Untersuchung zur Fahrtauglichkeit bei der Multiplen Sklerose: Datenerhebung im Rahmen einer prospektiven Studie zur Ermittlung des Einflusses von Vigilanz, Schlaf und Kognition bei MS-Erkrankten und Kontrollen

Fahrtauglichkeit bei Patienten mit Multipler Sklerose (MS) ist ein noch insgesamt wenig untersuchtes und möglicherweise unterschätztes Themengebiet, welches aufgrund seiner unumstritten hohen gesellschaftlichen Relevanz mehr Aufmerksamkeit zugesprochen werden sollte. Der bisherige Forschungskonsens beruht dabei auf einer vor allem hohen Bedeutung verschiedener kognitiver Defizite, wenn es um die Beeinträchtigung der fahrrelevanten Leistung geht. Mithilfe einer fragestellungsspezifischen Testdiagnostik sollte in dieser Arbeit erfasst werden, ob und welche relevanten, kognitiven Dimensionen bei MS-Patienten unterschiedlicher Krankheitsstadien die Fahrtauglichkeit in welchem Maße beeinträchtigen. Hierzu wurden MS-Patienten nach Stellung der Erstdiagnose (n=20), dazu nach Alter, Geschlecht und Berufsweg gematchte gesunde Kontrollen (n=20), sowie MS-Patienten mit längerem Krankheitsverlauf (n=20) in ein umfassendes Studiendesign eingeschlossen und bearbeiteten die umfassende, validierte und fahrtauglichkeitsspezifische Testbatterie „DRIVEPLS“ des Wiener Testsystem Verkehr der Firma Schuhfried AG. Bei MS-Patienten mit längerem Krankheitsverlauf konnten multiple Beeinträchtigungen diverser kognitiver Dimensionen im Vergleich zu beiden anderen Studienpools detektiert werden: Logisch- und schlussfolgerndes Denken (p=.001), Belastbarkeit (p<.001), Konzentration (p<.001), Aufmerksamkeit (p<.001), Orientierung (p<.001), visuelle Wahrnehmung (p=.001) sowie das Gesichtsfeld (p=.001). Im Gegensatz dazu zeigten MS-Patienten nach Erstdiagnose sowie die gesunden Kontrollen ähnliche Ergebnisse in allen Subtests des DRIVEPLS auf und erwiesen sich als vergleichbar mit der Normalpopulation. Insgesamt wurden dabei 60% der länger erkrankten MS-Patienten als nicht fahrtauglich detektiert, wohingegen nur 15% der Ersterkrankten und 10% der gesunden Kontrollen ein negatives Testergebnis erreichten. Diese Arbeit betont, dass MS-Patienten mit längerem Krankheitsverlauf multiple kognitive Defizite aufzeigen, die mit einer Reduktion der fahrtauglichkeitsspezifischen Leistungsfähigkeit einhergehen. Eine objektive und nach der Fragestellung ausgerichtete Testbatterie wie das DRIVEPLS könnte dabei als potentielles Screeningtool Einzug in den klinischen Alltag finden und sollte darüber hinaus auch mit den Ergebnissen einer Fahrprüfung verglichen werden. Weitere Studien zur Erfassung der zeitlichen Entwicklung dieser Defizite im Krankheitsverlauf sowie Interventionen zum Erhalt oder der Verbesserung der Fahrtauglichkeit sind in Zukunft notwendig, um ein tieferes Verständnis dieser Thematik zu erreichen

Generalized resistance to pruritogen-induced scratching in the C3H/HeJ strain

Previously the effect of the pruritogens, such as histamine and chloroquine, was tested in 11 inbred mouse strains, and this study aimed to identify resistant and sensitive strains, consistent with the observation that underlies the large variability in human populations. In the present study, we used the low responder C3H/HeJ (C3H) and the more sensitive C57BL/6J (C57) strain to find out if resistance and sensitivity to develop pruritus is restricted to only histamine and chloroquine or extends to other known pruritogens as well. We tested five additional commonly known pruritogens. We established dose-response relationships by injecting four concentrations of the pruritogens in the range of 0.3, 1, 3, and ten-fold in the nuchal fold. Then we assessed the scratching behavior for 30 min after injection with an automated custom-designed device based on the bilateral implantation of mini-magnets in the hind paws and on single cages placed within a magnetic coil. We found that the resistance to pruritogens is a general phenotype of the C3H strain and extends to all pruritogens tested, including not only histamine and chloroquine, but also endothelin, trypsin, 5-HT (serotonin), the short peptide SLIGRL, and Lysophosphatidic acid (LPA). C57 was more sensitive to all pruritogens and, in contrast to C3H, dose-response relationships were evident for some of the pruritogens. In general, comparable peak scratch responses were observed for the 0.3-fold concentrations of the pruritogens in C57 whereas C3H required at least the ten-fold concentration and still displayed only between 5 and 33% of the scratch responses observed in C57 for the respective pruritogen. The general resistance to pruritogens and the low level of scratching behavior found in the C3H strain is an interesting trait and represents a model for the study of the heritability of itch. It is accompanied in C3H with a higher sensitivity in assays of nociception

Langue allemande

Falk Bretschneider Cours de langue appliquée aux sciences sociales et humaines Compte rendu non communiqué. Falk Bretschneider et Marelke König Lire l’allemand d’hier : introduction aux sources de l’histoire moderne et contemporaine allemande et à la paléographie (en coopération avec l’Institut historique allemand) Compte rendu non communiqué. Nicole Reinhardt Cours de traduction de l’allemand Enseignement annulé

On the nontrivial projection problem

The Nontrivial Projection Problem asks whether every finite-dimensional normed space of dimension greater than one admits a well-bounded projection of non-trivial rank and corank or, equivalently, whether every centrally symmetric convex body (of arbitrary dimension greater than one) is approximately affinely equivalent to a direct product of two bodies of non-trivial dimension. We show that this is true "up to a logarithmic factor."Comment: 17 page

Predicting fever in neutropenia with safety-relevant events in children undergoing chemotherapy for cancer: The prospective multicenter SPOG 2015 FN Definition Study.

BACKGROUND Fever in neutropenia (FN) remains a frequent complication in pediatric patients undergoing chemotherapy for cancer. Preventive strategies, like primary antibiotic prophylaxis, need to be evidence-based. PROCEDURE Data on pediatric patients with any malignancy from the prospective multicenter SPOG 2015 FN Definition Study (NCT02324231) were analyzed. A score predicting the risk to develop FN with safety-relevant events (SRE; bacteremia, severe sepsis, intensive care unit admission, death) was developed using multivariate mixed Poisson regression. Its predictive performance was assessed by internal cross-validation and compared with the performance of published rules. RESULTS In 238 patients, 318 FN episodes were recorded, including 53 (17%) with bacteremia and 68 (21%) with SRE. The risk-prediction score used three variables: chemotherapy intensity, defined according to the expected duration of severe neutropenia, time since diagnosis, and type of malignancy. Its cross-validated performance, assessed by the time needed to cover (TNC) one event, exceeded the performance of published rules. A clinically useful score threshold of ≥11 resulted in 2.3% time at risk and 4.1 months TNC. Using external information on efficacy and timing of intermittent antibiotic prophylaxis, 4.3 months of prophylaxis were needed to prevent one FN with bacteremia, and 5.2 months to prevent one FN with SRE, using a threshold of ≥11. CONCLUSIONS This score, based on three routinely accessible characteristics, accurately identifies pediatric patients at risk to develop FN with SRE during chemotherapy. The score can help to design clinical decision rules on targeted primary antibiotic prophylaxis and corresponding efficacy studies

Periportal steatosis in mice affects distinct parameters of pericentral drug metabolism

Little is known about the impact of morphological disorders in distinct zones on metabolic zonation. It was described recently that periportal fibrosis did affect the expression of CYP proteins, a set of pericentrally located drug-metabolizing enzymes. Here, we investigated whether periportal steatosis might have a similar effect. Periportal steatosis was induced in C57BL6/J mice by feeding a high-fat diet with low methionine/choline content for either two or four weeks. Steatosis severity was quantified using image analysis. Triglycerides and CYP activity were quantified in photometric or fluorometric assay. The distribution of CYP3A4, CYP1A2, CYP2D6, and CYP2E1 was visualized by immunohistochemistry. Pharmacokinetic parameters of test drugs were determined after injecting a drug cocktail (caffeine, codeine, and midazolam). The dietary model resulted in moderate to severe mixed steatosis confined to periportal and midzonal areas. Periportal steatosis did not affect the zonal distribution of CYP expression but the activity of selected CYPs was associated with steatosis severity. Caffeine elimination was accelerated by microvesicular steatosis, whereas midazolam elimination was delayed in macrovesicular steatosis. In summary, periportal steatosis affected parameters of pericentrally located drug metabolism. This observation calls for further investigations of the highly complex interrelationship between steatosis and drug metabolism and underlying signaling mechanisms

Triterpene Acids from Frankincense and Semi-Synthetic Derivatives That Inhibit 5-Lipoxygenase and Cathepsin G

Age-related diseases, such as osteoarthritis, Alzheimer’s disease, diabetes, and cardiovascular disease, are often associated with chronic unresolved inflammation. Neutrophils play central roles in this process by releasing tissue-degenerative proteases, such as cathepsin G, as well as pro-inflammatory leukotrienes produced by the 5-lipoxygenase (5-LO) pathway. Boswellic acids (BAs) are pentacyclic triterpene acids contained in the gum resin of the anti-inflammatory remedy frankincense that target cathepsin G and 5-LO in neutrophils, and might thus represent suitable leads for intervention with age-associated diseases that have a chronic inflammatory component. Here, we investigated whether, in addition to BAs, other triterpene acids from frankincense interfere with 5-LO and cathepsin G. We provide a comprehensive analysis of 17 natural tetra- or pentacyclic triterpene acids for suppression of 5-LO product synthesis in human neutrophils. These triterpene acids were also investigated for their direct interference with 5-LO and cathepsin G in cell-free assays. Furthermore, our studies were expanded to 10 semi-synthetic BA derivatives. Our data reveal that besides BAs, several tetra- and pentacyclic triterpene acids are effective or even superior inhibitors of 5-LO product formation in human neutrophils, and in parallel, inhibit cathepsin G. Their beneficial target profile may qualify triterpene acids as anti-inflammatory natural products and pharmacological leads for intervention with diseases related to aging

Perception of one's social environment and loneliness: results of the nationally representative "Old age in Germany (D80+)" study

To examine the association between perception of one’s social environment (in terms of residential attachment and neighborhood trust) and loneliness among the oldest old and whether these associations differ by living arrangement. Methods: We used data from the nationally representative “Old Age in Germany (D80+)” study that included individuals residing in private households and institutionalized settings. The analytic sample was 9,621 individuals (average age: 85.5 years, SD: 4.1 years; 62% female). Data collection took place from November 2020 to April 2021. Multiple linear regressions were conducted with adjustment for relevant covariates. Results: Higher residential attachment (β=-0.02, p < .05) and higher neighborhood trust (β=-0.12, p < .001) were associated with less loneliness. The latter association was moderated by living arrangement (β=-0.09, p = .04) such that the association between neighborhood trust and loneliness was stronger among individuals living in institutionalized settings compared to individuals in private households. Conclusion: Greater residential attachment and neighborhood trust, particularly among individuals living in institutionalized settings, are associated with less loneliness among the oldest old. Finding ways to improve perceived attachment and trust may assist in avoiding loneliness among older individuals