Platelet Serotonin Aggravates Myocardial Ischemia/Reperfusion Injury via Neutrophil Degranulation

Background: Platelets store large amounts of serotonin that they release during thrombus formation or acute inflammation. This facilitates hemostasis and modulates the inflammatory response. Methods: Infarct size, heart function, and inflammatory cell composition were analyzed in mouse models of myocardial reperfusion injury with genetic and pharmacological depletion of platelet serotonin. These studies were complemented by in vitro serotonin stimulation assays of platelets and leukocytes in mice and men, and by measuring plasma serotonin levels and leukocyte activation in patients with acute coronary syndrome. Results: Platelet-derived serotonin induced neutrophil degranulation with release of myeloperoxidase and hydrogen peroxide (H2O2) and increased expression of membrane-bound leukocyte adhesion molecule CD11b, leading to enhanced inflammation in the infarct area and reduced myocardial salvage. In patients hospitalized with acute coronary syndrome, plasmatic serotonin levels correlated with CD11b expression on neutrophils and myeloperoxidase plasma levels. Long-term serotonin reuptake inhibition - reported to protect patients with depression from cardiovascular events - resulted in the depletion of platelet serotonin stores in mice. These mice displayed a reduction in neutrophil degranulation and preserved cardiac function. In line, patients with depression using serotonin reuptake inhibition, presented with suppressed levels of CD11b surface expression on neutrophils and lower myeloperoxidase levels in blood. Conclusions: Taken together, we identify serotonin as a potent therapeutic target in neutrophil-dependent thromboinflammation during myocardial reperfusion injury.Fil: Mauler, Maximilian. No especifíca;Fil: Herr, Nadine. No especifíca;Fil: Schoenichen, Claudia. No especifíca;Fil: Witsch, Thilo. No especifíca;Fil: Marchini, Timoteo Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Härdtner, Carmen. No especifíca;Fil: Koentges, Christoph. No especifíca;Fil: Kienle, Korbinian. Max Planck Institute Of Immunobiology And Epigenetics; AlemaniaFil: Ollivier, Véronique. Inserm; FranciaFil: Schell, Maximilian. No especifíca;Fil: Dorner, Ludwig. No especifíca;Fil: Wippel, Christopher. No especifíca;Fil: Stallmann, Daniela. No especifíca;Fil: Normann, Claus. No especifíca;Fil: Bugger, Heiko. No especifíca;Fil: Walther, Paul. Universitat Ulm; AlemaniaFil: Wolf, Dennis. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Ahrens, Ingo. No especifíca;Fil: Lämmermann, Tim. Max Planck Institute Of Immunobiology And Epigenetics; AlemaniaFil: Ho-Tin-Noé, Benoît. Inserm; FranciaFil: Ley, Klaus. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Bode, Christoph. No especifíca;Fil: Hilgendorf, Ingo. No especifíca;Fil: Duerschmied, Daniel. No especifíca

Digitale Grenzen überwinden: Praktiken der Spätmoderne zwischen Kreativität und Exploration. Ein Standortübergreifendes Lehrforschungsprojekt.

Ahlborn J, Gröschner M, Krückel F, Verständig D. Digitale Grenzen überwinden: Praktiken der Spätmoderne zwischen Kreativität und Exploration. Ein Standortübergreifendes Lehrforschungsprojekt. In: Wahl J, Schell-Kiehl I, Damberger T, eds. Pädagogik, Soziale Arbeit und Digitalität. Weinheim Basel: Beltz Juventa; 2021

Anosmia Testing as Early Detection of SARS-CoV-2 Positivity; A Prospective Study under Screening Conditions

Sudden onset of anosmia is a phenomenon often associated with developing COVID-19 disease and has even been described as an initial isolated symptom in individual cases. In this case-control study, we investigated the feasibility of this condition as a suitable screening test in a population at risk. We performed a prospective study with a total of 313 subjects with suspected SARS-CoV-2 infection. In parallel to routine PCR analysis, a modified commercial scent test was performed to objectify the presence of potential anosmia as a predictor of SARS-CoV-2 positivity. Furthermore, a structured interview assessment of the participants was conducted. A total of 12.1% of the study participants had molecular genetic detection of SARS-CoV-2 infection in the nasopharyngeal swab. It could be demonstrated that these subjects had a significantly weaker olfactory identification performance of the scents. Further analysis of the collected data from the scent test and medical history via random forest (Boruta) algorithm showed that no improvement of the prediction power was achieved by this design. The assay investigated in this study may be suitable for screening general olfactory function. For the screening of COVID-19, it seems to be affected by too many external and internal biases and requires too elaborate and selective pre-test screening

sj-docx-1-eso-10.1177_23969873231224200 – Supplemental material for Kidney dysfunction predicts 90 days mortality after stroke thrombectomy independent of cardiovascular risk factors and chronic kidney disease

Supplemental material, sj-docx-1-eso-10.1177_23969873231224200 for Kidney dysfunction predicts 90 days mortality after stroke thrombectomy independent of cardiovascular risk factors and chronic kidney disease by Marlene Heinze, Maximilian Schell, Felix Leonard Nägele, Bastian Cheng, Fabian Flottmann, Jens Fiehler, Christian Schmidt-Lauber and Götz Thomalla in European Stroke Journal</p

A common mutation in the fibroblast growth factor receptor 1 gene in Pfeiffer syndrome

Pfeiffer syndrome (PS) is one of the classic autosomal dominant craniosynostosis syndromes with craniofacial anomalies and characteristic broad thumbs and big toes. We have previously mapped one of the genes for PS to the centromeric region of chromosome 8 by linkage analysis. Here we present evidence that mutations in the fibroblast growth factor receptor-1 (FGFR1) gene, which maps to 8p, cause one form of familial Pfeiffer syndrome. A C to G transversion in exon 5, predicting a proline to arginine substitution in the putative extracellular domain, was identified in all affected members of five unrelated PS families but not in any unaffected individuals. FGFR1 therefore becomes the third fibroblast growth factor receptor to be associated with an autosomal dominant skeletal disorder

Association between Coffee Consumption and Brain MRI Parameters in the Hamburg City Health Study

Despite associations of regular coffee consumption with fewer neurodegenerative disorders, its association with microstructural brain alterations is unclear. To address this, we examined the association of coffee consumption with brain MRI parameters representing vascular brain damage, neurodegeneration, and microstructural integrity in 2316 participants in the population-based Hamburg City Health Study. Cortical thickness and white matter hyperintensity (WMH) load were measured on FLAIR and T1-weighted images. Microstructural white matter integrity was quantified as peak width of skeletonized mean diffusivity (PSMD) on diffusion-weighted MRI. Daily coffee consumption was assessed in five groups (&lt;1 cup, 1&ndash;2 cups, 3&ndash;4 cups, 5&ndash;6 cups, &gt;6 cups). In multiple linear regressions, we examined the association between brain MRI parameters and coffee consumption (reference group &lt;1 cup). After adjustment for covariates, 3&ndash;4 cups of daily coffee were associated with lower PSMD (p = 0.028) and higher cortical thickness (p = 0.015) compared to &lt;1 cup. Moreover, 1&ndash;2 cups per day was also associated with lower PSMD (p = 0.022). Associations with WMH load or other groups of coffee consumption were not significant (p &gt; 0.05). The findings indicate that regular coffee consumption is positively associated with microstructural white matter integrity and cortical thickness. Further research is necessary to determine longitudinal effects of coffee on brain microstructure

sj-docx-1-eso-10.1177_23969873231208277 – Supplemental material for Early neurological deterioration in patients with acute ischemic stroke is linked to unfavorable cerebral venous outflow

Supplemental material, sj-docx-1-eso-10.1177_23969873231208277 for Early neurological deterioration in patients with acute ischemic stroke is linked to unfavorable cerebral venous outflow by Christian Heitkamp, Laurens Winkelmeier, Jeremy J Heit, Gregory W Albers, Maarten G Lansberg, Helge Kniep, Gabriel Broocks, Christian Paul Stracke, Maximilian Schell, Adrien Guenego, Daniel Paech, Max Wintermark, Jens Fiehler and Tobias D Faizy in European Stroke Journal</p

A ligand-specific blockade of the integrin Mac-1 selectively targets pathologic inflammation while maintaining protective host-defense

Integrin-based therapeutics could block inflammatory processes but they also impair host defence, limiting their usefulness. Here the authors report an anti-Mac1 antibody that blocks its interaction with pro-inflammatory ligand CD40L but not other ligands, and show that it can protect against sepsis in mice