Ischemic stroke and concomitant gastrointestinal complications- a fatal combination for patient recovery

Stroke is primarily a neurodegenerative disease but can also severely impact the functions of other vital organs and deteriorate disease outcomes. A malfunction of the gastrointestinal tract (GIT), commonly observed in stroke patients, is often characterized by severe bowel obstruction, intestinal microbiota changes and inflammation. Over-activated immune cells after stroke are the major contributors to endorse intestinal inflammation and may induce damage to single-layer epithelial cell barriers. The post-stroke leakage of intestinal barriers may allow the translocation and dissemination of resident microflora to systemic organs and cause sepsis. This overshooting systemic immune reaction fuels ongoing inflammation in the degenerating brain and slows recovery. Currently, the therapeutic options to treat these GIT-associated anomalies are very limited and further research is required to develop novel treatments. In this mini-review, we first discuss the current knowledge from clinical studies and experimental stroke models that provide strong evidence of the existence of post-stroke GIT complications. Then, we review the literature regarding novel therapeutic approaches that might help to maintain GIT homeostasis and improve neurological outcomes in stroke patients

Direct Observation of Phagocytosis and NET-formation by Neutrophils in Infected Lungs using 2-photon Microscopy

After the gastrointestinal tract, the lung is the second largest surface for interaction between the vertebrate body and the environment. Here, an effective gas exchange must be maintained, while at the same time avoiding infection by the multiple pathogens that are inhaled during normal breathing. To achieve this, a superb set of defense strategies combining humoral and cellular immune mechanisms exists. One of the most effective measures for acute defense of the lung is the recruitment of neutrophils, which either phagocytose the inhaled pathogens or kill them by releasing cytotoxic chemicals. A recent addition to the arsenal of neutrophils is their explosive release of extracellular DNA-NETs by which bacteria or fungi can be caught or inactivated even after the NET releasing cells have died. We present here a method that allows one to directly observe neutrophils, migrating within a recently infected lung, phagocytosing fungal pathogens as well as visualize the extensive NETs that they have produced throughout the infected tissue. The method describes the preparation of thick viable lung slices 7 hours after intratracheal infection of mice with conidia of the mold Aspergillus fumigatus and their examination by multicolor time-lapse 2-photon microscopy. This approach allows one to directly investigate antifungal defense in native lung tissue and thus opens a new avenue for the detailed investigation of pulmonary immunity

A four-organ-chip for interconnected long-term co-culture of human intestine, liver, skin and kidney equivalents

Systemic absorption and metabolism of drugs in the small intestine, metabolism by the liver as well as excretion by the kidney are key determinants of efficacy and safety for therapeutic candidates. However, these systemic responses of applied substances lack in most in vitro assays. In this study, a microphysiological system maintaining the functionality of four organs over 28 days in co-culture has been established at a minute but standardized microsystem scale. Preformed human intestine and skin models have been integrated into the four-organ-chip on standard cell culture inserts at a size 100000-fold smaller than their human counterpart organs. A 3D-based spheroid, equivalent to ten liver lobules, mimics liver function. Finally, a barrier segregating the media flow through the organs from fluids excreted by the kidney has been generated by a polymeric membrane covered by a monolayer of human proximal tubule epithelial cells. A peristaltic on-chip micropump ensures pulsatile media flow interconnecting the four tissue culture compartments through microfluidic channels. A second microfluidic circuit ensures drainage of the fluid excreted through the kidney epithelial cell layer. This four-organ-chip system assures near to physiological fluid-to-tissue ratios. In-depth metabolic and gene analysis revealed the establishment of reproducible homeostasis among the co-cultures within two to four days, sustainable over at least 28 days independent of the individual human cell line or tissue donor background used for each organ equivalent. Lastly, 3D imaging two-photon microscopy visualised details of spatiotemporal segregation of the two microfluidic flows by proximal tubule epithelia. To our knowledge, this study is the first approach to establish a system for in vitro microfluidic ADME profiling and repeated dose systemic toxicity testing of drug candidates over 28 days.BMBF, 0315569, GO-Bio 3: Multi-Organ-Bioreaktoren für die prädiktive Substanztestung im Chipforma

Implementation in nursing and midwifery. A scoping review

Hintergrund: Evidenzbasiertes Wissen steht im Pflege- und Hebammenbereich zunehmend zur Verfügung, wird aber nicht automatisch in die Praxis umgesetzt. Implementationsforschung gewinnt daher immer grössere Bedeutung. Die international verfügbaren Forschungsergebnisse zu den Faktoren, die zum Gelingen einer Implementation beitragen, sind bislang noch nicht genügend aufbereitet worden. Gegenstand des Artikels: Im vorliegenden Scoping Review wird der Frage nachgegangen, welche Arbeiten zur gelungenen Vorbereitung, Durchführung und Aufrechterhaltung von Interventionen im Bereich der Pflege- und Hebammenarbeit vorliegen. Methode: In der für Scoping Reviews vorgesehenen, systematischen Vorgehensweise wurden einschlägige Datenbanken durchsucht, um Reviews und Studien zur Implementationsforschung im Bereich Pflege und Hebammenarbeit aufzufinden. Der Auswahlprozess, der zur Trefferliste führte, und die Charakteristika der eingeschlossenen Studien werden in Abbildungen und Tabellen strukturiert aufbereitet. Ergebnis: In vier Reviews und 38 Studien, die den Einschlusskriterien entsprechen, werden verschiedene Faktoren mit gelungener Implementation verbunden. Für die eingeschlossenen Studien werden folgende vier Kategorien aufgestellt: (1) Arbeitsplatzkultur mit 16 Nennungen, (2) Leitungskultur: 28 Nennungen, (3) Ressourcen: 4 Nennungen und (4) Training mit 22 Nennungen. Je nach Phase der Implementation (Vorbereitung, Durchführung oder Aufrechterhaltung) kommt ihnen eine etwas andere Bedeutung zu. Zusammenfassung: Das Review bietet eine Orientierung im Feld der Implementationsforschung und zeigt Design, Thema und Ergebnis der eingeschlossenen Studien auf. Nur wenige Studien berücksichtigen relevante Theorien und zeigen den Einfluss sowohl der Forschenden als auch der Zielgruppe auf den Implementationsprozess oder die genaue Beschreibung der Umstände, in denen die Implementation stattfindet, auf. Background: Evidence-based expertise in nursing and midwifery is growing but is not automatically turned into practice. The importance of implementation research is therefore increasing. International research results on factors facilitating implementation have not yet been sufficiently presented. Objective: This scoping review will explore the findings on successful preparation, realisation and maintenance of interventions in nursing and midwifery. Method: Based on an existing systematic approach, relevant data bases were accessed to identify original studies relating to implementation research in nursing and midwifery. The process of study selection and the characteristics of the included studies were charted. Findings: In the four reviews and 38 studies which met the inclusion criteria, various factors leading to successful implementation are identified. Based on the included studies, four facilitating factors can be pinpointed: (1) workplace culture (16 entries), (2) leadership culture (28 entries), (3) resources (4 entries), and (4) training (22 entries). Depending on the specific phase of the implementation process (preparation, realisation, or maintenance), these factors will vary in importance. Conclusion: This scoping review provides an orientation for the field of implementation research and it maps the design, themes and results of the studies included. It should be noted that few studies take into consideration the relevant theories, as well as the influence that the researchers and the target group may have on the implementation process, or provide an exact description of the setting in which the implementation takes place

During early stages of cancer, neutrophils initiate anti-tumor immune responses in tumor-draining lymph nodes

Tumor-draining lymph nodes (LNs) play a crucial role during cancer spread and in initiation of anti-cancer adaptive immunity. Neutrophils form a substantial population of cells in LNs with poorly understood functions. Here, we demonstrate that, during head and neck cancer (HNC) progression, tumor-associated neutrophils transmigrate to LNs and shape anti-tumor responses in a stage-dependent manner. In metastasis-free stages (N0), neutrophils develop an antigen-presenting phenotype (HLA-DR+CD80+CD86+ICAM1+PD-L1-) and stimulate T cells (CD27+Ki67highPD-1-). LN metastases release GM-CSF and via STAT3 trigger development of PD-L1+ immunosuppressive neutrophils, which repress T cell responses. The accumulation of neutrophils in T cell-rich zones of LNs in N0 constitutes a positive predictor for 5-year survival, while increased numbers of neutrophils in LNs of N1-3 stages predict poor prognosis in HNC. These results suggest a dual role of neutrophils as essential regulators of anti-cancer immunity in LNs and argue for approaches fostering immunostimulatory activity of these cells during cancer therapy

Rapid Immunomagnetic Negative Enrichment of Neutrophil Granulocytes from Murine Bone Marrow for Functional Studies In Vitro and In Vivo

Polymorphonuclear neutrophils (PMN) mediate early immunity to infection but can also cause host damage if their effector functions are not controlled. Their lack or dysfunction is associated with severe health problems and thus the analysis of PMN physiology is a central issue. One prerequisite for PMN analysis is the availability of purified cells from primary organs. While human PMN are easily isolated from peripheral blood, this approach is less suitable for mice due to limited availability of blood. Instead, bone marrow (BM) is an easily available reservoir of murine PMN, but methods to obtain pure cells from BM are limited. We have developed a novel protocol allowing the isolation of highly pure untouched PMN from murine BM by negative immunomagnetic isolation using a complex antibody cocktail. The protocol is simple and fast (∼1 h), has a high yield (5–10*106 PMN per animal) and provides a purity of cells equivalent to positive selection (>80%). Most importantly, cells obtained by this method are non-activated and remain fully functional in vitro or after adoptive transfer into recipient animals. This method should thus greatly facilitate the study of primary murine PMN in vitro and in vivo

The tracheal system of scutigeromorph centipedes and the evolution of respiratory systems of myriapods

The tracheal system of scutigeromorph centipedes (Chilopoda) is special, as it consists of dorsally arranged unpaired spiracles. In this study, we investigate the tracheal systems of five different scutigeromorph species. They are strikingly similar to each other but depict unique characters compared to the tracheal systems of pleurostigmophoran centipedes, which has engendered an ongoing debate over a single versus independent origin of tracheal systems in Chilopoda. Up to now, only the respiratory system of Scutigera coleoptrata was investigated intensively using LM-, TEM-, and SEM-techniques. We supplement this with data for species from all three families of Scutigeromorpha. These reveal interspecific differences in atrial width and the shape and branching pattern of the tracheal tubules. Further, we investigated the tracheal system of Scutigera coleoptrata with three additional techniques: light sheet microscopy, microCT and synchrotron radiation based microCT analysis. This set of techniques allows a comparison between fresh versus fixed and dried material. The question of a unique vs. multiple origin of tracheal systems in centipedes and in Myriapoda as a whole is discussed with regard to their structural similarities and differences and the presence of hemocyanin as an oxygen carrier. We used morphological and molecular data and the fossil record to evaluate the alternative hypotheses

Potenziale digitaler Lehre und digitaler Kooperations- und Unterstützungsangebote zur Förderung der Theorie-Praxis-Verzahnung in der Lehrer*innenbildung

Bulizek B, Freudenau T, Habicher A, et al. Potenziale digitaler Lehre und digitaler Kooperations- und Unterstützungsangebote zur Förderung der Theorie-Praxis-Verzahnung in der Lehrer*innenbildung. In: Beißwenger M, Bulizek B, Gryl I, Schacht F, eds. Digitale Innovationen und Kompetenzen in der Lehramtsausbildung. Duisburg: Universitätsverlag Rhein-Ruhr; 2020: 209-233

Implementation in nursing and midwifery. A scoping review / Implementationsprojekte in der Pflege und Hebammenarbeit. Scoping review

Evidence-based expertise in nursing and midwifery is growing but is not automatically turned into practice. The importance of implementation research is therefore increasing. International research results on factors facilitating implementation have not yet been sufficiently presented