STAT2 signaling restricts viral dissemination but drives severe pneumonia in SARS-CoV-2 infected hamsters

Emergence of SARS-CoV-2 causing COVID-19 has resulted in hundreds of thousands of deaths. In search for key targets of effective therapeutics, robust animal models mimicking COVID-19 in humans are urgently needed. Here, we show that Syrian hamsters, in contrast to mice, are highly permissive to SARS-CoV-2 and develop bronchopneumonia and strong inflammatory responses in the lungs with neutrophil infiltration and edema, further confirmed as consolidations visualized by micro-CT alike in clinical practice. Moreover, we identify an exuberant innate immune response as key player in pathogenesis, in which STAT2 signaling plays a dual role, driving severe lung injury on the one hand, yet restricting systemic virus dissemination on the other. Our results reveal the importance of STAT2-dependent interferon responses in the pathogenesis and virus control during SARS-CoV-2 infection and may help rationalizing new strategies for the treatment of COVID-19 patients. SARS-CoV-2 infection can result in severe lung inflammation and pathology, but host response remains incompletely understood. Here the authors show in Syrian hamsters that STAT2 signaling restricts systemic virus dissemination but also drives severe lung injury, playing a dual role in SARS-CoV-2 infection

De 60min-economie leidt tot betere resultaten dan de anderhalvemetereconomie: A under 60 economy has better outcomes than a one-and-a-halve meter economy

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Reproducibility of functional MR imaging results using two different MR systems

BACKGROUND AND PURPOSE: In the application of functional MR imaging for presurgical planning, high reproducibility is required. We investigated whether the reproducibility of functional MR imaging results in healthy volunteers depended on the MR system used. METHODS: Visual functional MR imaging reproducibility experiments were performed with 12 subjects, by using two comparable 1.5-T MR systems from different manufacturers. Each session consisted of two runs, and each subject underwent three sessions, two on one system and one on the other. Reproducibility measures D (distance in millimeters) and R(size) and R(overlap) (ratios) were calculated under three conditions: same session, which compared runs from one session; intersession, which compared runs from different sessions but from the same system; and intermachine, which compared runs from the two different systems. The data were averaged per condition and per system, and were compared. RESULTS: The average same-session values of the reproducibility measures did not differ significantly between the two systems. The average intersession values did not differ significantly as to the volume of activation (R(size)), but did differ significantly as to the location of this volume (D and R(overlap)). The average intermachine reproducibility did not differ significantly from the average intersession reproducibility of the MR system with the worst reproducibility. CONCLUSION: The location of activated voxels from visual functional MR imaging experiments varied more between sessions on one MR system than on other MR system. The amount of the activated voxels is independent of the MR system used. We suggest that sites performing functional MR imaging for presurgical planning measure the intersession reproducibility to determine an accurate surgical safety margi

Vertebra disc ratio as a parameter for bone marrow involvement and its application in Gaucher disease

Objective: To establish the vertebra disc ratio (VDR), the ratio of the average T1-weighted gray value of disc L3 and intervertebral disc L3/L4, as a parameter for bone marrow involvement. To explore its value as alternative for bone marrow fat fraction measured with Dixon Quantitative Chemical Shift Imaging (Ff) in Gaucher disease (GD). Methods: Age dependency and normal value for the VDR were determined in 46 controls. The VDR in untreated GD (n = 22) and long-treated GD (7.5 years; n = 19) were compared with it. The changes in VDR in treated (n = 33) and untreated (n 8) GD were calculated. The correlation between VDR and Ff was determined. Results: Age dependency was small. The normal VDR was 1.90 +/- 0.30, both untreated GD (1.29 +/- 0.31) and long-treated GD (1.70 +/- 0.33) differed significantly from normal. Changes in treated GD were significant in the first four treatment years, in untreated GD they were not. The correlation with Ff was 0.86. Conclusions: The VDR is a useful parameter for evaluation of bone marrow of patients with GD. The VDR correlates very well with Ff, so applicability is expected in diseases in which Ff has proven to be usefu

Recent-onset schizophrenia and adolescent cannabis use: MRI evidence for structural hyperconnectivity?

There is growing evidence that brain white matter abnormalities are implicated in the pathophysiology of schizophrenia. Cannabis use is an independent risk factor for schizophrenia.We tested the hypothesis that cannabis use during early adolescence is associated with white matter abnormalities in schizophrenia patients. Thirtyfive male recent-onset schizophrenia patients, with and without a history of cannabis use before age 17, and twenty-one matched healthy comparison men without illicit drug use were assessed with diffusion tensor imaging (DTI).White matter regions of interest were examined in co-registered DTI images. Compared to controls, patients with cannabis use before age 17 showed increased directional coherence in the bilateral uncinate fasciculus, anterior internal capsule and frontal white matter. These abnormalities were absent in patients without cannabis use before age 17. The abnormalities were not related to lifetime doses of cannabis or other illicit drugs.We could not exclude confounding effects of other illicit drugs. Recent-onset schizophrenia patients with start of cannabis use during early adolescence use may represent a subgroup of schizophrenia patients with increased white matter directional coherence, which may reflect structural hyperconnectivity. This is in contrast with most DTI studies in schizophrenia, which have produced evidence for hypoconnectivity. Further studies are necessary to assess the effect of adolescent cannabis and other illicit drug use on brain white matter in schizophreni

Value-added services for fibre to the home: market potential, time horizons and user groups

Currently, telecom operators are developing large-scale projects in the internet broadband sector in cooperation with utility companies and public institutions. The roll-out of fibre to the home network infrastructure is often justified by the supposed increasing user demand for high-bandwidth applications. Starting from a user-oriented perspective, however, it is important to consider the utility of fibre networks for future users and to explore those killer applications that can convince end-users to migrate from their current connections to high-bandwidth networks. By means of an international expert survey, this paper tries to identify value-added services that benefit from fibre’s network potential in terms of high speed, symmetry and low delay. In contrast to initial expectations, video delivery applications were found less convincing by the experts whereas health monitoring, online content storage and management services, and desktop sharing were identified as the most promising fibre applications. In terms of timing, content storage and management systems and desktop sharing are identified as more market-ready than health monitoring applications. Whereas the health monitoring and desktop sharing are mainly seen as a service only for the consumer and business market respectively, content management systems are considered useful for business as well as for consumer purposes

Smaller hippocampal volume in Dutch police officers with posttraumatic stress disorder

BACKGROUND: Previous magnetic resonance imaging studies of posttraumatic stress disorder (PTSD) have reported smaller hippocampal volume, especially in war and sexual abuse victims. Our aim was to assess hippocampal volume in traumatized police officers with and without PTSD in the absence of alcohol abuse and moderate to severe major depression. METHODS: In a case-matched control study, 14 police officers with current PTSD and 14 traumatized police officers without lifetime PTSD were examined using magnetic resonance imaging. Three temporal lobe areas were manually segmented: hippocampus, amygdala, and parahippocampal gyrus. Volumetric analysis was used to measure gray matter, white matter, and cerebrospinal fluid. RESULTS: After controlling for total brain volume, the hippocampal volume in the PTSD group was significantly smaller in comparison with the traumatized control group (total 10.6%; left 12.6%). Volumes of amygdala, parahippocampal gyrus, gray matter, white matter, and cerebrospinal fluid were not significantly altered. A significant negative correlation was found between reexperiencing symptoms and hippocampal volume in the PTSD group. CONCLUSIONS: We confirmed previous findings of smaller hippocampal volume in PTSD in a new population made up of police officers, excluding comorbidity as a confounder. The finding of smaller hippocampal volume was specific to PTS

Effects of psychotherapy on hippocampal volume in out-patients with post-traumatic stress disorder: a MRI investigation

BACKGROUND: Magnetic resonance imaging (MRI) studies have especially reported smaller hippocampal volume in patients with post-traumatic stress disorder (PTSD), most of them war or sexual abuse victims. The present study compares the hippocampal volumes of out-patients with PTSD who had low co-morbidity rates to those of trauma-exposed control subjects without PTSD, and measures hippocampal volume changes in these patients after brief eclectic psychotherapy. We hypothesized that smaller hippocampal volumes are specific to PTSD and that hippocampal volume changes after effective psychotherapy would be measurable. METHOD: Eighteen patients with PTSD and 14 traumatized control subjects were examined with MRI. In a randomized clinical trial, the PTSD patients were assigned to treatment (n = 9) or waiting-list group (n = 9). After the former received psychotherapy for 4 months, the MRI was repeated on both PTSD groups. Three temporal lobe structures were manually segmented: hippocampus, amygdala, and parahippocampal gyrus. Volumetric analysis was used to measure grey matter, white matter, and cerebrospinal fluid. RESULTS: PTSD patients had significantly smaller hippocampal volumes at baseline (total 13.8%, right 13.5%, left 14.1%) compared to the control subjects. After effective psychotherapy, however, no volume changes were found in the smaller hippocampi. CONCLUSIONS: We confirmed previous findings of smaller hippocampal volume in PTSD in a new population made up of out-patients who experienced different types of traumas, reducing co-morbidity to a minimum. Smaller hippocampal volumes did not change after effective psychotherapy, even while symptoms resolve