Entwicklung einer Messtechnik zur nicht-invasiven Bestimmung des Gesamtgehalts an N-Acetyl-L-Aspartat im Gehirn des Menschen in vivo

Lokalisierte 1H-MR-Spektroskopie (MRS) ermöglicht die nicht invasive Messung des Metaboliten N-Acetyl-L-Aspartat (NAA) in vivo im Gehirn des Menschen. Da neuronaler Zellverlust einher geht mit einer Abnahme des NAA-Gehalts, könnte der Verlauf von gehirnschädigenden Erkrankungen mit diesem Parameter verfolgt werden. In dieser Arbeit werden neben einem Vorschlag von O. Gonen et al. eigene Ansätze zur Bestimmung des gesamt-Gehalts an NAA im Gehirn (WBNAA) entwickelt und auf 1,5-T-Ganzkörper-MR-Tomographen implementiert. Die Techniken wurden erfolgreich an Phantomen und Probanden getestet. Im Hinblick auf eine klinische Anwendung wurden zudem verschiedene Methoden der absoluten Quantifizierung entwickelt und experimentell überprüft

Utilization of preventive care among migrants and non-migrants in Germany: results from the representative cross-sectional study ‘German health interview and examination survey for adults (DEGS1)’

Background In Germany, different health checks for adults are offered for primary and secondary prevention. Previous findings indicate that preventive care utilization varies according to social determinants, especially migration background. This study examined the extent to which migration background is associated with preventive care utilization, independent of factors like age and socioeconomic status and whether length of stay in Germany has a positive effect on the use of preventive care. Methods The first wave of the ‘German Health Interview and Examination Survey for Adults’ (DEGS1) is a comprehensive data collection facilitating the description of the utilization of general health checks, dental check-ups, skin cancer screening, and cervical cancer screening among people aged 18–79 years with and without migration background. Migration background was differentiated in first-generation migrants having immigrated to Germany themselves or second-generation migrants born in Germany. First-generation migrants were further differentiated by length of stay in Germany, and second-generation migrants as having one or two parents who were born abroad. Multivariate binary logistic regression models with average marginal effects were calculated to analyse the associations between preventive care utilization and migration background. Results The sample comprised 7987 participants, 1091 of whom had a migration background. Compared with non-migrants, women and men with migration background— particularly first-generation migrants with length of stay <=20 years in Germany — make less use of preventive care. This association was observed statistically independent from sociodemographic factors. For dental check-ups a significantly lower use was also found for first-generation migrants who have lived in Germany for more than 20 years and second-generation of migrants with two parents born abroad. Post-model predictions showed that the utilization rates of first-generation migrants are gradually converging to the average values for non-migrants. Conclusions Our findings suggest inequalities in realized access to preventive care for first-generation migrants particularly for those who have lived in Germany for 20 years or less. Barriers to the utilization of preventive care may be addressed by informing migrant communities about preventive health care services at an early stage after immigration using migrant-sensitive information strategies.Peer Reviewe

Migration and health: Moving towards diversity-oriented public health monitoring at the Robert Koch Institute

Summarizing categories, such as migration background or history of migration, do not reflect the diversity and heterogeneity of the population living in Germany and their health. A differentiated description of the health situation of people with a history of migration should consider migrationrelated, social, and structural determinants of health as well as their interactions. The findings obtained in the 'Improving Health Monitoring in Migrant Populations (IMIRA)' projects will help to improve the inclusion of people with a history of migration in future studies as well as in the RKI panel. This will enable an adequate description of the health situation of people with a history of migration and therefore of the general population in Germany. In future studies, the health status of people who have not been well included in health surveys so far, such as people who are not listed at the registration office, should be monitored. For this purpose, continuous development of sampling and survey methods is necessary

Association between Cardiac Auscultation and Echocardiographic Findings in Warmblood Horses

Heart murmurs are detected frequently when auscultating horses and certain murmurs can usually be linked to specific valvular regurgitations. Limited information exists about the accuracy of these broad rules in warmblood horses and the influence of grade of the regurgitation and dimensional changes on murmur intensity. This study aims to clarify the accuracy of cardiac auscultation in warmblood horses and the influence of the grade of regurgitation and dimensional changes on the loudness of the murmur. In this retrospective study, 822 warmblood horses presented for cardiac examination in a large equine referral center in northern Germany underwent a thorough cardiac auscultation. In total, 653 of these revealed one or more heart murmurs. Most common auscultatory findings were left-sided systolic murmurs (68%) or left-sided diastolic murmurs (15%). On 635 of these horses, an echocardiographic examination was performed, revealing regurgitations of the mitral valve as the most common valvular regurgitation (77%) followed by regurgitations of the aortic valve (23%). Thirty-one percent of horses that underwent echocardiographic examination displayed dimensional changes of one or more compartments of the heart, with the left atrium being most affected (21%), followed by the left ventricle (13%). The main goal of this study was to link certain auscultatory findings with results of the echocardiographic examinations, trying to determine whether auscultation and echocardiography agreed on the valve affected, as well as to find out if loudness of the murmur coincided with grade of regurgitation and presence of dimensional changes. Agreement between auscultation and cardiac ultrasound was substantial (Kappa 0.74) if one or more murmurs and regurgitations were present and almost perfect (Kappa 0.94) if only one murmur and one regurgitation were found. Auscultation was particularly well suited for detection of left-sided systolic and diastolic murmurs, with 87% of left-sided systolic murmurs being caused by a mitral valve regurgitation and 81% of left-sided diastolic murmurs originating from an aortic valve regurgitation. We found a fair agreement between the grade of regurgitation and the respective murmur. Association was particularly good between mild regurgitations and low-grade murmurs, while differentiation between moderate to severe regurgitation based upon the loudness of the murmur was less reliable. Dimensional changes were usually linked to more severe regurgitations and higher-grade murmurs. However, a direct correlation between murmur intensity and the presence or severity of dimensional changes, independent of the grade of valvular regurgitation, could not be established in this cohort of horses

Utilisation of dental services by refugees in Germany: Results of the population-based RESPOND survey

Background: The utilisation of outpatient dental services is an important indicator for monitoring healthcare provision in Germany. In the general population, the 12-month prevalence of dental service utilization is 82.2 %. For refugees, this indicator has hardly been measured, although studies suggest an objectively high need for dental care. Methodology: As part of the population-based cross-sectional RESPOND study (2018), self-reported health and healthcare, including the use of dental services, was assessed in three representative, random samples of refugees residing in reception and shared accommodation centres in Baden-Württemberg and Berlin. Results: The indicator was available for 68.8 % (594) of the 863 surveyed refugees. Overall, 38.2 % of the respondents stated that they had utilised dental services in the previous 12 months, whereas 41.4 % had never used any dental care in Germany. Conclusions: The utilisation of dental services among refugees is very low compared to the level of utilisation in the general population. It reflects a discrepancy between access and needs

13C spin hyperpolarization by PASADENA : Instrumentation, preparation of magnetic tracers, and NMR spectroscopy and imaging in vivo

Techniques for the enhancement of the nuclear spin polarization (hyperpolarization) have demonstrated ~10 5 fold amplification of 13C NMR signal: new applications like imaging of metabolic processes in real-time and in vivo are in reach. PASADENA is a unique technique reaching high nuclear polarization (P) within seconds in liquid state: spin order of parahydrogen is transferred to a third nucleus by an r.f. spin-order-transfer (SOT) sequence. In this work, a semi-automated PASADENA polarizer for hyperpolarization of biomolecules in aqueous solution was constructed: P ~ 0.1 on 13C was demonstrated (a ~10 5 fold 13C signal enhancement at B0 = 1 T and T = 293 K). A simulation of the spin dynamics of the PASADENA experiment was developed to calculate the parameters for the SOT sequence and to predict the hyperpolarization yield. New compounds were introduced: the metabolic tracer 1-13C, 2,3-D2 succinate (Suc) and the functional agent 2,2,3,3-D4 tetraflouropropyl 1-13C, 2,3,3-D3 propionate (TFPP) were hyperpolarized (P ~ 0.1). The stability of the hyperpolarization was investigated in experiment and simulations. The lifetimes of the 13C hyperpolarization of Suc, TFPP and 2,2,3,3-hydroxyethyl 1-13C 2,3,3-D3 propionate (HEP) were determined in dependence of molecular deuteration, solvent deuteration, pH and B0: the maximal T1 = (59.7 ± 3.2) s of Suc prolongs the window for in vivo detection significantly. Strong enhancement of 13C NMR signal was observed in vivo after injection of hyperpolarized Suc and HEP in animals and cell cultures, demonstrating the potential biologically relevant molecules hyperpolarized by PASADENA in biomedical research

Singlet state encoded magnetic resonance (SISTEM) spectroscopy

Magnetic resonance spectroscopy (MRS) allows the analysis of biochemical processes non invasively and in vivo. Still, its application in clinical diagnostics is rare. Routine MRS is limited to spatial, chemical and temporal resolutions of cubic centimetres, mM and minutes. In fact, the signal of many metabolites is strong enough for detection, but the resonances significantly overlap, exacerbating identification and quantification. In addition, the signals of water and lipids are much stronger and dominate the entire spectrum. To suppress the background and isolate selected signals, usually, relaxation times, J-coupling and chemical shifts are used. Here, we propose methods to isolate the signals of selected molecular groups within endogenous metabolites by using long-lived spin states (LLS). We exemplify the method by preparing the LLSs of coupled protons in the endogenous molecules N-acetyl-L-aspartic acid (NAA). First, we store polarization in long-lived, double spin states and then apply saturation pulses and double quantum filters to suppress background signals. We show that LLS can be used to selectively prepare and measure the signals of chosen metabolites or drugs in the presence of water, inhomogeneous field and highly concentrated fatty solutions. The pH measurement presented here is one of the possible applications.Comment: 15 pages, 5 figures and supporting material

Implementierung und Verwendung der Normalkoordinatenanalyse in einer integrierten graphischen Benutzeroberfläche sowie quantenmechanische Untersuchungen an organischen Zinn-Silizium-Verbindungen

In dieser Arbeit geht es sowohl um die Implementierung und Anwendung der Normalkoordinatenanalyse in einer integrierten graphischen Benutzeroberfläche als auch um quantenmechanische Berechnungen an Zinn/Silizium-Organylen. Die Normalkoordinatenanalyse zeigt sich als wertvolle Methode, schnell die möglichen Schwingungsformen eines Moleküls zu berechnen. Dies wird durch eine graphische Benutzeroberfläche mit Kraftkonstantendatenbank sehr erleichtert. Diese Benutzeroberfläche wurde im Rahmen dieser Arbeit entwickelt. Die Ausgabe der Schwingungsformen erfolgt ebenfalls graphisch intern im Programm (OpenGL) oder extern als webfähige VRML-Datei. Die Darstellung chemischer Reaktionsmechanismen wird auch heute noch vielfach zweidimensional betrieben. Die Anwendung von Computern zur Darstellung von Reaktionsmechanismen steckt noch in den Kinderschuhen, auch weil die zur Visualisierung notwendigen Programme noch fehlen. Im Laufe dieser Arbeit wurde ein Programm entwickelt, um dreidimensionale, in ihrem Ausschnitt wählbare Animationen von Reaktionsmechanismen und Schwingungen zu erstellen. Die Animation von Reaktionsmechanismen erfolgt aus einer Datei mit Atomkoordinaten, wobei Erweiterungen auf andere Datenformate möglich und in der Programmstruktur vorgesehen sind. Die Ausgabe erfolgt ebenso wie im obigen Programm. Am Lehrstuhl Krause werden mit Hilfe polymer gebundener Salicylsäureester diastereoselektive Protonierungen durchgeführt. Die hiermit erzeugbaren Stoffe können z.B. als Grundstoffe zur Synthese von Naturstoffen dienen. Die einzelnen Reaktionsschritte einer typischen Verbindung dieser Verbindungsklasse ausgehend von 5-Hydroxy-Salicylsäure bis zum polymer gebundenen Salicylsäureethylester (Copolymer mit Styrol) werden als Beispiel der Anwendung des entstandenen Normalkoordinatenprogrammes aufgeführt. Die Ergebnisse lassen auf eine gute Anwendbarkeit des Programms im Laborkontext schließen. Während sich die Normalkoordinatenanalyse gut dazu eignet, schnell ein Schwingungsspektrum einer bekannten oder unbekannten Substanz zu erzeugen, ist sie nicht dazu geeignet, Aussagen über die Reaktivität oder das unterschiedliche Reaktionsverhalten von einander ähnlichen Molekülen zu treffen. Hier muss auf quantenmechanische Berechnungen zurückgegriffen werden. Im Rahmen einer Zusammenarbeit mit der Arbeitsgruppe F. Uhlig, wurden Untersuchungen zum Reaktionsverhalten einiger zinnmodifierter Polysilane durchgeführt. In dieser Arbeitsgruppe werden seit mehreren Jahren Untersuchungen an Polysilanen des Typs [R2Sn]x[R'2Si]y durchgeführt. Offenkettige Stannasilane stellen wichtige Ausgangsbausteine zur Darstellung solcher Si-Sn-Polymere dar, welche die Änderung und Anpassung der Materialeigenschaften von Polysilanen ermöglichen. Diese Stannasilane müssen in ringförmige Verbindungen überführt werden, bevor eine Polymerisation möglich wird. Hierzu ist eine Lithiierung notwendig, wobei beim untersuchten tBu2(H)Sn-(SiMe2)2-Sn(H)tBu2 eine Dilithiierung möglich und bevorzugt ist, während es beim ebenfalls untersuchten tBu2(H)Sn-SiMe2-Sn(H)tBu2 beim Versuch einer zweiten Lithiierung zur Spaltung der Si-Sn Bindungen kommt. Im Rahmen dieser Arbeit konnte ein Erklärungsansatz für obiges experimentelles Ergebnis gefunden werden

Simultaneous observation of high order multiple quantum coherences at ultralow magnetic fields

We present a method for the simultaneous observation of heteronuclear multi-quantum coherences (up to the 3rd order), which give an additional degree of freedom for ultralow magnetic field (ULF) MR experiments, where the chemical shift is negligible. The nonequilibrium spin state is generated by Signal Amplification By Reversible Exchange (SABRE) and detected at ULF with SQUID-based NMR. We compare the results obtained by the heteronuclei Correlated SpectroscopY (COSY) with a Flip Angle FOurier Series (FAFOS) method. COSY allows a quantitative analysis of homo- and heteronuclei quantum coherences