Evaluation of hypochlorous acid as an ear flush in dogs with chronic otitis externa

BackgroundChronic otitis externa (OE) in dogs frequently requires anaesthetised ear flushing. ObjectivesTo evaluate hypochlorous acid as an ear flushing and antimicrobial agent in dogs with chronic OE. AnimalsTwenty dogs with chronic OE caused by the same organisms bilaterally. Materials and MethodsOne ear was flushed under anaesthesia with hypochlorous acid, the other with saline solution. Subsequently, the ear flushed with hypochlorous acid was cleaned with the same solution twice daily for 2 weeks, the other ear with a commercial ear cleaner. An ear medication containing miconazole, polymyxin B and prednisolone was used once daily in both ears. Clinical scores were determined before the flush. Ear cytological results were obtained, a hearing test was conducted before and after the ear flush, and a culture was taken directly after flushing. Ears were evaluated after 2 weeks of therapy. ResultsYeast was present in the ears of 11, cocci in one and a mixed infection in eight dogs. Five ears were negative on culture after flushing with hypochlorous acid, one after the saline flush. Clinical and cytological scores decreased significantly with both solutions after 2 weeks of treatment. There was no difference between treatments in any of the scores at any time point between treatments and in the results of the hearing test before and after the flushing procedure. Adverse effects were not seen. Conclusions and Clinical RelevanceHypochlorous acid is a suitable cleaning solution for canine OE

A randomised, double-blinded comparison between subcutaneous rush and intralympathic allergen immunotherapy induction in atopic dogs

BackgroundAtopic dermatitis (AD) is one of the most common skin diseases in small animal practice. Allergen immunotherapy (AIT) is the only curative treatment for the disease, and oral, subcutaneous and intralymphatic administration of allergens are commonly employed. ObjectivesTo compare the efficacy of AIT following an induction phase with intralymphatic injections (ILIT) or rush immunotherapy (RIT). AnimalsFifty privately owned dogs with AD. Materials and MethodsIn a double-blinded study, dogs were randomly assigned to either four monthly ILIT of allergen extract or RIT with five injections administered subcutaneously at hourly intervals on the first day. They were assessed by validated scores;Canine Atopic Dermatitis Lesion Index (CADLI) and pruritus Visual Analog Scale (PVAS) at the beginning of the study and after 1, 3, 6 and 12 months. The latter were performed daily for 7 days before each revisit. Medication scores and a total clinical score were calculated and compared between each group and time point. ResultsThere was no significant difference in CADLI and PVAS scores, or CADLI and medication scores between groups at any of the time points. A significant improvement with both ILIT and RIT was seen in total and pruritus scores, respectively. An owner global assessment of good-to-excellent treatment efficacy was seen in 40% of the dogs;total scores improved by 27% and 35% in the RIT and ILIT group, respectively. Adverse effects were not seen. Conclusions and Clinical RelevanceInduction of AIT can be conducted either as RIT or ILIT with no loss in efficacy

rAAV Engineering for Capsid-Protein Enzyme Insertions and Mosaicism Reveals Resilience to Mutational, Structural and Thermal Perturbations

Feiner R, Teschner J, Teschner K, et al. rAAV Engineering for Capsid-Protein Enzyme Insertions and Mosaicism Reveals Resilience to Mutational, Structural and Thermal Perturbations. International Journal of Molecular Sciences. 2019;20(22): 5702.Recombinant adeno-associated viruses (rAAV) provide outstanding options for customization and superior capabilities for gene therapy. To access their full potential, facile genetic manipulation is pivotal, including capsid loop modifications. Therefore, we assessed capsid tolerance to modifications of the structural VP proteins in terms of stability and plasticity. Flexible glycine-serine linkers of increasing sizes were, at the genetic level, introduced into the 587 loop region of the VP proteins of serotype 2, the best studied AAV representative. Analyses of biological function and thermal stability with respect to genome release of viral particles revealed structural plasticity. In addition, insertion of the 29 kDa enzyme β-lactamase into the loop region was tested with a complete or a mosaic modification setting. For the mosaic approach, investigation of VP2 trans expression revealed that a Kozak sequence was required to prevent leaky scanning. Surprisingly, even the full capsid modification with β-lactamase allowed for the assembly of capsids with a concomitant increase in size. Enzyme activity assays revealed lactamase functionality for both rAAV variants, which demonstrates the structural robustness of this platform technology.</jats:p

Potenzial biogener Abfälle im Freistaat Sachsen

Untersucht wurden das tatsächliche und potenzielle Aufkommen und die Behandlung biogener Abfälle und Reststoffe im Freistaat Sachsen. Für die im Haushalt anfallenden Küchen- und Grünschnittabfälle ergibt sich eine potenzielle Sammelmenge von insgesamt 528.759 Mg bzw. 125 kg je Einwohner und Jahr. Für Grünschnitt ergeben sich vor allem im Bereich der Pflegemaßnahmen auf öffentlichen Flächen und der Landschaftspflege Mengenpotenziale für die Verwertung. Mit der Vermeidung von Speiseabfällen, der Intensivierung der Erfassung und der effizienten Verwertung der biogenen Abfälle und Reststoffe zeigen sich positive Effekte auf die Klimabilanz

Myeloid checkpoint blockade improves killing of T-acute lymphoblastic leukemia cells by an IgA2 variant of daratumumab

Antibody-based immunotherapy is increasingly employed to treat acute lymphoblastic leukemia (ALL) patients. Many T-ALL cells express CD38 on their surface, which can be targeted by the CD38 antibody daratumumab (DARA), approved for the treatment of multiple myeloma. Tumor cell killing by myeloid cells is relevant for the efficacy of many therapeutic antibodies and can be more efficacious with human IgA than with IgG antibodies. This is demonstrated here by investigating antibody-dependent cellular phagocytosis (ADCP) by macrophages and antibody-dependent cell-mediated cytotoxicity (ADCC) by polymorphonuclear (PMN) cells using DARA (human IgG1) and an IgA2 isotype switch variant (DARA-IgA2) against T-ALL cell lines and primary patient-derived tumor cells. ADCP and ADCC are negatively regulated by interactions between CD47 on tumor cells and signal regulatory protein alpha (SIRPα) on effector cells. In order to investigate the impact of this myeloid checkpoint on T-ALL cell killing, CD47 and glutaminyl-peptide cyclotransferase like (QPCTL) knock-out T-ALL cells were employed. QPTCL is an enzymatic posttranslational modifier of CD47 activity, which can be targeted by small molecule inhibitors. Additionally, we used an IgG2σ variant of the CD47 blocking antibody magrolimab, which is in advanced clinical development. Moreover, treatment of T-ALL cells with all- trans retinoic acid (ATRA) increased CD38 expression leading to further enhanced ADCP and ADCC, particularly when DARA-IgA2 was applied. These studies demonstrate that myeloid checkpoint blockade in combination with IgA2 variants of CD38 antibodies deserves further evaluation for T-ALL immunotherapy

Workshop Deutsch als Zweitsprache, Migration und Mehrsprachigkeit: Jahresschrift - Band 16

Im November 2021 fand der 16. Workshop für Deutsch als Zweitsprache, Migration und Mehrsprachigkeit an der Pädagogischen Hochschule Freiburg statt. Der Workshop war ursprünglich für das Jahr 2020 geplant und bedingt durch die Pandemie um ein Jahr verschoben worden. Aufgrund der pandemischen Entwicklungen im Jahr 2021 wurde auf ein digitales Format umgestellt. Das thematische und methodische Spektrum der Beiträge war auch im 16. Workshop in Freiburg sehr breit gefächert. Wir freuen uns daher, in diesem Band einen Großteil der Beiträge dokumentieren zu können, da sie einen Ausschnitt aus der vielfältigen nationalen und internationalen Forschung zu Mehrsprachigkeit, Deutsch als Zweitsprache und Migration wiedergeben

Measurement of triple gauge boson couplings from WW production at LEP energies up to 189 GeV

A measurement of triple gauge boson couplings is presented, based on W-pair data recorded by the OPAL detector at LEP during 1998 at a centre-of-mass energy of 189 GeV with an integrated luminosity of 183 pb^-1. After combining with our previous measurements at centre-of-mass energies of 161-183 GeV we obtain k_g=0.97 +0.20 -0.16, g_1^z=0.991 +0.060 -0.057 and lambda_g=-0.110 +0.058 -0.055, where the errors include both statistical and systematic uncertainties and each coupling is determined by setting the other two couplings to their SM values. These results are consistent with the Standard Model expectations.Comment: 28 pages, 8 figures, submitted to Eur. Phys. J.

The Small Molecule Inhibitor QLT0267 Radiosensitizes Squamous Cell Carcinoma Cells of the Head and Neck

BACKGROUND: The constant increase of cancer cell resistance to radio- and chemotherapy hampers improvement of patient survival and requires novel targeting approaches. Integrin-Linked Kinase (ILK) has been postulated as potent druggable cancer target. On the basis of our previous findings clearly showing that ILK transduces antisurvival signals in cells exposed to ionizing radiation, this study evaluated the impact of the small molecule inhibitor QLT0267, reported as putative ILK inhibitor, on the cellular radiation survival response of human head and neck squamous cell carcinoma cells (hHNSCC). METHODOLOGY/PRINCIPAL FINDINGS: Parental FaDu cells and FaDu cells stably transfected with a constitutively active ILK mutant (FaDu-IH) or empty vectors, UTSCC45 cells, ILK(floxed/floxed(fl/fl)) and ILK(-/-) mouse fibroblasts were used. Cells grew either two-dimensionally (2D) on or three-dimensionally (3D) in laminin-rich extracellular matrix. Cells were treated with QLT0267 alone or in combination with irradiation (X-rays, 0-6 Gy single dose). ILK knockdown was achieved by small interfering RNA transfection. ILK kinase activity, clonogenic survival, number of residual DNA double strand breaks (rDSB; gammaH2AX/53BP1 foci assay), cell cycle distribution, protein expression and phosphorylation (e.g. Akt, p44/42 mitogen-activated protein kinase (MAPK)) were measured. Data on ILK kinase activity and phosphorylation of Akt and p44/42 MAPK revealed a broad inhibitory spectrum of QLT0267 without specificity for ILK. QLT0267 significantly reduced basal cell survival and enhanced the radiosensitivity of FaDu and UTSCC45 cells in a time- and concentration-dependent manner. QLT0267 exerted differential, cell culture model-dependent effects with regard to radiogenic rDSB and accumulation of cells in the G2 cell cycle phase. Relative to corresponding controls, FaDu-IH and ILK(fl/fl) fibroblasts showed enhanced radiosensitivity, which failed to be antagonized by QLT0267. A knockdown of ILK revealed no change in clonogenic survival of the tested cell lines as compared to controls. CONCLUSIONS/SIGNIFICANCE: Our data clearly show that the small molecule inhibitor QLT0267 has potent cytotoxic and radiosensitizing capability in hHNSCC cells. However, QLT0267 is not specific for ILK. Further in vitro and in vivo studies are necessary to clarify the potential of QLT0267 as a targeted therapeutic in the clinic

Overview: On the transport and transformation of pollutants in the outflow of major population centres – observational data from the EMeRGe European intensive operational period in summer 2017

Megacities and other major population centres (MPCs) worldwide are major sources of air pollution, both locally as well as downwind. The overall assessment and prediction of the impact of MPC pollution on tropospheric chemistry are challenging. The present work provides an overview of the highlights of a major new contribution to the understanding of this issue based on the data and analysis of the EMeRGe (Effect of Megacities on the transport and transformation of pollutants on the Regional to Global scales) international project. EMeRGe focuses on atmospheric chemistry, dynamics, and transport of local and regional pollution originating in MPCs. Airborne measurements, taking advantage of the long range capabilities of the High Altitude and LOng Range Research Aircraft (HALO, https://www.halo-spp.de, last access: 22 March 2022), are a central part of the project. The synergistic use and consistent interpretation of observational data sets of different spatial and temporal resolution (e.g. from ground-based networks, airborne campaigns, and satellite measurements) supported by modelling within EMeRGe provide unique insight to test the current understanding of MPC pollution outflows. In order to obtain an adequate set of measurements at different spatial scales, two field experiments were positioned in time and space to contrast situations when the photochemical transformation of plumes emerging from MPCs is large. These experiments were conducted in summer 2017 over Europe and in the inter-monsoon period over Asia in spring 2018. The intensive observational periods (IOPs) involved HALO airborne measurements of ozone and its precursors, volatile organic compounds, aerosol particles, and related species as well as coordinated ground-based ancillary observations at different sites. Perfluorocarbon (PFC) tracer releases and model forecasts supported the flight planning, the identification of pollution plumes, and the analysis of chemical transformations during transport. This paper describes the experimental deployment and scientific questions of the IOP in Europe. The MPC targets – London (United Kingdom; UK), the Benelux/Ruhr area (Belgium, the Netherlands, Luxembourg and Germany), Paris (France), Rome and the Po Valley (Italy), and Madrid and Barcelona (Spain) – were investigated during seven HALO research flights with an aircraft base in Germany for a total of 53 flight hours. An in-flight comparison of HALO with the collaborating UK-airborne platform Facility for Airborne Atmospheric Measurements (FAAM) took place to assure accuracy and comparability of the instrumentation on board. Overall, EMeRGe unites measurements of near- and far-field emissions and hence deals with complex air masses of local and distant sources. Regional transport of several European MPC outflows was successfully identified and measured. Chemical processing of the MPC emissions was inferred from airborne observations of primary and secondary pollutants and the ratios between species having different chemical lifetimes. Photochemical processing of aerosol and secondary formation or organic acids was evident during the transport of MPC plumes. Urban plumes mix efficiently with natural sources as mineral dust and with biomass burning emissions from vegetation and forest fires. This confirms the importance of wildland fire emissions in Europe and indicates an important but discontinuous contribution to the European emission budget that might be of relevance in the design of efficient mitigation strategies. The present work provides an overview of the most salient results in the European context, with these being addressed in more detail within additional dedicated EMeRGe studies. The deployment and results obtained in Asia will be the subject of separate publications