Percutaneous treatment of spontaneous left main coronary artery dissection using drug-eluting stent

Background

Previous studies indicated that the clustering of major cardiovascular disease (CVD) risk factors is common, and multiple unhealthy lifestyles are responsible for the clustering of CVD risk factors. However, little is known about the direct association between the volume load and the clustering of CVD risk factors in general population.

Methods

We investigated the association of the clustering of CVD risk factors (defined as two or more of the following factors: hypertension, diabetes, dyslipidemia and overweight) with volume load, which was evaluated by bioelectrical impedance analysis. Hypovolaemia was defined as extracellular water/total body water (ECW/TBW) at and under the 10th percentile for the normal population.

Results

Among the 7900 adults, only 29.3% were free of any pre-defined CVD risk factors and 40.8% had clustering of CVD risk factors. Hypovolaemia in clustering group was statistically higher than that either in the single or in the none risk factor group, which was 23.7% vs. 17.0% and 10.0%, respectively (P <0.001). As a categorical outcome, the percentage of the lowest quartiles of ECW/TBW and TBW/TBWwatson in clustering group were statistically higher than either those in the single or in the none risk factor group, which were 44.9% vs. 36.9% and 25.1% (P <0.001), 36.2% vs. 32.2% and 25.0%, respectively (P <0.001). After adjusting of potential confounders, hypovolaemia was significantly associated with clustering of CVD risk factors, with an OR of 1.66 (95% CI, 1.45-1.90).

Conclusions

Hypovolaemia was associated with clustering of major CVD risk factors, which further confirms the importance of lifestyle for the development of CVD.

     

Specific Disruption of Hippocampal Mossy Fiber Synapses in a Mouse Model of Familial Alzheimer's Disease

The earliest stages of Alzheimer''s disease (AD) are characterized by deficits in memory and cognition indicating hippocampal pathology. While it is now recognized that synapse dysfunction precedes the hallmark pathological findings of AD, it is unclear if specific hippocampal synapses are particularly vulnerable. Since the mossy fiber (MF) synapse between dentate gyrus (DG) and CA3 regions underlies critical functions disrupted in AD, we utilized serial block-face electron microscopy (SBEM) to analyze MF microcircuitry in a mouse model of familial Alzheimer''s disease (FAD). FAD mutant MF terminal complexes were severely disrupted compared to control – they were smaller, contacted fewer postsynaptic spines and had greater numbers of presynaptic filopodial processes. Multi-headed CA3 dendritic spines in the FAD mutant condition were reduced in complexity and had significantly smaller sites of synaptic contact. Significantly, there was no change in the volume of classical dendritic spines at neighboring inputs to CA3 neurons suggesting input-specific defects in the early course of AD related pathology. These data indicate a specific vulnerability of the DG-CA3 network in AD pathogenesis and demonstrate the utility of SBEM to assess circuit specific alterations in mouse models of human disease.     

Microsatellite and Wolbachia analysis in Rhagoletis cerasi natural populations: population structuring and multiple infections

Rhagoletis cerasi (Diptera: Tephritidae) is a major pest of sweet and sour cherries in Europe and parts of Asia. Despite its economic significance, there is a lack of studies on the genetic structure of R. cerasi populations. Elucidating the genetic structure of insects of economic importance is crucial for developing phenological‐predictive models and environmental friendly control methods. All natural populations of R. cerasi have been found to harbor the endosymbiont Wolbachia pipientis, which widely affects multiple biological traits contributing to the evolution of its hosts, and has been suggested as a tool for the biological control of insect pests and disease vectors. In the current study, the analysis of 18 R. cerasi populations collected in Greece, Germany, and Russia using 13 microsatellite markers revealed structuring of R. cerasi natural populations, even at close geographic range. We also analyzed the Wolbachia infection status of these populations using 16S rRNA‐, MLST‐ and wsp‐based approaches. All 244 individuals screened were positive for Wolbachia. Our results suggest the fixation of the wCer1 strain in Greece while wCer2, wCer4, wCer5, and probably other uncharacterized strains were also detected in multiply infected individuals. The role of Wolbachia and its potential extended phenotypes needs a thorough investigation in R. cerasi. Our data suggest an involvement of this symbiont in the observed restriction in the gene flow in addition to a number of different ecological factors.     

Mitochondrial and nuclear DNA phylogeography of Crassostrea angulata, the Portuguese oyster endangered in Europe

The respective status of the Portuguese oyster, Crassostrea angulata, and the Pacific oyster, Crassostrea gigas, has long been a matter of controversy. Morphological and physiological similarities, homogeneity of allozyme allelic frequencies between populations of the two taxa and the demonstration of hybridization lead most authors to suggest that they should be regrouped within the same species. The risk of introgression and the present expansion of C. gigas aquaculture in Europe raises the question of the need for preservation of C. angulata in Europe, as only a few populations remain. We studied European and Asian populations of C. gigas and C. angulata using microsatellite and mitochondrial DNA markers to estimate their genetic diversity and differentiation. The analysis of genetic distances and the distribution of allelic and haplotype frequencies revealed significant genetic differences between taxa, showing two clusters: (1) C. gigas French and Japanese populations and (2) C. angulata Portuguese and Taiwanese populations. The Asian origin of the Crassostrea angulata taxa is therefore confirmed. Unlike previous studies based on allozymes, significant nuclear genome differences were noted between C. angulata and C. gigas. Despite the presumed history of the introduction of C. angulata into Southern Europe, these populations did not show any significant reduction of variability compared to Taiwanese populations. Any conservation plans for European C. angulata populations should take its non-native origin into account. They represent a valuable genetic resources for European breeding program.     

TAT Peptide-Conjugated Magnetic PLA-PEG Nanocapsules for the Targeted Delivery of Paclitaxel: <Emphasis Type="Italic">In Vitro</Emphasis> and Cell Studies

Paclitaxel (PTX) and organophilic iron oxide nanocrystals of 7 nm average size were co-encapsulated in the oily core of poly(lactide)-poly(ethyleneglycol) (PLA-PEG) nanocapsules in order to develop magnetically responsive nanocarriers of PTX. The nanocapsules were prepared by a solvent displacement technique and exhibited satisfactory drug and iron oxide loading efficiency, high colloidal stability, and sustained drug release properties. Drug release also proved responsive to an alternating magnetic field. Magnetophoresis experiments showed that the magnetic responsiveness of the nanocapsules depended on their SPION content. The PTX-loaded nanocapsules exhibited comparable to free PTX cytotoxicity against the A549 lung cancer cell line at 24 h of incubation but higher cytotoxicity than free drug at 48 h of incubation. The conjugation of a cysteine-modified TAT peptide (HCys-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH₂) on the surface of the nanocapsules resulted to highly increased uptake of nanocapsules by cancer cells, as well as to profound improvement of their cytotoxicity against the cancer cells. The results obtained justify further investigation of the prospects of these multifunctional PLA-PEG nanocapsules as a targeted delivery system of paclitaxel.     

Plasmodium falciparum expresses a multidrug resistance-associated protein

Plasmodium falciparum proteins that efflux toxic metabolic products such as oxidised glutathione (GSSG) are possible targets for anti-malarial drug development. Proteins capable of transporting GSSG and glutathione conjugates include the multidrug resistance-associated transporters (MRPs). A gene, PFA0590w, encoding a MRP homologue, has been identified in P. falciparum. Here we show the presence of full-length mRNA (5.5 kb) of this PfMRP in trophozoites by RT-PCR and Northern blotting. A polyclonal anti-PfMRP antibody generated against two unique, hydrophilic peptides in the predicted sequence produced a strong immunoreactive protein band of 210-215 kDa on Western blots of schizonts of chloroquine-sensitive and chloroquine-resistant strains, confirming expression of PfMRP protein. Using confocal microscopy the protein was seen to be localised at the edge of the schizonts with no obvious staining of the food vacuole. We suggest that PfMRP may act as the GSSG transporter in the parasite plasma membrane.     

Origin, diversification, and historical biogeography of the genus Trachurus (Perciformes: Carangidae)

We addressed phylogenetic relationships in the genus Trachurus using cytochrome b gene and D-loop sequences. The trees showed five groups: (1) the Southwest Pacific species (T. japonicus, T. novaezelandiae, and T. declivis); (2) The Mediterranean Sea and Eastern Atlantic species (T. mediterraneus); (3) The Atlantic Ocean species (T. lathami and T. trecae); (4) Eastern Atlantic species (T. trachurus and T. capensis); and (5) a group of highly mobile pelagic species, two from the Eastern Pacific (T. symmetricus and T. murphyi) and one from the Eastern Atlantic (T. picturatus). The phylogeny based on Cyt b, supports the molecular clock hypothesis and our results agree with the reported fossil indicating that the origin of this genus occur when the Thetys Sea closed (around 18.4 MYA). In addition, a very slow neutral substitution rate is reported identified only two periods of maximum diversification: the first occurring between 18.4 and 15.0 MYA and the second between 8.4 MYA and present day.     

The Network of Counterparty Risk: Analysing Correlations in OTC Derivatives

Counterparty risk denotes the risk that a party defaults in a bilateral contract. This risk not only depends on the two parties involved, but also on the risk from various other contracts each of these parties holds. In rather informal markets, such as the OTC (over-the-counter) derivative market, institutions only report their aggregated quarterly risk exposure, but no details about their counterparties. Hence, little is known about the diversification of counterparty risk. In this paper, we reconstruct the weighted and time-dependent network of counterparty risk in the OTC derivatives market of the United States between 1998 and 2012. To proxy unknown bilateral exposures, we first study the co-occurrence patterns of institutions based on their quarterly activity and ranking in the official report. The network obtained this way is further analysed by a weighted k-core decomposition, to reveal a core-periphery structure. This allows us to compare the activity-based ranking with a topology-based ranking, to identify the most important institutions and their mutual dependencies. We also analyse correlations in these activities, to show strong similarities in the behavior of the core institutions. Our analysis clearly demonstrates the clustering of counterparty risk in a small set of about a dozen US banks. This not only increases the default risk of the central institutions, but also the default risk of peripheral institutions which have contracts with the central ones. Hence, all institutions indirectly have to bear (part of) the counterparty risk of all others, which needs to be better reflected in the price of OTC derivatives.