364 research outputs found

    Umweltfreundliches Reinigungs- und Hygienemanagement in Lebensmittelbetrieben

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    Ziel des Projektes ist es, für Lebensmittel herstellende Unternehmen und vor- und nachgelagerte Unternehmen (Landwirtschaft, Handel) Handlungsanweisungen für – unter Umweltgesichtspunkten – optimierte Strategien zum Reinigungs- und Hygienemanagement zu entwickeln. Dazu wurde eine quantitative Befragung von Lebensmittel herstellenden Unternehmen sowie eine qualitative Befragung von Reinigungs- und Desinfektionsmittelherstellern durchgeführt. Außerdem wurden bei Lebensmittelherstellern Betriebsbesuche und Interviews durchgeführt. Die Ergebnisse wurden dokumentiert und für weitere Arbeiten im Projekt berücksichtigt. In Lebensmittel verarbeitenden Betrieben wurden mikrobiologische Hygienekontrollen und Rückstandsuntersuchungen auf Reinigungs- und Desinfektionsmittel vorgenommen. Von fünf besuchten Beispielbetrieben wurden drei für die Darstellung im Leitfaden ausgewählt. Als Grundlage für die Bewertung von kommerziellen Reinigungs- und Desinfektionsmitteln wurde ein Kriterienkatalog mit einem Bewertungsschema für Wirkstoffe erstellt. Dabei wurden auch Substanzbeschreibungen von nicht als konform eingestuften und deshalb unerwünschten Stoffen erarbeitet. Anhand der auch im Bundesverband Ökologische Lebensmittelwirtschaft (BÖLW) abgestimmten Kriterien wurden Handelsprodukte bewertet und eine erste FiBL-Liste „Betriebsmittel für die Ökoverarbeitung“ mit konformen Reinigungs- und Desinfektionsmitteln zusammengestellt. Ein Leitfaden mit Merkblatt für „Umweltfreundliches Reinigungs- und Hygienemanagement in Lebensmittelbetrieben“ wurde erarbeitet

    Regulation of CCR5 expression and immunosuppressive phenotype of MDSC in melanoma

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    MDSC play a major role in immunosuppression and tumor progression in melanoma. Their recruitment to the tumor is mediated by chemokine receptors and their ligands, in particular by chemokine receptor CCR5. The aims of this thesis were to study the mechanisms of CCR5 upregulation on murine MDSC in melanoma and of the previously observed stronger immunosuppressive phenotype of CCR5+ MDSC as compared to their CCR5- counterparts. IL-6, GM-CSF and IFN-g upregulated Ccr5 mRNA expression in murine myeloid cells, whereas the CCR5 ligands, tumor-derived extracellular vesicles, toll-like receptor ligands and IL-1b failed to affect Ccr5 expression. IL-6 and GM-CSF were able to induce CCR5 surface expression during MDSC in vitro differentiation for four days by a STAT3 dependent mechanism. Importantly, we found four putative STAT3 binding sites in the murine Ccr5 promoters. In addition, the STAT3 inhibitor Stattic abrogated Ccr5 upregulation induced by IL-6 and GM-CSF. In the RET transgenic mouse model of malignant melanoma, IL-6 levels in the tumors correlated with the frequency of tumor-infiltrating CCR5+ MDSC. CCR5+ MDSC showed increased phosphorylated STAT3 levels. In addition to the upregulation of CCR5, IL-6 was responsible for stimulation of Arginase (Arg)1 activity and ROS production upon MDSC in vitro differentiation, inducing increased capacity of MDSC to suppress CD8+ T cell proliferation in a co-culture assay. The upregulation of Arg1 by IL-6 was also STAT3 dependent. In contrast to IL-6, CCR5 ligands failed to induce increased immunosuppressive capacity of MDSC. Altogether, IL-6 upregulated CCR5 and immunosuppressive capacity of MDSC in vitro in parallel, which could explain the elevated expression of immunosuppressive factors Arg1 and ROS on CCR5+ MDSC and their increased ability to suppress CD8+ T cell proliferation. However, we found only a slight increase in tumor-infiltrating MDSC and no increase in CCR5 expression or immunosuppressive factors detectable upon s.c. injection of IL-6 overexpressing Ret cells into wild type mice. In the same model, the tumor growth and mouse survival remained unaltered. Finally, we blocked IL-6 in vivo in RET transgenic melanoma-bearing mice by an anti-IL-6 antibody to decrease CCR5+ MDSC recruitment to the tumor and to inhibit IL-6-induced increase in MDSC immunosuppressive capacity, thereby neutralizing the immunosuppression in the tumor and preventing melanoma progression. Unexpectedly, the anti-IL-6 therapy resulted in accelerated tumor progression and earlier death of mice, which was most likely due to the negative effect of anti-IL-6 on T cell activation which was reflected by decreased CD4+ conventional T cells in the tumor. Altogether, we found IL-6 to upregulate CCR5 and immunosuppressive capacity of MDSC in vitro making this cytokine an interesting target for immunotherapy. However, further research should be performed to understand the delicate balance of IL-6 signaling in melanoma immunity in vivo and the challenges of IL-6 blocking immunotherapy for melanoma treatment

    Severe infections of Panton-Valentine leukocidin positive Staphylococcus aureus in children

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    Infections caused by Panton-Valentine leukocidin-positive Staphylococcus aureus (PVL-SA) mostly present as recurrent skin abscesses and furunculosis. However, life-threatening infections (eg, necrotizing pneumonia, necrotizing fasciitis, and osteomyelitis) caused by PVL-SA have also been reported.We assessed the clinical phenotype, frequency, clinical implications (surgery, length of treatment in hospitals/intensive care units, and antibiotic treatments), and potential preventability of severe PVL-SA infections in children.Total, 75 children treated for PVL-SA infections in our in- and outpatient units from 2012 to 2017 were included in this retrospective study.Ten out of 75 children contracted severe infections (PVL-methicillin resistant S aureus n = 4) including necrotizing pneumonia (n = 4), necrotizing fasciitis (n = 2), pyomyositis (n = 2; including 1 patient who also had pneumonia), mastoiditis with cerebellitis (n = 1), preorbital cellulitis (n = 1), and recurrent deep furunculosis in an immunosuppressed patient (n = 1). Specific complications of PVL-SA infections were venous thrombosis (n = 2), sepsis (n = 5), respiratory failure (n = 5), and acute respiratory distress syndrome (n = 3). The median duration of hospital stay was 14 days (range 5-52 days). In 6 out of 10 patients a history suggestive for PVL-SA colonization in the patient or close family members before hospital admission was identified.PVL-SA causes severe to life-threatening infections requiring lengthy treatments in hospital in a substantial percentage of symptomatic PVL-SA colonized children. More than 50% of severe infections might be prevented by prompt testing for PVL-SA in individuals with a history of abscesses or furunculosis, followed by decolonization measures

    Integrating new approaches to atrial fibrillation management: the 6th AFNET/EHRA Consensus Conference.

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    There are major challenges ahead for clinicians treating patients with atrial fibrillation (AF). The population with AF is expected to expand considerably and yet, apart from anticoagulation, therapies used in AF have not been shown to consistently impact on mortality or reduce adverse cardiovascular events. New approaches to AF management, including the use of novel technologies and structured, integrated care, have the potential to enhance clinical phenotyping or result in better treatment selection and stratified therapy. Here, we report the outcomes of the 6th Consensus Conference of the Atrial Fibrillation Network (AFNET) and the European Heart Rhythm Association (EHRA), held at the European Society of Cardiology Heart House in Sophia Antipolis, France, 17-19 January 2017. Sixty-two global specialists in AF and 13 industry partners met to develop innovative solutions based on new approaches to screening and diagnosis, enhancing integration of AF care, developing clinical pathways for treating complex patients, improving stroke prevention strategies, and better patient selection for heart rate and rhythm control. Ultimately, these approaches can lead to better outcomes for patients with AF

    A chemokine network of T cell exhaustion and metabolic reprogramming in renal cell carcinoma

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    Renal cell carcinoma (RCC) is frequently infiltrated by immune cells, a process which is governed by chemokines. CD8+ T cells in the RCC tumor microenvironment (TME) may be exhausted which most likely influence therapy response and survival. The aim of this study was to evaluate chemokine-driven T cell recruitment, T cell exhaustion in the RCC TME, as well as metabolic processes leading to their functional anergy in RCC. Eight publicly available bulk RCC transcriptome collectives (n=1819) and a single cell RNAseq dataset (n=12) were analyzed. Immunodeconvolution, semi-supervised clustering, gene set variation analysis and Monte Carlo-based modeling of metabolic reaction activity were employed. Among 28 chemokine genes available, CXCL9/10/11/CXCR3, CXCL13/CXCR5 and XCL1/XCR1 mRNA expression were significantly increased in RCC compared to normal kidney tissue and also strongly associated with tumor-infiltrating effector memory and central memory CD8+ T cells in all investigated collectives. M1 TAMs, T cells, NK cells as well as tumor cells were identified as the major sources of these chemokines, whereas T cells, B cells and dendritic cells were found to predominantly express the cognate receptors. The cluster of RCCs characterized by high chemokine expression and high CD8+ T cell infiltration displayed a strong activation of IFN/JAK/STAT signaling with elevated expression of multiple T cell exhaustion-associated transcripts. Chemokinehigh RCCs were characterized by metabolic reprogramming, in particular by downregulated OXPHOS and increased IDO1-mediated tryptophan degradation. None of the investigated chemokine genes was significantly associated with survival or response to immunotherapy. We propose a chemokine network that mediates CD8+ T cell recruitment and identify T cell exhaustion, altered energy metabolism and high IDO1 activity as key mechanisms of their suppression. Concomitant targeting of exhaustion pathways and metabolism may pose an effective approach to RCC therapy

    Changes in soil mechanical and hydraulic properties through regenerative cultivation measures in long-term and farm experiments in Germany

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    Regenerative agriculture has been associated with improved soil structure and soil fertility. However, conclusive evidence of its efficacy has remained elusive owing to a lack of long-term experimental studies. In this study, we assessed the impact of diverse regenerative agricultural measures on soil mechanical and hydraulic properties and indicators. Tested treatment factors included reduced tillage versus plowing, along with different levels of compost, mulch, and the application of ferments and compost tea. We measured in situ soil strength via soil penetration (from 0 to 0.8 m depth) and shear resistance (at 0.08 and 0.23 m depth) and assessed field-saturated hydraulic conductivity and ex situ soil aggregate stability (at 0.07 and 0.23 m depth). The experiments were conducted at five sites in Hesse, Germany, including one organic long-term experiment (LTE, since 2010) in Neu-Eichenberg and three organic and one conventional on-farm experiments to cover different soil types, weather conditions, and field practices. The soil types are classified as Luvisol and Vertic Cambisols, and the soil texture ranges from silt loam to silty clay loam. In the LTE, significant differences in aggregate stability and shear resistance were noted between treatments, with a higher geometric mean aggregate diameter at 0.07 m depth in 2021 and 2022 and a higher shear resistance at 0.19 m and 0.23 m in 2020 and in 2021, respectively, in the reduced tillage systems. However, no significant differences were observed among treatments for field-saturated hydraulic conductivity, which was overall very high, showing that reduced tillage did not negatively influence saturated infiltration, albeit bulk density is higher than in the conventionally plowed system. The soil penetration resistance was generally higher for the reduced tillage treatments across depths of 0.0–0.30 m, albeit not statistically significant (p > 0.05). Significantly higher water-stable aggregates and geometric mean diameters were observed for regenerative agricultural treatments in three of the on-farm experiments at a depth of 0.07 m. The shear resistance was significantly higher in regenerative agriculture units in specific years and depths. Although the outcomes are encouraging, the variability of the effects of reduced tillage and organic amendments in affecting soil properties highlights the need for further long-term research including farm trials. This is essential to fully understand the effects of regenerative practices on soil physical quality

    Literatur-Rundschau

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