High shear stress relates to intraplaque haemorrhage in asymptomatic carotid plaques

AbstractBackground and aimsCarotid artery plaques with vulnerable plaque components are related to a higher risk of cerebrovascular accidents. It is unknown which factors drive vulnerable plaque development. Shear stress, the frictional force of blood at the vessel wall, is known to influence plaque formation. We evaluated the association between shear stress and plaque components (intraplaque haemorrhage (IPH), lipid rich necrotic core (LRNC) and/or calcifications) in relatively small carotid artery plaques in asymptomatic persons.MethodsParticipants (n = 74) from the population-based Rotterdam Study, all with carotid atherosclerosis assessed on ultrasound, underwent carotid MRI. Multiple MRI sequences were used to evaluate the presence of IPH, LRNC and/or calcifications in plaques in the carotid arteries. Images were automatically segmented for lumen and outer wall to obtain a 3D reconstruction of the carotid bifurcation. These reconstructions were used to calculate minimum, mean and maximum shear stresses by applying computational fluid dynamics with subject-specific inflow conditions. Associations between shear stress measures and plaque composition were studied using generalized estimating equations analysis, adjusting for age, sex and carotid wall thickness.ResultsThe study group consisted of 93 atherosclerotic carotid arteries of 74 participants. In plaques with higher maximum shear stresses, IPH was more often present (OR per unit increase in maximum shear stress (log transformed) = 12.14; p = 0.001). Higher maximum shear stress was also significantly associated with the presence of calcifications (OR = 4.28; p = 0.015).ConclusionsHigher maximum shear stress is associated with intraplaque haemorrhage and calcifications

High shear stress relates to intraplaque haemorrhage in asymptomatic carotid plaques

Background and aims Carotid artery plaques with vulnerable plaque components are related to a higher risk of cerebrovascular accidents. It is unknown which factors drive vulnerable plaque development. Shear stress, the frictional force of blood at the vessel wall, is known to influence plaque formation. We evaluated the association between shear stress and plaque components (intraplaque haemorrhage (IPH), lipid rich necrotic core (LRNC) and/or calcifications) in relatively small carotid artery plaques in asymptomatic persons. Methods Participants (n = 74) from the population-based

Autologous stem cell transplantation may be curative for patients with follicular lymphoma with early therapy failure without the need for immunotherapy

Objective/Background: Patients with follicular lymphoma (FL) with early therapy failure (ETF) within 2 years of frontline therapy have poor overall survival (OS). We recently reported the results of autologous stem cell transplantation (ASCT) in patients from the Grupo Español de Linfomas y Trasplantes de Médula Ósea (GELTAMO) registry treated with rituximab prior to ASCT and with ETF after first-line immunochemotherapy, leading to 81% 5-year OS since ASCT. We explored whether ASCT is also an effective option in the pre-rituximab era—that is, in patients treated in induction and rescued only with chemotherapy. Methods: ETF was defined as relapse/progression within 2 years of starting first-line therapy. We identified two groups: the ETF cohort (n = 87) and the non-ETF cohort (n = 47 patients receiving ASCT but not experiencing ETF following first-line therapy). Results: There was a significant difference in 5-year progression-free survival between the ETF and non-ETF cohorts (43% vs. 57%, respectively; p = .048). Nevertheless, in patients with ETF with an interval from first relapse after primary treatment to ASCT of <1 year, no differences were observed in 5-year progression-free survival (48% vs. 66%, respectively; p = .44) or in 5-year OS (69% vs. 77%, p = .4). Patients in the ETF cohort transplanted in complete remission showed a plateau in the OS curves, at 56%, beyond 13.7 years of follow-up. Conclusion: ASCT may be a curative option for ETF in patients who respond to rescue chemotherapy, without the need for immunotherapy or other therapies, and should be considered as an early consolidation, especially in patients with difficult access to rituximab

A competitive strategy for atrial and aortic tract segmentation based on deformable models

Multiple strategies have previously been described for atrial region (i.e. atrial bodies and aortic tract) segmentation. Although these techniques have proven their accuracy, inadequate results in the mid atrial walls are common, restricting their application for specific cardiac interventions. In this work, we introduce a novel competitive strategy to perform atrial region segmentation with correct delineation of the thin mid walls, and integrated it into the B-spline Explicit Active Surfaces framework. A double stage segmentation process is used, which starts with a fast contour growing followed by a refinement stage with local descriptors. Independent functions are used to define each region, being afterward combined to compete for the optimal boundary. The competition locally constrains the surface evolution, prevents overlaps and allows refinement to the walls. Three different scenarios were used to demonstrate the advantages of the proposed approach, through the evaluation of its segmentation accuracy, and its performance for heterogeneous mid walls. Both computed tomography and magnetic resonance imaging datasets were used, presenting results similar to the state-of-the-art methods for both atria and aorta. The competitive strategy showed its superior performance with statistically significant differences against the traditional free-evolution approach in cases with bad image quality or missed atrial/aortic walls. Moreover, only the competitive approach was able to accurately segment the atrial/aortic wall. Overall, the proposed strategy showed to be suitable for atrial region segmentation with a correct segmentation of the mid thin walls, demonstrating its added value with respect to the traditional techniques.The authors acknowledge Fundacao para a Ciencia e a Tecnologia (FCT), in Portugal, and the European Social Found, European Union, for funding support through the "Programa Operacional Capital Humano" (POCH) in the scope of the PhD grants SFRH/BD/95438/2013 (P. Morais) and SFRH/BD/93443/2013 (S. Queiros).Authors gratefully acknowledge the funding of projects NORTE-01-0145-FEDER-000013 and NORTE-01-0145-FEDER-000022, co-financed by "Programa Operacional Regional do Norte" (NORTE2020), through "Fundo Europeu de Desenvolvimento Regional" (FEDER).info:eu-repo/semantics/publishedVersio

Foaming of EVA/starch blends: Characterization of the structure, physical properties, and biodegradability

Foams produced from blends of an ethylene-vinyl acetate copolymer (EVA) with high VA (vinyl acetate) content (28%) and corn starch have been successfully fabricated using an improved compression molding technique. A detailed characterization of the structure and physical properties has been carried out. The results showed that the corn starch acts as filler for EVA, showing a good compatibility with the polyolefin. Different types of cellular structure (closed, partially interconnected, and fully interconnected) and cell sizes were obtained depending on the relative density and the amount of starch included in the composition. Besides, the addition of starch allows tailoring the physical properties of the composite foams. An increase in the starch content leads to an increase of the density, compressive strength, hardness, and thermal conductivity and a decrease of the elasticity. Finally, biodegradability tests showed how increases the biodegradation with the amount of starch in the foam, which reaches 60% at 100 days for the foam with 70% of starch. POLYM. ENG. SCI., 2012. (C) 2011 Society of Plastics EngineersFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

The hepatokine fetuin-A disrupts functional maturation of pancreatic beta cells.

AIMS/HYPOTHESIS: Neonatal beta cells carry out a programme of postnatal functional maturation to achieve full glucose responsiveness. A partial loss of the mature phenotype of adult beta cells may contribute to a reduction of functional beta cell mass and accelerate the onset of type 2 diabetes. We previously found that fetuin-A, a hepatokine increasingly secreted by the fatty liver and a determinant of type 2 diabetes, inhibits glucose-stimulated insulin secretion (GSIS) of human islets. Since fetuin-A is a ubiquitous fetal glycoprotein that declines peripartum, we examined here whether fetuin-A interferes with the functional maturity of beta cells. METHODS: The effects of fetuin-A were assessed during in vitro maturation of porcine neonatal islet cell clusters (NICCs) and in adult human islets. Expression alterations were examined via microarray, RNA sequencing and reverse transcription quantitative real-time PCR (qRT-PCR), proteins were analysed by western blotting and immunostaining, and insulin secretion was quantified in static incubations. RESULTS: NICC maturation was accompanied by the gain of glucose-responsive insulin secretion (twofold stimulation), backed up by mRNA upregulation of genes governing beta cell identity and function, such as NEUROD1, UCN3, ABCC8 and CASR (Log2 fold change [Log2FC] &gt; 1.6). An active TGFβ receptor (TGFBR)-SMAD2/3 pathway facilitates NICC maturation, since the TGFBR inhibitor SB431542 counteracted the upregulation of aforementioned genes and de-repressed ALDOB, a gene disallowed in mature beta cells. In fetuin-A-treated NICCs, upregulation of beta cell markers and the onset of glucose responsiveness were suppressed. Concomitantly, SMAD2/3 phosphorylation was inhibited. Transcriptome analysis confirmed inhibitory effects of fetuin-A and SB431542 on TGFβ-1- and SMAD2/3-regulated transcription. However, contrary to SB431542 and regardless of cMYC upregulation, fetuin-A inhibited beta cell proliferation (0.27 ± 0.08% vs 1.0  ± 0.1% Ki67-positive cells in control NICCs). This effect was sustained by reduced expression (Log2FC ≤ -2.4) of FOXM1, CENPA, CDK1 or TOP2A. In agreement, the number of insulin-positive cells was lower in fetuin-A-treated NICCs than in control NICCs (14.4 ± 1.2% and 22.3 ± 1.1%, respectively). In adult human islets fetuin-A abolished glucose responsiveness, i.e. 1.7- and 1.1-fold change over 2.8&nbsp;mmol/l glucose in control- and fetuin-A-cultured islets, respectively. In addition, fetuin-A reduced SMAD2/3 phosphorylation and suppressed expression of proliferative genes. Of note, in non-diabetic humans, plasma fetuin-A was negatively correlated (p = 0.013) with islet beta cell area. CONCLUSIONS/INTERPRETATION: Our results suggest that the perinatal decline of fetuin-A relieves TGFBR signalling in islets, a process that facilitates functional maturation of neonatal beta cells. Functional maturity remains revocable in later life, and the occurrence of a metabolically unhealthy milieu, such as liver steatosis and elevated plasma fetuin-A, can impair both function and adaptive proliferation of beta cells. DATA AVAILABILITY: The RNAseq datasets and computer code produced in this study are available in the Gene Expression Omnibus (GEO): GSE144950; https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE144950