Urban Logistics Micro Hubs: Standardisation Meets Uniqueness

Parcel service companies regularly follow a business strategy which aims for efficiency through large volumes of highly standardized services. However, possibilities to increase efficiency are limited andstandardization bears the risk that a company is replaced by competitors. Therefore, expanding the service portfolio with customer-specific services can be a promising option. A possible place for offering such customer-centered services are logistics micro hubs in urban areas, i.e., logistic infrastructure facilities for storage, transhipment and distribution, located close to recipients of parcel deliveries. An online-survey among Austrian consumers has been carried out, allowing prioritization of consumers’ requirements. Then, the relation of the prioritized services to the capabilities of urban logistics micro-hubs is determined by logical conclusion. The results should be useful to determine new services for further evaluation and development

Oncogenic role of miR-155 in anaplastic large cell lymphoma lacking the t(2;5) translocation.

Anaplastic large cell lymphoma (ALCL) is a rare, aggressive, non-Hodgkin's lymphoma that is characterized by CD30 expression and disease onset in young patients. About half of ALCL patients bear the t(2;5)(p23;q35) translocation, which results in the formation of the nucleophosmin-anaplastic lymphoma tyrosine kinase (NPM-ALK) fusion protein (ALCL ALK(+)). However, little is known about the molecular features and tumour drivers in ALK-negative ALCL (ALCL ALK(-)), which is characterized by a worse prognosis. We found that ALCL ALK(-), in contrast to ALCL ALK(+), lymphomas display high miR-155 expression. Consistent with this, we observed an inverse correlation between miR-155 promoter methylation and miR-155 expression in ALCL. However, no direct effect of the ALK kinase on miR-155 levels was observed. Ago2 immunoprecipitation revealed miR-155 as the most abundant miRNA, and enrichment of target mRNAs C/EBPβ and SOCS1. To investigate its function, we over-expressed miR-155 in ALCL ALK(+) cell lines and demonstrated reduced levels of C/EBPβ and SOCS1. In murine engraftment models of ALCL ALK(-), we showed that anti-miR-155 mimics are able to reduce tumour growth. This goes hand-in-hand with increased levels of cleaved caspase-3 and high SOCS1 in these tumours, which leads to suppression of STAT3 signalling. Moreover, miR-155 induces IL-22 expression and suppresses the C/EBPβ target IL-8. These data suggest that miR-155 can act as a tumour driver in ALCL ALK(-) and blocking miR-155 could be therapeutically relevant. Original miRNA array data are to be found in the supplementary material (Table S1).This work was supported by the SCRI-LIMCR GmbH, the “Jubiläumsfond der Österreichischen Nationalbank” (grant-no. 14856 to O.M.), R.G. was supported by grant SFB P021 from the Austrian Science Funds (FWF), L.K. was supported by grant FWF, P26011, R.M. was supported by FWF grants SFB F28 and SFB F47. S.D.T. is a Senior Lecturer supported with funding from Leukemia and Lymphoma Research.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/path.453

L-Alpha-glycerylphosphorylcholine can be cytoprotective or cytotoxic in neonatal rat cardiac myocytes

L-Alpha-glycerylphosphorylcholine (GPC) is a widely used food supplement. GPC has been shown to exert beneficial effects in several organs; however, the cardiac effects of GPC have yet to be investigated. The aim of the present study was therefore to map out the effects of GPC on cardiac myocytes, with or without ischemia-reperfusion insult. Neonatal rat cardiac myocytes were treated with GPC at 1, 10, 80, and 100 µM concentrations for 15 min, 3 h, or 24 h, respectively. Cell viability by calcein assay and the degree of oxidative stress by DHE (superoxide level) and H2DCF (total ROS accumulation) staining were measured. In separate experiments, cardiomyocytes were pre-treated with the optimal concentration of GPC for 3 h and then cells were exposed to 4 h of simulated ischemia followed by 2 h of reperfusion (SI/R). Cell viability was measured at the end of the SI/R protocol. In normoxic conditions, the 15-min and the 3-h GPC treatment did not affect cell viability, total ROS, and superoxide levels. Under SI/R conditions, the 3-h GPC treatment protected the cardiac myocytes from SI/R-induced cell death and did not alter the level of oxidative stress. The 24-h GPC treatment in normoxic conditions resulted in significant cell death and increased oxidative stress at each concentration. Here we provide the first evidence for the cytoprotective effect of short-term GPC treatment. However, long-term administration of GPC may exert cytotoxicity in a wide concentration range in cardiac myocytes. These results may draw attention to a comprehensive cardiac safety protocol for the testing of GPC

Mitochondrial Side Effects of Surgical Prophylactic Antibiotics Ceftriaxone and Rifaximin Lead to Bowel Mucosal Damage

Despite their clinical effectiveness, a growing body of evidence has shown that many classes of antibiotics lead to mitochondrial dysfunction. Ceftriaxone and Rifaximin are first choice perioperative antibiotics in gastrointestinal surgery targeting fundamental processes of intestinal bacteria; however, may also have negative consequences for the host cells. In this study, we investigated their direct effect on mitochondrial functions in vitro, together with their impact on ileum, colon and liver tissue. Additionally, their impact on the gastrointestinal microbiome was studied in vivo, in a rat model. Rifaximin significantly impaired the oxidative phosphorylation capacity (OxPhos) and leak respiration in the ileal mucosa, in line with increased oxidative tissue damage and histological changes following treatment. Ceftriaxone prophylaxis led to similar changes in the colon mucosa. The composition and diversity of bacterial communities differed extensively in response to antibiotic pre-treatment. However, the relative abundances of the toxin producing species were not increased. We have confirmed the harmful effects of prophylactic doses of Rifaximin and Ceftriaxone on the intestinal mucosa and that these effects were related to the mitochondrial dysfunction. These experiments raise awareness of mitochondrial side effects of these antibiotics that may be of clinical importance when evaluating their adverse effects on bowel mucosa

Increasing test specificity without impairing sensitivity: lessons learned from SARS-CoV-2 serology

Background: Serological tests are widely used in various medical disciplines for diagnostic and monitoring purposes. Unfortunately, the sensitivity and specificity of test systems are often poor, leaving room for false-positive and false-negative results. However, conventional methods were used to increase specificity and decrease sensitivity and vice versa. Using SARS-CoV-2 serology as an example, we propose here a novel testing strategy: the € sensitivity improved two-test' or € SIT²' algorithm. Methods: SIT² involves confirmatory retesting of samples with results falling in a predefined retesting zone of an initial screening test, with adjusted cut-offs to increase sensitivity. We verified and compared the performance of SIT² to single tests and orthogonal testing (OTA) in an Austrian cohort (1117 negative, 64 post-COVID-positive samples) and validated the algorithm in an independent British cohort (976 negatives and 536 positives). Results: The specificity of SIT² was superior to single tests and non-inferior to OTA. The sensitivity was maintained or even improved using SIT² when compared with single tests or OTA. SIT² allowed correct identification of infected individuals even when a live virus neutralisation assay could not detect antibodies. Compared with single testing or OTA, SIT² significantly reduced total test errors to 0.46% (0.24-0.65) or 1.60% (0.94-2.38) at both 5% or 20% seroprevalence. Conclusion: For SARS-CoV-2 serology, SIT² proved to be the best diagnostic choice at both 5% and 20% seroprevalence in all tested scenarios. It is an easy to apply algorithm and can potentially be helpful for the serology of other infectious diseases

Inhaled Methane limits the mitochondrial electron transport chain dysfunction during experimental liver ischemia-reperfusion injury

Background: Methanogenesis can indicate the fermentation activity of the gastrointestinal anaerobic flora. Methane also has a demonstrated anti-inflammatory potential. We hypothesized that enriched methane inhalation can influence the respiratory activity of the liver mitochondria after an ischemia-reperfusion (IR) challenge. Methods: The activity of oxidative phosphorylation system complexes was determined after in vitro methane treatment of intact liver mitochondria. Anesthetized Sprague-Dawley rats subjected to standardized 60-min warm hepatic ischemia inhaled normoxic air (n = 6) or normoxic air containing 2.2% methane, from 50 min of ischemia and throughout the 60-min reperfusion period (n = 6). Measurement data were compared with those on sham-operated animals (n = 6 each). Liver biopsy samples were subjected to high-resolution respirometry; whole-blood superoxide and hydrogen peroxide production was measured; hepatocyte apoptosis was detected with TUNEL staining and in vivo fluorescence laser scanning microscopy. Results: Significantly decreased complex II-linked basal respiration was found in the normoxic IR group at 55 min of ischemia and a lower respiratory capacity (∼60%) and after 5 min of reperfusion. Methane inhalation preserved the maximal respiratory capacity at 55 min of ischemia and significantly improved the basal respiration during the first 30 min of reperfusion. The IR-induced cytochrome c activity, reactive oxygen species (ROS) production and hepatocyte apoptosis were also significantly reduced. Conclusions: The normoxic IR injury was accompanied by significant functional damage of the inner mitochondrial membrane, increased cytochrome c activity, enhanced ROS production and apoptosis. An elevated methane intake confers significant protection against mitochondrial dysfunction and reduces the oxidative damage of the hepatocytes. © 2016 Strifler et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Kooperation lernen im Praktikum?

Kooperation zwischen Lehrpersonen wird im aktuellen Diskurs um die Qualität von Schule und Unterricht als wichtiger Bestandteil von Schulentwicklung und pädagogischer Professionalität verstanden (z.B. Fussangel & Gräsel, 2011). Um zukünftige Lehrerinnen und Lehrer bestmöglich auf einen kompetenten Berufseinstieg vorzubereiten, bedarf es Lerngelegenheiten, in denen sie kooperative Fähigkeiten erwerben können. Besondere Kooperationsmöglichkeiten bieten Teampraktika, in deren Rahmen Studierende zu zweit oder in Gruppen zusammenarbeiten. Zu berücksichtigen ist dabei insbesondere die Art der Gestaltung der Kooperation, deren Qualität sowie der Umgang mit Herausforderungen (Baeten & Simons, 2014). Erstaunlicherweise ist die Forschungslage zu dieser Thematik noch recht dürftig. So wurde bisher kaum untersucht, welche Kooperationsmöglichkeiten und -formen Teampraktika bieten (z.B. Welche Formen der Kooperation werden eingesetzt? Wie hilfreich werden diese Formen von den Studierenden erlebt?). Des Weiteren ist offen, ob Lerngelegenheiten im Teamteaching zu einer Entwicklung der Kooperationsfähigkeit der Lehramtsstudierenden führen sowie deren Einstellungen zum kooperativen Arbeiten verändern. Im längsschnittlich konzipierten Forschungsprojekt „Kooperation im Praktikum“ (KiP) werden Studierende der Vorschul- und Primarstufe der PH Bern in ihren berufspraktischen Phasen begleitet. Die Studierenden einer Kohorte wurden vor und nach dem ersten Praktikum schriftlich befragt (8 Halbtage im sowie 2 Wochen nach dem 1. Semester). Eine dritte Befragung fand nach dem Praktikum 2 statt, welches nach dem 2. Semester während zwei Wochen durchgeführt wurde. Die Teamteaching-Formen wurden mit Hilfe von Aussagen erfragt, welche von den Studierenden in Bezug auf die Häufigkeit und Nützlichkeit auf einer 3-stufigen bzw. 4-stufigen Skala eingeschätzt wurden (z.B. „Ein/e Student/in hat die Hauptverantwortung für den Unterricht, die/der andere assistiert“). Die Einstellung zur Kooperation wurde mit einer neu konzipierten Skala gemessen, die 10 Items enthält (z.B. „Durch Teamarbeit kann man sich gegenseitig gut unterstützen“). Die Kooperationsfähigkeit der Studierenden wurde anhand der beiden Dimensionen „Aktive Mitgestaltung des Kooperationsprozesses“ (5 Items, z.B. „In der Regel gelingt es mir gut, mit anderen zusammenzuarbeiten“) und „Einbezug anderer“ (4 Items, z.B. „Ich kann mich gut den Wünschen anderer anpassen“) erfasst. Alle Skalen wurden auf einer 5-stufigen Likertskala von 1 = „stimme nicht zu“/“gelingt mir überhaupt nicht“ bis 5 = „stimme zu“/“gelingt mir sehr gut“ gemessen und weisen eine zufriedenstellende Reliabilität über die drei Messzeitpunkte hinweg auf. Die Ergebnisse der Befragung nach dem ersten Praktikum zeigen, dass bereits im Einführungspraktikum unterschiedlichste Teamteaching-Formen von wenig und loser Kollaboration (Beobachtung) bis zu stark kollaborativ ausgerichteten Formen (gemeinsames Unterrichten mit geteilter Verantwortung) eingesetzt werden. Formen mit eher schwacher Kollaboration kommen häufiger vor. Die Variation an unterschiedlichen Teamteaching-Modellen setzt sich im Praktikum 2 fort. Im Längsschnittvergleich zeigen sich keine bedeutenden Veränderungen der Einstellungen der Studierenden zur Kooperation, wohingegen die kooperativen Fähigkeiten der beiden Dimensionen „Aktive Mitgestaltung des Kooperationsprozesses“ und „Einbezug anderer“ nach den Praktika 1 und 2 leicht höher eingeschätzt werden als vor dem Praktikum. Die Befunde werden mit Bezug auf die Gestaltung von kooperativen Praktika diskutiert