Rapid and simple LC-MS/MS-Screening of 64 novel psychoactive substances using dried blood spots

The range of novel psychoactive substances (NPS) including phenethylamines, cathinones, piperazines, tryptamines, etc. is continuously growing. Therefore, fast and reliable screening methods for these compounds are essential and needed. The use of dried blood spots (DBS) for a fast straightforward approach helps to simplify and shorten sample preparation significantly. DBS were produced from 10 µl of whole blood and extracted offline with 500 µl methanol followed by evaporation and reconstitution in mobile phase. Reversed-phase chromatographic separation and mass spectrometric detection (RP-LC-MS/MS) was achieved within a run time of 10 min. The screening method was validated by evaluating the following parameters: limit of detection (LOD), matrix effect, selectivity and specificity, extraction efficiency, and short-term and long-term stability. Furthermore, the method was applied to authentic samples and results were compared with those obtained with a validated whole blood method used for Routine analysis of NPS. LOD was between 1 and 10 ng/ml. No interference from Matrix compounds was observed. The method was proven to be specific and selective for the analytes, although with limitations for 3-FMC/flephedrone and MDDMA/MDEA. Mean extraction efficiency was 84.6 %. All substances were stable in DBS for at least a week when cooled. Cooling was essential for the stability of cathinones. Prepared samples were stable for at least 3 days. Comparison to the validated whole blood method yielded similar results. DBS were shown to be useful in developing a rapid screening method for NPS with simplified sample preparation. Copyright © 2013 John Wiley & Sons, Ltd

Coronary artery stents: influence of adaptive statistical iterative reconstruction on image quality using 64-HDCT

OBJECTIVE: The assessment of coronary stents with present-generation 64-detector row computed tomography (HDCT) scanners is limited by image noise and blooming artefacts. We evaluated the performance of adaptive statistical iterative reconstruction (ASIR) for noise reduction in coronary stent imaging with HDCT. METHODS AND RESULTS: In 50 stents of 28 patients (mean age 64 ± 10 years) undergoing coronary CT angiography (CCTA) on an HDCT scanner the mean in-stent luminal diameter, stent length, image quality, in-stent contrast attenuation, and image noise were assessed. Studies were reconstructed using filtered back projection (FBP) and ASIR-FBP composites. ASIR resulted in reduced image noise vs. FBP (P < 0.0001). Two readers graded the CCTA stent image quality on a 4-point Likert scale and determined the proportion of interpretable stent segments. The best image quality for all clinical images was obtained with 40 and 60% ASIR with significantly larger luminal area visualization compared with FBP (+42.1 ± 5.4% with 100% ASIR vs. FBP alone; P < 0.0001) while the stent length was decreased (-4.7 ± 0.9%,

Eine siyāḥa als Bildungsroman? Überlegungen zur Organisation des Reisetextes von Ḥannā Diyāb (1763/64)

Ḥannā Diyābs siyāḥa umfasst Reiseerfahrungen eines jungen Maroniten aus Aleppo, der den französischen Gesandten Paul Lucas im Jahre 1707 auf seiner Rückkehr an den französischen Hof begleitet, eine Zeit lang in Paris bleibt und allein zurückkehrt. Die Hinreise führt über den Libanon, Zypern, Nordafrika und Italien, die Rückkehr nach einer Schiffsreise über das Mittelmeer durch Kleinasien. Der Text versammelt viele Topoi, die aus anderen arabischen Reisetexten bekannt sind: Seesturm, Schiffbruch und Piraten, zerstörte Gebäude und wunderschöne Gärten. Ebenso enthält er Anekdoten, Legenden und Episoden, die vermutlich zum Staunen anregen sollen sowie Frömmigkeit und Tugenden vermitteln. Das Besondere an dem Text liegt in der Kraft des Erzählens, mit der unterschiedliche Textteile – informative, dokumentarische wie unterhaltsame Abschnitte – zu einer zusammenhängenden Reiseerzählung verwoben werden. Die offensichtliche Einschreibung in eine bestimmte, meist als faktual verstandene Textsorte (riḥla, safra oder siyāḥa) und der Authentizitätsanspruch des Erzählers werden mit einer Neigung zur Fiktionalität kombiniert, die sich besonders in der Hervorhebung einzigartiger (Selbst-)Erlebnisse äußert. In dem Vortrag sollen die verschiedenen Facetten von Diyābs siyāḥa als erste Ergebnisse eines close reading des Textes präsentiert werden. Es wird dabei der Arbeitshypothese des Dissertationsprojekts nachgegangen: Die siyāḥa lässt sich als eine Kompilation verschiedener Textsorten, Themen und Schreibweisen interpretieren und liefert daher einen Zugang zu Wissenshorizonten und Wissensordnungen im Aleppo des 18. Jahrhunderts. Ziel ist es allerdings auch, das Funktionieren und den Zweck dieses Textes als individuelles literarisches Ereignis zu bestimmen. In diesem Sinne soll schließlich diskutiert werden, in welcher Hinsicht diese siyāḥa als Bildungsroman verstanden werden kann.

SwissScoring--a nationwide survey of NEMS assessing practices and its accuracy.

BACKGROUND The nine equivalents of nursing manpower use score (NEMS) is used to evaluate critical care nursing workload and occasionally to define hospital reimbursements. Little is known about the caregivers' accuracy in scoring, about factors affecting this accuracy and how validity of scoring is assured. METHODS Accuracy in NEMS scoring of Swiss critical care nurses was assessed using case vignettes. An online survey was performed to assess training and quality control of NEMS scoring and to collect structural and organizational data of participating intensive care units (ICUs). Aggregated structural and procedural data of the Swiss ICU Minimal Data Set were used for matching. RESULTS Nursing staff from 64 (82%) of the 78 certified adult ICUs participated in this survey. Training and quality control of scoring shows large variability between ICUs. A total of 1378 nurses scored one out of 20 case vignettes: accuracy ranged from 63.7% (intravenous medications) to 99.1% (basic monitoring). Erroneous scoring (8.7% of all items) was more frequent than omitted scoring (3.2%). Mean NEMS per case was 28.0 ± 11.8 points (reference score: 25.7 ± 14.2 points). Mean bias was 2.8 points (95% confidence interval: 1.0-4.7); scores below 37.1 points were generally overestimated. Data from units with a greater nursing management staff showed a higher bias. CONCLUSION Overall, nurses assess the NEMS score within a clinically acceptable range. Lower scores are generally overestimated. Inaccurate assessment was associated with a greater size of the nursing management staff. Swiss head nurses consider themselves motivated to assure appropriate scoring and its validation.

Copper-64 Labeled Macrobicyclic Sarcophagine Coupled to a GRP Receptor Antagonist Shows Great Promise for PET Imaging of Prostate Cancer

The gastrin-releasing peptide receptor (GRPr) is an important molecular target for the visualization and therapy of tumors and can be targeted with radiolabeled bombesin derivatives. The present study aims to develop statine-based bombesin receptor antagonists suitable for labeling with 64Cu for imaging by positron emission tomography (PET). The potent GRPr antagonist D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 was conjugated to the sarcophagine (3,6,10,13,16,19-hexaazabicyclo[6.6.6] icosane=Sar) derivative 5-(8-methyl-3,6,10,13,16,19-hexaaza-bicyclo[6.6.6]icosan-1-ylamino)-5-oxopentanoic acid (MeCOSar) via PEG4 (LE1) and PEG2 (LE2) spacers and radiolabeled with 64Cu2+ with >95% yield and specific activities of about 100 MBq/nmol. Both Cu(II) conjugates have high affinity for GRPr (IC50: natCu-LE1, 1.4±0.1 nM; natCu-LE2, 3.8±0.6 nM). The antagonistic properties of both conjugates were confirmed by Ca2+-flux measurements. Biodistribution studies of Cu-64-LE1 exhibited specific targeting of the tumor (19.6±4.7% IA/g at 1 h p.i.) and GRPr-positive organs. Biodistribution and PET images at 4 and 24 h postinjection showed increasing tumor-to-background ratios with time. This was illustrated by the acquisition of PET images showing high tumor-to-normal tissue contrast. This study demonstrates the high affinity of the MeCOSar-PEGx-bombesin conjugates to GRPr. The stability of 64Cu complexes of MeCOSar, the long half-life of 64Cu, and the suitable biodistribution profile of the 64Cu-labeled peptides lead to PET images of high contrast suitable for potential translation into the clinic.

Life style habits such as alcohol consumption and physical activity in relation to serum apoB / apoA-I ratio amongst 64-year-old women with varying degrees of glucose tolerance.

OBJECTIVES To investigate how life style factors such as alcohol consumption and physical activity relate to the serum apoB / apoA-I ratio in a cohort of middle-aged women with varying degrees of glucose tolerance. DESIGN Observational, cross-sectional cohort study. SETTING Research laboratory at a University Hospital. SUBJECTS A screened cohort of 64-year-old postmenopausal women with varying degrees of glucose tolerance, ranging from diabetes (n = 232), impaired (n = 212) and normal (n = 191) glucose tolerance. MAIN OUTCOME MEASURE ApoB / apoA-I ratio in relation to alcohol consumption and physical activity as assessed by questionnaires. RESULTS Alcohol consumption and regular physical activity at high levels were inversely associated with the serum apoB / apoA-I ratio independently of confounding factors such as obesity, lipid-lowering treatment, degree of glucose tolerance and hormone replacement therapy. Alcohol seemed related to the apoB / apoA-I ratio mainly through increasing apoA-I, whereas physical activity seemed mainly related to lowering of apoB. Alcohol consumption above a daily intake of 8.9 g, i.e. less than a glass of wine was accompanied by a decrease in apoB / apoA-I ratio. CONCLUSIONS Amongst these 64-year-old women with varying degrees of glucose tolerance, a moderate alcohol intake and regular physical exercise leading to sweating were associated with lower apoB / apoA-I ratio and these effects seem to be additive.