ATLS® and damage control in spine trauma

Substantial inflammatory disturbances following major trauma have been found throughout the posttraumatic course of polytraumatized patients, which was confirmed in experimental models of trauma and in vitro settings. As a consequence, the principle of damage control surgery (DCS) has developed over the last two decades and has been successfully introduced in the treatment of severely injured patients. The aim of damage control surgery and orthopaedics (DCO) is to limit additional iatrogenic trauma in the vulnerable phase following major injury. Considering traumatic brain and acute lung injury, implants for quick stabilization like external fixators as well as decided surgical approaches with minimized potential for additional surgery-related impairment of the patient's immunologic state have been developed and used widely. It is obvious, that a similar approach should be undertaken in the case of spinal trauma in the polytraumatized patient. Yet, few data on damage control spine surgery are published to so far, controlled trials are missing and spinal injury is addressed only secondarily in the broadly used ATLS® polytrauma algorithm. This article reviews the literature on spine trauma assessment and treatment in the polytrauma setting, gives hints on how to assess the spine trauma patient regarding to the ATLS® protocol and recommendations on therapeutic strategies in spinal injury in the polytraumatized patient

Tumor necrosis factor-mediated inhibition of interleukin-18 in the brain: a clinical and experimental study in head-injured patients and in a murine model of closed head injury.

Tumor necrosis factor (TNF) and interleukin-(IL)-18 are important mediators of neuroinflammation after closed head injury (CHI). Both mediators have been previously found to be significantly elevated in the intracranial compartment after brain injury, both in patients as well as in experimental model systems. However, the interrelation and regulation of these crucial cytokines within the injured brain has not yet been investigated. The present study was designed to assess a potential regulation of intracranial IL-18 levels by TNF based on a clinical study in head-injured patients and an experimental model in mice. In the first part, we investigated the interrelationship between the daily TNF and IL-18 cerebrospinal fluid levels in 10 patients with severe CHI for up to 14 days after trauma. In the second part of the study, the potential TNF-dependent regulation of intracerebral IL-18 levels was further characterized in an experimental set-up in mice: (1) in a standardized model of CHI in TNF/lymphotoxin-α gene-deficient mice and wild-type (WT) littermates, and (2) by intracerebro-ventricular injection of mouse recombinant TNF in WT C57BL/6 mice. The results demonstrate an inverse correlation of intrathecal TNF and IL-18 levels in head-injured patients and a TNF-dependent inhibition of IL-18 after intracerebral injection in mice. These findings imply a potential new anti-inflammatory mechanism of TNF by attenuation of IL-18, thus confirming the proposed "dual" function of this cytokine in the pathophysiology of traumatic brain injury

Impedimetric Microfluidic Sensor-in-a-Tube for Label-Free Immune Cell Analysis

Analytical platforms based on impedance spectroscopy are promising for non-invasive and label-free analysis of single cells as well as of their extracellular matrix, being essential to understand cell function in the presence of certain diseases. Here, an innovative rolled-up impedimetric microfulidic sensor, called sensor-in-a-tube, is introduced for the simultaneous analysis of single human monocytes CD14+ and their extracellular medium upon liposaccharides (LPS)-mediated activation. In particular, rolled-up platinum microelectrodes are integrated within for the static and dynamic (in-flow) detection of cells and their surrounding medium (containing expressed cytokines) over an excitation frequency range from 102 to 5 × 106 Hz. The correspondence between cell activation stages and the electrical properties of the cell surrounding medium have been detected by electrical impedance spectroscopy in dynamic mode without employing electrode surface functionalization or labeling. The designed sensor-in-a-tube platform is shown as a sensitive and reliable tool for precise single cell analysis toward immune-deficient diseases diagnosis

Three-Dimensional Superconducting Nanohelices Grown by He+-Focused-Ion-Beam Direct Writing

Novel schemes based on the design of complex three-dimensional (3D) nanoscale architectures are required for the development of the next generation of advanced electronic components. He+ focused-ion-beam (FIB) microscopy in combination with a precursor gas allows one to fabricate 3D nanostructures with an extreme resolution and a considerably higher aspect ratio than FIB-based methods, such as Ga+ FIB-induced deposition, or other additive manufacturing technologies. In this work, we report the fabrication of 3D tungsten carbide nanohelices with on-demand geometries via controlling key deposition parameters. Our results show the smallest and highest-densely packed nanohelix ever fabricated so far, with dimensions of 100 nm in diameter and aspect ratio up to 65. These nanohelices become superconducting at 7 K and show a large critical magnetic field and critical current density. In addition, given its helical 3D geometry, fingerprints of vortex and phase-slip patterns are experimentally identified and supported by numerical simulations based on the time-dependent Ginzburg-Landau equation. These results can be understood by the helical geometry that induces specific superconducting properties and paves the way for future electronic components, such as sensors, energy storage elements, and nanoantennas, based on 3D compact nanosuperconductors. © 2019 American Chemical Society

Inhibition of the alternative complement activation pathway in traumatic brain injury by a monoclonal anti-factor B antibody: a randomized placebo-controlled study in mice

BACKGROUND: The posttraumatic response to traumatic brain injury (TBI) is characterized, in part, by activation of the innate immune response, including the complement system. We have recently shown that mice devoid of a functional alternative pathway of complement activation (factor B-/- mice) are protected from complement-mediated neuroinflammation and neuropathology after TBI. In the present study, we extrapolated this knowledge from studies in genetically engineered mice to a pharmacological approach using a monoclonal anti-factor B antibody. This neutralizing antibody represents a specific and potent inhibitor of the alternative complement pathway in mice. METHODS: A focal trauma was applied to the left hemisphere of C57BL/6 mice (n = 89) using a standardized electric weight-drop model. Animals were randomly assigned to two treatment groups: (1) Systemic injection of 1 mg monoclonal anti-factor B antibody (mAb 1379) in 400 μl phosphate-buffered saline (PBS) at 1 hour and 24 hours after trauma; (2) Systemic injection of vehicle only (400 μl PBS), as placebo control, at identical time-points after trauma. Sham-operated and untreated mice served as additional negative controls. Evaluation of neurological scores and analysis of brain tissue specimens and serum samples was performed at defined time-points for up to 1 week. Complement activation in serum was assessed by zymosan assay and by murine C5a ELISA. Brain samples were analyzed by immunohistochemistry, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) histochemistry, and real-time RT-PCR. RESULTS: The mAb 1379 leads to a significant inhibition of alternative pathway complement activity and to significantly attenuated C5a levels in serum, as compared to head-injured placebo-treated control mice. TBI induced histomorphological signs of neuroinflammation and neuronal apoptosis in the injured brain hemisphere of placebo-treated control mice for up to 7 days. In contrast, the systemic administration of an inhibitory anti-factor B antibody led to a substantial attenuation of cerebral tissue damage and neuronal cell death. In addition, the posttraumatic administration of the mAb 1379 induced a neuroprotective pattern of intracerebral gene expression. CONCLUSION: Inhibition of the alternative complement pathway by posttraumatic administration of a neutralizing anti-factor B antibody appears to represent a new promising avenue for pharmacological attenuation of the complement-mediated neuroinflammatory response after head injury

Modularity and hormone sensitivity of the Drosophila melanogaster insulin receptor/target of rapamycin interaction proteome

First systematic analysis of the evolutionary conserved InR/TOR pathway interaction proteome in Drosophila.Quantitative mass spectrometry revealed that 22% of identified protein interactions are regulated by the growth hormone insulin affecting membrane proximal as well as intracellular signaling complexes.Systematic RNA interference linked a significant fraction of network components to the control of dTOR kinase activity.Combined biochemical and genetic data suggest dTTT, a dTOR-containing complex required for cell growth control by dTORC1 and dTORC2 in vivo

Stress resilience during the coronavirus pandemic

The epidemic of the 2019 novel coronavirus SARS-CoV-2, causing the coronavirus disease 2019 (COVID-19) is a global public health emergency with multifaceted severe consequences for people's lives and their mental health. In this article, as members of the European College of Neuropsychopharmacology (ECNP) Resilience, we will discuss the urgent need for a focus on resilience during the current coronavirus pandemic. Resilience is pivotal to cope with stress and vital to stay in balance. We will discuss the importance of resilience at the individual and societal level, but also the implication for patients with a psychiatric condition and health care workers. We not only advocate for an increased focus on mental health during the coronavirus pandemic but also highlight the urgent need of augmenting our focus on resilience and on strategies to enhance it. The epidemic of the 2019 novel coronavirus SARS-CoV-2, causing the coronavirus disease 2019 (COVID-19), first expanded within the Wuhan region in China and quickly spread to Europe and to the rest of the world (Zhou et al., 2020). The outbreak of COVID-19 is a global public health emergency with multifaceted severe consequences for people's lives and their mental health. In this article, as members of the European College of Neuropsychopharmacology (ECNP) Resilience, we will discuss the urgent need for a focus on resilience during the current coronavirus pandemic. Resilience is pivotal to cope with stress and vital to stay in balance. We will discuss the importance of resilience at the individual and societal level, but also the implication for patients with a psychiatric condition and health care workers

Optical and Infrared Diagnostics of SDSS galaxies in the SWIRE Survey

We present the rest-frame optical and infrared colours of a complete sample of 1114 z<0.3 galaxies from the Spitzer Wide-area InfraRed Extragalactic Legacy Survey (SWIRE) and the Sloan Digital Sky Survey (SDSS). We discuss the optical and infrared colours of our sample and analyse in detail the contribution of dusty star-forming galaxies and AGN to optically selected red sequence galaxies. We propose that the optical (g-r) colour and infrared log(L_{24}/L_{3.6}) colour of galaxies in our sample are determined primarily by a bulge-to-disk ratio. The (g-r) colour is found to be sensitive to the bulge-to-disk ratio for disk-dominated galaxies, whereas the log(L_{24}/L_{3.6}) colour is more sensitive for bulge-dominated systems. We identify ~18% (195 sources) of our sample as having red optical colours and infrared excess. Typically, the infrared luminosities of these galaxies are found to be at the high end of star-forming galaxies with blue optical colours. Using emission line diagnostic diagrams, 78 are found to have an AGN contribution, and 117 are identified as star-forming systems. The red (g-r) colour of the star-forming galaxies could be explained by extinction. However, their high optical luminosities cannot. We conclude that they have a significant bulge component. The number densities of optically red star-forming galaxies are found to correspond to ~13% of the total number density of our sample. In addition, these systems contribute ~13% of the total optical luminosity density, and 28% of the total infrared luminosity density of our SWIRE/SDSS sample. These objects may reduce the need for "dry-mergers".Comment: 14 pages, 8 figures, 4 tables. Accepted for publication in MNRA

Mouse nuclear myosin I knock-out shows interchangeability and redundancy of myosin isoforms in the cell nucleus.

Nuclear myosin I (NM1) is a nuclear isoform of the well-known "cytoplasmic" Myosin 1c protein (Myo1c). Located on the 11(th) chromosome in mice, NM1 results from an alternative start of transcription of the Myo1c gene adding an extra 16 amino acids at the N-terminus. Previous studies revealed its roles in RNA Polymerase I and RNA Polymerase II transcription, chromatin remodeling, and chromosomal movements. Its nuclear localization signal is localized in the middle of the molecule and therefore directs both Myosin 1c isoforms to the nucleus. In order to trace specific functions of the NM1 isoform, we generated mice lacking the NM1 start codon without affecting the cytoplasmic Myo1c protein. Mutant mice were analyzed in a comprehensive phenotypic screen in cooperation with the German Mouse Clinic. Strikingly, no obvious phenotype related to previously described functions has been observed. However, we found minor changes in bone mineral density and the number and size of red blood cells in knock-out mice, which are most probably not related to previously described functions of NM1 in the nucleus. In Myo1c/NM1 depleted U2OS cells, the level of Pol I transcription was restored by overexpression of shRNA-resistant mouse Myo1c. Moreover, we found Myo1c interacting with Pol II. The ratio between Myo1c and NM1 proteins were similar in the nucleus and deletion of NM1 did not cause any compensatory overexpression of Myo1c protein. We observed that Myo1c can replace NM1 in its nuclear functions. Amount of both proteins is nearly equal and NM1 knock-out does not cause any compensatory overexpression of Myo1c. We therefore suggest that both isoforms can substitute each other in nuclear processes

Union inclusiveness and temporary agency workers: the role of power resources and union ideology

This article investigates the determinants of union inclusiveness towards agency workers in Western Europe, using an index which combines unionization rates with dimensions of collective agreements covering agency workers. Using fuzzy-set Qualitative Comparative Analysis, we identify two combinations of conditions leading to inclusiveness: the ‘Northern path’ includes high union density, high bargaining coverage and high union authority, and is consistent with the power resources approach. The ‘Southern path’ combines high union authority, high bargaining coverage, statutory regulations of agency work and working-class orientation, showing that ideology rather than institutional incentives shapes union strategies towards the marginal workforce