Successful Left Atrial Appendage Occlusion with the New Generation Amulet® Device after Late-Occurring Embolization of an Amplatzer® Cardiac Plug in a Patient with Repetitive Strokes

The Amplatzer Cardiac Plug (ACP) is one of the most commonly used devices for percutaneous left atrial appendage (LAA) closure in order to prevent a stroke in patients with atrial fibrillation and contraindication for long-term oral anticoagulation therapy. We have previously described a patient who had experienced an embolization of the ACP device about 12 months after implantation and the device could be percutaneously retrieved. A few years later, he suffered from a posterior stroke and a stroke located in the brainstem as well as a transischemic attack (TIA). In order to protect him from further cardioembolic events a reocclusion of the LAA with the new generation of ACP device, the Amplatzer Amulet, was performed. A stable position of the device within follow-up period could be confirmed and the patient was free of additional strokes/TIA or bleeding events. This case stresses the importance of proper LAA sizing in order to prevent device embolization and notes that LAA size is not static. Moreover, it demonstrates that repeated implantation of an LAA occlusion device was still possible; one should be aware of undersizing the LAA dimensions and that the modifications of new generation LAA occlusion devices may overcome limitations of first-generation devices in order to prevent a cardioembolic stroke

Time projection chambers for the T2K near detectors

The T2K experiment is designed to study neutrino oscillation properties by directing a high intensity neutrino beam produced at J-PARC in Tokai, Japan, towards the large Super-Kamiokande detector located 295 km away, in Kamioka, Japan. The experiment includes a sophisticated near detector complex, 280 m downstream of the neutrino production target in order to measure the properties of the neutrino beam and to better understand neutrino interactions at the energy scale below a few GeV. A key element of the near detectors is the ND280 tracker, consisting of two active scintillator-bar target systems surrounded by three large time projection chambers (TPCs) for charged particle tracking. The data collected with the tracker is used to study charged current neutrino interaction rates and kinematics prior to oscillation, in order to reduce uncertainties in the oscillation measurements by the far detector. The tracker is surrounded by the former UA1/Nomad dipole magnet and the TPCs measure the charges, momenta, and particle types of charged particles passing through them. Novel features of the TPC design include its rectangular box layout constructed from composite panels, the use of bulk micromegas detectors for gas amplification, electronics readout based on a new ASIC, and a photoelectron calibration system. This paper describes the design and construction of the TPCs, the micromegas modules, the readout electronics, the gas handling system, and shows the performance of the TPCs as deduced from measurements with particle beams, cosmic rays, and the calibration system

In-vivo X-ray Dark-Field Chest Radiography of a Pig

X-ray chest radiography is an inexpensive and broadly available tool for initial assessment of the lung in clinical routine, but typically lacks diagnostic sensitivity for detection of pulmonary diseases in their early stages. Recent X-ray dark-field (XDF) imaging studies on mice have shown significant improvements in imaging-based lung diagnostics. Especially in the case of early diagnosis of chronic obstructive pulmonary disease (COPD), XDF imaging clearly outperforms conventional radiography. However, a translation of this technique towards the investigation of larger mammals and finally humans has not yet been achieved. In this letter, we present the first in-vivo XDF full-field chest radiographs (32 × 35 cm²) of a living pig, acquired with clinically compatible parameters (40s scan time, approx. 80 μSv dose). For imaging, we developed a novel high-energy XDF system that overcomes the limitations of currently established setups. Our XDF radiographs yield sufficiently high image quality to enable radiographic evaluation of the lungs. We consider this a milestone in the bench-to-bedside translation of XDF imaging and expect XDF imaging to become an invaluable tool in clinical practice, both as a general chest X-ray modality and as a dedicated tool for high-risk patients affected by smoking, industrial work and indoor cooking

Genetic architecture of subcortical brain structures in 38,851 individuals

Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease

Genetic architecture of subcortical brain structures in 38,851 individuals

Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease

Substrate Elasticity Exerts Functional Effects on Primary Microglia

Microglia—the brain’s primary immune cells—exert a tightly regulated cascade of pro- and anti-inflammatory effects upon brain pathology, either promoting regeneration or neurodegeneration. Therefore, harnessing microglia emerges as a potential therapeutic concept in neurological research. Recent studies suggest that—besides being affected by chemokines and cytokines—various cell entities in the brain relevantly respond to the mechanical properties of their microenvironment. For example, we lately reported considerable effects of elasticity on neural stem cells, regarding quiescence and differentiation potential. However, the effects of elasticity on microglia remain to be explored.Under the hypothesis that the elasticity of the microenvironment affects key characteristics and functions of microglia, we established an in vitro model of primary rat microglia grown in a polydimethylsiloxane (PDMS) elastomer-based cell culture system. This way, we simulated the brain’s physiological elasticity range and compared it to supraphysiological stiffer PDMS controls. We assessed functional parameters of microglia under “resting” conditions, as well as when polarized towards a pro-inflammatory phenotype (M1) by lipopolysaccharide (LPS), or an anti-inflammatory phenotype (M2) by interleukin-4 (IL-4). Microglia viability was unimpaired on soft substrates, but we found various significant effects with a more than two-fold increase in microglia proliferation on soft substrate elasticities mimicking the brain (relative to PDMS controls). Furthermore, soft substrates promoted the expression of the activation marker vimentin in microglia. Moreover, the M2-marker CD206 was upregulated in parallel to an increase in the secretion of Insulin-Like Growth Factor-1 (IGF-1). The upregulation of CD206 was abolished by blockage of stretch-dependent chloride channels. Our data suggest that the cultivation of microglia on substrates of brain-like elasticity promotes a basic anti-inflammatory activation state via stretch-dependent chloride channels. The results highlight the significance of the omnipresent but mostly overlooked mechanobiological effects exerted on microglia and contribute to a better understanding of the complex spatial and temporal interactions between microglia, neural stem cells, and glia, in health and disease