Systemic and cerebral vascular endothelial growth factor levels increase in murine cerebral malaria along with increased Calpain and caspase activity and can be reduced by erythropoietin treatment

The pathogenesis of cerebral malaria (CM) includes compromised microvascular perfusion, increased inflammation, cytoadhesion, and endothelial activation. These events cause blood–brain barrier disruption and neuropathology and associations with the vascular endothelial growth factor (VEGF) signaling pathway have been shown. We studied this pathway in mice infected with Plasmodium berghei ANKA causing murine CM with or without the use of erythropoietin (EPO) as adjunct therapy. ELISA and western blotting was used for quantification of VEGF and relevant proteins in brain and plasma. CM increased levels of VEGF in brain and plasma and decreased plasma levels of soluble VEGF receptor 2. EPO treatment normalized VEGF receptor 2 levels and reduced brain VEGF levels. Hypoxia-inducible factor (HIF)-1α was significantly upregulated whereas cerebral HIF-2α and EPO levels remained unchanged. Furthermore, we noticed increased caspase-3 and calpain activity in terminally ill mice, as measured by protease-specific cleavage of α-spectrin and p35. In conclusion, we detected increased cerebral and systemic VEGF as well as HIF-1α, which in the brain were reduced to normal in EPO-treated mice. Also caspase and calpain activity was reduced markedly in EPO-treated mice

Silent hypoxia in patients with SARS CoV-2 infection before hospital discharge

OBJECTIVE: To assess the degree of hypoxia and subjective dyspnea elicited by a 6-minute walking test (6MWT) in COVID-19 patients prior to discharge. METHODS: A 6MWT was performed in 26 discharge-ready COVID-19 patients without chronic pulmonary disease or cardiac failure. Heart rate, oxyhemoglobin saturation (SpO2), respiratory rate, and subjective dyspnea measured on the Borg CR-10 scale were measured before and immediately after the 6MWT, with continuous monitoring of SpO2 and heart rate during the 6MWT. The 6MWT was terminated if SpO2 dropped below 90%. A historical cohort of 204 patients with idiopathic pulmonary fibrosis (IPF) was used for comparison. RESULTS: 13 (50%) of the COVID-19 patients developed exercise-induced hypoxia (SpO2 < 90%) during the 6MWT, of which one third had pulmonary embolism. COVID-19 patients experienced less hypoxia-related dyspnea during the 6MWT compared with patients with IPF. CONCLULSION: The 6MWT is a potential tool in the diagnosis of asymptomatic exercise-induced hypoxia in hospitalized COVID-19 patients prior to discharge. Due to important methodological limitations, further studies are needed to confirm our findings and to investigate their clinical consequences

The black hole population in low-mass galaxies in large-scale cosmological simulations

Recent systematic searches for massive black holes (BHs) in local dwarf galaxies led to the discovery of a population of faint Active Galactic Nuclei (AGN). We investigate the agreement of the BH and AGN populations in the Illustris, TNG, Horizon-AGN, EAGLE, and SIMBA simulations with current observational constraints in low-mass galaxies. We find that some of these simulations produce BHs that are too massive, and that the BH occupation fraction at z=0 is not inherited from the simulation seeding modeling. The ability of BHs and their host galaxies to power an AGN depends on BH and galaxy subgrid modeling. The fraction of AGN in low-mass galaxies is not used to calibrate the simulations, and thus can be used to differentiate galaxy formation models. AGN fractions at z=0 span two orders of magnitude at fixed galaxy stellar mass in simulations, similarly to observational constraints, but uncertainties and degeneracies affect both observations and simulations. The agreement is difficult to interpret due to differences in the masses of simulated and observed BHs, BH occupation fraction affected by numerical choices, and an unknown fraction of obscured AGN. Our work advocates for more thorough comparisons with observations to improve the modeling of cosmological simulations, and our understanding of BH and galaxy physics in the low-mass regime. The mass of BHs, their ability to efficiently accrete gas, and the AGN fraction in low-mass galaxies have important implications for the build-up of the entire BH and galaxy populations with time.Comment: Accepted in MNRAS, 21 pages, 11 figures, 1 tabl

Fully automated preoperative liver volumetry incorporating the anatomical location of the central hepatic vein

The precise preoperative calculation of functional liver volumes is essential prior major liver resections, as well as for the evaluation of a suitable donor for living donor liver transplantation. The aim of this study was to develop a fully automated, reproducible, and quantitative 3D volumetry of the liver from standard CT examinations of the abdomen as part of routine clinical imaging. Therefore, an in-house dataset of 100 venous phase CT examinations for training and 30 venous phase ex-house CT examinations with a slice thickness of 5 mm for testing and validating were fully annotated with right and left liver lobe. Multi-Resolution U-Net 3D neural networks were employed for segmenting these liver regions. The Sorensen-Dice coefficient was greater than 0.9726 +/- 0.0058, 0.9639 +/- 0.0088, and 0.9223 +/- 0.0187 and a mean volume difference of 32.12 +/- 19.40 ml, 22.68 +/- 21.67 ml, and 9.44 +/- 27.08 ml compared to the standard of reference (SoR) liver, right lobe, and left lobe annotation was achieved. Our results show that fully automated 3D volumetry of the liver on routine CT imaging can provide reproducible, quantitative, fast and accurate results without needing any examiner in the preoperative work-up for hepatobiliary surgery and especially for living donor liver transplantation.Projekt DEA

Structure Functions are not Parton Probabilities

The common view that structure functions measured in deep inelastic lepton scattering are determined by the probability of finding quarks and gluons in the target is not correct in gauge theory. We show that gluon exchange between the fast, outgoing partons and target spectators, which is usually assumed to be an irrelevant gauge artifact, affects the leading twist structure functions in a profound way. This observation removes the apparent contradiction between the projectile (eikonal) and target (parton model) views of diffractive and small x_{Bjorken} phenomena. The diffractive scattering of the fast outgoing quarks on spectators in the target causes shadowing in the DIS cross section. Thus the depletion of the nuclear structure functions is not intrinsic to the wave function of the nucleus, but is a coherent effect arising from the destructive interference of diffractive channels induced by final state interactions. This is consistent with the Glauber-Gribov interpretation of shadowing as a rescattering effect.Comment: 35 pages, 8 figures. Discussion of physical consequences of final state interactions amplified. Material on light-cone gauge choices adde

Birth mode is associated with development of atopic dermatitis in infancy and early childhood

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