Neoatherosclerosis as reason for stent failures beyond 5 years after drug-eluting stent implantation

A 69-year-old male (case 1) was admitted due to acute non-ST-segment elevation myocardial infarction (NSTEMI). Eight years earlier, he had previously undergone treatment with a sirolimus-eluting stent (SES). Four years after stent implantation, a follow-up angiography was obtained showing a patent stent without obstructive in-stent restenosis (Panel A). Angiograms obtained at the time of NSTEMI (Panel B) disclosed subtotal occlusion in the middle of the SES (arrowheads). Optical coherence tomography revealed a signal intense luminal layer with an underlying, highly attenuating, diffusely demarcated area, suggestive for an instent fibroatheroma (Panel D) with a minimal cap thickness of 80 µm. Accordingly, ischaemia was caused by the high degree of stenosis (Panel E). Similarly, a 59-year-old male (case 2) was admitted due to STEMI. Nine years before, he had received a paclitaxel-eluting stent (PES). Five years after stent implantation, a follow-up angiography revealed a patent stent (Panel F). Angiograms obtained at the time of STEMI (Panel G) disclosed total occlusion in the proximal of PES (arrowheads). Optical coherence tomography showed a rupture of thin cap fibroatheroma within the stented segment (Panel I). The thin cap fibroatheroma caused a severe stenosis with superimposed thrombus (Panel J). Neoatherosclerosis has been recently described as particular disease entity being responsible for very late stent failures. These two cases illustrate that the presence of a favourable long-term angiographic result years after DES implantation does not exclude a future neoatherosclerosis-related event (restenosis or stent thrombosis). Large observational and long-term intracoronary imaging studies are required to fully elucidate the dynamics and clinical relevance of neoatherosclerosis.

MQN-Mapplet: Visualization of Chemical Space with Interactive Maps of DrugBank, ChEMBL, PubChem, GDB-11, and GDB-13

The MQN-mapplet is a Java application giving access to the structure of small molecules in large databases via color-coded maps of their chemical space. These maps are projections from a 42-dimensional property space defined by 42 integer value descriptors called molecular quantum numbers (MQN), which count different categories of atoms, bonds, polar groups, and topological features and categorize molecules by size, rigidity, and polarity. Despite its simplicity, MQN-space is relevant to biological activities. The MQN-mapplet allows localization of any molecule on the color-coded images, visualization of the molecules, and identification of analogs as neighbors on the MQN-map or in the original 42-dimensional MQN-space. No query molecule is necessary to start the exploration, which may be particularly attractive for nonchemists. To our knowledge, this type of interactive exploration tool is unprecedented for very large databases such as PubChem and GDB-13 (almost one billion molecules). The application is freely available for download at www.gdb.unibe.ch.

Interactive Diffraction from Biological Nanostructures

We describe a technique for interactive rendering of diffraction effects produced by biological nanostructures such as snake skin surface gratings. Our approach uses imagery from atomic force microscopy that accurately captures the nanostructures responsible for structural coloration, that is, coloration due to wave interference, in a variety of animals. We develop a rendering technique that constructs bidirectional reflection distribution functions (BRDFs) directly from the measured data and leverages precomputation to achieve interactive performance. We demonstrate results of our approach using various shapes of the surface grating nanostructures. Finally, we evaluate the accuracy of our precomputation-based technique and compare to a reference BRDF construction technique.

The additive and interactive roles of aggression, prosocial behavior, and social preference in predicting resource control in young children

Distinguishing between physical and social aggression, this study examined whether the predictive effect of aggression on resource control a) is moderated by prosocial behavior and b) corresponds to a linear or a curvilinear trend. Moderating effects of children’s social preference among peers and child sex in this context were also tested. Based on a sample of 682 kindergarten children (348 girls; average age 72.7 months, 3.6 SD), multilevel regressions revealed additive linear effects of social preference and prosociality on resource control. Moderate (but not high) levels of social aggression also facilitated resource control for disliked children. There was no such threshold effect for well liked children, who increasingly controlled the resource the more socially aggressive they were. In contrast, physical aggression hampered resource control unless used very modestly. The present study has a number of positive features. First, the distinction between physical and social aggression improves our understanding of the relation between aggression and social competence and sketches a more differentiated picture of the role of different forms of aggression in resource control. Second, this study combines the concept of resource control with the concept of social preference and investigates curvilinear effects of aggression. Third, the direct observation of resource control in the Movie Viewer increases the internal validity of this study.

COGNITIVE IMPACT OF INTERACTIVE MULTIMEDIA

Technology has been gradually introduced in heath education. One of the most attractive features of this technology-based education is the use of multimedia. In this article we explore the research evidence about the role that multimedia is playing in education. From that analysis we describe the most relevant features of this technology to prepare a common ground of discussion about the evaluation of its impact on educational outcomes. As part of this analysis, we organize current research evidence on the use of technology in medical education, distinguishing diverse variables involved in the process, like knowledge (declarative, procedural), learner characteristics, curricular scenario, etc. This article presents an overview of the Distributed Representations theory and its relationship with research on educational outcomes and multimedia. Next we discuss the relationship between media and diverse learning theories, proposing a theory based taxonomy for educational multimedia.

Signatures of slope failures and river-delta collapses in a perialpine lake (Lake Lucerne, Switzerland)

Historical reports from the 17th Century document two destructive tsunamis with runups exceeding 5 m, affecting proximal basins of Lake Lucerne (Switzerland). One event in AD 1601 is coeval with a strong nearby earthquake (MW ca 5.9), which caused extensive slope failures in many parts of the lake. The second event in AD 1687 is associated with an apparently spontaneous partial collapse of the Muota river delta. This study combines high-resolution bathymetry, reflection seismic and lithological data in order to document the sedimentary and morphological signatures of the two subaqueous mass movements that probably generated the observed tsunamis. Such mass movements are significant as a common sedimentation process and as natural hazard in fjord-type lakes and similar environments. The deposits, covering large parts of the basins with thicknesses reaching >10 m, consist of two subunits: A lower ‘massflow deposit’ contains variably deformed sediments from the source areas. Its emplacement affected pre-existing sediments, incorporating thin sediment slices into the deposit and increasing its volume. Deep-reaching deformation near This is an Accepted Article that has been peer-reviewed and approved for publication in the Sedimentology, but has yet to undergo copy-editing and proof correction.

Role of protein kinase C in short-term sensitization of {\it Aplysia}

Plasticity at the connections between sensory neurons and their follower cells in Aplysia has been used extensively as a model system to examine mechanisms of simple forms of learning, such as sensitization. Sensitization is induced, at least in part, by the transmitter serotonin (5-HT) and expressed in several forms, including facilitation of sensorimotor connections. Spike broadening has been believed to be a key mechanism underlying facilitation of nondepressed synapses. Previously, this broadening was believed to be dependent primarily on cAMP/protein kinase A (PKA)-mediated reduction of a noninactivating, relatively voltage-independent K$\sp{+}$ current termed the S-K$\sp+$ current (I$\sb{\rm K{,}S}$). Recent evidence, however, suggests that 5-HT-induced somatic spike broadening is composed of at least two components: a cAMP-dependent, rapidly developing component and a cAMP-independent, slowly developing component.^ Phorbol esters, activators of protein kinase C (PKC), mimicked the cAMP-independent component of 5-HT-induced broadening. Staurosporine, which inhibits PKC, had little effect on the rapidly developing component of 5-HT-induced broadening, but inhibited significantly the slowly developing component. These results suggest that PKC is involved in the cAMP-independent component of 5-HT-induced broadening. The membrane currents responsible for the slowly developing component of broadening were examined. Activation of PKC mimicked, and partially occluded, 5-HT-induced modulation of membrane currents above 0 mV, where a voltage-dependent K$\sp+$ current (I$\sb{\rm K{,}V}$) is significantly activated. This modulation was complex because it was associated with a reduction in the magnitude of I$\sb{\rm K{,}V}$, as well as a slowing of both activation and inactivation kinetics of I$\sb{\rm K{,}V}$. These results support the hypothesis that PKC modulates I$\sb{\rm K{,}V}$ and that this modulation contributes to the slowly developing component of 5-HT-induced broadening. Based on these results and others, a new scheme for 5-HT-induced spike broadening is proposed in which the modulatory effects are mediated via two second messenger/protein kinase systems converging and diverging on multiple ionic conductances.^ The relationship between spike broadening and synaptic facilitation was also examined. Pharmacological reduction of I$\sb{\rm K{,}V}$ by low concentrations of 4-aminopyridine (4-AP) led to spike broadening and facilitation of the nondepressed sensorimotor connections, indicating that spike broadening via the reduction of I$\sc{K,V}$ can facilitate the synaptic connection. Further analyses, however, revealed that 4-AP-induced facilitation has qualitative differences from 5-HT- and PKC-induced facilitation. These results suggest that 5-HT- and PKC-induced facilitation of nondepressed synapses is mediated, at least in part, by spike-duration independent (SDI) processes. Under certain conditions, the PKC inhibitor, staurosporine, significantly inhibited the 5-HT-induced facilitation of sensorimotor connections.^ Finally, it was found that activation of PKC increased a basal level of cAMP and that PKC caused desensitization of the 5-HT receptor, which may be a possible negative feedback mechanism through which an extracellular ligand, 5-HT, is regulated. These results suggest that these two second messenger/protein kinase pathways can interact in the sensory neuron. Thus, neuronal plasticity that may contribute to learning and memory appears to involve several complex and interactive processes. ^

Interactive effects of mycorrhizae and a root hemiparasite on plant community productivity and diversity

Plant communities can be affected both by arbuscular mycorrhizal fungi (AMF) and hemiparasitic plants. However, little is known about the interactive effects of these two biotic factors on the productivity and diversity of plant communities. To address this question, we set up a greenhouse study in which different AMF inocula and a hemiparasitic plant (Rhinanthus minor) were added to experimental grassland communities in a fully factorial design. In addition, single plants of each species in the grassland community were grown with the same treatments to distinguish direct AMF effects from indirect effects via plant competition. We found that AMF changed plant community structure by influencing the plant species differently. At the community level, AMF decreased the productivity by 15-24%, depending on the particular AMF treatment, mainly because two dominant species, Holcus lanatus and Plantago lanceolata, showed a negative mycorrhizal dependency. Concomitantly, plant diversity increased due to AMF inoculation and was highest in the treatment with a combination of two commercial AM strains. AMF had a positive effect on growth of the hemiparasite, and thereby induced a negative impact of the hemiparasite on host plant biomass which was not found in non-inoculated communities. However, the hemiparasite did not increase plant diversity. Our results highlight the importance of interactions with soil microbes for plant community structure and that these indirect effects can vary among AMF treatments. We conclude that mutualistic interactions with AMF, but not antagonistic interactions with a root hemiparasite, promote plant diversity in this grassland community.

Total surgical aortic arch replacement as a safe strategy to treat complex multisegmental proximal thoracic aortic pathology.

OBJECTIVE To analyse the results after elective open total aortic arch replacement. METHODS We analysed 39 patients (median age 63 years, median logistic EuroSCORE 18.4) who underwent elective open total arch replacement between 2005 and 2012. RESULTS In-hospital mortality was 5.1% (n = 2) and perioperative neurological injury was 12.8% (n = 5). The indication for surgery was degenerative aneurysmal disease in 59% (n = 23) and late aneurysmal formation following previous surgery of type A aortic dissection in 35.9% (n = 14); 5.1% (n = 2) were due to anastomotical aneurysms after prior ascending repair. Fifty-nine percent (n = 23) of the patients had already undergone previous proximal thoracic aortic surgery. In 30.8% (n = 12) of them, a conventional elephant trunk was added to total arch replacement, in 28.2% (n = 11), root replacement was additionally performed. Median hypothermic circulatory arrest time was 42 min (21-54 min). Selective antegrade cerebral perfusion was used in 95% (n = 37) of patients. Median follow-up was 11 months [interquartile range (IQR) 1-20 months]. There was no late death and no need for reoperation during this period. CONCLUSIONS Open total aortic arch replacement shows very satisfying results. The number of patients undergoing total arch replacement as a redo procedure and as a part of a complex multisegmental aortic pathology is high. Future strategies will have to emphasize neurological protection in extensive simultaneous replacement of the aortic arch and adjacent segments.