Computed Tomography Imaging in Simulated Ongoing Cardiopulmonary Resuscitation: No Need to Switch Off the Chest Compression Device during Image Acquisition

Computed tomography (CT) represents the current standard for imaging of patients with acute life-threatening diseases. As some patients present with circulatory arrest, they require cardiopulmonary resuscitation. Automated chest compression devices are used to continue resuscitation during CT examinations, but tend to cause motion artifacts degrading diagnostic evaluation of the chest. The aim was to investigate and evaluate a CT protocol for motion-free imaging of thoracic structures during ongoing mechanical resuscitation. The standard CT trauma protocol and a CT protocol with ECG triggering using a simulated ECG were applied in an experimental setup to examine a compressible thorax phantom during resuscitation with two different compression devices. Twenty-eight phantom examinations were performed, 14 with AutoPulse and 14 with corpuls cpr. With each device, seven CT examinations were carried out with ECG triggering and seven without. Image quality improved significantly applying the ECG-triggered protocol (p < 0.001), which allowed almost artifact-free chest evaluation. With the investigated protocol, radiation exposure was 5.09% higher (15.51 mSv vs. 14.76 mSv), and average reconstruction time of CT scans increased from 45 to 76 s. Image acquisition using the proposed CT protocol prevents thoracic motion artifacts and facilitates diagnosis of acute life-threatening conditions during continuous automated chest compression

Concentration Kinetics of Serum MMP-9 and TIMP-1 after Blunt Multiple Injuries in the Early Posttraumatic Period

Metalloproteinases are secreted in response to a variety of inflammatory mediators and inhibited by tissue inhibitors of matrixmetalloproteinases (TIMPs). Two members of these families, MMP-9 and TIMP-1, were differentially expressed depending on clinical parameters in a previous genomewide mRNA analysis. The aim of this paper was now to evaluate the posttraumatic serum levels and the time course of both proteins depending on distinct clinical parameters. 60 multiple traumatized patients (ISS > 16) were included. Blood samples were drawn on admission and 6 h, 12 h, 24 h, 48 h, and 72 h after trauma. Serum levels were quantified by ELISA. MMP-9 levels significantly decreased in the early posttraumatic period (P < 0.05) whereas TIMP-1 levels significantly increased in all patients (P < 0.05). MMP-9 and TIMP-1 serum concentration kinetics became manifest in an inversely proportional balance. Furthermore, MMP-9 presented a stronger decrease in patients with severe trauma and non-survivors in contrast to minor traumatized patients (ISS ≤ 33) and survivors, initially after trauma

Basal body stability and ciliogenesis requires the conserved component Poc1

Centrioles are the foundation for centrosome and cilia formation. The biogenesis of centrioles is initiated by an assembly mechanism that first synthesizes the ninefold symmetrical cartwheel and subsequently leads to a stable cylindrical microtubule scaffold that is capable of withstanding microtubule-based forces generated by centrosomes and cilia. We report that the conserved WD40 repeat domain–containing cartwheel protein Poc1 is required for the structural maintenance of centrioles in Tetrahymena thermophila. Furthermore, human Poc1B is required for primary ciliogenesis, and in zebrafish, DrPoc1B knockdown causes ciliary defects and morphological phenotypes consistent with human ciliopathies. T. thermophila Poc1 exhibits a protein incorporation profile commonly associated with structural centriole components in which the majority of Poc1 is stably incorporated during new centriole assembly. A second dynamic population assembles throughout the cell cycle. Our experiments identify novel roles for Poc1 in centriole stability and ciliogenesis

Experiments in Support of Pressure Enhanced Penetration with Shaped Charge Perforators

Computational analysis demonstrated that the penetration of a shaped charge could be substantially enhanced by imploding the liner in a high pressure light gas atmosphere. The gas pressure helps confine the jet on the axis of penetration in the latter stages of formation. A light gas, such as helium or hydrogen, is required in order to keep the gas density low enough so as not to inhibit liner collapse. These results have now been confirmed by experiment. Identical 5-foot long guns, each containing 37 perforators at a shot density of 12 SPF, were inserted in two API Section 1 concrete targets, poured on the same day and cured for the same period. One of the guns was fired with interior ambient (0.1 MPa) air pressure and the other with helium at 13.8 MPa (2,000 psia). The average penetration from the 37 perforations with the helium system increased 40.3% over that obtained with the conventional system

The exonuclease Xrn1 activates transcription and translation of mRNAs encoding membrane proteins

The highly conserved 5'-3' exonuclease Xrn1 regulates gene expression in eukaryotes by coupling nuclear DNA transcription to cytosolic mRNA decay. By integrating transcriptome-wide analyses of translation with biochemical and functional studies, we demonstrate an unanticipated regulatory role of Xrn1 in protein synthesis. Xrn1 promotes translation of a specific group of transcripts encoding membrane proteins. Xrnl-dependence for translation is linked to poor structural RNA contexts for translation initiation, is mediated by interactions with components of the translation initiation machinery and correlates with an Xrnl-dependence for mRNA localization at the endoplasmic reticulum, the translation compartment of membrane proteins. Importantly, for this group of mRNAs, Xrn1 stimulates transcription, mRNA translation and decay. Our results uncover a crosstalk between the three major stages of gene expression coordinated by Xrn1 to maintain appropriate levels of membrane proteins

Australian health care providers' views on opt-out HIV testing

Background: Opt-out HIV testing is a novel concept in Australia. In the opt-out approach, health care providers (HCPs) routinely test patients for HIV unless they explicitly decline or defer. Opt-out HIV testing is only performed with the patients' consent, but pre-test counselling is abbreviated. Australian national testing guidelines do not currently recommend opt-out HIV testing for the general population. Non-traditional approaches to HIV testing (such as opt-out) could identify HIV infections and facilitate earlier treatment, which is particularly important now that HIV is a chronic, manageable disease. Our aim was to explore HCPs' attitudes toward opt-out HIV testing in an Australian context, to further understanding of its acceptability and feasibility. Methods: In this qualitative study, we used purposeful sampling to recruit HCPs who were likely to have experience with HIV testing in Western Australia. We interviewed them using a semi-structured guide and used content analysis as per Graneheim to code the data. Codes were then merged into subcategories and finally themes that unified the underlying concepts. We refined these themes through discussion among the research team. Results: Twenty four HCPs participated. Eleven participants had a questioning attitude toward opt-out HIV testing, while eleven favoured the approach. The remaining two participants had more nuanced perspectives that incorporated some characteristics of the questioning and favouring attitudes. Participants' views about opt-out HIV testing largely fell into two contrasting themes: normalisation and routinisation versus exceptionalism; and a need for proof versus openness to new approaches. Conclusion: Most HCPs in this study had dichotomous attitudes toward opt-out HIV testing, reflecting contrasting analytical styles. While some HCPs viewed it favourably, with the perceived benefits outweighing the perceived costs, others preferred to have evidence of efficacy and cost-effectiveness

SAS6-like protein in Plasmodium indicates that conoid-associated apical complex proteins persist in invasive stages within the mosquito vector

The SAS6-like (SAS6L) protein, a truncated paralogue of the ubiquitous basal body/centriole protein SAS6, has been characterised recently as a flagellum protein in trypanosomatids, but associated with the conoid in apicomplexan Toxoplasma. The conoid has been suggested to derive from flagella parts, but is thought to have been lost from some apicomplexans including the malaria-causing genus Plasmodium. Presence of SAS6L in Plasmodium, therefore, suggested a possible role in flagella assembly in male gametes, the only flagellated stage. Here, we have studied the expression and role of SAS6L throughout the Plasmodium life cycle using the rodent malaria model P. berghei. Contrary to a hypothesised role in flagella, SAS6L was absent during gamete flagellum formation. Instead, SAS6L was restricted to the apical complex in ookinetes and sporozoites, the extracellular invasive stages that develop within the mosquito vector. In these stages SAS6L forms an apical ring, as we show is also the case in Toxoplasma tachyzoites. The SAS6L ring was not apparent in blood-stage invasive merozoites, indicating that the apical complex is differentiated between the different invasive forms. Overall this study indicates that a conoid-associated apical complex protein and ring structure is persistent in Plasmodium in a stage-specific manner

Comparability: manufacturing, characterization and controls, report of a UK Regenerative Medicine Platform Pluripotent Stem Cell Platform Workshop, Trinity Hall, Cambridge, 14–15 September 2015

This paper summarizes the proceedings of a workshop held at Trinity Hall, Cambridge to discuss comparability and includes additional information and references to related information added subsequently to the workshop. Comparability is the need to demonstrate equivalence of product after a process change; a recent publication states that this ‘may be difficult for cell-based medicinal products’. Therefore a well-managed change process is required which needs access to good science and regulatory advice and developers are encouraged to seek help early. The workshop shared current thinking and best practice and allowed the definition of key research questions. The intent of this report is to summarize the key issues and the consensus reached on each of these by the expert delegates

A mutated dph3 gene causes sensitivity of Schizosaccharomyces pombe cells to cytotoxic agents

Dph3 is involved in diphthamide modification of the eukaryotic translation elongation factor eEF2 and in Elongator-mediated modifications of tRNAs, where a 5-methoxycarbonyl-methyl moiety is added to wobble uridines. Lack of such modifications affects protein synthesis due to inaccurate translation of mRNAs at ribosomes. We have discovered that integration of markers at the msh3 locus of Schizosaccharomyces pombe impaired the function of the nearby located dph3 gene. Such integrations rendered cells sensitive to the cytotoxic drugs hydroxyurea and methyl methanesulfonate. We constructed dph3 and msh3 strains with mutated ATG start codons (ATGmut), which allowed investigating drug sensitivity without potential interference by marker insertions. The dph3- ATGmut and a dph3::loxP-ura4-loxM gene disruption strain, but not msh3-ATGmut, turned out to be sensitive to hydroxyurea and methyl methanesulfonate, likewise the strains with cassettes integrated at the msh3 locus. The fungicide sordarin, which inhibits diphthamide modified eEF2 of Saccharomyces cerevisiae, barely affected survival of wild type and msh3Δ S. pombe cells, while the dph3Δ mutant was sensitive. The msh3-ATG mutation, but not dph3Δ or the dph3-ATG mutation caused a defect in mating-type switching, indicating that the ura4 marker at the dph3 locus did not interfere with Msh3 function. We conclude that Dph3 is required for cellular resistance to the fungicide sordarin and to the cytotoxic drugs hydroxyurea and methyl methanesulfonate. This is likely mediated by efficient translation of proteins in response to DNA damage and replication stress