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Background Preserving dynamism and recreating the sinuses in the Dacron graft are thought to be important for optimizing results of aortic valve-conserving operations. Methods We describe a novel technique that preserves dynamism and recreates the sinotubular junction. In addition, it tailors 3 sinuses of defined longitudinal and transverse curvatures in a straight Dacron tube during the operation. The technique has been used in 6 patients with varied aortic root pathology. We performed preoperative and postoperative multimodality imaging using computerized image analysis as well as 3-dimensional models. Results There was no early or midterm death. Upon discharge, patients were clinically well, with echocardiographic evidence of minimal (3 patients) or mild (3 patients) aortic regurgitation. Computed tomography and cardiac magnetic resonance imaging with extensive image analysis of the aortic root size, shape, and function showed partial or complete normalization of these parameters. This included the shape and dynamism of the aortic annulus and the size and shape of the geometric (effective) orifice. The 4-dimensional magnetic resonance imaging pattern of flow in the sinuses and ascending aorta showed favorable vortices in the sinuses, right-handed helical flow, and marked diminution of energy loss in the ascending aorta. Conclusions The novel technique described here is simple, practical, and cost-effective because it uses a widely available straight Dacron tube. The technique does not use rigid internal or external support. The early results are encouraging. Larger series with longer follow-up are required.

MRI is an important problem-solving tool for accurate characterization of liver lesions. Chronic liver disease alters the typical imaging characteristics and complicates liver imaging. Awareness of imaging pitfalls and technical artifacts and ways to mitigate them allows for more accurate and timely diagnosis.

Purpose: To characterize the genetic architecture of left ventricular noncompaction (LVNC) and investigate the extent to which it may represent a distinct pathology or a secondary phenotype associated with other cardiac diseases. Methods: We performed rare variant association analysis with 840 LVNC cases and 125,748 gnomAD population controls, and compared results to similar analyses on dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). Results: We observed substantial genetic overlap indicating that LVNC often represents a phenotypic variation of DCM or HCM. In contrast, truncating variants in MYH7, ACTN2, and PRDM16 were uniquely associated with LVNC and may reflect a distinct LVNC etiology. In particular, MYH7 truncating variants (MYH7tv), generally considered nonpathogenic for cardiomyopathies, were 20-fold enriched in LVNC cases over controls. MYH7tv heterozygotes identified in the UK Biobank and healthy volunteer cohorts also displayed significantly greater noncompaction compared with matched controls. RYR2 exon deletions and HCN4 transmembrane variants were also enriched in LVNC, supporting prior reports of association with arrhythmogenic LVNC phenotypes. Conclusion: LVNC is characterized by substantial genetic overlap with DCM/HCM but is also associated with distinct noncompaction and arrhythmia etiologies. These results will enable enhanced application of LVNC genetic testing and help to distinguish pathological from physiological noncompaction.

Previous experimental studies have provided evidence of notable changes in thyroid hormone signaling that corresponds to alterations in myocardial function in animal models of heart failure (HF). The present study further explores whether oral thyroid hormone treatment can change left ventricular (LV) mechanics and functional status in patients with idiopathic dilated cardiomyopathy (IDCM) or not.Sixty IDCM patients who were receiving conventional HF treatment were randomized to oral L-thyroxine (n = 40) or placebo (n = 20) for 3 months. Fifty-two (86.7%) of all IDCM patients were symptomatic, their mean age was 41 ± 12 years, and their ejection fraction was 32% ± 7%. At baseline, the two groups were comparable in clinical and echocardiographic variables. Vector velocity imaging was utilized to assess LV mechanics. Myocardial longitudinal peak systolic strain, systolic strain rate, early and late diastolic strain rate, circumferential strain, LV dyssynchrony, plasma tri-iodothyronine, thyroxine, and thyroid stimulating hormone levels were measured at baseline and 3 months after treatment.All patients receiving L-thyroxine significantly improved in functional status (New York Heart Association class; P .001) and echocardiographic parameters including end-diastolic diameter (P .001), end-systolic diameter (P .001), mitral regurgitation severity reduction (P .001), and increased ejection fraction (P .001). Left ventricular mechanics showed marked improvement at segmental and global levels of both longitudinal and circumferential myocardial strain (P .005) when compared with placebo group.Short-term L-thyroxine therapy is well tolerated in IDCM patients. It improves cardiac mechanics and functional status, which might support the potential role of synthetic thyroid hormones in HF treatment.

Objective The neonatal arterial switch operation is currently the procedure of choice for patients with transposition of the great arteries. However, a large number of patients present too late for the arterial switch operation and are best managed with the atrial switch operation. Methods We have used the Mustard operation in its original form or following a new modification designed to enhance the atrial functions and filling of the left ventricle in an attempt to improve long-term results. Results Between July 2013 and November 2018, a total of 101 patients underwent the Mustard operation, 86 with the new modification. The median age at operation was 16 months (6 months to 27 years). A total of 75 patients (74.3%) were male. Median preoperative oxygen saturation was 71%. There were no early deaths and there were 3 late deaths during a median follow-up period of 24.2 months (all in patients with large ventricular septal defect and established pulmonary vascular disease). At the latest follow-up, all patients were in stable sinus rhythm. There were no baffle leaks. Seven patients had asymptomatic narrowing of the superior baffle, and 1 patient required balloon dilatation. Follow-up is 100% complete and includes computed tomography and magnetic resonance imaging at regular intervals (75 patients to date). Computerized analysis of representative subsets showed enhanced rate and pattern of filling of the left ventricle in the modified operation compared with the classic operation. Conclusions The use of the Mustard operation, particularly the modified technique should play an important role in treating late-presenting patients with transposition of the great arteries. Improving the pattern of filling of the left ventricle could enhance the long-term results of the Mustard operation.

Recent advancement was the use of laser radiation to photobiostimulate the methanogenic bacteria in order to increase the biogas and methane production from the anaerobic digestion (AD) of livestock manure. However, the environmental impact of using the laser radiation as anaerobic bacteria stimulator still not evaluated. The objective of this paper is to conduct a comparative environmental impact evaluation of manure treatment with different laser radiation times for biogas production. A life-cycle assessment (LCA) methodology was implemented for this purpose. The treatments under evaluation were 0.5 h, 1 h and 2 h of laser irradiation compared to 1 h incandescent lighting and the control (neither laser irradiation nor light was used). The highest biogas yield, methane content and overall Energy were achieved with 0.5 h laser irradiation and were 335251 m3, 63.1% and 2043353 kWh, respectively. The results were presented in the form of the specific impacts on global warming and greenhouse gas (GHG) emissions mitigation of producing and utilizing biogas as an energy source. It was concluded that the photobiostimulation of anaerobic bacteria using laser irradiation has no negative environmental impact compared to the control, where no irradiation was applied.

The aim of this work is to build a Computational fluid dynamics (CFD) model to study the flowability of fungal spores and pollen grains to predict their ability to flow to the deep lung in order to relate this to the potentiality of allergies, and predict the possibility of using spores/pollen grains-mimicking microparticles for pulmonary drug delivery. The CFD model was designed using COMSOL Multiphysics to calculate the drag forces exerted on the pollens and spores by the air in the upper and lower lung bronchioles. Experimental verification was conducted by comparing the aerosolization of Aspergillus spores and spherical microparticles, as a control shape, using Next Generation Impactor as a lung-simulation device. The CFD model showed that the drag force exerted on the spores and pollen grains can affect their pathogenicity. In addition, the shapes of some spores (e.g. Alternaria, Drechslera and Aspergillus) or pollens (e.g. Quercus and Eucalyptus) have low drag and can be used for drug delivery to the deep lung. The experimental results coincided with the CFD model and showed that the shape of Aspergillus spores can reach the deep lung with about 1.6-fold higher dose than the spherical shape. The obtained results indicate that shapes of some spores and pollen grains are drag-minimizing allowing them to spread and to be inhaled to the deep lung; so they can be used for the development of dry powder inhaler formulations.

Whether early vs. delayed referral to septal reduction therapies (SRT, alcohol septal ablation or surgical myectomy) bears prognostic relevance in hypertrophic obstructive cardiomyopathy (HOCM) is unresolved. We analyzed the impact of SRT timing on the outcome of HOCM patients.We followed 126 patients for 5 ± 4 years after SRT (mean age 53 ± 15 years; 55 post-ASA and 71 post-SM). Based on time-to-treatment (TTT; from HOCM diagnosis to SRT), patients were divided into three groups: "3" years, N = 50; "3-5" years, N = 25; "5" years, N = 51.Patients with TTT 5 years were younger at diagnosis and more often had atrial fibrillation (AF). Left ventricular outflow tract (LVOT) gradients were comparable in the 3 TTT groups. Two patients died peri-operatively, all with TTT 5. Long-term, 8 patients died (3 suddenly and 5 due to heart failure). Mortality increased progressively with TTT (2% vs. 4% vs. 12% for TTT "3", "3-5", and "5" years, p for trend = 0.039). Independent predictors of disease progression (new-onset AF, worsening to NYHA III/IV symptoms, re-intervention or death) were TTT ("3-5" vs. "3" years: HR: 4.988, 95%CI: 1.394-17.843; "5" vs. "3" years: HR: 3.420, 95%CI: 1.258-9.293, overall p-value = 0.025), AF at baseline (HR: 1.896, 95%CI: 1.002-3.589, p = 0.036) and LVOT gradient (HR per mm Hg increase: 1.022, 95%CI: 1.007-1.024, p = 0.023).Delay in SRT referral has significant impact on long-term outcome of patients with HOCM, particularly when5 years from first detection of gradient, even when successful relief of symptoms and gradient is achieved. Earlier interventions are associated with lower complication rates and better prognosis, suggesting the importance of timely SRT to maximize treatment benefit and prevent late HOCM-related complications.

The ideal aortic valve substitute for young and middle-aged adults remains elusive. The Ross procedure (pulmonary autograft replacement) is the only operation that allows replacement of the diseased aortic valve with a living substitute. However, use of this procedure has declined significantly due to concerns over increased surgical risk and potential long-term failure of the operation. Several recent publications from expert centers have shown that in the current era, the Ross procedure can be performed safely and reproducibly in appropriately selected patients. Furthermore, an increasing body of evidence suggests that the Ross procedure is associated with better long-term outcomes compared with conventional aortic valve replacement in young and middle-aged adults. In this paper, the authors review the indications and technical considerations of the Ross procedure, describe its advantages and drawbacks, and discuss patient selection criteria. Finally, the authors provide a comprehensive synthesis of the current Ross published reports to enable cardiologists and surgeons to make appropriate decisions for their patients with aortic valve disease.

Background The calcific aortic valve disease (CAVD) is a common heart pathology that involves inflammation, fibrosis, and calcification of aortic valve leaflets. All these processes could be affected by changes in the extracellular purinergic signaling that depend on the activity of ectonucleotidases, mainly ectonucleoside triphosphate diphosphohydrolase 1 (CD39, eNTPD1) and ecto-5’nucleotidase (CD73, e5NT). Objective and methods We investigated the localization of CD39 and CD73 proteins in human noncalcified and calcified aortic valves using immunohistochemistry together with analysis of NTPDases and e5NT activities in aortic valve homogenates by analysis of substrate into product conversion by high-performance liquid chromatography. We also measured the rates of extracellular nucleotide catabolism on the surface of isolated cultured aortic valve endothelial (hAVECs) and interstitial cells (hAVICs) as well as characterized cellular CD39 and CD73 distribution. Results In noncalcified valves, CD39 and CD73 were expressed in both endothelial and interstitial cells, while in calcified valves, the expressions of CD39 and CD73 were significantly down-regulated with the exception of calcified regions where the expression of CD73 was maintained. This correlated with activities in valve homogenates. NTPDase was reduced by 35% and e5NT activity by 50% in calcified vs. noncalcified valve. CD39 and CD73 were present mainly in the cell membrane of hAVECs, but in hAVICs, these proteins were also present intracellularly. The rates of extracellular adenosine triphosphate and adenosine monophosphate hydrolysis in isolated hAVECs and hAVICs were comparable. Conclusion The presence of ectonucleotidases in valves and especially in aortic valve interstitial cells highlights important local role of purinergic signaling and metabolism. Changes in the local expression and hence the activity of CD39 and CD73 in calcified valves suggest their potential role in CAVD.

McNeal first described the zonal anatomy of the prostate about 40 years ago, outlining 4 zones of the prostate and defining their relation to the urethra and the ejaculatory ducts. The zonal anatomy remains the accepted model for describing the prostate and the zones are well-depicted on MR imaging, including the central zone, which until recently was grouped with the transition zone in the radiology literature. An accurate understanding of the zonal anatomy and periprostatic anatomy is key for accurate interpretation of the prostate MR imaging.

Aortic valve diseases are among the most common cardiovascular defects. Since a non-functioning valve results in disturbed blood flow conditions, the diagnosis of such defects is based on identification of stenosis via echocardiography. Calculation of disease parameters such as valve orifice area or transvalvular pressure gradient using echocardiography is associated with substantial errors. Computational fluid dynamics (CFD) modeling has emerged as an alternative approach for accurate assessment of aortic valve hemodynamics. Fluid-structure interaction (FSI) modeling is adapted in these models to account for counter-interacting forces of flowing blood and deforming leaflets for most accurate results. However, implementation of this approach is difficult using custom built codes and algorithms. In this paper, we present an FSI modeling methodology for aortic valve hemodynamics using a commercial modeling software, ANSYS. We simulated the problem using fluid flow solver FLUENT and structural solver MECHANICAL APDL under ANSYS and coupled the solutions using System Coupling Module to enable FSI. This approach minimized adaptation problems that would raise if separate solvers were used. As an example case, we investigated influence of leaflet calcification on hemodynamic stresses and flow patterns. Model geometries were generated using b-mode echocardiography images of an aortic valve. A Doppler velocity measurement was used as velocity inlet boundary condition in the models. Simulation results were validated by comparing leaflet movements in the simulations with b-mode echo recordings. Wall shear stress levels, pressure levels and flow patterns agree well with previous studies demonstrating the accuracy of our results. Our modeling methodology can be easily adopted by researchers that are familiar with ANSYS and other similar CFD software to investigate similar biomedical problems. This research was supported by a Marie Curie International Reintegration Grant within the Seventh European Community Framework Programme (IRG276987 to HCY) and by The Scientific and Technological Research Council of Turkey, Tubitak (112M148 to HCY and 112M895 to HCY).

Introduction La lymphangite carcinomateuse (LC) est une forme de diffusion de certains cancers notamment les carcinomes. Elle est caracterisee par une embolisation des cellules tumorales dans les vaisseaux lymphatiques. La LC pulmonaire est la forme la plus frequente et la plus connue. Les localisations digestives sont exceptionnelles. Nous rapportons trois cas de LC digestive : 2 coliques et une duodenale. Patients et methodes Nous rapportons trois cas de LC digestive. Le diagnostic a ete retenu sur les donnees de l’histologie sur biopsies per-endoscopiques ou sur pieces de resection chirurgicales. Resultats Observation 1 : il s’agissait d’une patiente âgee de 42 ans, sans antecedents pathologiques, exploree pour douleurs hypogastriques evoluant depuis trois jours associees a une constipation et des rectorragies. L’examen physique etait sans anomalies. A la biologie, il existait une anemie ferriprive a 9 g/dL et un syndrome inflammatoire biologique (vitesse de sedimentation a 70 mm et une C-reactive proteine [CRP] a 45 mg/L). Le taux de l’antigene carcinoembryonnaire (ACE) etait normal. La coloscopie a objective un epaississement sous muqueux circonferentiel, non ulcere, congestif et granuleux situe a 20 cm de la marge anale. Elle retrouvait par ailleurs, a 30 cm de la marge anale, une large lesion ulceree et stenosante. L’etude anatomopathologique des biopsies effectuees au niveau de la premiere lesion montrait des vaisseaux lymphatiques dilates renfermant des cellules neoplasiques agregees : aspect compatible avec une LC colique. L’etude anatomopathologique des biopsies realisees au niveau de la deuxieme lesion concluait a un adenocarcinome colique. Le scanner thoraco-abdomino-pelvien a montre une tumeur localement avancee avec une carcinose peritoneale. L’evolution etait fatale malgre un traitement par chimiotherapie. Observation 2 : il s’agissait d’une patiente âgee de 65 ans, non taree, presentant des epigastralgies et des douleurs de l’hypochondre droit sans autres signes associes. L’examen physique montrait une sensibilite au niveau de l’hypochondre droit. L’ACE etait eleve a 271 ng/mL et le reste du bilan biologique etait normal. L’endoscopie digestive haute objectivait un epaississement des plis de Kreckening bulbaires dont la surface prenait un aspect ponctue, granuleux et rougeâtre. La muqueuse gastrique etait d’aspect normal. L’etude anatomopathologique des biopsies realisees au niveau de la lesion montrait une muqueuse duodenale d’aspect normal avec presence dans la partie haute de la lamina propria de vaisseaux lymphatiques dilates renfermant des cellules neoplasiques agregees. Le diagnostic de LC duodenale a ete retenu. Un bilan etiologique exhaustif a la recherche d’une tumeur primitive avait conclu a un adenocarcinome de l’endometre metastase au niveau du foie associe a une LC duodenale. Une chimiotherapie neo-adjuvante a ete indiquee mais la patiente est decedee avant meme d’entamer la chimiotherapie. Observation 3 : il s’agissait d’un patient âge de 70 ans sans antecedents pathologiques qui a consulte pour une constipation chronique, des rectorragies intermittentes et un syndrome anemique fonctionnel. Le bilan biologique a revele une anemie ferriprive a 5 g/dL. Le taux de l’ACE etait normal. L’exploration endoscopique a revele a partir de 15 cm de la marge anale un epaississement congestif non ulcere des plis coliques etendu sur 25 cm. Les biopsies ont conclu a une LC colique. L’evolution etait marquee par la survenue d’un syndrome occlusif ayant necessite une intervention chirurgicale en urgence. Le patient a eu une resection segmentaire basse et une double stomie. Les constatations peroperatoires ont permis de localiser la tumeur primitive au niveau du colon sigmoide. Le bilan d’extension a distance a montre des lesions hepatiques secondaires et des nodules de carcinose. Une chimiotherapie palliative a ete indiquee et le patient est encore en vie. Conclusion Le diagnostic d’une LC digestive est a evoquer devant l’aspect endoscopique mais reste a confirmer par l’etude anatomopathologique. Le pronostic est tres pejoratif malgre les therapeutiques adaptees.

Purpose To evaluate the dosimetric benefits of MRI-based brachytherapy in small and large high-risk clinical target volume (HR-CTV) in cervical cancer. Methods and Materials Twenty-eight fractions obtained from sixteen cervical cancer patients treated with MRI-based high-dose-rate brachytherapy with standard tandem and ovoid applicators were used; original fractions were optimized to HR-CTV D90. Fractions were separated based on the median volume into small and large (HR-CTV 25 cm3) lesion groups. Retrospective plans prescribed to Point A were created for each fraction. D0.1 cc, D2 cc, and International Commission of Radiation Unit and Measurements (ICRU) points were used to compare Point A vs. HR-CTV D90 plans for bladder, rectum, and sigmoid. Results In the small lesion group, Point A plans vs. HR-CTV D90 plans had significantly higher D0.1 cc, D2 cc, and ICRU points for bladder, rectum, and sigmoid (p < 0.05). In the large lesion group, there was no significant difference between Point A and HR-CTV D90 plans for D0.1 cc, D2 cc, and ICRU points to the organs at risk (OARs). Conclusions The dosimetric advantages to OARs offered by MRI-based brachytherapy with prescription to HR-CTV D90 compared to Point A is most distinct for patients with smaller HR-CTV ( 25 cm3. Incorporation of interstitial needles for patients with larger HR-CTV is likely the best method to decrease dose to OARs and improve tumor coverage.

Acute rheumatic fever and rheumatic heart disease remain major global health problems. Although strategies for primary and secondary prevention are well established, their worldwide implementation is suboptimum. In patients with advanced valvular heart disease, mechanical approaches (both percutaneous and surgical) are well described and can, for selected patients, greatly improve outcomes; however, access to centres with experienced staff is very restricted in regions that have the highest prevalence of disease. Development of diagnostic strategies that can be locally and regionally provided and improve access to expert centres for more advanced disease are urgent and, as yet, unmet clinical needs. We outline current management strategies for valvular rheumatic heart disease on the basis of either strong evidence or expert consensus, and highlight areas needing future research and development.

Thoracic aortic aneurysms remain an important cause of death in the general population. The key to improving patient prognosis with thoracic aortic dilatation lies in early identification and tailored management strategies. Advances in the understanding of the molecular mechanisms of aneurysm formation, the natural history of disease, and clinical risk factors have led to significant improvements in patient management and overall outcomes. In the past decade, identification of the genetic basis of disease, together with wider availability of molecular testing, ushered in a new era for a tailored approach to the management of patients with thoracic aortic aneurysms. In this viewpoint, we explore these various iterative steps and future challenges.

Introduction La majorite des patients suivis pour maladie inflammatoire chronique de l’intestin (MICI) sont traites par des immunosuppresseurs (azathioprine notamment) et des immunomodulateurs (anti-tumornecrosis factor [anti-TNF] alpha). Ces therapeutiques ne sont pas denuees de risques et exposent a un risque d’infections opportunistes et de reactivation tuberculeuse. Le but de ce travail etait d’etudier les complications infectieuses des anti-TNF alpha chez les patients suivis pour MICI. Patients et methodes Nous avons effectue une etude retrospective descriptive sur une periode de 5 ans, incluant 39 patients consecutifs, suivis pour une MICI a type de maladie de Crohn (MC) ou de rectocolite hemorragique (RCH) et traites par anti-TNF alpha. Les donnees cliniques, biologiques et endoscopiques ainsi que le bilan pre-therapeutique, notamment le depistage de la tuberculose (TBC) ont ete colligees. Les differentes complications infectieuses et les modalites de leur prise en charge ont ete consignees. Le diagnostic de la TBC etait retenu sur des criteres radiologiques et histologiques et/ou bacteriologiques. Le diagnostic des autres infections bacteriennes ou virales etait base sur des criteres specifiques. Resultats Trente-neuf patients ayant une MICI sous anti-TNF alpha ont ete colliges, d’âge moyen egal a 32,3 ans [16–58] avec un sex-ratio (H/F) de 1,43. Trente-quatre avaient une MC (87,2 %) et cinq avaient une RCH (12,8 %). Les principales indications des anti-TNF alpha etaient : la presence de fistules anoperineales complexes (n = 20), l’echec de l’azathioprine en monotherapie (n = 4), une MC ileale etendue (> 50 cm) (n = 4) et une corticoresistance (n = 3). Le delai moyen entre le diagnostic de la MICI et la prescription des anti-TNF alpha etait de 30,4 mois [0–168 mois]. Trente-cinq patients etaient sous infliximab et quatre sous adalimumab. Chez 36 malades l’anti-TNF alpha etait associe a l’azathioprine en combotherapie (92,3 %). Les principaux effets indesirables observes etaient une reactivation tuberculeuse chez quatre malades. Dans tous les cas la localisation de la TBC etait pulmonaire. Le bilan pre-therapeutique (intradermoreaction a la tuberculine [IDR] ou Quantiferon®) etait negatif chez trois malades et le Quantiferon® etait positif chez un seul malade qui a recu une antibioprophylaxie anti-tuberculeuse. Le principal signe d’appel etait une fievre vesperale (n = 4). La toux etait presente chez uniquement deux malades. L’IDR ainsi que le test au Quantiferon® etaient positifs chez les quatre malades. La recherche du Bacille de Koch etait positive dans un seul cas. L’evolution etait bonne apres arret temporaire de l’anti-TNF alpha et initiation du traitement antituberculeux. Outre la TBC, sept cas d’infections bacteriennes ont ete colliges, motivant le report des perfusions d’anti-TNF alpha : infection bronchopulmonaire (n = 4) et urinaire (n = 3). L’evolution etait toujours favorable sous antibiotherapie adaptee. L’âge avance (> 40 ans), le genre, le type de la MICI, l’hypoalbuminemie et le diabete n’etaient pas des facteurs predictifs de survenue d’effets indesirables. Conclusion Dans notre serie les principaux effets indesirables d’ordre infectieux des anti-TNF alpha chez les patients MICI sont : la reactivation tuberculeuse et les infections bacteriennes. Aucun facteur n’a ete associe a leur survenue.

The use of trace metals as additives to the biogas production process to increase the biogas yield has been identified as a very common approach. Such additives can biostimulate the methanogenic bacteria to increase the biogas and methane production from the anaerobic digestion (AD) of livestock manure. The environmental impact of using the trace elements as manure additives still not evaluated. The objective of this paper is to conduct a comparative environmental impact evaluation of manure treatment with different trace elements for biogas production. The trace metals under evaluation were in the form of the chlorides of nickel (Ni), cobalt (Co) and iron (Fe) which were used as additives to the anaerobic digestion of livestock manure. The results were shown in the form of the specific impacts on global warming and greenhouse gas (GHG) emissions mitigation of producing and utilizing biogas as a bioenergy source. The results of this investigation show that the use of 1 g/m3 cobalt chloride (CoCl2) causes the lowest greenhouse gas emissions among all other evaluated trace metals which were calculated on the basis of CO2-equivalent. An important observation is that the greenhouse gas emissions from the electricity generated using biogas produced without any additives, i.e. without trace metals, were the highest among all other variants/scenarios.

BackgroundSystemic lupus erythematosus (SLE) is a systemic autoimmune disease with complex genetic inheritance. Many reports have provided evidence that signal transducer and activator of transcription-4 (STAT4) may participate in the pathogenesis of SLE.Aim of the workThe aim was to investigate the clinical significance and possible association of STAT4 (G/T) genetic polymorphism and the susceptibility to SLE in a cohort of Egyptian female patients.Patients and methodsSixty-five Egyptian SLE female patients and 100 age and sex-matched unrelated female healthy blood donors who served as controls, were included in the study. STAT4 genotyping was performed by real time PCR-allelic discrimination technique.ResultsSTAT4 genotyping in patients revealed that 63.1% had GG, 32.3% GT and 6.15% wild (TT) genotype. There was a non-significant difference in the distribution of STAT4 genotypes between patients and controls. Vasculitis, photosensitivity and lupus nephritis were significantly increased in patients with the homomutant (GG and TT) compared to heteromutant (GT) genotype (p=0.01, p=0.04 and p

Multiparametric magnetic resonance (MR) imaging of the prostate is gaining acceptance in the management of prostate cancer. Emerging indications of prostate MR imaging may expand its use in the work-up of localized prostate cancer. Improvements in the standardization of prostate MR imaging techniques and reporting are needed for further establishment of the emerging roles of prostate MR imaging. This article describes the prostate MR imaging techniques and provides an approach for interpretation of prostate MR imaging studies. Established and emerging indications for prostate MR imaging are also reviewed.

The discovery of substantial myocardial improvement following the mechanical unloading afforded by left ventricular assist device (LVAD) therapy challenged the dogma of heart failure being irreversible. Since then, a significant experience with the use of LVAD therapy as a bridge to recovery has accumulated. The discovery of substantial structural and functional changes (reverse remodeling) in the myocardium has resulted in an intensive effort to define the biologic determinants of the reversibility of these changes. Herein the scientific foundations, clinical practice, and future of the use of LVADs as a bridge to recovery are reviewed.

Objective: Valve calcification is mediated by increases in pro-calcifying mediators and a loss in protective mediators such as nitric oxide (NO) and C-type natriuretic peptide (CNP). NO and CNP ind...

Biology is complex, messy and richly various like real life —Peter Medawar [(1)][1] Life imparts almost magical powers to the individual, organ, or tissue. Heart valves are no exception [(2)][2]. It is now well established that the living valve performs extremely sophisticated functions that

The heart failure epidemic continues largely unabated, with more than 26 million people affected worldwide [(1,2)][1]. Despite “optimal medical treatment,” severe forms of the disease carry a very poor prognosis [(3–6)][2], with cardiac transplantation being the only long-term solution. Due to

Although patients with hypertrophic cardiomyopathy (HCM) have normal ejection fractions at rest, the investigators hypothesized that these patients have differentially abnormal systolic function reserves, limiting their exercise capacity compared with patients with hypertension (HTN).Forty patients with HCM (mean age, 39.1 ± 12 years), 20 patients with HTN with LVH, and 33 healthy individuals underwent resting and peak exercise echocardiography using two-dimensional strain imaging. Peak longitudinal systolic strain (εsys) and strain rate were measured in apical views. Circumferential εsys and left ventricular (LV) twist were analyzed from short-axis views. LV systolic dyssynchrony was measured from regional longitudinal strain curves as the standard deviation of time to peak strain (time from the beginning of the Q wave on electrocardiography to peak εsys) between 12 segments. The differences between resting and peak exercise values were analyzed, and functional reserve was calculated as the difference divided by the resting value.In patients with HCM, resting values for longitudinal εsys, systolic strain rate, early diastolic strain rate, and atrial diastolic strain rate were significantly lower, while circumferential εsys and twist were higher, compared with patients with HTN and controls (P .0001). Functional systolic reserve increased during exercise in controls (17 ± 6%), increased to a lesser extent in patients with HTN (10 ± 16%), and was markedly attenuated in patients with HCM (-23 ± 28%) (P .001). At peak exercise, even with augmented circumferential εsys and twist in patients with HCM (P .01) compared with those with HTN, both remained lower than in controls (P .001). LV dyssynchrony was amplified during exercise in patients with HCM compared with those with HTN (P .001). Within the entire population, exercise capacity was clearly correlated with systolic functional reserve. However when taken separately, it was mainly related to resting LV dyssynchrony and diastolic function in patients with HCM, whereas it was linked to age and LV wall thickness in those with HTN.Patients with HCM have significantly limited systolic function reserve and more dynamic dyssynchrony with exercise compared with those with HTN. Two-dimensional strain imaging during stress may provide a new and reliable method to identify patients at higher cardiovascular risk.

Objectives The objective of the study is to determine cardiac autonomic control in patients undergoing assessment for and/or LVAD therapy. Methods Heart rate variability (HRV) was measured in 17 explanted LVAD, 17 implanted LVAD and 23 NYHA III-IV classified chronic heart failure (CHF) patients and ten healthy matched controls under three conditions: supine free breathing, standing and supine controlled breathing. Five measures of HRV were assessed: mean R-R interval (mR-R), high frequency (HF) and low frequency (LF) spectral power, LF in normalised units (LFnu), and LF to HF (LF:HF) ratio. Results Repeat measures ANOVA showed significant (p < 0.05) differences in HRV between all three conditions within groups. Lower values were observed in CHF for LF(in log natural units) compared with explanted patients (- 1.4 [95% CI - 2.6 to - 0.7], p = 0.04) and controls (- 2.1 [- 3.5 to - 0.7], p = 0.001) and for LF:HF compared with implanted patients under paced breathing conditions (z = - 2.7, p = 0.007) and controls in standing (z = - 2.9, p = 0.004) and paced breathing conditions (z = - 2.3, p = 0.02). However, no significant differences were seen between explanted, implanted and control groups under any condition. Conclusions Patients implanted with an LVAD and explanted from a LVAD following myocardial recovery demonstrate a more normal dynamic response to autonomic stimuli and have a lower HRV risk profile compared to CHF patients. © 2013 Elsevier Ireland Ltd.

Arterial endothelial cells maintain vascular homeostasis and vessel tone in part through the secretion of nitric oxide (NO). In this study, we determined how aortic valve endothelial cells (VEC) regulate aortic valve interstitial cell (VIC) phenotype and matrix calcification through NO. Using an anchored in vitro collagen hydrogel culture system, we demonstrate that three-dimensionally cultured porcine VIC do not calcify in osteogenic medium unless under mechanical stress. Co-culture with porcine VEC, however, significantly attenuated VIC calcification through inhibition of myofibroblastic activation, osteogenic differentiation, and calcium deposition. Incubation with the NO donor DETA-NO inhibited VIC osteogenic differentiation and matrix calcification, whereas incubation with the NO blocker l-NAME augmented calcification even in 3D VIC–VEC co-culture. Aortic VEC, but not VIC, expressed endothelial NO synthase (eNOS) in both porcine and human valves, which was reduced in osteogenic medium. eNOS expression was reduced in calcified human aortic valves in a side-specific manner. Porcine leaflets exposed to the soluble guanylyl cyclase inhibitor ODQ increased osteocalcin and α-smooth muscle actin expression. Finally, side-specific shear stress applied to porcine aortic valve leaflet endothelial surfaces increased cGMP production in VEC. Valve endothelial-derived NO is a natural inhibitor of the early phases of valve calcification and therefore may be an important regulator of valve homeostasis and pathology.

Background Left ventricular assist devices (LVAD)-induced unloading appear to cause reverse cardiac remodeling. However, its effect on arrhythmogenicity is a controversial issue, and prospective data are lacking. We sought to investigate the impact of LVAD-induced unloading on the electrical properties of the failing heart. Methods We prospectively studied the effects of LVAD therapy on QRS, QT, and QTc durations and ventricular arrhythmias from electrocardiograms and 24-hour ambulatory electrocardiograms recorded before and during 6 months of mechanical support in 12 LVAD patients and 7 other patients with advanced nonischemic cardiomyopathy untreated with LVAD. Results After 1 week of LVAD support, QTc duration had decreased from 479 ± 79 ms to 411 ± 57 ms ( p = 0.037), and QRS duration from 150 ± 46 ms to 134 ± 32 ms ( p = 0.029). At 6 months, QTc was found to be 372 ± 56 ms ( p = 0.046 versus baseline, 15% shortening) and QRS 118 ± 25 ms ( p = 0.028 versus baseline, 11% shortening). A strong correlation was found between QTc shortening and increase in left ventricular ejection fraction and decrease in left ventricular filling pressures. After 2 months of LVAD support, premature ventricular contractions had decreased from 3,507 ± 4,252 to 483 ± 417 in 24 hours ( p = 0.043), ventricular couplets from 82 ± 99 to 29 ± 25 in 24 hours ( p = 0.05), and ventricular runs from 9 ± 8 to 10 ± 9 (not significant). No patient died suddenly or suffered a symptomatic arrhythmic event during follow-up. No significant electrocardiographic, functional, or hemodynamic change was observed in the 7 patients untreated with LVAD. Conclusions The LVAD support caused progressive shortening of QTc and QRS intervals, consistent with reverse remodeling of the failing heart's electrical properties, accompanied by a decrease in frequency of ventricular arrhythmias.

Peak cardiac power output (CPO), as a direct measurement of overall cardiac function, has been shown to be a most powerful predictor of prognosis for patients with chronic heart failure. The present study assessed CPO and exercise performance in patients implanted with a left ventricular assist device (LVAD), those explanted due to myocardial recovery, and those with moderate to severe heart failure. Hemodynamic and respiratory gas exchange measurements were undertaken at rest and at peak graded exercise. These were performed in 54 patients-20 with moderate to severe heart failure, 18 with implanted LVADs, and 16 with explanted LVADs. At rest there was a nonsignificant difference in CPO among groups (p >0.05). Peak CPO was significantly higher in the explanted LVAD than in the heart failure and implanted LVAD groups (heart failure 1.90 +/- 0.45 W, implanted LVAD 2.37 +/- 0.55 W, explanted LVAD 3.39 +/- 0.61 W, p

Currently, the arterial switch operation (ASO) is the treatment of choice for the majority of patients with TGA. However, in low and middle-income countries, a significant number of patients present too late for ASO. A new modified Mustard operation (MMO) designed to improve contractile and

The field of myocardial regeneration (angiogenesis and myogenesis) might prove to play an important role in the future management of cardiovascular disease. Stem cells are currently undergoing testing in Phase I and Phase II clinical trials. Methods of delivery will affect the outcome of such therapies, perhaps significantly. This document provides suggested guidance in 4 methods of delivery: endocardial, intracoronary, coronary sinus, and epicardial.

Objectives The aims of this study were to compare long-term results after homograft versus Freestyle (Medtronic Inc., Minneapolis, Minnesota) aortic root replacement. Background The ideal substitute for aortic root replacement remains undetermined. Methods Between 1997 and 2005, 166 patients (age 65 ± 8 years) undergoing total aortic root replacement were randomized to receive a homograft (n = 76) or a Freestyle bioprosthesis (n = 90). Six patients randomly assigned to homograft crossed over to Freestyle because of unavailability of suitably sized homografts. Median follow-up was 7.6 years (maximum 11 years; 1,035 patient-years). “Evolving” aortic valve dysfunction was defined as aortic regurgitation ≥2/4 and/or peak gradient >20 mm Hg. Results Patient characteristics were comparable between groups. Concomitant procedures were performed in 44% and 47% of Freestyle and homograft patients, respectively (p = 0.5). Overall hospital mortality was 4.8% (1% for isolated root replacement). Eight-year survival was 80 ± 5% in the Freestyle group versus 77 ± 6% in the homograft group (p = 0.9). Freedom from need for reoperation at 8 years was significantly higher after Freestyle root replacement (100 ± 0% vs. 90 ± 5% after homograft replacement; p = 0.02). All reoperations were secondary to structural valve deterioration (n = 6). At last echocardiographic follow-up, actuarial freedom from evolving aortic valve dysfunction was 86 ± 5% for Freestyle bioprostheses versus 37 ± 7% for homografts (p Conclusions In this patient group, late survival is similar after homograft versus Freestyle root replacement. However, Freestyle aortic root replacement is associated with significantly less progressive aortic valve dysfunction and a lower need for reoperations.

Objectives The purpose of this study was to analyze the effects of left ventricular assist devices (LVADs) on myocardial sympathetic innervation of the failing heart. Background Ventricular unloading by LVADs seems to cause reverse remodeling of the failing heart, but little is known about the sympathetic nerve activity during long-term mechanical unloading. Methods We studied the effects of LVADs on myocardial sympathetic innervation, by iodine 123-meta-iodobenzylguanidine (123I-mIBG) scintigraphy performed before and 3 months after LVAD implantation in 12 end-stage heart failure patients. We calculated the: 1) heart-to-mediastinum (H/M) uptake ratio on early and delayed images, indicating myocardial accumulation of 123I-mIBG; and 2) rate of 123I-mIBG washout after initial accumulation. Similar 123I-mIBG imaging and functional and hemodynamic measurements were made 3 months apart in 6 other heart failure patients not treated with an LVAD. Results After 3 months of LVAD support, the mean left ventricular ejection fraction had increased from 19 ± 6% to 29 ± 9% (p = 0.006), peak oxygen consumption increased from 9 ± 4 ml/kg/min to 13 ± 3 ml/kg/min (p = 0.058), serum sodium increased from 135 ± 4 mEq/l to 140 ± 2 mEq/l (p = 0.014), whereas the left ventricular end-diastolic diameter decreased from 72 ± 7 mm to 56 ± 3 mm (p = 0.002), pulmonary capillary wedge pressure decreased from 30 ± 6 mm Hg to 5 ± 3 mm Hg (p = 0.012), serum creatinine decreased from 1.5 ± 0.6 mg/dl to 1.0 ± 0.4 mg/dl (p = 0.011), and B-type natriuretic peptide decreased from 2,279 ± 1,900 pg/ml to 102 ± 5 pg/ml (p = 0.003). After 3 months of LVAD, the H/M ratio increased on delayed images from 1.25 ± 0.18 to 1.43 ± 0.13 (p = 0.01) and on early images from 1.35 ± 0.19 to 1.44 ± 0.11 (p = 0.028), and the washout rate decreased from 51.0 ± 23.2% to 30.6 ± 8.7%, (p = 0.015). There was a significant correlation between the late H/M mIBG ratio and B-type natriuretic peptide (R = 0.77, p = 0.01) and systolic pulmonary pressure (R = 0.7, p = 0.05). No significant scintigraphic, functional or hemodynamic change was observed between the 2 evaluations in the 6 patients not treated with an LVAD. Conclusions Ventricular unloading caused clinical, functional, and hemodynamic improvements accompanied by improvements in sympathetic innervation in the failing heart.

The aortic valve was long considered a passive structure that opens and closes in response to changes in transvalvular pressure. Recent evidence suggests that the aortic valve performs highly sophisticated functions as a result of its unique microscopic structure. These functions allow it to adapt to its hemodynamic and mechanical environment. Understanding the cellular and molecular mechanisms involved in normal valve physiology is essential to elucidate the mechanisms behind valve disease. We here review the structure and developmental biology of aortic valves; we examine the role of its cellular parts in regulating its function and describe potential pathophysiological and clinical implications.

Genetic mutations in bone morphogenetic protein receptor 2 (BMPR2) have been shown to occur in patients with familial and idiopathic pulmonary arterial hypertension (PAH). However the interactions between ligands for this receptor and other mediators implicated in heritable PAH have not been investigated. This study examines the regulation of endothelin-1 (ET-1), a potent vasoconstrictor and comitogen that is implicated in the pathogenesis of heritable PAH, by ligands for the BMPR2. Immunohistochemical studies showed that pulmonary artery segments removed from normotensive human lungs express BMPR2 and bone morphogenetic proteins 2, 4 and 7 (BMP2, BMP4 and BMP7). In the presence of BMP7 and BMP4 there was a significant inhibition of ET-1 release, induced by cytokines, from cultured pulmonary artery smooth muscle cells. Fresh ring segments of pulmonary artery were assessed for their response to ET-1 in the presence and absence of BMP2, BMP4 and BMP7. BMP7 inhibited contraction in response to ET-1 in a concentration-dependent manner. BMP2 and BMP4 had no significant effect on the response to ET-1. These results suggest that BMP7 has the ability to regulate the effects of endothelin-1 in the pulmonary circulation. Genetic mutations in BMPR2 may lead to a loss of these regulatory mechanisms and contribute to the pathogenesis of pulmonary hypertension.

Cell transplantation is an emerging therapy for treating post-infarction heart failure. Although the paracrine effect has been proposed to be an important mechanism for the therapeutic benefits, details remain largely unknown. This study compared various aspects of the paracrine effect after transplantation of either bone marrow mononuclear cells (BMC) or skeletal myoblasts (SMB) into the post-infarction chronically failing heart. Three weeks after left coronary artery ligation, adult rats received intramyocardial injection of either BMC, SMB or PBS only. Echocardiography demonstrated that injection of either cell type improved cardiac function compared to PBS injection. Interestingly, BMC injection markedly improved neovascularization in the border areas surrounding infarcts, while SMB injection decreased fibrosis in both the border and remote areas. Injection of either cell type similarly reduced hypertrophy of cardiomyocytes as assessed by cell-size planimetry using isolated cardiomyocytes. Quantitative RT-PCR revealed that, among 15 candidate mediators of paracrine effects studied, Fgf2 and Hgf were upregulated only after BMC injection, while Mmp2 and Timp4 were modulated after SMB injection. Additional investigations of signalling pathways relevant to heart failure by western blotting showed that p38 and STAT3 were temporarily activated after BMC injection, in contrast, ERK1/2 and JNK were activated after SMB injection. There was no difference in activation of Akt, PKD or Smad3 among groups. These data suggest that paracrine effects observed after cell transplantation in post-infarction heart failure were noticeably different between cell types in terms of mediators, signal transductions and consequent effects.

The C34T T allele of the adenosine monophosphate deaminase-1 (AMPD1) gene has been associated with improved outcome in patients with cardiac dysfunction. We hypothesized that possession of this allele by donor hearts plays a role in the outcome of cardiac transplantation; 262 cardiac donors and 190 of their recipients were studied. AMPD1 C34T genotype was determined using 5' exonuclease chemistry. Requirement for inotropic agents before organ donation, 1-year post-transplantation survival, cause of death, and factors known to affect survival after transplantation were also studied. Multiple regression models for factors affecting survival were constructed. A significant yearly increase in frequency of the T allele in donors was noted (0.06 to 0.18 from 1994 to 1999). Donors with the CT or TT genotype required less inotropic support than those with the CC genotype (mean number of inotropes per donor with CT or TT genotype 0.27 compared with 0.47 per donor with CC genotype, n = 206, p = 0.03). Recipients of T-allele-carrying organs showed worse 1-year survival after transplantation (59% vs 79%, p0.001). Excess deaths in these patients was due to early graft dysfunction (odds ratio for early graft dysfunction 6.6, 95% confidence interval 2 to 21.6, p = 0.0001). Multivariate analysis showed donor AMPD1 genotype, recipient age, and pretransplantation anemia to independently affect 1-year post-transplantation survival (adjusted hazard ratios 3.7, 1.06, and 2.6, respectively). In conclusion, possession of the AMPD1 T allele is associated with decreased inotropic requirements before heart donation. The incidence of early graft dysfunction, however, was significantly higher in recipients who received AMPD1 T-allele-possessing organs resulting in worse 1-year survival.

Background Abnormalities in the extracellular matrix (ECM) can occur in heart failure. In this study we analyzed ECM gene expression in patients with advanced dilated cardiomyopathy who did and did not develop sustained myocardial recovery after left ventricular asst device (LVAD) unloading combined with pharmacologic therapy. Methods Myocardial gene expression of collagens (COL1A1 and COL3A1), fibronectin (FN), matrix metalloproteinases (MMPs 1 to 14), tissue inhibitors of metalloproteinases (TIMPs 1 to 4), connective tissue growth factor (CTGF), transforming growth factor-beta1 (TGF-β1) and THY1 was measured by real-time reverse transcriptase–polymerase chain reaction (RT-PCR) at LVAD implantation and again at explantation (recovery, n = 11) or transplantation (non-recovery, n = 5). Results The non-recovery group had higher levels of pro-fibrotic markers (COL1A1, TGF-β1 and THY1) at implantation compared with the recovery group (1.82 ± 0.74-, 1.81 ± 0.69- and 3.01 ± 1.70-fold, respectively; p ≤ 0.05). Both recovery and non-recovery groups showed no significant difference in gene expression after treatment, but levels of pro-fibrotic genes (COL1A1, COL3A1, FN and THY1) correlated negatively with post-explant ejection fraction in the recovery group. Of all genes analyzed only TIMP4 showed a significant change, with expression reduced during recovery (0.55 ± 0.25-fold at explant vs implant, p = 0.001). All other genes showed complex patterns between individuals with both increased and decreased expression of pro-fibrotic markers, MMPs and TIMPs in recovery patients. Conclusions Patients who did not recover had higher myocardial expression of pro-fibrotic genes at LVAD implantation, and in recovered patients higher levels at explant were negatively associated with subsequent ejection fraction. However, individual patients showed complex expression patterns and a decrease in pro-fibrotic markers was not required for recovery.