Although the bone marrow contains most hematopoietic activity during adulthood, hematopoietic stem and progenitor cells can be recovered from various extramedullary sites. Cells with hematopoietic progenitor properties have even been reported in the adult brain under steady‐state conditions, but their nature and localization remain insufficiently defined. Here, we describe a heterogeneous population of myeloid progenitors in the leptomeninges of adult C57BL/6 mice. This cell pool included common myeloid, granulocyte/macrophage, and megakaryocyte/erythrocyte progenitors. Accordingly, it gave rise to all major myelo‐erythroid lineages in clonogenic culture assays. Brain‐associated progenitors persisted after tissue perfusion and were partially inaccessible to intravenous antibodies, suggesting their localization behind continuous blood vessel endothelium such as the blood‐arachnoid barrier. Flt3\(^{Cre}\) lineage tracing and bone marrow transplantation showed that the precursors were derived from adult hematopoietic stem cells and were most likely continuously replaced via cell trafficking. Importantly, their occurrence was tied to the immunologic state of the central nervous system (CNS) and was diminished in the context of neuroinflammation and ischemic stroke. Our findings confirm the presence of myeloid progenitors at the meningeal border of the brain and lay the foundation to unravel their possible functions in CNS surveillance and local immune cell production.

Background: Proportions of patients dying from the coronavirus disease-19 (COVID-19) vary between different countries. We report the characteristics; clinical course and outcome of patients requiring intensive care due to COVID-19 induced acute respiratory distress syndrome (ARDS). Methods: This is a retrospective, observational multicentre study in five German secondary or tertiary care hospitals. All patients consecutively admitted to the intensive care unit (ICU) in any of the participating hospitals between March 12 and May 4, 2020 with a COVID-19 induced ARDS were included. Results: A total of 106 ICU patients were treated for COVID-19 induced ARDS, whereas severe ARDS was present in the majority of cases. Survival of ICU treatment was 65.0%. Median duration of ICU treatment was 11 days; median duration of mechanical ventilation was 9 days. The majority of ICU treated patients (75.5%) did not receive any antiviral or anti-inflammatory therapies. Venovenous (vv) ECMO was utilized in 16.3%. ICU triage with population-level decision making was not necessary at any time. Univariate analysis associated older age, diabetes mellitus or a higher SOFA score on admission with non-survival during ICU stay. Conclusions: A high level of care adhering to standard ARDS treatments lead to a good outcome in critically ill COVID-19 patients.

The understanding of excimer formation and its interplay with the singlet-correlated triplet pair state \(^{1}\)(TT) is of high significance for the development of efficient organic electronics. Here, we study the photoinduced dynamics of the tetracene dimer in the gas phase by time-resolved photoionisation and photoion imaging experiments as well as nonadiabatic dynamics simulations in order to obtain mechanistic insight into the excimer formation dynamics. The experiments are performed using a picosecond laser system for excitation into the S\(_{2}\) state and reveal a biexponential time dependence. The time constants, obtained as a function of excess energy, lie in the range between ≈10 ps and 100 ps and are assigned to the relaxation of the excimer on the S\(_{1}\) surface and to its deactivation to the ground state. Simulations of the quantum-classical photodynamics are carried out in the frame of the semi-empirical CISD and TD-lc-DFTB methods. Both theoretical approaches reveal a dominating relaxation pathway that is characterised by the formation of a perfectly stacked excimer. TD-lc-DFTB simulations have also uncovered a second relaxation channel into a less stable dimer conformation in the S\(_{1}\) state. Both methods have consistently shown that the electronic and geometric relaxation to the excimer state is completed in less than 10 ps. The inclusion of doubly excited states in the CISD dynamics and their diabatisation further allowed to observe a transient population of the \(^{1}\)(TT) state, which, however, gets depopulated on a timescale of 8 ps, leading finally to the trapping in the excimer minimum.

Nonalcoholic steatohepatitis (NASH), a primary cause of liver disease, leads to complications such as fibrosis, cirrhosis, and carcinoma, but the pathophysiology of NASH is incompletely understood. Epstein-Barr virus-induced G protein-coupled receptor 2 (EBI2) and its oxysterol ligand 7 alpha,25-dihydroxycholesterol (7 alpha,25-diHC) are recently discovered immune regulators. Several lines of evidence suggest a role of oxysterols in NASH pathogenesis, but rigorous testing has not been performed. We measured oxysterol levels in the livers of NASH patients by LC-MS and tested the role of the EBI2-7 alpha,25-diHC system in a murine feeding model of NASH. Free oxysterol profiling in livers from NASH patients revealed a pronounced increase in 24- and 7-hydroxylated oxysterols in NASH compared with controls. Levels of 24- and 7-hydroxylated oxysterols correlated with histological NASH activity. Histological analysis of murine liver samples demonstrated ballooning and liver inflammation. No significant genotype-related differences were observed in Ebi2(-/-) mice and mice with defects in the 7 alpha,25-diHC synthesizing enzymes CH25H and CYP7B1 compared with wild-type littermate controls, arguing against an essential role of these genes in NASH pathogenesis. Elevated 24- and 7-hydroxylated oxysterol levels were confirmed in murine NASH liver samples. Our results suggest increased bile acid synthesis in NASH samples, as judged by the enhanced level of 7 alpha-hydroxycholest-4-en-3-one and impaired 24S-hydroxycholesterol metabolism as characteristic biochemical changes in livers affected by NASH.

Hintergrund Die Versorgung von Patellafrakturen ist technisch anspruchsvoll. Auch wenn die radiologischen Ergebnisse zumeist zufriedenstellend sind, deckt sich dies häufig nicht mit der subjektiven Einschätzung der Patienten. Die klassische Versorgung mittels Drahtzuggurtung weist einige Komplikationen auf. Die winkelstabile Plattenosteosynthese hat sich in den letzten Jahren biomechanisch als vorteilhaft erwiesen. Fragestellung Von wem werden Patellafrakturen in Deutschland versorgt? Wie sieht der aktuelle Versorgungsstandard aus? Haben sich „moderne“ Osteosyntheseformen durchgesetzt? Was sind die häufigsten Komplikationen? Material und Methoden Die Mitglieder der Deutschen Gesellschaft für Orthopädie und Unfallchirurgie sowie der Deutschen Kniegesellschaft wurden aufgefordert, an einer Onlinebefragung teilzunehmen. Ergebnisse Insgesamt wurden 511 komplett ausgefüllte Fragebogen ausgewertet. Die Befragten sind zum größten Teil auf Unfallchirurgie spezialisiert (51,5 %) und verfügen über langjährige Berufserfahrung in Traumazentren. Die Hälfte der Operateure versorgt ≤5 Patellafrakturen jährlich. In knapp 40 % der Fälle wird die präoperative Bildgebung um eine Computertomographie ergänzt. Die klassische Zuggurtung ist noch die bevorzugte Osteosyntheseform bei allen Frakturtypen (Querfraktur 52 %, Mehrfragmentfrakturen 40 %). Bei Mehrfragmentfrakturen entscheiden sich 30 % der Operateure für eine winkelstabile Plattenosteosynthese. Bei Beteiligung des kaudalen Pols dient als zusätzliche Sicherung die McLaughlin-Schlinge (60 %). Diskussion Der Versorgungsstandard von Patellafrakturen in Deutschland entspricht weitgehend der aktualisierten S2e-Leitlinie. Nach wie vor wird die klassische Zuggurtungsosteosynthese als Verfahren der Wahl genutzt. Weitere klinische (Langzeit‑)Studien werden benötigt, um die Vorteile der winkelstabilen Plattenosteosynthese zu verifizieren.