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Entwicklung und Validierung einer Gerneral Unknown Screening Methode mittels LC-MS für die Systematische Toxikologische Analyse
No full textIn dieser Arbeit wird ein LC-MS-Analysenverfahren für ein General Unknown Screening zum Nachweis von Drogen und Medikamentenwirkstoffen im Rahmen der Systematischen Toxikologischen Analyse (STA) beschrieben. Die Methode verwendet in-source CID für die strukturspezifische Fragmentionenbildung und eine Massenspektrenbibliothek zur Substanzidentifizierung. Als Ausgangspunkt diente eine hersteller- und gerätespezifische Massenspektrenbibliothek, die um weitere Substanzen und Metabolite erweitert wurde. Anhand von 27 Wirkstoffen und Metabolite der Benzodiazepine-Gruppe aus Urin wurde beispielhaft eine vollständige Validierung mit Untersuchung der Matrixeffekte, Extraktionseffizienz und Bestimmung der Nachweisgrenze durchgeführt. Durch Vergleichsanalysen von Urin- und Serumproben wurde die Anwendbarkeit der LC-MS-Methode für Routineanalysen überprüft und Limitierungen diskutiert
The Rowman & Littlefield Handbook of Peace and Conflict Studies: Perspectives from the Global South
No full textDigitalization in orthopaedics: a narrative review
No full textAdvances in technology and digital tools like the Internet of Things (IoT), artificial intelligence (AI), and sensors are shaping the field of orthopaedic surgery on all levels, from patient care to research and facilitation of logistic processes. Especially the COVID-19 pandemic, with the associated contact restrictions was an accelerator for the development and introduction of telemedical applications and digital alternatives to classical in-person patient care. Digital applications already used in orthopaedic surgery include telemedical support, online video consultations, monitoring of patients using wearables, smart devices, surgical navigation, robotic-assisted surgery, and applications of artificial intelligence in forms of medical image processing, three-dimensional (3D)-modelling, and simulations. In addition to that immersive technologies like virtual, augmented, and mixed reality are increasingly used in training but also rehabilitative and surgical settings. Digital advances can therefore increase the accessibility, efficiency and capabilities of orthopaedic services and facilitate more data-driven, personalized patient care, strengthening the self-responsibility of patients and supporting interdisciplinary healthcare providers to offer for the optimal care for their patients
A Comprehensive Review of the Nutritional Composition and Toxicological Profile of Date Seed Coffee (Phoenix dactylifera)
No full textApproximately 8 million tons of dates (Phoenix dactylifera) are produced globally each year. The seeds of the fruit, which make up 10–15% of its weight, are typically discarded. Date seed coffee is a sustainable food system innovation rooted in the traditions of high date-producing regions. Dating back to the late 19th century, date seed coffee has evolved from a historical coffee substitute to a modern caffeine-free alternative. Date seed coffee has a long history of consumption in the European Union (EU). This indicates that it may not require novel food authorization. The composition of date seeds is evaluated in this review and a toxicological risk assessment for date seed coffee is conducted. Subchronic studies show that consuming date seed or date seed coffee has no adverse effects. Therefore, currently unavailable chronic toxicity, carcinogenicity, and reproductive toxicity studies may be unnecessary. However, for a comprehensive evaluation, it is recommended to conduct an in vitro mutagenicity test. This review provides information on the safety of date seed coffee and highlights the need for further research
Development of the High-Affinity Carborane-Based Cannabinoid Receptor Type 2 PET Ligand [18F]LUZ5‑d8
No full textThe development of cannabinoid receptor type 2 (CB2R) radioligands for positron emission tomography (PET) imaging was intensively explored. To overcome the low metabolic stability and simultaneously increase the binding affinity of known CB2R radioligands, a carborane moiety was used as a bioisostere. Here we report the synthesis and characterization of carborane-based 1,8-naphthyridinones and thiazoles as novel CB2R ligands. All tested compounds showed low nanomolar CB2R affinity, with (Z)-N-[3-(4-fluorobutyl)-4,5-dimethylthiazole-2(3H)-ylidene]-(1,7-dicarba-closo-dodecaboranyl)-carboxamide (LUZ5) exhibiting the highest affinity (0.8 nM). Compound [18F]LUZ5-d8 was obtained with an automated radiosynthesizer in high radiochemical yield and purity. In vivo evaluation revealed the improved metabolic stability of [18F]LUZ5-d8 compared to that of [18F]JHU94620. PET experiments in rats revealed high uptake in spleen and low uptake in brain. Thus, the introduction of a carborane moiety is an appropriate tool for modifying literature-known CB2R ligands and gaining access to a new class of high-affinity CB2R ligands, while the in vivo pharmacology still needs to be addressed
Efficient Estimates of Surface Diffusion Parameters for Spatio-Temporally Resolved Virus Replication Dynamics
No full textAdvanced methods of treatment are needed to fight the threats of virus-transmitted diseases and pandemics. Often, they are based on an improved biophysical understanding of virus replication strategies and processes in their host cells. For instance, an essential component of the replication of the hepatitis C virus (HCV) proceeds under the influence of nonstructural HCV proteins (NSPs) that are anchored to the endoplasmatic reticulum (ER), such as the NS5A protein. The diffusion of NSPs has been studied by in vitro fluorescence recovery after photobleaching (FRAP) experiments. The diffusive evolution of the concentration field of NSPs on the ER can be described by means of surface partial differential equations (sufPDEs). Previous work estimated the diffusion coefficient of the NS5A protein by minimizing the discrepancy between an extended set of sufPDE simulations and experimental FRAP time-series data. Here, we provide a scaling analysis of the sufPDEs that describe the diffusive evolution of the concentration field of NSPs on the ER. This analysis provides an estimate of the diffusion coefficient that is based only on the ratio of the membrane surface area in the FRAP region to its contour length. The quality of this estimate is explored by a comparison to numerical solutions of the sufPDE for a flat geometry and for ten different 3D embedded 2D ER grids that are derived from fluorescence z-stack data of the ER. Finally, we apply the new data analysis to the experimental FRAP time-series data analyzed in our previous paper, and we discuss the opportunities of the new approach
Efficient Estimates of Surface Diffusion Parameters for Spatio-Temporally Resolved Virus Replication Dynamics
No full textAdvanced methods of treatment are needed to fight the threats of virus-transmitted diseases and pandemics. Often, they are based on an improved biophysical understanding of virus replication strategies and processes in their host cells. For instance, an essential component of the replication of the hepatitis C virus (HCV) proceeds under the influence of nonstructural HCV proteins (NSPs) that are anchored to the endoplasmatic reticulum (ER), such as the NS5A protein. The diffusion of NSPs has been studied by in vitro fluorescence recovery after photobleaching (FRAP) experiments. The diffusive evolution of the concentration field of NSPs on the ER can be described by means of surface partial differential equations (sufPDEs). Previous work estimated the diffusion coefficient of the NS5A protein by minimizing the discrepancy between an extended set of sufPDE simulations and experimental FRAP time-series data. Here, we provide a scaling analysis of the sufPDEs that describe the diffusive evolution of the concentration field of NSPs on the ER. This analysis provides an estimate of the diffusion coefficient that is based only on the ratio of the membrane surface area in the FRAP region to its contour length. The quality of this estimate is explored by a comparison to numerical solutions of the sufPDE for a flat geometry and for ten different 3D embedded 2D ER grids that are derived from fluorescence z-stack data of the ER. Finally, we apply the new data analysis to the experimental FRAP time-series data analyzed in our previous paper, and we discuss the opportunities of the new approach