyst using CO as a probe molecule to remove highly active oxygen species formed during the thermal treatment, providing unprecedented insight into the interplay between pretreatment and surface reactivity of Co3O4 nanoparticles
Boron in Soil, Drainage Water and Groundwater in Long-Term Irrigated Area by Treated Wastewater in Northeast Tunisia
Full text linkBoron (B) in soils originates from both natural and human sources, such as agriculture and industry, which contribute boron via fertilizers and irrigation water. Using treated wastewater (TWW) for irrigation is a strategy to address water scarcity in agriculture within arid areas like Tunisia; however, it introduces a risk of B contamination. Thus, the primary objective of this study is to assess the levels of B contamination throughout the entire irrigation system of the TWW “Cebala Borj-Touil” in Northeast Tunisia. To evaluate the lasting impact of TWW irrigation on B and the dynamics of physicochemical parameters across the entire system, soil samples were collected from various depths (0–150 cm) in a control area and gathered both prior to and following irrigation (two campaigns). Water samples utilized for irrigation and water released from drainage were gathered throughout an irrigation cycle. Groundwater sampling took place over two campaigns in April and September of 2018. The findings indicated that B concentrations in irrigation water were below the Tunisian standards (NT 106.03), while in drainage and groundwater, B levels exceeded the standard slightly during some periods. Throughout a three-decade cycle, the patterns of irrigation caused a notable transfer of boron from the topsoil to the groundwater. Therefore, it is essential to regularly supervise the irrigated area system and enhance the drainage system
Seasonal Dynamics of Planktonic Algae in the Danjiangkou Reservoir: Nutrient Fluctuations and Ecological Implications
Full text linkFreshwater reservoirs serve as vital water sources for numerous residential areas. However, the excessive presence of nutrients, such as nitrogen and phosphorus, stimulates rapid algal proliferation, leading to the occurrence of algal blooms. To prevent this phenomenon, it is imperative to conduct regular ecological surveys aimed at assessing water quality and monitoring the dynamic composition of aquatic biological communities within the reservoir’s ecosystem. In this study, seasonal changes in water quality parameters and the spatial and temporal distribution of planktonic algae at 14 sampling sites in the Danjiangkou reservoir were analyzed. A total of 136 taxonomic units of planktonic algae were identified, belonging to 8 phyla, 41 families, and 88 genera, with the dominant algae belonging to the phyla Chlorophyta, Bacillariophyta, and Cyanophyta. The order of abundance of the algae was summer > autumn > spring > winter and Hanku > Intake > Danku > Outflow. WT, pH, DO, CODMn, and Chl a were the primary drivers influencing the changes in the planktonic algal community within the reservoir. Two dominant algae, Chlamydomonas debaryana and Scenedesmus quadricauda, were isolated and cultured indoors to simulate the growth behaviors of algae in the Danjiangkou reservoir. The results show that the growth of C. debaryana was severely limited by the temperature, light, and nutrient concentration, whereas the growth of S. quadricauda was slightly affected under different temperature and light conditions and could occur at low concentrations of nitrogen and phosphorus nutrients. [...]. This study examined the growth characteristics of the dominant algae in the Danjiangkou reservoir under laboratory conditions and delved into their interdependencies with environmental factors, aiming to furnish a theoretical and experimental foundation for investigating algal community dynamics and preventing algal blooms within the freshwater reservoir