Entwicklung von forensisch-toxikologischen Untersuchungsverfahren für die Materialanalytik von ‚Spice‘-Produkten, Arznei- und Dopingmitteln

Für die Charakterisierung von forensisch-toxikologischen Materialien werden qualitative und/oder quantitative Ergebnisse benötigt. Einen entscheidenden Faktor spielt dabei die Analysenzeit (Probenvorbereitung, Messzeit) der verwendeten Methode. Aus diesem Grund befasst sich diese Arbeit mit der Analytik von Spice-, Doping- und Arzneiprodukten mittels Desorptions-Elektrospray-Ionisierung (DESI) gekoppelt an ein Ionenfallenmassenspektrometer (IT-MS). Durch die Verwendung der DESI-Technik ist eine direkte massenspektrometrische Untersuchung von festen Materialien möglich und die Verwendung eines IT-MS erlaubt die Differenzierung zwischen Regio- und Strukturisomeren. Neben diesen direkten Analysemöglichkeiten werden Methoden für die quantitative Analyse der vollsynthetischen Wirkstoffe in Spice-Produkten und die Quantifizierung einzelner Steroidester in öligen Dopingmittelzubereitungen beschrieben.<br/

Leader Cells Define Directionality of Trunk, but Not Cranial, Neural Crest Cell Migration.

Collective cell migration is fundamental for life and a hallmark of cancer. Neural crest (NC) cells migrate collectively, but the mechanisms governing this process remain controversial. Previous analyses in Xenopus indicate that cranial NC (CNC) cells are a homogeneous population relying on cell-cell interactions for directional migration, while chick embryo analyses suggest a heterogeneous population with leader cells instructing directionality. Our data in chick and zebrafish embryos show that CNC cells do not require leader cells for migration and all cells present similar migratory capacities. In contrast, laser ablation of trunk NC (TNC) cells shows that leader cells direct movement and cell-cell contacts are required for migration. Moreover, leader and follower identities are acquired before the initiation of migration and remain fixed thereafter. Thus, two distinct mechanisms establish the directionality of CNC cells and TNC cells. This implies the existence of multiple molecular mechanisms for collective cell migration.D11I1096 Fondo de Fomento al Desarrollo Científico y TecnológicoThis is the final version of the article. It first appeared from Cell Press via httsp://doi.org/10.1016/j.celrep.2016.04.06

A tri-dimensional approach for auditing brand loyalty

Over the past twenty years brand loyalty has been an important topic for both marketing practitioners and academics. While practitioners have produced proprietary brand loyalty audit models, there has been little academic research to make transparent the methodology that underpins these audits and to enable practitioners to understand, develop and conduct their own audits. In this paper, we propose a framework for a brand loyalty audit that uses a tri-dimensional approach to brand loyalty, which includes behavioural loyalty and the two components of attitudinal loyalty: emotional and cognitive loyalty. In allowing for different levels and intensity of brand loyalty, this tri-dimensional approach is important from a managerial perspective. It means that loyalty strategies that arise from a brand audit can be made more effective by targeting the market segments that demonstrate the most appropriate combination of brand loyalty components. We propose a matrix with three dimensions (emotional, cognitive and behavioural loyalty) and two levels (high and low loyalty) to facilitate a brand loyalty audit. To demonstrate this matrix, we use the example of financial services, in particular a rewards-based credit card

Isosexual precocious pseudopuberty during mitotane treatment in a child with adrenocortical carcinoma:A case report

Background Mitotane is employed as adjuvant therapy in managing adrenocortical carcinoma in pediatric patients. While various adverse effects, such as estrogen-like manifestations, are well-documented in adults, there is limited knowledge regarding pediatric-specific toxicity. This report details an uncommon case of isosexual precocious pseudopuberty induced during childhood due to the estrogen-like effects of mitotane. Case report A 2.8-year-old female diagnosed with adrenocortical carcinoma (pT4 pN0 M0) underwent adjuvant treatment with mitotane and cytotoxic chemotherapy following incomplete resection (tumor stage III). Approximately eight months into mitotane treatment, she exhibited signs of puberty (Tanner stage 2), including progressive breast development, uterine enlargement, vaginal discharge, and an advancement of bone age by nearly two years. Gonadotrophin-dependent puberty and endogenous estrogen production were ruled out. The precocious pseudopuberty was attributed to previously reported estrogen-like effects of mitotane therapy. Subsequent administration of the aromatase inhibitor anastrozole in combination with mitotane led to a reduction in clinical signs of puberty. Conclusion Monitoring for estrogen-like effects of mitotane is crucial, particularly in pre-pubertal children, to avert potentially irreversible changes associated with precocious pseudopuberty. Aromatase inhibitors may serve as a prompt therapeutic option, enabling the continuation of mitotane treatment

The Sunrise Mission

The first science flight of the balloon-borne \Sunrise telescope took place in June 2009 from ESRANGE (near Kiruna/Sweden) to Somerset Island in northern Canada. We describe the scientific aims and mission concept of the project and give an overview and a description of the various hardware components: the 1-m main telescope with its postfocus science instruments (the UV filter imager SuFI and the imaging vector magnetograph IMaX) and support instruments (image stabilizing and light distribution system ISLiD and correlating wavefront sensor CWS), the optomechanical support structure and the instrument mounting concept, the gondola structure and the power, pointing, and telemetry systems, and the general electronics architecture. We also explain the optimization of the structural and thermal design of the complete payload. The preparations for the science flight are described, including AIV and ground calibration of the instruments. The course of events during the science flight is outlined, up to the recovery activities. Finally, the in-flight performance of the instrumentation is briefly summarized.Comment: 35 pages, 17 figure

Effects of Endurance Exercise Training and Crataegus Extract WS® 1442 in Patients with Heart Failure with Preserved Ejection Fraction - A Randomized Controlled Trial

Impaired exercise capacity is the core symptom of heart failure with preserved ejection fraction (HFpEF). We assessed effects of exercise training and Crataegus extract WS 1442 in HFpEF and aimed to identify mechanisms of action in an exploratory trial (German Clinical Trials Register DRKS00000259). 140 sedentary HFpEF NYHA II patients on standard treatment received eight weeks of aerobic endurance training and half were randomized to WS 1442 900 mg/day. Symptoms, 2 km walking time (T2km), parameters of exercise tolerance, cardiac and vascular function, muscular efficiency and skeletal muscular haemoglobin oxygen saturation (SO2) measured during a treadmill protocol were captured at baseline and after eight weeks. Adverse events were recorded during the trial. Mechanisms of action were explored by correlation and path analyses of changes. Symptoms and exercise capacity improved with training, but correlations between improvements were low and path models were rejected. SO2 increased, decreased or undulated with increasing exercise intensity in individual patients and was not altered by training. WS 1442 improved T2km (-12.7% vs. -8.4%, p = 0.019), tended to improve symptoms and to pronounce SO2-decrease with increasing exercise, an indicator of oxygen utilisation. Endurance training and WS 1442 were safe and well tolerated in combination with standard drug treatment

Homeopathic medical practice: Long-term results of a cohort study with 3981 patients

BACKGROUND: On the range of diagnoses, course of treatment, and long-term outcome in patients who chose to receive homeopathic medical treatment very little is known. We investigated homeopathic practice in an industrialized country under everyday conditions. METHODS: In a prospective, multicentre cohort study with 103 primary care practices with additional specialisation in homeopathy in Germany and Switzerland, data from all patients (age >1 year) consulting the physician for the first time were observed. The main outcome measures were: Patient and physician assessments (numeric rating scales from 0 to 10) and quality of life at baseline, and after 3, 12, and 24 months. RESULTS: A total of 3,981 patients were studied including 2,851 adults (29% men, mean age 42.5 ± 13.1 years; 71% women, 39.9 ± 12.4 years) and 1,130 children (52% boys, 6.5 ± 3.9 years; 48% girls, 7.0 ± 4.3 years). Ninety-seven percent of all diagnoses were chronic with an average duration of 8.8 ± 8 years. The most frequent diagnoses were allergic rhinitis in men, headache in women, and atopic dermatitis in children. Disease severity decreased significantly (p < 0.001) between baseline and 24 months (adults from 6.2 ± 1.7 to 3.0 ± 2.2; children from 6.1 ± 1.8 to 2.2 ± 1.9). Physicians' assessments yielded similar results. For adults and young children, major improvements were observed for quality of life, whereas no changes were seen in adolescents. Younger age and more severe disease at baseline were factors predictive of better therapeutic success. CONCLUSION: Disease severity and quality of life demonstrated marked and sustained improvements following homeopathic treatment period. Our findings indicate that homeopathic medical therapy may play a beneficial role in the long-term care of patients with chronic diseases

Astrocyte-to-neuron communication through integrin-engaged Thy-1/CBP/Csk/Src complex triggers neurite retraction via the RhoA/ROCK pathway.

Two key proteins for cellular communication between astrocytes and neurons are αvβ3 integrin and the receptor Thy-1. Binding of these molecules in the same (cis) or on adjacent (trans) cellular membranes induces Thy-1 clustering, triggering actin cytoskeleton remodeling. Molecular events that could explain how the Thy-1-αvβ3 integrin interaction signals have only been studied separately in different cell types, and the detailed transcellular communication and signal transduction pathways involved in neuronal cytoskeleton remodeling remain unresolved. Using biochemical and genetic approaches, single-molecule tracking, and high-resolution nanoscopy, we provide evidence that upon binding to αvβ3 integrin, Thy-1 mobility decreased while Thy-1 nanocluster size increased. This occurred concomitantly with inactivation and exclusion of the non-receptor tyrosine kinase Src from the Thy-1/C-terminal Src kinase (Csk)-binding protein (CBP)/Csk complex. The Src inactivation decreased the p190Rho GTPase activating protein phosphorylation, promoting RhoA activation, cofilin, and myosin light chain II phosphorylation and, consequently, neurite shortening. Finally, silencing the adaptor CBP demonstrated that this protein was a key transducer in the Thy-1 signaling cascade. In conclusion, these data support the hypothesis that the Thy-1-CBP-Csk-Src-RhoA-ROCK axis transmitted signals from astrocytic integrin-engaged Thy-1 (trans) to the neuronal actin cytoskeleton. Importantly, the β3 integrin in neurons (cis) was not found to be crucial for neurite shortening. This is the first study to detail the signaling pathway triggered by αvβ3, the endogenous Thy-1 ligand, highlighting the role of membrane-bound integrins as trans acting ligands in astrocyte-neuron communication