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Acute pulmonary embolism can be a life-threatening condition with a high mortality. The treatment choice is a matter of debate. The early and late outcomes of patients treated with surgical pulmonary embolectomy for acute pulmonary embolism in a single center were analyzed.

This study analyzes the myocardial force-generating capacity in infective endocarditis (IE) using an experimental model of isolated human atrial myocardium. In vivo, it is difficult to decide whether or not alterations in myocardial contractile behavior are due to secondary effects associated with infection such as an altered heart rate, alterations of preload and afterload resulting from valvular defects, and altered humoral processes. Our in vitro model using isolated human myocardium, in contrast, guarantees exactly defined experimental conditions with respect to preload, afterload, and contraction frequency, thus not only preventing confounding by in vivo determinants of contractility but also excluding effects of other factors associated with sepsis, hemodynamics, humoral influences, temperature, and medical treatment.

In a long-term study six Norway spruce, Picea abies, clones from two different provenance regions were exposed to two different concentrations of ozone in open top chambers. Differential screening of subtractive cDNA libraries made from mRNA of ozone-treated trees identified several cDNA clones of ozone-responsive genes. The spruce clones varied in the level of accumulation for the mRNA. This is discussed under the aspect of ozone-induced early senescence because the two phenotypically most ozone-tolerant spruce clones showed the lowest levels of accumulation for both mRNA.

Abstract The effect of viral infections on the Crassulacean Acid Metabolism (CAM) was determined in two orchid species. Plants of a Sophrolaeliocattleya (SLC) commercial hybrid were inoculated with either the orchid strain of the Tabacco Mosaic Virus (TMV-O), with Cymbidium Mosaic Virus (CybMV) or with a mixture of both viruses. Plants of Epidendrum elongatum, a wild terrestrial orchid, were inoculated either with TMV-O or with TMV-O and CybMV simultaneously. Virus infected plants started to show a systemic mosaic on the leaves 3 to 4 years after inoculation, the symptoms being more appreciable in SLC than in E. elongatum. Double inoculation with TMV-O and CybMV proved to the lethal for the SLC plants. TMV-O infection caused 58 % and 24 % reduction in nocturnal leaf titratable acidity (TA) in SLC and E. elongatum, respectively. TMV-O also changed the daily pattern of leaf nonstructural carbohydrates typical of CAM plants. A 50 % decrease in TA at dawn and a mid-morning peak of sugar accumulation were measured in leaves of doubly inoculated E. elongatum plants. In SLC CybMV infection inhibited CAM and induced an accumulation of glucans in the leaves. Cytoplasmic agglomerations of CybMV, but not of TMV-O, were detected in SLC infected cells, whereas TMV-O particles were clearly observed in the cytoplasm of E. elongatum. Infection by TMV-O or CybMV in SLC caused an increase in chloroplasts volume and distortion of the grana due to high glucan accumulation. In contrast, TMV-O infection in E. elongatum induced a lesser degree of damage in the cell ultrastructure. [ABSTRACT FROM AUTHOR]

Abstract Background The receptor for advanced glycation endproducts, RAGE, is involved in the pathogenesis of many inflammatory conditions, which is mostly related to its strong activation of NF-κB but also due to its function as ligand for the β2-integrin Mac-1. To further dissect the stimulus-dependent role of RAGE on leukocyte recruitment during inflammation, we investigated β2-integrin-dependent leukocyte adhesion in RAGE-/- and Icam1-/- mice in different cremaster muscle models of inflammation using intravital microscopy. Results We demonstrate that RAGE, but not ICAM-1 substantially contributes to N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced leukocyte adhesion in TNF-α-pretreated cremaster muscle venules in a Mac-1-dependent manner. In contrast, fMLP-stimulated leukocyte adhesion in unstimulated cremaster muscle venules is independent of RAGE, but dependent on ICAM-1 and its interaction with LFA-1. Furthermore, chemokine CXCL1-stimulated leukocyte adhesion in surgically prepared cremaster muscle venules was independent of RAGE but strongly dependent on ICAM-1 and LFA-1 suggesting a differential and stimulus-dependent regulation of leukocyte adhesion during inflammation in vivo. Conclusion Our results demonstrate that RAGE and ICAM-1 differentially regulate leukocyte adhesion in vivo in a stimulus-dependent manner.

Progranulin (PGRN) haploinsufficiency is a major risk factor for frontotemporal lobar degeneration with TAR DNA-binding protein 43 (TDP-43) pathology (FTLD- GRN ). Multiple therapeutic strategies are in clinical development to restore PGRN in the CNS, including gene therapy. However, a limitation of current gene therapy approaches aimed to alleviate FTLD-associated pathologies may be their inefficient brain exposure and biodistribution. We therefore developed an adeno-associated virus (AAV) targeting the liver (L) to achieve sustained peripheral expression of a transferrin receptor (TfR) binding, brain-penetrant (b) PGRN variant [AAV(L):bPGRN] in two mouse models of FTLD- GRN , namely, Grn knockout and GrnxTmem106b double knockout mice. This therapeutic strategy avoids potential safety and biodistribution issues of CNS-administered AAVs and maintains sustained concentrations of PGRN in the brain after a single dose. AAV(L):bPGRN treatment reduced several FTLD- GRN -associated pathologies including severe motor function deficits, aberrant TDP-43 phosphorylation, dysfunctional protein degradation, lipid metabolism, gliosis, and neurodegeneration in the brain. The potential translatability of our findings was tested in an in vitro model using cocultured human induced pluripotent stem cell (hiPSC)-derived microglia lacking PGRN and TMEM106B and wild-type hiPSC-derived neurons. As in mice, aberrant TDP-43, lysosomal dysfunction, and neuronal loss were ameliorated after treatment with exogenous TfR-binding protein transport vehicle fused to PGRN (PTV:PGRN). Together, our studies suggest that peripherally administered brain-penetrant PGRN replacement strategies ameliorate FTLD- GRN relevant phenotypes including TDP-43 pathology, neurodegeneration, and behavioral deficits. Our data provide preclinical proof of concept for the use of this AAV platform for treatment of FTLD- GRN and potentially other CNS disorders.

Transcatheter aortic-valve replacement (TAVR) is increasingly being used for the treatment of aortic-valve stenosis. Therefore, the total number of patients with an aortic-valve prosthesis is increasing, causing the incidence of prosthetic-valve endocarditis to increase., Methods: Between March 2016 and July 2019, ten patients underwent surgery due to prosthetic-valve endocarditis after TAVR. They were identified in our institutional database and analyzed., Results: Infective endocarditis was diagnosed 17 ± 16 month after TAVR. Mean age was 79 ± 4.4 years. Microbiological detection showed 6/10 positive blood cultures for enterococcus faecalis. Median EuroScore II was 24.64%. The mean size of the surgically replaced aortic prosthesis was 23.6 ± 1.3 and that of the TAVR was 28.4 ± 2.3 mm. The surgically implanted aortic valves had a mean gradient of 8.5 ± 2.2 mmHg. One patient died in hospital due to septic multiorgan failure. After discharge, all patients survived with a mean follow-up of 9 ± 8 month., Conclusions: With a rising number of patients after TAVR, prosthetic-valve endocarditis will increasingly occur in patients who were previously considered high or intermediate risk. Our results show that patients with TAVR infective endocarditis can be operated on with good results. Surgical therapy should not be withheld from TAVR patients with infective endocarditis.

Amyloid-β (Aβ) deposition is an initiating factor in Alzheimer's disease (AD). Microglia are the brain immune cells that surround and phagocytose Aβ plaques, but their phagocytic capacity declines in AD. This is in agreement with studies that associate AD risk loci with genes regulating the phagocytic function of immune cells. Immunotherapies are currently pursued as strategies against AD and there are increased efforts to understand the role of the immune system in ameliorating AD pathology. Here, we evaluated the effect of the Aβ targeting ACI-24 vaccine in reducing AD pathology in an amyloidosis mouse model. ACI-24 vaccination elicited a robust and sustained antibody response in APPPS1 mice with an accompanying reduction of Aβ plaque load, Aβ plaque-associated ApoE and dystrophic neurites as compared to non-vaccinated controls. Furthermore, an increased number of NLRP3-positive plaque-associated microglia was observed following ACI-24 vaccination. In contrast to this local microglial activation at Aβ plaques, we observed a more ramified morphology of Aβ plaque-distant microglia compared to non-vaccinated controls. Accordingly, bulk transcriptomic analysis revealed a trend towards the reduced expression of several disease-associated microglia (DAM) signatures that is in line with the reduced Aβ plaque load triggered by ACI-24 vaccination. Our study demonstrates that administration of the Aβ targeting vaccine ACI-24 reduces AD pathology, suggesting its use as a safe and cost-effective AD therapeutic intervention.