Advanced Analysis Techniques for Intra-cardiac Flow Evaluation from 4D Flow MRI

Time-resolved 3D velocity-encoded MR imaging with velocity encoding in three directions (4D Flow) has emerged as a novel MR acquisition technique providing detailed information on flow in the cardiovascular system. In contrast to other clinically available imaging techniques such as echo-Doppler, 4D Flow MRI provides the 3D Flow velocity field within a volumetric region of interest over the cardiac cycle. This work reviews the most recent advances in the development and application of dedicated image analysis techniques for the assessment of intra-cardiac flow features from 4D Flow MRI.Novel image analysis techniques have been developed for extraction of relevant intra-cardiac flow features from 4D Flow MRI, which have been successfully applied in various patient cohorts and volunteer studies. Disturbed flow patterns have been linked with valvular abnormalities and ventricular dysfunction. Recent technical advances have resulted in reduced scan times and improvements in image quality, increasing the potential clinical applicability of 4D Flow MRI.4D Flow MRI provides unique capabilities for 3D visualization and quantification of intra-cardiac blood flow. Contemporary knowledge on 4D Flow MRI shows promise for further exploration of the potential use of the technique in research and clinical applications

Deletion of L-Selectin Increases Atherosclerosis Development in ApoE−/− Mice

Atherosclerosis is an inflammatory disease characterized by accumulation of leukocytes in the arterial intima. Members of the selectin family of adhesion molecules are important mediators of leukocyte extravasation. However, it is unclear whether L-selectin (L-sel) is involved in the pathogenesis of atherosclerosis. In the present study, mice deficient in L-selectin (L-sel−/−) animals were crossed with mice lacking Apolipoprotein E (ApoE−/−). The development of atherosclerosis was analyzed in double-knockout ApoE/L-sel (ApoE−/− L-sel−/−) mice and the corresponding ApoE−/− controls fed either a normal or a high cholesterol diet (HCD). After 6 weeks of HCD, aortic lesions were increased two-fold in ApoE−/− L-sel−/− mice as compared to ApoE−/− controls (2.46%±0.54% vs 1.28%±0.24% of total aortic area; p<0.05). Formation of atherosclerotic lesions was also enhanced in 6-month-old ApoE−/− L-sel−/− animals fed a normal diet (10.45%±2.58% vs 1.87%±0.37%; p<0.05). In contrast, after 12 weeks of HCD, there was no difference in atheroma formation between ApoE−/− L-sel−/− and ApoE−/− mice. Serum cholesterol levels remained unchanged by L-sel deletion. Atherosclerotic plaques did not exhibit any differences in cellular composition assessed by immunohistochemistry for CD68, CD3, CD4, and CD8 in ApoE−/− L-sel−/− as compared to ApoE−/− mice. Leukocyte rolling on lesions in the aorta was similar in ApoE−/− L-sel−/− and ApoE−/− animals. ApoE−/− L-sel−/− mice exhibited reduced size and cellularity of peripheral lymph nodes, increased size of spleen, and increased number of peripheral lymphocytes as compared to ApoE−/− controls. These data indicate that L-sel does not promote atherosclerotic lesion formation and suggest that it rather protects from early atherosclerosis

The role of childhood social position in adult type 2 diabetes: Evidence from the English Longitudinal Study of Ageing

Copyright @ 2014 Pikhartova et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.This article has been made available through the Brunel Open Access Publishing Fund.Background: Socioeconomic circumstances in childhood and early adulthood may influence the later onset of chronic disease, although such research is limited for type 2 diabetes and its risk factors at the different stages of life. The main aim of the present study is to examine the role of childhood social position and later inflammatory markers and health behaviours in developing type 2 diabetes at older ages using a pathway analytic approach. Methods. Data on childhood and adult life circumstances of 2,994 men and 4,021 women from English Longitudinal Study of Ageing (ELSA) were used to evaluate their association with diabetes at age 50 years and more. The cases of diabetes were based on having increased blood levels of glycated haemoglobin and/or self-reported medication for diabetes and/or being diagnosed with type 2 diabetes. Father's job when ELSA participants were aged 14 years was used as the measure of childhood social position. Current social characteristics, health behaviours and inflammatory biomarkers were used as potential mediators in the statistical analysis to assess direct and indirect effects of childhood circumstances on diabetes in later life. Results: 12.6 per cent of participants were classified as having diabetes. A disadvantaged social position in childhood, as measured by father's manual occupation, was associated at conventional levels of statistical significance with an increased risk of type 2 diabetes in adulthood, both directly and indirectly through inflammation, adulthood social position and a risk score constructed from adult health behaviours including tobacco smoking and limited physical activity. The direct effect of childhood social position was reduced by mediation analysis (standardised coefficient decreased from 0.089 to 0.043) but remained statistically significant (p = 0.035). All three indirect pathways made a statistically significantly contribution to the overall effect of childhood social position on adulthood type 2 diabetes. Conclusions: Childhood social position influences adult diabetes directly and indirectly through inflammatory markers, adulthood social position and adult health behaviours. © 2014Pikhartova et al.; licensee BioMed Central Ltd.Economic and Social Research Council-funded International Centre for Life Course Studies in Society and Health (RES-596-28-0001)

Endothelial Cells Obtained from Patients Affected by Chronic Venous Disease Exhibit a Pro-Inflammatory Phenotype

The inflammatory properties of vein endothelium in relation to chronic venous disease (CVD) have been poorly investigated. Therefore, new insights on the characteristics of large vein endothelium would increase our knowledge of large vessel physiopathology. METHODOLOGY/PRINCIPAL FINDINGS: Surgical specimens of veins were obtained from the tertiary venous network (R3) and/or saphenous vein (SF) of patients affected by CVD and from control individuals. Highly purified venous endothelial cell (VEC) cultures obtained from CVD patients were characterized for morphological, phenotypic and functional properties compared to control VEC. An increase of CD31/PECAM-1, CD146 and ICAM-1 surface levels was documented at flow cytometry in pathological VEC with respect to normal controls. Of note, the strongest expression of these pro-inflammatory markers was observed in VEC obtained from patients with more advanced disease. Similarly, spontaneous cell proliferation and resistance to starvation was higher in pathological than in normal VEC, while the migratory response of VEC showed an opposite trend, being significantly lower in VEC obtained from pathological specimens. In addition, in keeping with a higher baseline transcriptional activity of NF-kB, the release of the pro-inflammatory cytokines osteoprotegerin (OPG) and vascular endothelial growth factor (VEGF) was higher in pathological VEC cultures with respect to control VEC. Interestingly, there was a systemic correlation to these in vitro data, as demonstrated by higher serum OPG and VEGF levels in CVD patients with respect to normal healthy controls. CONCLUSION/SIGNIFICANCE: Taken together, these data indicate that large vein endothelial cells obtained from CVD patients exhibit a pro-inflammatory phenotype, which might significantly contribute to systemic inflammation in CVD patients

Consequences of the size structure of fish populations for their effects on a generalist avian predator

Size-structured interspecific interactions can shift between predation and competition, depending on ontogenetic changes in size relationships. I examined the effects of common carp (Cyprinus carpio), an omnivorous fish, on the reproductive success of the red-necked grebe (Podiceps grisegena), an avian gape-limited predator, along a fish size gradient created by stocking distinct age-cohorts in seminatural ponds. Young-of-the-year (0+) carp were an essential food source for young grebes. Only adult birds were able to consume 1-year-old (1+) fish, while 2-year-old (2+) fish attained a size refuge from grebes. Amphibian larvae were the principal alternative prey to fish, followed by macroinvertebrates, but the abundance of both dramatically decreased along the carp size gradient. Fledging success was 2.8 times greater in ponds with 0+ versus 1+ carp; in ponds with 1+ carp, chicks received on average 2.6–3 times less prey biomass from their parents, and over 1/3 of broods suffered total failure. Breeding birds avoided settling on 2+ ponds. These results show that changes in prey fish size structure can account for shifts from positive trophic effects on the avian predator to a negative impact on the predator’s alternative resources. However, competition did not fully explain the decrease in grebe food resources in the presence of large fish, as carp and grebes overlapped little in diet. In experimental cages, 1+ carp totally eliminated young larvae of amphibians palatable to fish. In field conditions, breeding adults of palatable taxa avoided ponds with 1+ and older carp. Non-trophic interactions such as habitat selection by amphibians or macroinvertebrates to avoid large fish may provide an indirect mechanism strengthening the adverse bottom-up effects of fish on birds

Eight common genetic variants associated with serum dheas levels suggest a key role in ageing mechanisms

Dehydroepiandrosterone sulphate (DHEAS) is the most abundant circulating steroid secreted by adrenal glands-yet its function is unknown. Its serum concentration declines significantly with increasing age, which has led to speculation that a relative DHEAS deficiency may contribute to the development of common age-related diseases or diminished longevity. We conducted a meta-analysis of genome-wide association data with 14,846 individuals and identified eight independent common SNPs associated with serum DHEAS concentrations. Genes at or near the identified loci include ZKSCAN5 (rs11761528; p = 3.15×10-36), SULT2A1 (rs2637125; p = 2.61×10-19), ARPC1A (rs740160; p = 1.56×10-16), TRIM4 (rs17277546; p = 4.50×10-11), BMF (rs7181230; p = 5.44×10-11), HHEX (rs2497306; p = 4.64×10-9), BCL2L11 (rs6738028; p = 1.72×10-8), and CYP2C9 (rs2185570; p = 2.29×10-8). These genes are associated with type 2 diabetes, lymphoma, actin filament assembly, drug and xenobiotic metabolism, and zinc finger proteins. Several SNPs were associated with changes in gene expression levels, and the related genes are connected to biological pathways linking DHEAS with ageing. This study provides much needed insight into the function of DHEAS

Bioavailability in soils

The consumption of locally-produced vegetables by humans may be an important exposure pathway for soil contaminants in many urban settings and for agricultural land use. Hence, prediction of metal and metalloid uptake by vegetables from contaminated soils is an important part of the Human Health Risk Assessment procedure. The behaviour of metals (cadmium, chromium, cobalt, copper, mercury, molybdenum, nickel, lead and zinc) and metalloids (arsenic, boron and selenium) in contaminated soils depends to a large extent on the intrinsic charge, valence and speciation of the contaminant ion, and soil properties such as pH, redox status and contents of clay and/or organic matter. However, chemistry and behaviour of the contaminant in soil alone cannot predict soil-to-plant transfer. Root uptake, root selectivity, ion interactions, rhizosphere processes, leaf uptake from the atmosphere, and plant partitioning are important processes that ultimately govern the accumulation ofmetals and metalloids in edible vegetable tissues. Mechanistic models to accurately describe all these processes have not yet been developed, let alone validated under field conditions. Hence, to estimate risks by vegetable consumption, empirical models have been used to correlate concentrations of metals and metalloids in contaminated soils, soil physico-chemical characteristics, and concentrations of elements in vegetable tissues. These models should only be used within the bounds of their calibration, and often need to be re-calibrated or validated using local soil and environmental conditions on a regional or site-specific basis.Mike J. McLaughlin, Erik Smolders, Fien Degryse, and Rene Rietr

A Novel Biochemical Route for Fuels and Chemicals Production from Cellulosic Biomass

The conventional biochemical platform featuring enzymatic hydrolysis involves five key steps: pretreatment, cellulase production, enzymatic hydrolysis, fermentation, and product recovery. Sugars are produced as reactive intermediates for subsequent fermentation to fuels and chemicals. Herein, an alternative biochemical route is proposed. Pretreatment, enzymatic hydrolysis and cellulase production is consolidated into one single step, referred to as consolidated aerobic processing, and sugar aldonates are produced as the reactive intermediates for biofuels production by fermentation. In this study, we demonstrate the viability of consolidation of the enzymatic hydrolysis and cellulase production steps in the new route using Neurospora crassa as the model microorganism and the conversion of cellulose to ethanol as the model system. We intended to prove the two hypotheses: 1) cellulose can be directed to produce cellobionate by reducing β-glucosidase production and by enhancing cellobiose dehydrogenase production; and 2) both of the two hydrolysis products of cellobionate—glucose and gluconate—can be used as carbon sources for ethanol and other chemical production. Our results showed that knocking out multiple copies of β-glucosidase genes led to cellobionate production from cellulose, without jeopardizing the cellulose hydrolysis rate. Simulating cellobiose dehydrogenase over-expression by addition of exogenous cellobiose dehydrogenase led to more cellobionate production. Both of the two hydrolysis products of cellobionate: glucose and gluconate can be used by Escherichia coli KO 11 for efficient ethanol production. They were utilized simultaneously in glucose and gluconate co-fermentation. Gluconate was used even faster than glucose. The results support the viability of the two hypotheses that lay the foundation for the proposed new route

The relationship of the factor V Leiden mutation or the deletion-deletion polymorphism of the angiotensin converting enzyme to postoperative thromboembolic events following total joint arthroplasty

BACKGROUND: Although all patients undergoing total joint arthroplasty are subjected to similar risk factors that predispose to thromboembolism, only a subset of patients develop this complication. The objective of this study was to determine whether a specific genetic profile is associated with a higher risk of developing a postoperative thromboembolic complication. Specifically, we examined if the Factor V Leiden (FVL) mutation or the deletion polymorphism of the angiotensin-converting enzyme (ACE) gene increased a patient's risk for postoperative thromboembolic events. The FVL mutation has been associated with an increased risk of idiopathic thromboembolism and the deletion polymorphism of the ACE gene has been associated with increased vascular tone, attenuated fibrinolysis and increased platelet aggregation. METHODS: The presence of these genetic profiles was determined for 38 patients who had a postoperative symptomatic pulmonary embolus or proximal deep venous thrombosis and 241 control patients without thrombosis using molecular biological techniques. RESULTS: The Factor V Leiden mutation was present in none of the 38 experimental patients and in 3% or 8 of the 241 controls (p = 0.26). Similarly there was no difference detected in the distribution of polymorphisms for the ACE gene with the deletion-deletion genotype present in 36% or 13 of the 38 experimental patients and in 31% or 74 of the 241 controls (p = 0.32). CONCLUSIONS: Our results suggest that neither of these potentially hypercoaguable states are associated with an increased risk of symptomatic thromboembolic events following total hip or knee arthroplasty in patients receiving pharmacological thromboprophylaxis

The impact of a minimal smoking cessation intervention for pregnant women and their partners on perinatal smoking behaviour in primary health care: A real-life controlled study

<p>Abstract</p> <p>Background</p> <p>There is a demand for strategies to promote smoking cessation in high-risk populations like smoking pregnant women and their partners. The objectives of this study were to investigate parental smoking behaviour during pregnancy after introduction of a prenatal, structured, multi-disciplinary smoking cessation programme in primary care, and to compare smoking behaviour among pregnant women in the city of Trondheim with Bergen and Norway.</p> <p>Methods</p> <p>Sequential birth cohorts were established to evaluate the intervention programme from September 2000 to December 2004 in primary care as a part of the Prevention of Allergy among Children in Trondheim study (PACT). The primary outcome variables were self reported smoking behaviour at inclusion and six weeks postnatal. Data from the Medical Birth Registry of Norway (MBR) were used to describe smoking cessation during pregnancy in Trondheim, Bergen and Norway 1999–2004.</p> <p>Results</p> <p>Maternal smoking prevalence at inclusion during pregnancy were 5% (CI 95% 4–6) in the intervention cohort compared to 7% (CI 95% 6–9), p = 0.03, in the control cohort. Of the pre-pregnancy maternal smokers 25% (CI 95% 20–31) and 32% (CI 95% 26–38), p = 0.17, were still smoking at inclusion in the intervention and control cohorts, respectively. Six weeks postnatal 72% (CI 95% 59–83) and 68% (CI 95% 57–77), p = 0.34 of the maternal smokers at inclusion still smoked. No significant difference in paternal smoking between the cohorts was found after the intervention period. Data from the MBR showed a significantly higher proportion of women who stopped smoking during pregnancy in Trondheim than in Bergen in 2003 and 2004, p = 0.03 and < 0.001, respectively.</p> <p>Conclusion</p> <p>No impact on parental smoking behaviour between the cohorts was observed after the smoking intervention programme. Of the women who stopped smoking during pregnancy most of them stopped smoking before the intervention. However, we observed a significantly higher quitting rate in Trondheim than in Bergen in 2003 and 2004 which may have been facilitated by the supplemental attention on smoking behaviour the PACT study initiated.</p