Mechanisms to explain the poor results of carotid artery stenting (CAS) in symptomatic patients to date and options to improve CAS outcomes

BackgroundCarotid artery stenting (CAS) is considered by many as an alternative to carotid endarterectomy (CEA) for the management of carotid artery stenosis. However, recent trials demonstrated inferior results for CAS in symptomatic patients compared with CEA. We reviewed the literature to evaluate the appropriateness of CAS for symptomatic carotid artery stenosis and to determine the pathogenetic mechanism(s) associated with stroke following the treatment of such lesions. Based on this, we propose steps to improve the results of CAS for the treatment of symptomatic carotid stenosis.MethodsPubMed/Medline was searched up to March 25, 2010 for studies investigating the efficacy of CAS for the management of symptomatic carotid stenosis. Search terms used were “carotid artery stenting,” “symptomatic carotid artery stenosis,” “carotid endarterectomy,” “stroke,” “recurrent carotid stenosis,” and “long-term results” in various combinations.ResultsCurrent data suggest that CAS is not equivalent to CEA for the treatment of symptomatic carotid stenosis. Differences in carotid plaque morphology and a higher incidence of microemboli and cerebrovascular events during and after CAS compared with CEA may account for these inferior results.ConclusionsCurrently, most symptomatic patients are inappropriate candidates for CAS. Improved CAS technology referable to stent design and embolic protection strategies may alter this conclusion in the future

How to identify which patients with asymptomatic carotid stenosis could benefit from endarterectomy or stenting

Offering routine carotid endarterectomy (CEA) or carotid artery stenting (CAS) to patients with asymptomatic carotid artery stenosis (ACS) is no longer considered as the optimal management of these patients. Equally suboptimal, however, is the policy of offering only best medical treatment (BMT) to all patients with ACS and not considering any of them for prophylactic CEA. In the last few years, there have been many studies aiming to identify reliable predictors of future cerebrovascular events that would allow the identification of patients with high-risk ACS and offer a prophylactic carotid intervention only to these patients to prevent them from becoming symptomatic. All patients with ACS should receive BMT. The present article will summarise the evidence suggesting ways to identify these high-risk asymptomatic individuals, namely: (1) microemboli detection on transcranial Doppler, (2) plaque echolucency on Duplex ultrasound, (3) progression in the severity of ACS, (4) silent embolic infarcts on brain CT/MRI, (5) reduced cerebrovascular reserve, (6) increased size of juxtaluminal hypoechoic area, (7) identification of intraplaque haemorrhage using MRI and (8) carotid ulceration. The evidence suggests that approximately 10%-15% of patents with asymptomatic stenosis might benefit from intervention; this will become more clear after publication of ongoing studies comparing stenting or endarterectomy with best medical therapy. In the meantime, no patient should be offered intervention unless there is evidence of high risk of ipsilateral stroke, from modalities such as those discussed here

Growth and Characterization of Ce- Substituted Nd2Fe14B Single Crystals

Single crystals of (Nd1-xCex)2Fe14B are grown out of Fe-(Nd,Ce) flux. Chemical and structural analysis of the crystals indicates that (Nd1-xCex)2Fe14B forms a solid solution until at least x = 0.38 with a Vegard-like variation of the lattice constants with x. Refinements of single crystal neutron diffraction data indicate that Ce has a slight site preference (7:3) for the 4g rare earth site over the 4f site. Magnetization measurements show that for x = 0.38 the saturation magnetization at 400 K, a temperature important to applications, falls from 29.8 for the parent Nd2Fe14B to 27.6 (mu)B/f.u., the anisotropy field decreases from 5.5 T to 4.7 T, and the Curie temperature decreases from 586 to 543 K. First principles calculations carried out within density functional theory are used to explain the decrease in magnetic properties due to Ce substitution. Though the presence of the lower-cost and more abundant Ce slightly affects these important magnetic characteristics, this decrease is not large enough to affect a multitude of applications. Ce-substituted Nd2Fe14B is therefore a potential high-performance permanent magnet material with substantially reduced Nd content.Comment: 11 Pages, 8 figures, 5 table

Molecular diet analysis in mussels and other metazoan filter feeders and an assessment of their utility as natural eDNA samplers

Molecular gut content analysis is a popular tool to study food web interactions and has recently been suggested as an alternative source for DNA-based biomonitoring. However, the overabundant consumer's DNA often outcompetes that of its diet during PCR. Lineage-specific primers are an efficient means to reduce consumer amplification while retaining broad specificity for dietary taxa. Here, we designed an amplicon sequencing assay to monitor the eukaryotic diet of mussels and other metazoan filter feeders and explore the utility of mussels as natural eDNA samplers to monitor planktonic communities. We designed several lineage-specific rDNA primers with broad taxonomic suitability for eukaryotes. The primers were tested using DNA extracts of different limnic and marine mussel species and the results compared to eDNA water samples collected next to the mussel colonies. In addition, we analysed several 25-year time series samples of mussels from German rivers. Our primer sets efficiently prevent the amplification of mussels and other metazoans. The recovered DNA reflects a broad dietary preference across the eukaryotic tree of life and considerable taxonomic overlap with filtered water samples. We also show the utility of a reversed version of our primers, which prevents amplification of nonmetazoan taxa from complex eukaryote community samples, by enriching fauna associated with the marine brown algae Fucus vesiculosus. Our protocol will enable large-scale dietary analysis in metazoan filter feeders, facilitate aquatic food web analysis and allow surveying of aquacultures for pathogens. Moreover, we show that mussels and other aquatic filter feeders can serve as complementary DNA source for biomonitoring

Deep-Manager: a versatile tool for optimal feature selection in live-cell imaging analysis

One of the major problems in bioimaging, often highly underestimated, is whether features extracted for a discrimination or regression task will remain valid for a broader set of similar experiments or in the presence of unpredictable perturbations during the image acquisition process. Such an issue is even more important when it is addressed in the context of deep learning features due to the lack of a priori known relationship between the black-box descriptors (deep features) and the phenotypic properties of the biological entities under study. In this regard, the widespread use of descriptors, such as those coming from pre-trained Convolutional Neural Networks (CNNs), is hindered by the fact that they are devoid of apparent physical meaning and strongly subjected to unspecific biases, i.e., features that do not depend on the cell phenotypes, but rather on acquisition artifacts, such as brightness or texture changes, focus shifts, autofluorescence or photobleaching. The proposed Deep-Manager software platform offers the possibility to efficiently select those features having lower sensitivity to unspecific disturbances and, at the same time, a high discriminating power. Deep-Manager can be used in the context of both handcrafted and deep features. The unprecedented performances of the method are proven using five different case studies, ranging from selecting handcrafted green fluorescence protein intensity features in chemotherapy-related breast cancer cell death investigation to addressing problems related to the context of Deep Transfer Learning. Deep-Manager, freely available at https://github.com/BEEuniroma2/Deep-Manager, is suitable for use in many fields of bioimaging and is conceived to be constantly upgraded with novel image acquisition perturbations and modalities

Por Secretion System-Dependent Secretion and Glycosylation of Porphyromonas gingivalis Hemin-Binding Protein 35

The anaerobic Gram-negative bacterium Porphyromonas gingivalis is a major pathogen in severe forms of periodontal disease and refractory periapical perodontitis. We have recently found that P. gingivalis has a novel secretion system named the Por secretion system (PorSS), which is responsible for secretion of major extracellular proteinases, Arg-gingipains (Rgps) and Lys-gingipain. These proteinases contain conserved C-terminal domains (CTDs) in their C-termini. Hemin-binding protein 35 (HBP35), which is one of the outer membrane proteins of P. gingivalis and contributes to its haem utilization, also contains a CTD, suggesting that HBP35 is translocated to the cell surface via the PorSS. In this study, immunoblot analysis of P. gingivalis mutants deficient in the PorSS or in the biosynthesis of anionic polysaccharide-lipopolysaccharide (A-LPS) revealed that HBP35 is translocated to the cell surface via the PorSS and is glycosylated with A-LPS. From deletion analysis with a GFP-CTD[HBP35] green fluorescent protein fusion, the C-terminal 22 amino acid residues of CTD[HBP35] were found to be required for cell surface translocation and glycosylation. The GFP-CTD fusion study also revealed that the CTDs of CPG70, peptidylarginine deiminase, P27 and RgpB play roles in PorSS-dependent translocation and glycosylation. However, CTD-region peptides were not found in samples of glycosylated HBP35 protein by peptide map fingerprinting analysis, and antibodies against CTD-regions peptides did not react with glycosylated HBP35 protein. These results suggest both that the CTD region functions as a recognition signal for the PorSS and that glycosylation of CTD proteins occurs after removal of the CTD region. Rabbits were used for making antisera against bacterial proteins in this study