Spatial correlations between MRI-derived wall shear stress and vessel wall thickness in the carotid bifurcation

BACKGROUND: To explore the possibility of creating three-dimensional (3D) estimation models for patient-specific wall thickness (WT) maps using patient-specific and cohort-averaged WT, wall shear stress (WSS), and vessel diameter maps in asymptomatic atherosclerotic carotid bifurcations. METHODS: Twenty subjects (aged 75 ± 6 years [mean ± standard deviation], eight women) underwent a 1.5-T MRI examination. Non-gated 3D phase-contrast gradient-echo images and proton density-weighted echo-planar images were retrospectively assessed for WSS, diameter estimation, and WT measurements. Spearman's ρ and scatter plots were used to determine correlations between individual WT, WSS, and diameter maps. A bootstrapping technique was used to determine correlations between 3D cohort-averaged WT, WSS, and diameter maps. Linear regression between the cohort-averaged WT, WSS, and diameter maps was used to predict individual 3D WT. RESULTS: Spearman's ρ averaged over the subjects was - 0.24 ± 0.18 (p < 0.001) and 0.07 ± 0.28 (p = 0.413) for WT versus WSS and for WT versus diameter relations, respectively. Cohort-averaged ρ, averaged over 1000 bootstraps, was - 0.56 (95% confidence interval [- 0.74,- 0.38]) for WT versus WSS and 0.23 (95% confidence interval [- 0.06, 0.52]) for WT versus diameter. Scatter plots did not reveal relationships between individual WT and WSS or between WT and diameter data. Linear relationships between these parameters became apparent after averaging over the cohort. Spearman's ρ between the original and predicted WT maps was 0.21 ± 0.22 (p < 0.001). CONCLUSIONS: With a combination of bootstrapping and cohort-averaging methods, 3D WT maps can be predicted from the individual 3D WSS and diameter maps. The methodology may help to elucidate pathological processes involving WSS in carotid atherosclerosis

Elastic response of cross-laminated engineered bamboo panels subjected to in-plane loading

© ICE Publishing: All rights reserved. Novel cross-laminated bamboo panels comprising three and five layers (G-XLam3 and G-XLam5) were tested in compression along the main (0°) and the transverse (90°) directions. Linear variable differential transformer (LVDT) and non-contact three-dimensional digital image correlation (DIC) measuring techniques were used separately to measure deformation in the elastic region, and the elastic moduli, Ep C,0 and Ep C,90, were derived. Mean elastic modulus values obtained using LVDTs exhibited a good match with analytically predicted values. In contrast, the elastic values obtained by the DIC method were considerably higher and presented a considerable scatter of results. For instance, the Ep C,0 for G-XLam3 and G-XLam5 panels were 17·22 and 15·67 GPa, and 14·86 and 12·48 GPa, using the DIC and LVDT methods, respectively. In general, G-XLam panels with a fifth of the cross-sectional thickness and twice the density of analogous cross-laminated timber exhibited an approximately two-fold increase in Ep C,0 and Ep C,90. Overall, this research provides guidelines for the assessment and standardisation of the testing procedures for similar engineered bamboo products using contact and non-contact methods and highlights the potential of using G-XLam panels in stiffness-driven applications and in combination with wood for structural purposes

Short and long term outcome of neonatal hyperglycemia in very preterm infants: a retrospective follow-up study

<p>Abstract</p> <p>Background</p> <p>Hyperglycemia in premature infants is associated with increased morbidity and mortality, but data on long-term outcome are limited. We investigated the effects of neonatal hyperglycemia (blood glucose ≥ 10 mmol/l, treated with insulin for ≥ 12 hours) on growth and neurobehavioral outcome at 2 years of age.</p> <p>Methods</p> <p>Retrospective follow-up study at 2 years of age among 859 infants ≤32 weeks of gestation admitted to a tertiary neonatal center between January 2002 and December 2006. Thirty-three survivors treated with insulin for hyperglycemia and 63 matched controls without hyperglycemia were evaluated at a corrected age of 2 years. Outcome measures consisted of growth (weight, length, and head circumference) and neurological and behavioural development.</p> <p>Results</p> <p>66/859 (8%) infants ≤ 32 weeks of gestation developed hyperglycemia. Mortality during admission was 27/66 (41%) in the hyperglycemia group versus 62/793 (8%) in those without hyperglycemia (p < 0.001). Mortality was higher in infants with hyperglycemia with a birth weight ≤1,000 gram (p = 0.005) and/or gestational age of 24-28 weeks (p = 0.009) than in control infants without hyperglycemia. Sepsis was more prominent in infants with hyperglycemia and a birth weight of >1,000 gram (p = 0.002) and/or gestational age of 29-32 weeks (p = 0.009) than in control infants without hyperglycemia. Growth at 2 years of age was similar, but neurological and behavioural development was more frequently abnormal among those with neonatal hyperglycemia (p = 0.036 and 0.021 respectively).</p> <p>Conclusions</p> <p>Mortality was higher in very preterm infants with hyperglycemia treated with insulin during the neonatal period. At 2 years of age survivors showed normal growth, but a higher incidence of neurological and behavioural problems. Better strategies to manage hyperglycemia may improve outcome of very preterm infants.</p

CHMP1A encodes an essential regulator of BMI1-INK4A in cerebellar development

Charged multivesicular body protein 1A (CHMP1A; also known as chromatin-modifying protein 1A) is a member of the ESCRT-III (endosomal sorting complex required for transport-III) complex but is also suggested to localize to the nuclear matrix and regulate chromatin structure. Here, we show that loss-of-function mutations in human CHMP1A cause reduced cerebellar size (pontocerebellar hypoplasia) and reduced cerebral cortical size (microcephaly). CHMP1A-mutant cells show impaired proliferation, with increased expression of INK4A, a negative regulator of stem cell proliferation. Chromatin immunoprecipitation suggests loss of the normal INK4A repression by BMI in these cells. Morpholino-based knockdown of zebrafish chmp1a resulted in brain defects resembling those seen after bmi1a and bmi1b knockdown, which were partially rescued by INK4A ortholog knockdown, further supporting links between CHMP1A and BMI1-mediated regulation of INK4A. Our results suggest that CHMP1A serves as a critical link between cytoplasmic signals and BMI1-mediated chromatin modifications that regulate proliferation of central nervous system progenitor cells

Expression of Bmi-1 is a prognostic marker in bladder cancer

<p>Abstract</p> <p>Background</p> <p>The molecular mechanisms of the development and progression of bladder cancer are poorly understood. The objective of this study was to analyze the expression of Bmi-1 protein and its clinical significance in human bladder cancer.</p> <p>Methods</p> <p>We examined the expression of Bmi-1 mRNA and Bmi-1 protein by RT-PCR and Western blot, respectively in 14 paired bladder cancers and the adjacent normal tissues. The expression of Bmi-1 protein in 137 specimens of bladder cancer and 30 specimens of adjacent normal bladder tissue was determined by immunohistochemistry. Statistical analyses were applied to test the relationship between expression of Bmi-1, and clinicopathologic features and prognosis.</p> <p>Results</p> <p>Expression of Bmi-1 mRNA and protein was higher in bladder cancers than in the adjacent normal tissues in 14 paired samples (<it>P </it>< 0.01). By immunohistochemical examination, five of 30 adjacent normal bladder specimens (16.7%) versus 75 of 137 bladder cancers (54.3%) showed Bmi-1 protein expression (<it>P </it>< 0.05). Bmi-1 protein expression was intense in 20.6%, 54.3%, and 78.8% of tumors of histopathological stages G1, G2, and G3, respectively (<it>P </it>< 0.05). Expression of Bmi-1 protein was greater in invasive bladder cancers than in superficial bladder cancers (81.5% versus 32.5%, <it>P </it>< 0.05). In invasive bladder cancers, the expression of Bmi-1 protein in progression-free cancers was similar to that of cancers that have progressed (80.0% versus 82.4%, <it>P </it>> 0.5). In superficial bladder cancers, the expression of Bmi-1 protein in recurrent cases was higher than in recurrence-free cases (62.5% versus 13.7%, <it>P </it>< 0.05). Bmi-1 expression was positively correlated with tumor classification and TNM stage (<it>P </it>< 0.05), but not with tumor number (<it>P </it>> 0.05). Five-year survival in the group with higher Bmi-1 expression was 50.8%, while it was 78.5% in the group with lower Bmi-1 expression (<it>P </it>< 0.05). Patients with higher Bmi-1 expression had shorter survival time, whereas patients with lower Bmi-1 expression had longer survival time (<it>P </it>< 0.05).</p> <p>Conclusion</p> <p>Expression of Bmi-1 was greater in bladder cancers than in the adjacent normal tissues. The examination of Bmi-1 protein expression is potentially valuable in prognostic evaluation of bladder cancer.</p

Bmi1 Is Down-Regulated in the Aging Brain and Displays Antioxidant and Protective Activities in Neurons

Aging increases the risk to develop several neurodegenerative diseases, although the underlying mechanisms are poorly understood. Inactivation of the Polycomb group gene Bmi1 in mice results in growth retardation, cerebellar degeneration, and development of a premature aging-like phenotype. This progeroid phenotype is characterized by formation of lens cataracts, apoptosis of cortical neurons, and increase of reactive oxygen species (ROS) concentrations, owing to p53-mediated repression of antioxidant response (AOR) genes. Herein we report that Bmi1 expression progressively declines in the neurons of aging mouse and human brains. In old brains, p53 accumulates at the promoter of AOR genes, correlating with a repressed chromatin state, down-regulation of AOR genes, and increased oxidative damages to lipids and DNA. Comparative gene expression analysis further revealed that aging brains display an up-regulation of the senescence-associated genes IL-6, p19Arf and p16Ink4a, along with the pro-apoptotic gene Noxa, as seen in Bmi1-null mice. Increasing Bmi1 expression in cortical neurons conferred robust protection against DNA damage-induced cell death or mitochondrial poisoning, and resulted in suppression of ROS through activation of AOR genes. These observations unveil that Bmi1 genetic deficiency recapitulates aspects of physiological brain aging and that Bmi1 over-expression is a potential therapeutic modality against neurodegeneration