Identifying vertebral end plate lesions (schmorl's nodes) using a semi-automatic method

INTRODUCTION There is a large range in the reported prevalence of end plate lesions (EPLs), sometimes referred to as Schmorl's nodes in the general population (3.8-76%). One possible reason for this large range is the differences in definitions used by authors. Previous research has suggested that EPLs may potentially be a primary disturbance of growth plates that leads to the onset of scoliosis. The aim of this study was to develop a technique to measure the size, prevalence and location of EPLs on Computed Tomography (CT) images of scoliosis patients in a consistent manner. METHODS A detection algorithm was developed and applied to measure EPLs for five adolescent females with idiopathic scoliosis (average age 15.1 years, average major Cobb 60°). In this algorithm, the EPL definition was based on the lesion depth, the distance from the edge of the vertebral body and the gradient of the lesion edge. Existing low-dose, CT scans of the patients' spines were segmented semi-automatically to extract 3D vertebral endplate morphology. Manual sectioning of any attachments between posterior elements of adjacent vertebrae and, if necessary, endplates was carried out before the automatic algorithm was used to determine the presence and position of EPLs. RESULTS EPLs were identified in 15 of the 170 (8.8%) endplates analysed with an average depth of 3.1mm. 73% of the EPLs were seen in the lumbar spines (11/15). A sensitivity study demonstrated that the algorithm was most sensitive to changes in the minimum gradient required at the lesion edge. CONCLUSION An imaging analysis technique for consistent measurement of the prevalence, location and size of EPLs on CT images has been developed. Although the technique was tested on scoliosis patients, it can be used to analyse other populations without observer errors in EPL definitions.

Dynamic, invivo, real-time detection of retinal oxidative status in a model of elevated intraocular pressure using a novel, reversibly responsive, profluorescent nitroxide probe

Changes to the redox status of biological systems have been implicated in the pathogenesis of a wide variety of disorders including cancer, Ischemia-reperfusion (I/R) injury and neurodegeneration. In times of metabolic stress e.g. ischaemia/reperfusion, reactive oxygen species (ROS) production overwhelms the intrinsic antioxidant capacity of the cell, damaging vital cellular components. The ability to quantify ROS changes in vivo, is therefore essential to understanding their biological role. Here we evaluate the suitability of a novel reversible profluorescent probe containing a redox-sensitive nitroxide moiety (methyl ester tetraethylrhodamine nitroxide, ME-TRN), as an in vivo, real-time reporter of retinal oxidative status. The reversible nature of the probe's response offers the unique advantage of being able to monitor redox changes in both oxidizing and reducing directions in real time. After intravitreal administration of the ME-TRN probe, we induced ROS production in rat retina using an established model of complete, acute retinal ischaemia followed by reperfusion. After restoration of blood flow, retinas were imaged using a Micron III rodent fundus fluorescence imaging system, to quantify the redox-response of the probe. Fluorescent intensity declined during the first 60 min of reperfusion. The ROS-induced change in probe fluorescence was ameliorated with the retinal antioxidant, lutein. Fluorescence intensity in non-Ischemia eyes did not change significantly. This new probe and imaging technology provide a reversible and real-time response to oxidative changes and may allow the in vivo testing of antioxidant therapies of potential benefit to a range of diseases linked to oxidative stress

Atmospheric pressure gas plasma-induced colorectal cancer cell death is mediated by Nox2-ASK1 apoptosis pathways and oxidative stress is mitigated by Srx-Nrf2 anti-oxidant system

Atmospheric pressure gas plasma (AGP) generates reactive oxygen species (ROS) that induce apoptosis in cultured cancer cells. The majority of cancer cells develop a ROS-scavenging anti-oxidant system regulated by Nrf2, which confers resistance to ROS-mediated cancer cell death. Generation of ROS is involved in the AGP-induced cancer cell death of several colorectal cancer cells (Caco2, HCT116 and SW480) by activation of ASK1-mediated apoptosis signaling pathway without affecting control cells (human colonic sub-epithelial myofibroblasts; CO18, human fetal lung fibroblast; MRC5 and fetal human colon; FHC). However, the identity of an oxidase participating in AGP-induced cancer cell death is unknown. Here, we report that AGP up-regulates the expression of Nox2 (NADPH oxidase) to produce ROS. RNA interference designed to target Nox2 effectively inhibits the AGP-induced ROS production and cancer cell death. In some cases both colorectal cancer HT29 and control cells showed resistance to AGP treatment. Compared to AGP-sensitive Caco2 cells, HT29 cells show a higher basal level of the anti-oxidant system transcriptional regulator Nrf2 and its target protein sulfiredoxin (Srx) which are involved in cellular redox homeostasis. Silencing of both Nrf2 and Srx sensitized HT29 cells, leads to ROS overproduction and decreased cell viability. This indicates that in HT29 cells, Nrf2/Srx axis is a protective factor against AGP-induced oxidative stress. The inhibition of Nrf2/Srx signaling should be considered as a central target in drug-resistant colorectal cancer treatments.

Plantar pressure in diabetic peripheral neuropathy patients with active foot ulceration, previous ulceration and no history of ulceration: A meta-analysis of observational studies

Aims Elevated dynamic plantar pressures are a consistent finding in diabetes patients with peripheral neuropathy with implications for plantar foot ulceration. This meta-analysis aimed to compare the plantar pressures of diabetes patients that had peripheral neuropathy and those with neuropathy with active or previous foot ulcers. Methods Published articles were identified from Medline via OVID, CINAHL, SCOPUS, INFORMIT, Cochrane Central EMBASE via OVID and Web of Science via ISI Web of Knowledge bibliographic databases. Observational studies reporting barefoot dynamic plantar pressure in adults with diabetic peripheral neuropathy, where at least one group had a history of plantar foot ulcers were included. Interventional studies, shod plantar pressure studies and studies not published in English were excluded. Overall mean peak plantar pressure (MPP) and pressure time integral (PTI) were primary outcomes. The six secondary outcomes were MPP and PTI at the rear foot, mid foot and fore foot. The protocol of the meta-analysis was published with PROPSERO, (registration number CRD42013004310). Results Eight observational studies were included. Overall MPP and PTI were greater in diabetic peripheral neuropathy patients with foot ulceration compared to those without ulceration (standardised mean difference 0.551, 95% CI 0.290–0.811, p<0.001; and 0.762, 95% CI 0.303–1.221, p = 0.001, respectively). Sub-group analyses demonstrated no significant difference in MPP for those with neuropathy with active ulceration compared to those without ulcers. A significant difference in MPP was found for those with neuropathy with a past history of ulceration compared to those without ulcers; (0.467, 95% CI 0.181– 0.753, p = 0.001). Statistical heterogeneity between studies was moderate. Conclusions Plantar pressures appear to be significantly higher in patients with diabetic peripheral neuropathy with a history of foot ulceration compared to those with diabetic neuropathy without a history of ulceration. More homogenous data is needed to confirm these findings.

Numerical analysis for the interlayer toughening of piezoelectric smart composite plate

The piezoelectric composite material could engender stress concentration resulting from small cracks during layers easily, as the cracks growth will lead to the failure of the whole structure. In this paper, a finite element model for piezoelectric composite materials by ABAQUS including interlayer crack was established, and the J integral and crack tip stress of different types PZT patches were calculated by using the equivalent integral method. Then, the J integral for adhesive layers with different thickness, elastic modulus considering and not considering piezoelectricity was investigated. The results show that the J integral of mode I, II reduces with thicker adhesive layer and lower elastic modules, and the J integral of mode II decreases more sharply than that of mode I.

Genome-wide association study of intraocular pressure identifies the GLCCI1/ICA1 region as a glaucoma susceptibility locus

To discover quantitative trait loci for intraocular pressure, amajor risk factor for glaucoma and the only modifiable one,weperformed agenome-wide association studyonadiscoverycohort of2175individualsfromSydney, Australia. We found a novel association between intraocular pressure and a common variant at 7p21 near to GLCCI1 and ICA1. The findings in this region were confirmed through two UK replication cohorts totalling 4866 individuals (rs59072263, Pcombined = 1.10 × 10-8). A copy of the G allele at this SNP is associated with an increase in mean IOP of 0.45 mmHg (95%CI = 0.30-0.61 mmHg). These results lend support to the implication of vesicle trafficking and glucocorticoid inducibility pathways in the determination of intraocular pressure and in the pathogenesis of primary open-angle glaucoma.

Genome-wide association study identifies eight loci associated with blood pressure

Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N 71,225 European ancestry, N 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N = 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10 24), CYP1A2 (P = 1 × 10 23), FGF5 (P = 1 × 10 21), SH2B3 (P = 3 × 10 18), MTHFR (P = 2 × 10 13), c10orf107 (P = 1 × 10 9), ZNF652 (P = 5 × 10 9) and PLCD3 (P = 1 × 10 8) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.

The measurement of intraocular pressure over positive soft contact lenses by rebound tonometry [Medición de la presión intraocular sobre lentes de contacto blandas positivas, mediante tonometría de rebote]

Purpose To investigate if the accuracy of intraocular pressure (IOP) measurements using rebound tonometry over disposable hydrogel (etafilcon A) contact lenses (CL) is affected by the positive power of the CLs. Methods The experimental group comprised 26 subjects, (8 male, 18 female). IOP measurements were undertaken on the subjects’ right eyes in random order using a Rebound Tonometer (ICare). The CLs had powers of +2.00D and +6.00D. Measurements were taken over each contact lens and also before and after the CLs had been worn. Results The IOP measure obtained with both CLs was significantly lower compared to the value without CLs (t test; p<0.001) but no significant difference was found between the two powers of CLs. Conclusions Rebound tonometry over positive hydrogel CLs leads to a certain degree of IOP underestimation. This result didn’t change for the two positive lenses used in the experiment, despite their large difference in power and therefore in lens thickness. Optometrists should bear this in mind when measuring IOP with the rebound tonometer over plus power contact lenses.

Fatigue crack growth under pulsatile pressure and plaque rupture

Identification of vulnerable plaque pre-rupture is extremely important for patient risk stratification. The mechanism of plaque rupture is still not entirely clear, but it is thought to be a process involving multiple factors. From a biomechanical viewpoint, plaque rupture is usually seen as a structural failure when the plaque cannot resist the hemodynamic blood pressure and shear stress exerted on it. However, the cardiovascular system is naturally a cyclical hemodynamic environment, and myocardial infarction can be a symptomatically quiescent but potentially progressive process when plaque ruptures at stresses much lower than its strength. Therefore, fatigue accumulation is a possible mechanism for plaque rupture. In this study, a crack growth model was developed, and the previously-mentioned hypothesis was tested by conducting a comparative study between 18 symptomatic and 16 asymptomatic patients with carotid stenosis.

Plantar pressure distribution character in young female with mild hallux valgus wearing high-heeled shoes

Young females with mild hallux valgus (HV) have been identified as having an increased risk of first ray deformation. Little is known, however, about the biomechanical changes that might contribute to this increased risk. The purpose of this study was to compare kinetics changes during walking for mild HV subjects with high-heel-height shoes. Twelve female subjects (six with mild HV and six controls) participated in this study with heel height varying from 0 cm (barefoot) to 4.5 cm. Compared to healthy controls, patients had significantly higher peak pressure on the big toe area during barefoot walking. When the heel height increased, loading was transferred to medial side of the forefoot, and the big toe area suffered more impact compared to barefoot in mild HV. This study also demonstrated that the center of pressure (COP) inclines to medial side alteration after high-heeled shoes wearing. These findings indicate that mild HV people should be discouraged from wearing high-heeled shoes.

Impact of coronary tortuosity on coronary pressure: Numerical simulation study

Background: Coronary tortuosity (CT) is a common coronary angiographic finding. Whether CT leads to an apparent reduction in coronary pressure distal to the tortuous segment of the coronary artery is still unknown. The purpose of this study is to determine the impact of CT on coronary pressure distribution by numerical simulation. Methods: 21 idealized models were created to investigate the influence of coronary tortuosity angle (CTA) and coronary tortuosity number (CTN) on coronary pressure distribution. A 2D incompressible Newtonian flow was assumed and the computational simulation was performed using finite volume method. CTA of 30°, 60°, 90°, 120° and CTN of 0, 1, 2, 3, 4, 5 were discussed under both steady and pulsatile conditions, and the changes of outlet pressure and inlet velocity during the cardiac cycle were considered. Results: Coronary pressure distribution was affected both by CTA and CTN. We found that the pressure drop between the start and the end of the CT segment decreased with CTA, and the length of the CT segment also declined with CTA. An increase in CTN resulted in an increase in the pressure drop. Conclusions: Compared to no-CT, CT can results in more decrease of coronary blood pressure in dependence on the severity of tortuosity and severe CT may cause myocardial ischemia.

Image-based midsole insert design and the material effects on heel plantar pressure distribution during simulated walking loads

The primary objective of this paper is to study the use of medical image-based finite element (FE) modelling in subjectspecific midsole design and optimisation for heel pressure reduction using a midsole plug under the calcaneus area (UCA). Plugs with different relative dimensions to the size of the calcaneus of the subject have been incorporated in the heel region of the midsole. The FE foot model was validated by comparing the numerically predicted plantar pressure with biomechanical tests conducted on the same subject. For each UCA midsole plug design, the effect of material properties and plug thicknesses on the plantar pressure distribution and peak pressure level during the heel strike phase of normal walking was systematically studied. The results showed that the UCA midsole insert could effectively modify the pressure distribution, and its effect is directly associated with the ratio of the plug dimension to the size of the calcaneus bone of the subject. A medium hardness plug with a size of 95% of the calcaneus has achieved the best performance for relieving the peak pressure in comparison with the pressure level for a solid midsole without a plug, whereas a smaller plug with a size of 65% of the calcaneus insert with a very soft material showed minimum beneficial effect for the pressure relief.

The mechanical triggers of plaque rupture: Shear stress vs pressure gradient

The aim of this study was to evaluate the mechanical triggers that may cause plaque rupture. Wall shear stress (WSS) and pressure gradient are the direct mechanical forces acting on the plaque in a stenotic artery. Their influence on plaque stability is thought to be controversial. This study used a physiologically realistic, pulsatile flow, two-dimensional, cine phase-contrast MRI sequence in a patient with a 70% carotid stenosis. Instead of considering the full patient-specific carotid bifurcation derived from MRI, only the plaque region has been modelled by means of the idealised flow model. WSS reached a local maximum just distal to the stenosis followed by a negative local minimum. A pressure drop across the stenosis was found which varied significantly during systole and diastole. The ratio of the relative importance of WSS and pressure was assessed and was found to be less than 0.07% for all time phases, even at the throat of the stenosis. In conclusion, although the local high WSS at the stenosis may damage the endothelium and fissure plaque, the magnitude of WSS is small compared with the overall loading on plaque. Therefore, pressure may be the main mechanical trigger for plaque rupture and risk stratification using stress analysis of plaque stability may only need to consider the pressure effect.

The impact of wall shear stress and pressure drop on the stability of the atherosclerotic plaque

Rupture of vulnerable atheromatous plaque in the carotid and coronary arteries often leads to stroke and heart attack respectively. The mechanism of blood flow and plaque rupture in stenotic arteries is still not fully understood. A three dimensional rigid wall model was solved under steady state conditions and unsteady conditions by assuming a time-varying inlet velocity profile to investigate the relative importance of axial forces and pressure drops in arteries with asymmetric stenosis. Flow-structure interactions were investigated for the same geometry and the results were compared with those retrieved with the corresponding 2D cross-section structural models. The Navier-Stokes equations were used as the governing equations for the fluid. The tube wall was assumed hyperelastic, homogeneous, isotropic and incompressible. The analysis showed that the three dimensional behavior of velocity, pressure and wall shear stress is in general very different from that predicted by cross-section models. Pressure drop across the stenosis was found to be much higher than shear stress. Therefore, pressure may be the more important mechanical trigger for plaque rupture other than shear stress, although shear stress is closely related to plaque formation and progression.