Novel Aspects of 3D Echocardiography in Percutaneous Mitral Valve Interventions: Update 2013

The rapidly increasing importance of percutaneous treatment options for mitral valve diseases promotes the demand for reliable periprocedural guidance by transesophageal echocardiographic imaging. For several interventional mitral leaflet repair techniques real-time 3-dimensional transesophageal echocardiographic (RT3D TEE) guidance has been described to be indispensible. RT3DE TEE provides excellent insight into the mitral valve pathology, which improves procedure planning, safe guidance of device navigation and direct assessment of procedural success. For balloon mitral valvuloplasty 3D echocardiography has shown to effectively accelerate the procedure. The complexity of transcatheter mitral valve repair as well as transcatheter closure of paravalvular leakages of mitral valve prosthesis demands accurate evaluation of the target lesion and guidance of the navigation of the device catheter. All these features have recently found to be uniquely provided by three-dimensional echocardiography. The benefits of RT3D TEE led to its recommendation for percutaneous mitral valve repair procedures in current guidelines. This review of recent literature reports current applications and requirements for refinements in using 3D imaging modalities.     

Bordetella Pertussis Toxin does not induce the release of pro-inflammatory cytokines in human whole blood

Pertussis Toxin (PTx) is one of the most important virulence factors of Bordetella pertussis, the cause of whooping cough. Therefore, the inactivated toxin is an obligatory constituent of acellular pertussis vaccines. It is described in the literature that both native PTx and recombinant Pertussis Toxin (PTg) activate human monocytes whereas others report an inhibition of mammalian monocytes during pertussis infection. B. pertussis, as a Gram-negative bacterium, harbours naturally lipopolysaccharide (LPS, also known as endotoxin), one of the strongest stimulators of monocytes. The latter is triggered via the interaction of endotoxin with inter alia the surface receptor CD14. Consequently, it is necessary to consider a potential contamination of Pertussis Toxin preparations with LPS. First, we determined the LPS content in different preparations of PTx and PTg. All preparations examined were contaminated with LPS; therefore, possible PTx- and PTg-driven monocyte activation independently of LPS was investigated. To meet these aims, we examined monocyte response to PTx and PTg while blocking the LPS receptor CD14 with a specific monoclonal antibody (anti-CD14 mAb). In addition, all toxin preparations examined underwent an LPS depletion. Our results show that it is contaminating LPS, not Pertussis Toxin, which activates human monocytes. Blocking the CD14 receptor prevents Pertussis Toxin-mediated induction of pro-inflammatory cytokines in human monocytes. The depletion of LPS from Pertussis Toxin leads to the same effect. Additionally, the PTx toxicity after LPS depletion procedure was confirmed by animal tests. In contrast, the original Pertussis Toxin preparations not treated as mentioned above generate strong monocyte activation. The results in this publication allow the conclusion that purified Pertussis Toxin preparations do not induce the release of pro-inflammatory cytokines in human whole blood.     

Efficient influenza B virus propagation due to deficient interferon-induced antiviral activity in MDCK cells

Influenza B virus infections are mainly restricted to humans, which is partially caused by the inability of influenza B virus NS1 protein to counteract the innate immune response of other species. However, for cell culture-based influenza vaccine production non-human cells, such as Madin-Darby canine kidney (MDCK) cells, are commonly used. Therefore, the impact of cellular pathogen defence mechanisms on influenza B virus propagation in MDCK cells was analysed in this study. Activation of the cellular antiviral defence by interferon stimulation slowed down influenza B virus replication at early time points but after 48 h the same virus titres were reached in stimulated and control cells. Furthermore, suppression of the antiviral host defence by transient expression of a viral antagonist, the rabies virus phosphoprotein, could not increase influenza B virus replication. Finally, canine Myxovirus resistance (Mx) proteins showed no antiviral activity in an influenza B virus-specific minireplicon assay in contrast to the murine Mx1 protein. Taken together, these results indicate that an insufficient antiviral defence in MDCK cells promotes efficient influenza B virus replication favouring the use of MDCK cells in influenza vaccine production.     

Prehospital intubation of the moderately injured patient: a cause of morbidity? A matched-pairs analysis of 1,200 patients from the DGU Trauma Registry

Introduction  

Hypoxia and hypoxemia can lead to an unfavorable outcome after severe trauma, by both direct and delayed mechanisms. Prehospital intubation is meant to ensure pulmonary gas exchange. Limited evidence exists regarding indications for intubation after trauma. The aim of this study was to analyze prehospital intubation as an independent risk factor for the posttraumatic course of moderately injured patients. Therefore, only patients who, in retrospect, would not have required intubation were included in the matched-pairs analysis to evaluate the risks related to intubation.     

Age-related changes in the plasticity and toughness of human cortical bone at multiple length scales

The structure of human cortical bone evolves over multiple length scales from its basic constituents of collagen and hydroxyapatite at the nanoscale to osteonal structures at near-millimeter dimensions, which all provide the basis for its mechanical properties. To resist fracture, bone's toughness is derived intrinsically through plasticity (e.g., fibrillar sliding) at structural scales typically below a micrometer and extrinsically (i.e., during crack growth) through mechanisms (e.g., crack deflection/bridging) generated at larger structural scales. Biological factors such as aging lead to a markedly increased fracture risk, which is often associated with an age-related loss in bone mass (bone quantity). However, we find that age-related structural changes can significantly degrade the fracture resistance (bone quality) over multiple length scales. Using in situ small-angle X-ray scattering and wide-angle X-ray diffraction to characterize submicrometer structural changes and synchrotron X-ray computed tomography and in situ fracture-toughness measurements in the scanning electron microscope to characterize effects at micrometer scales, we show how these age-related structural changes at differing size scales degrade both the intrinsic and extrinsic toughness of bone. Specifically, we attribute the loss in toughness to increased nonenzymatic collagen cross-linking, which suppresses plasticity at nanoscale dimensions, and to an increased osteonal density, which limits the potency of crack-bridging mechanisms at micrometer scales. The link between these processes is that the increased stiffness of the cross-linked collagen requires energy to be absorbed by "plastic" deformation at higher structural levels, which occurs by the process of microcracking.     

Case study: simulated and real-life energy expenditure during a 3-week expedition

During prolonged periods of high energy expenditure (EE), restricted food intake can lead to a loss of body mass. This case study describes the preexpedition support for an unsupported 3-wk crossing of the Atacama Desert in Chile. The goals were to simulate the energy requirements of walking under varying conditions and to predict energy intake and EE to evaluate whether the expected weight loss was in acceptable limits. The expeditionist (male, 35 yr, 197 cm, basal weight 80 ± 0.5 kg) was a well-trained endurance athlete with experience of multiple expeditions. During the simulation, he walked on a treadmill at speeds of 2-7 km/hr under varying conditions of inclination (0%, 7.5%), backpack weight (0 kg, 30 kg), and altitude (sea level, simulated altitude of 3,500 m). Under all conditions, the lowest EE was observed at 5 km/ hr. Based on the simulation data, we predicted an average EE of 4,944 kcal/day for the expedition. Because energy intake was restricted to 2,249 kcal/day, we expected the expeditionist to lose considerable weight and consequently advised him to gain 5 kg of body-fat reserves. During the actual desert crossing, he covered a distance of 26 ± 7 km/day at an average speed of 3.8 ± 0.4 km/hr. Daily EE (4,817 ± 794 kcal/day) exceeded energy intake (1,771 ± 685 kcal/day), and the negative energy balance was in agreement with the actual weight loss of 10.5 kg, which was most notable in the lower trunk.