Holmanmogensen5622
Extracellular vesicles, small vesicles carrying inter alia proteins, miRNA and RNA, are important mediators of intercellular communication. The purpose of this study was to assess the distribution of extracellular vesicles from highly malignant breast cancer and their subsequent effect on the immune cell infiltrate in target organs of metastasis.
Extracellular vesicles were isolated from the tissue culture supernatant of highly malignant 4T1 breast cancer cells or the serum of healthy BALB/c mice. The purity of the isolate was verified by electron microscopy and western blotting. Extracellular vesicles were additionally subjected to proteome analysis. After labeling with the fluorescent dye DiR, extracellular vesicles were injected into healthy BALB/c mice and their in vivo distribution was assessed using fluorescence reflectance imaging (FRI). Following ex vivo imaging of the organs, lung tissue samples were analyzed for extracellular vesicle-mediated changes of myeloid cells and T cell numbers, using florgans of metastasis, using a specific proteome cargo.
Death certification is often used to identify patients with certain diseases in epidemiologic research. There have been few studies looking at the accuracy of recording of parkinsonian diagnoses, any associated dementia and the cause of death on death certificates in people with parkinsonian conditions. This study aimed to assess this.
Data for these analyses were derived from a prospective incident cohort of degenerative/vascular parkinsonian syndromes with lifelong follow-up from Scotland, UK (the PINE study). In those who died, the available research and clinical care records were reviewed to establish the cause for each patient's death. The sensitivity of death certificates was calculated to detect any parkinsonian diagnosis mentioned on the death certificate, the correct specific diagnosis and the presence of dementia. The causes of death were compared between clinical records and death certificates.
Two hundred and seventy-seven patients had died (180 men), mean age at diagnosis and death 76.9years and 81.9years respectively. 66.8% of death certificates mentioned any parkinsonian syndrome but only 49.5% had the correct diagnosis. Sensitivity was highest for Parkinson's disease, those who had parkinsonian-related deaths, had longer disease durations and died out of hospital. Death certificates detected 51.2% of those with dementia. The commonest causes of death were pneumonia, end-stage Parkinsonism and vascular disease with moderate agreement between case-note review and death certification.
Deaths certificates often do not mention underlying Parkinsonism or associated dementia and so epidemiological studies should not rely on this as a sole method of identifying cases or studying mortality.
Deaths certificates often do not mention underlying Parkinsonism or associated dementia and so epidemiological studies should not rely on this as a sole method of identifying cases or studying mortality.
Treatment outside office hours has been associated with increased workflow times for intravenous thrombolysis (IVT) in acute ischemic stroke (AIS). Limited data suggest that this "off-hours effect" also exists for endovascular treatment (EVT). We investigated this phenomenon in a well-organized acute stroke care region in the Netherlands.
Retrospective, observational cohort study of consecutive patients with AIS who received reperfusion therapy in the Greater Amsterdam Area, consisting of 14 primary stroke centers and 1 comprehensive stroke center (IVT 2009-2015, EVT 2014-2017). Office hours were defined as presentation during weekdays between 8AM and 5PM, excluding National Festive days. Primary outcome was door-to-treatment time (door-to-needle [DNT] for IVT, door-to-groin [DGT] for EVT). For DGT, we used the door time of the first hospital. Other outcomes were in-hospital mortality, modified Rankin Scale (mRS) score at 90days and symptomatic intracranial hemorrhage (sICH). We performed multivariable linear and logistic regression analyses and used multiple imputation to account for missing values.
In total, 59% (2450/4161) and 61% (239/395) of patients treated with IVT and EVT, respectively, presented outside office hours. Median DNT was minimally longer outside office hours (32 vs. 30min, p = 0.024, adjusted difference 2.5min, 95% CI 0.7-4.2). Presentation outside office hours was not associated with a longer DGT (median 130min for both groups, adjusted difference 7.0min, 95% CI - 4.2 to 18.1). Clinical outcome and sICH rate also did not differ.
Presentation outside office hours did not lead to clinically relevant treatment delays for reperfusion therapy in patients with AIS.
Presentation outside office hours did not lead to clinically relevant treatment delays for reperfusion therapy in patients with AIS.Ferroptosis is considered a distinctive form of cell death compared to other types of death such as apoptosis. It is known to result from iron-dependent accumulation of lipid peroxides rather than caspase activation. However, we reported recently that ferroptosis interplays with apoptosis. In this study, we investigated a possible mechanism of this interplay between ferroptosis and apoptosis. PF-06650833 chemical structure Results from our studies reveal that combined treatment of the ferroptotic agent erastin and the apoptotic agent TRAIL effectively disrupted mitochondrial membrane potential (ΔΨm) and subsequently promoted caspase activation. The alterations of mitochondrial membrane potential are probably due to an increase in oligomerization of BAX and its accumulation at the mitochondria during treatment with erastin and TRAIL. Interestingly, the combined treatment-promoted apoptosis was effectively inhibited in BAX-deficient HCT116 cells, but not BAK-deficient cells. These results indicate that the BAX-associated mitochondria-dependent pathway plays a pivotal role in erastin-enhanced TRAIL-induced apoptosis.Earlier we have reported that thymic regulatory T cells (Treg) are resistant to in vivo glucocorticoid hormone (GC)-induced apoptosis, while the most GC-sensitive DP thymocytes died through the activation of mitochondrial apoptotic pathway. Here we analyzed the apoptosis-inducing effect of high dose (10-6 M) in vitro dexamethasone (DX) treatment in mouse thymic- and splenic Tregs and CD4+ T cells. Activation of both extrinsic and intrinsic apoptotic pathways started after 2 h of DX treatment in CD4 SP thymocytes and was 3 × higher than in CD4+ splenocytes, while in Treg cells, weak activation of the extrinsic apoptotic pathway started only after 3 h. We also investigated the expression of 21 apoptosis-related molecules using a protein array and found higher level of both pro-and anti-apoptotic molecules in Tregs compared to CD4+ T cells. 4 h in vitro DX treatment induced upregulation of most apoptosis-related molecules both in Tregs and CD4+ T cells, except for the decrease of Bcl-2 expression in CD4+ T cells.
