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

Utilization and biodegradation of starch stillage (distillery wastewater)

Stillage (distillery wastewater) is the main by-product originating in distilleries, and its volume is approximately 10 times that of ethanol produced. It is not surprising that the utilization of the stillage raises serious problems, and that many attempts have been made all over the world to solve them. In Poland most of the ethanol (about 90%) is produced from starch-based feedstocks, i.e. grains and potatoes. Starch feedstocks are widely used for spirit production also in other European countries, as well as outside Europe. The manuscript provides an overview of global fuel ethanol production and information on methods used for starch-based stillage biodegradation and utilization. The methods presented in this paper have been classified into two major groups. One of these includes the mode of utilizing starch stillage, the other one comprises methods, both aerobic and anaerobic, by which the stillage can be biodegraded

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

CHARITY: Chagas cardiomyopathy bisoprolol intervention study: a randomized double-blind placebo force-titration controlled study with Bisoprolol in patients with chronic heart failure secondary to Chagas cardiomyopathy [NCT00323973]

BACKGROUND: Chagas' disease is the major cause of disability secondary to tropical diseases in young adults from Latin America, and around 20 million people are currently infected by T. cruzi. Heart failure due to Chagas cardiomyopathy is the main clinical presenation in Colombia. Heart failure due to Chagas' disease may respond to digoxin, diuretics and vasodilator therapy. Beta-adrenoreceptor antagonism seems to protect against the increased risk of cardiac arrhythmia and sudden death due to chronic sympathetic stimulation. The aim of this study is to evaluate the effects of the selective beta-adrenergic receptor blocker Bisoprolol on cardiovascular mortality, hospital readmission due to progressive heart failure and functional status in patients with heart failure secondary to Chagas' cardiomyopathy. METHODS/DESIGN: A cohort of 500 T. cruzi seropositive patients (250 per arm) will be selected from several institutions in Colombia. During the pretreatment period an initial evaluation visit will be scheduled in which participants will sign consent forms and baseline measurements and tests will be conducted including blood pressure measurements, twelve-lead ECG and left ventricular ejection fraction assessment by 2D echocardiography. Quality of life questionnaire will be performed two weeks apart during baseline examination using the "Minnesota living with heart failure" questionnaire. A minimum of two 6 minutes corridor walk test once a week over a two-week period will be performed to measure functional class. During the treatment period patients will be randomly assigned to receive Bisoprolol or placebo, initially taking a total daily dose of 2.5 mgrs qd. The dose will be increased every two weeks to 5, 7.5 and 10 mgrs qd (maximum maintenance dose). Follow-up assessment will include clinical check-up, and blood collection for future measurements of inflammatory reactants and markers. Quality of life measurements will be obtained at six months. This study will allow us to explore the effect of beta-blockers in chagas' cardiomyopathy

The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of pathway/genome databases

The MetaCyc database (http://metacyc.org/) provides a comprehensive and freely accessible resource for metabolic pathways and enzymes from all domains of life. The pathways in MetaCyc are experimentally determined, small-molecule metabolic pathways and are curated from the primary scientific literature. MetaCyc contains more than 1800 pathways derived from more than 30 000 publications, and is the largest curated collection of metabolic pathways currently available. Most reactions in MetaCyc pathways are linked to one or more well-characterized enzymes, and both pathways and enzymes are annotated with reviews, evidence codes and literature citations. BioCyc (http://biocyc.org/) is a collection of more than 1700 organism-specific Pathway/Genome Databases (PGDBs). Each BioCyc PGDB contains the full genome and predicted metabolic network of one organism. The network, which is predicted by the Pathway Tools software using MetaCyc as a reference database, consists of metabolites, enzymes, reactions and metabolic pathways. BioCyc PGDBs contain additional features, including predicted operons, transport systems and pathway-hole fillers. The BioCyc website and Pathway Tools software offer many tools for querying and analysis of PGDBs, including Omics Viewers and comparative analysis. New developments include a zoomable web interface for diagrams; flux-balance analysis model generation from PGDBs; web services; and a new tool called Web Groups

Novel selective β1-adrenoceptor antagonists for concomitant cardiovascular and respiratory disease

β-Blockers reduce mortality and improve symptoms in people with heart disease. However, current clinically available β-blockers have poor selectivity for the cardiac β1-adrenoceptor (AR) over the lung β2-AR. Unwanted β2-blockade risks causing life-threatening bronchospasm and a reduction in the efficacy of β2-agonist emergency rescue therapy. Thus current life-prolonging β-blockers are contraindicated in people with both heart disease and asthma. Here we describe NDD-713 and NDD-825, novel highly β1-selective neutral antagonists with good pharmaceutical properties that can potentially overcome this limitation. Radioligand binding studies and functional assays using human receptors expressed in CHO cells demonstrate that NDD-713 and NDD-825 have nanomolar β1-AR affinity, greater than 500-fold β1-AR vs β2-AR selectivity and no agonism. Studies in conscious rats demonstrated that they are orally bioavailable and cause pronounced β1-mediated reduction of heart rate while showing no effect on β2-mediated hindquarters vasodilatation. The compounds also have good disposition properties and show no adverse toxicological effects. They potentially offer a truly cardioselective β-blocker therapy for the large number of people with heart and respiratory, or peripheral vascular comorbidities

The PPCD1 Mouse: Characterization of a Mouse Model for Posterior Polymorphous Corneal Dystrophy and Identification of a Candidate Gene

The PPCD1 mouse, a spontaneous mutant that arose in our mouse colony, is characterized by an enlarged anterior chamber resulting from metaplasia of the corneal endothelium and blockage of the iridocorneal angle by epithelialized corneal endothelial cells. The presence of stratified multilayered corneal endothelial cells with abnormal patterns of cytokeratin expression are remarkably similar to those observed in human posterior polymorphous corneal dystrophy (PPCD) and the sporadic condition, iridocorneal endothelial syndrome. Affected eyes exhibit epithelialized corneal endothelial cells, with inappropriate cytokeratin expression and proliferation over the iridocorneal angle and posterior cornea. We have termed this the “mouse PPCD1” phenotype and mapped the mouse locus for this phenotype, designated “Ppcd1”, to a 6.1 Mbp interval on Chromosome 2, which is syntenic to the human Chromosome 20 PPCD1 interval. Inheritance of the mouse PPCD1 phenotype is autosomal dominant, with complete penetrance on the sensitive DBA/2J background and decreased penetrance on the C57BL/6J background. Comparative genome hybridization has identified a hemizygous 78 Kbp duplication in the mapped interval. The endpoints of the duplication are located in positions that disrupt the genes Csrp2bp and 6330439K17Rik and lead to duplication of the pseudogene LOC100043552. Quantitative reverse transcriptase-PCR indicates that expression levels of Csrp2bp and 6330439K17Rik are decreased in eyes of PPCD1 mice. Based on the observations of decreased gene expression levels, association with ZEB1-related pathways, and the report of corneal opacities in Csrp2bptm1a(KOMP)Wtsi heterozygotes and embryonic lethality in nulls, we postulate that duplication of the 78 Kbp segment leading to haploinsufficiency of Csrp2bp is responsible for the mouse PPCD1 phenotype. Similarly, CSRP2BP haploinsufficiency may lead to human PPCD

Clinical and surgical data of affected members of a classic CFEOM 1 family

BACKGROUND: Congenital fibiosis of the extraocular muscles (CFEOM1) refers to a group of congenital eye movement disorders that are characterized by non-progressive restrictive ophthalmoplegia. We present clinical and surgical data on affected members of a classic CFEOM1 family. METHODS: Ten members of a fifteen-member, three-generation Italian family affected by classic CFEOM participated in this study. Each affected family member underwent ophthalmologic (corrected visual acuity, pupillary function, anterior segment and fundus examination), orthoptic (cover test, cover-uncover test, prism alternate cover test), and preoperative examinations. Eight of the ten affected members had surgery and underwent postoperative examinations. Surgical procedures are listed. RESULTS: All affected members were born with varying degrees of bilateral ptosis and ophthalmoplegia with both eyes fixed in a hypotropic position (classic CFEOM). The affected members clinical data prior to surgery, surgery procedures and postoperative outcomes are presented. On 14 operated eyes to correct ptosis there was an improvement in 12 eyes. In addition, the head position improved in all patients. CONCLUSIONS: Surgery is effective at improving ptosis in the majority of patients with classic CFEOM. However, the surgical approach should be individualized to each patient, as inherited CFEOM exhibits variable expressivity and the clinical features may differ markedly between affected individuals, even within the same family

Rationale and study design of a cross sectional study documenting the prevalence of Heart Failure amongst the minority ethnic communities in the UK: the E-ECHOES Study (Ethnic - Echocardiographic Heart of England Screening Study)

Background: Heart failure is an important cause of cardiovascular morbidity and mortality. Studies to date have not established the prevalence heart failure amongst the minority ethnic community in the UK. The aim of the E-ECHOES (Ethnic - Echocardiographic Heart of England Screening Study) is to establish, for the first time, the community prevalence and severity of left ventricular systolic dysfunction (LVSD) and heart failure amongst the South Asian and Black African-Caribbean ethnic groups in the UK.Methods/Design: This is a community based cross-sectional population survey of a sample of South Asian (i.e. those originating from India, Pakistan, Bangladesh) and Black African-Caribbean male and female subjects aged 45 years and over. Data collection undertaken using a standardised protocol comprising a questionnaire incorporating targeted clinical history taking, physical examination, and investigations with resting electrocardiography and echocardiography; and blood sampling with consent. This is the largest study on heart failure amongst these ethnic groups. Full data collection started in September 2006 and will be completed by August 2009.Discussion: The E-ECHOES study will enable the planning and delivery of clinically and cost-effective treatment of this common and debilitating condition within these communities. In addition it will increase knowledge of the aetiology and management of heart failure within minority ethnic communities

Feasibility and validation of trans-valvular flow derived by four-dimensional flow cardiovascular magnetic resonance imaging in patients with atrial fibrillation

Background: Four-dimensional (4D) flow cardiovascular magnetic resonance imaging (MRI) is an emerging technique used for intra-cardiac blood flow assessment. The role of 4D flow cardiovascular MRI in the assessment of trans-valvular flow in patients with atrial fibrillation (AF) has not previously been assessed. The purpose of this study was to assess the feasibility, image quality, and internal validity of 4D flow cardiovascular MRI in the quantification of trans-valvular flow in patients with AF. Methods: Patients with AF and healthy controls in sinus rhythm underwent cardiovascular MRI, including 4D flow studies. Quality assurance checks were done on the raw data and streamlines. Consistency was investigated by trans-valvular flow assessment between the mitral valve (MV) and the aortic valve (AV). Results: Eight patients with AF (88% male, mean age 62±13 years, mean heart rate (HR) 83±16 beats per minute (bpm)) were included and compared with ten healthy controls (70% male, mean age 41±20 years, mean HR 68.5±9 bpm). All scans were of either good quality with minimal blurring artefacts, or excellent quality with no artefacts. No significant bias was observed between the AV and MV stroke volumes in either healthy controls (–4.8, 95% CI –15.64 to 6.04; P=0.34) or in patients with AF (1.64, 95% CI –4.7 to 7.94; P=0.56). A significant correlation was demonstrated between MV and AV stroke volumes in both healthy controls (r=0.87, 95% CI 0.52 to 0.97; P=0.001) and in AF patients (r=0.82, 95% CI 0.26 to 0.97; P=0.01). Conclusions: In patients with AF, 4D flow cardiovascular MRI is feasible with good image quality, allowing for quantification of trans-valvular flow