Search

The molecular interactions of the sarcomeric proteins are essential in the regulation of various cardiac functions. Mutations in the gene MYBPC3 coding for cardiac myosin-binding protein-C (cMyBP-C), a multi-domain protein, are the most common cause of hypertrophic cardiomyopathy (HCM). The N-terminal complex, C1-motif-C2 is a central region in cMyBP-C for the regulation of cardiac muscle contraction. However, the mechanism of binding/unbinding of this complex during health and disease is unknown. Here, we study possible mechanisms of unbinding using steered molecular dynamics simulations for the complex in the wild type, in single mutations (E258K in C1, E441K in C2), as well as in a double mutation (E258K in C1 + E441K in C2), which are associated with severe HCM. The observed molecular events and the calculation of force utilized for the unbinding suggest the following: (i) double mutation can encourage the formation of rigid complex that required large amount of force and long-time to unbind, (ii) C1 appears to start to unbind ahead of C2 regardless of the mutation, and (iii) unbinding of C2 requires larger amount of force than C1. This molecular insight suggests that key HCM-causing mutations might significantly modify the native affinity required for the assembly of the domains in cMyBP-C, which is essential for normal cardiac function.

Personalised treatment of heart disease requires an understanding of the patient-specific characteristics, which can vary over time. A newly developed implantable surface acoustic wave pressure sensor, capable of continuous monitoring of the left ventricle filling pressure, is a novel device for personalised management of patients with heart disease. However, a one-size-fits-all approach to device sizing will affect its positioning within the pulmonary artery and its relationship to the interrogating device on the chest wall on a patient-specific level. In this paper, we analyse the spatial orientation and morphology of the pulmonary artery and its main branches in patients who could benefit from the device and normal controls. The results could optimise the design of the sensor, its stent, and importantly its placement, ensuring long-term monitoring in patient groups.

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.

Extracellular nucleotide metabolism controls thrombosis and inflammation and may affect degeneration and calcification of aortic valve prostheses. We evaluated the effect of different decellularization strategies on enzyme activities involved in extracellular nucleotide metabolism. Porcine valves were tested intact or decellularized either by detergent treatment or hypotonic lysis and nuclease digestion. The rates of ATP hydrolysis, AMP hydrolysis, and adenosine deamination were estimated by incubation of aorta or valve leaflet sections with substrates followed by HPLC analysis. We demonstrated relatively high activities of ecto-enzymes on porcine valve as compared to the aortic wall. Hypotonic lysis/nuclease digestion preserved >80 % of ATP and AMP hydrolytic activity but reduced adenosine deamination to

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.

Sulfotransferases (SULTs) family plays a significant role in the biotransformation of a variety of xenobiotics and endogenous compounds by which carcinogenesis and mutagenicity of different malignancies are increasingly affected. Recent data identified various genetically polymorphic SULTs enzymes with significant variations in the enzyme activity. This study aimed to investigate the impact of SULT1A1 gene polymorphism and and its potential risk on females with breast cancer in Jordan using a PCR-RFLP and Sanger Sequencing methods. The analysis showed that 24.7% of the patients and 25.3% of the controls were homozygous for the SULT1A1*1 allele (SULT1A1*1/SULT1A1*1) compared to 8.8% and 5.7% homozygous for the SULT1A1*2 allele (SULT1A1*2/SULT1A1*2) for patients and controls respectively. Most of the patients and controls were heterozygous for SULT1A1*1 allele (SULT1A1*1/SULT1A1*2) with rates of 66.5% and 69.0% in patients and controls respectively. In addition, the frequencies of the mutant SULT1A1*2 allele were 0.42 and 0.4 in the patient and control groups respectively. No significant difference in genotype and allele distribution was noted between the breast cancer and control groups. The risk of breast cancer in individuals carrying the SULT1A1*2 allele was determined by combining the SULT1A1*1/SULT1A1*2 and ULT1A1*2/SULT1A1*2 genotypes. No association was observed between SULT1A1 polymorphism and breast cancer incidence (P = 0.63; OR, 0.93; 95% CI, 0.68–1.26). However, SULT1A1*2 allele was found to increase the risk of breast cancer by 1.26-fold.

Septal myectomy is currently the gold standard treatment for symptomatic patients with hypertrophic cardiomyopathy. The procedure needs to be tailored and performed in a personalized fashion, taking into consideration the anatomical spectrum of this disease.The procedure needs to address the various components that contribute to the clinical and pathological picture of this disease including, the fibrous trigones, accessory tissues, papillary muscles, mitral valve and myocardial bridges. The operation can be performed with very low mortality and morbidity in high-volume experienced centers with predictable excellent short and long-term outcomes. There is a need for broadening the experience of this procedure to the rest of the world and for future development of new enhanced precision imaging and surgical tools.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. The Liver Imaging and Reporting Data System (LI-RADS) is a comprehensive system for standardizing the terminology, technique, interpretation, reporting, and data collection of liver imaging with the overarching goal of improving communication, clinical care, education, and research relating to patients at risk for or diagnosed with hepatocellular carcinoma (HCC). In 2018, the American Association for the Study of Liver Diseases (AASLD) integrated LI-RADS into its clinical practice guidance for the imaging-based diagnosis of HCC. The harmonization between the AASLD and LI-RADS diagnostic imaging criteria required minor modifications to the recently released LI-RADS v2017 guidelines, necessitating a LI-RADS v2018 update. This article provides an overview of the key changes included in LI-RADS v2018 as well as a look at the LI-RADS v2018 diagnostic algorithm and criteria, technical recommendations, and management suggestions. Substantive changes in LI-RADS v2018 are the removal of the requirement for visibility on antecedent surveillance ultrasound for LI-RADS 5 (LR-5) categorization of 10-19 mm observations with nonrim arterial phase hyper-enhancement and nonperipheral “washout”, and adoption of the Organ Procurement and Transplantation Network definition of threshold growth (≥ 50% size increase of a mass in ≤ 6 months). Nomenclatural changes in LI-RADS v2018 are the removal of -us and -g as LR-5 qualifiers.

Extracellular nucleotide catabolism contributes to immunomodulation, cell differentiation and tissue mineralization by controlling nucleotide and adenosine concentrations and its purinergic effects. Disturbances of purinergic signaling in valves may lead to its calcification. This study aimed to investigate the side-specific changes in extracellular nucleotide and adenosine metabolism in the aortic valve during calcific aortic valve disease (CAVD) and to identify the individual enzymes that are involved in these pathways as well as their cellular origin.Stenotic aortic valves were characterized by reduced levels of extracellular ATP removal and impaired production of adenosine. Respectively, already reduced levels of extracellular adenosine were immediately degraded further due to the elevated rate of adenosine deamination. For the first time, we revealed that this metabolic pattern was observed only on the fibrosa surface of stenotic valve that is consistent with the mineral deposition on the aortic side of the valve. Furthermore, we demonstrated that non-stenotic valves expressed mostly ecto-nucleoside triphosphate diphosphohydrolase 1 (eNTPD1) and ecto-5’nucleotidase (e5NT), while stenotic valves ecto-nucleotide pyrophosphatase/ phosphodiesterase 1, alkaline phosphatase and ecto-adenosine deaminase (eADA). On the surface of endothelial cells, isolated from non-stenotic valves, high activities of eNTPD1 and e5NT were found. Whereas, in valvular interstitial cells, eNPP1 activity was also detected. Stenotic valve immune infiltrate was an additional source of eADA. We demonstrated the presence of A1, A2a and A2b adenosine receptors in both, non-stenotic and stenotic valves with diminished expression of A2a and A2b in the former.Extracellular nucleotide and adenosine metabolism that involves complex ecto-enzyme pathways and adenosine receptor signaling were adversely modified in CAVD. In particular, diminished activities of eNTPD1 and e5NT with the increase in eADA that originated from valvular endothelial and interstitial cells as well as from immune inflitrate may affect aortic valve extracellular nucleotide concentrations to favor a proinflammatory milieu, highlighting a potential mechanism and target for CAVD therapy.

Anomalous origin of the left main coronary artery from the right coronary sinus is associated with sudden cardiac death. We present a young adult who was diagnosed with this anomaly after an aborted sudden cardiac death. He underwent a complete anatomical repair by translocating the left coronary artery to the left coronary sinus of Valsalva, with excellent 10 years outcome.

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.

[first paragraph of article]This year marks the 51st anniversary of the first human heart transplant operation by Christiaan Barnard at the Groote Schuur Hospital in Cape Town. This event has had a profound effect on Science, Medicine and Humanity, almost beyond expectations. The anniversary calls for celebrations, and evaluation, as with maturity comes accountability. We here attempt to summarise the reasons for celebrations, and highlight the remaining many challenges and expectations. Regarding the celebrations, this anniversary exemplifies and calls for celebration of at least four human attributes; courage, innovation, compassion, and human spirit.

More than 6 billion people live outside industrialized countries and have insufficient access to cardiac surgery. Given the recently confirmed high prevailing mortality for rheumatic heart disease in many of these countries together with increasing numbers of patients needing interventions for lifestyle diseases due to an accelerating epidemiological transition, a significant need for cardiac surgery could be assumed. Yet, need estimates were largely based on extrapolated screening studies while true service levels remained unknown. A multi-author effort representing 16 high-, middle-, and low-income countries was undertaken to narrow the need assessment for cardiac surgery including rheumatic and lifestyle cardiac diseases as well as congenital heart disease on the basis of existing data deduction. Actual levels of cardiac surgery were determined in each of these countries on the basis of questionnaires, national databases, or annual reports of national societies. Need estimates range from 200 operations per million in low-income countries that are nonendemic for rheumatic heart disease to >1,000 operations per million in high-income countries representing the end of the epidemiological transition. Actually provided levels of cardiac surgery range from 0.5 per million in the assessed low- and lower-middle income countries (average 107 ± 113 per million; representing a population of 1.6 billion) to 500 in the upper-middle-income countries (average 270 ± 163 per million representing a population of 1.9 billion). By combining need estimates with the assessment of de facto provided levels of cardiac surgery, it emerged that a significant degree of underdelivery of often lifesaving open heart surgery does not only prevail in low-income countries but is also disturbingly high in middle-income countries.

The following is an illustrative review of common pitfalls in liver MRI that may challenge interpretation. This article reviews common technical and diagnostic challenges encountered when interpreting dynamic multiphasic T

Brachytherapy (BT), the use of a locally placed or implanted radioactive source for treatment of an adjacent tumor, is an important component in the treatment of patients with both early- and advanced-stage cervical cancer and is increasingly part of the standard treatment protocol. When it is feasible, many radiation oncologists choose to include a magnetic resonance (MR) imaging examination for planning BT treatment (ie, an MR imaging examination after placement of the applicator but before radiation dosing). MR imaging provides excellent soft-tissue contrast and allows radiation oncologists to individualize the radiation dose to the target volume and minimize the dose to adjacent organs that are at risk for radiation damage. However, traditionally, the radiology department has not performed imaging studies for planning, and the requirements are different compared with those of standard diagnostic imaging. In addition, many applicators are available for use in BT treatment of cervical cancer, and each must considered separately to determine MR safety and to define the best imaging parameters. Starting and supporting a robust gynecologic BT program includes implementing imaging protocols that are helpful to both radiation oncologists and diagnostic radiologists. By becoming more familiar with this treatment modality and the logistics of imaging patients undergoing BT, radiologists can provide imaging support for colleagues in the radiation oncology department and better care for patients. ©RSNA, 2018.

Rheumatic heart disease (RHD) is a preventable heart condition that remains endemic among vulnerable groups in many countries. After a period of relative neglect, there has been a resurging interest in RHD worldwide over the past decade. In this Scientific Expert Panel, the authors summarize recent advances in the science of RHD and sketch out priorities for current action and future research. Key questions for laboratory research into disease pathogenesis and epidemiological research on the burden of disease are identified. The authors present a variety of pressing clinical research questions on optimal RHD prevention and advanced care. In addition, they propose a policy and implementation research agenda that can help translate current evidence into tangible action. The authors maintain that, despite knowledge gaps, there is sufficient evidence for national and global action on RHD, and they argue that RHD is a model for strengthening health systems to address other cardiovascular diseases in limited-resource countries.

[first paragraph of article]Kawasaki disease (KD) continues to interest, intrigue, and challenge clinicians, basic scientists, and engineers. One of the defining features of the disease is the development of coronary aneurysms of varying sizes and shapes, reproducing the phenomenon of ‘‘River into a lake’’, and introducing profound changes in the coronary circulation. These changes reflect many physical, engineering and even cultural beliefs which might be of interest to the readers of this special issue of the Journal dealing with KD. Some of these ideas are presented in this article.

Epicardial adipose tissue (EAT) has been proposed to modulate underlying coronary plaque features. The study aimed to determine the relation between segmental EAT (sEAT) volume, assessed by cardiac magnetic resonance (CMR), and underlying coronary plaque characteristics, as estimated by multidetector computed tomography (CT) (MDCT).The study included 32 male patients with stable angina pectoris and 11 age-matched healthy controls. For each CAD patient, sEAT volume around 8 coronary segments (3 in left anterior descending artery, 3 in right coronary artery, and 2 in left circumflex artery) was quantified by CMR. By MDCT, plaques in each coronary segment were characterized in terms of plaque volume, type, CT attenuation, and severity of luminal stenosis. Serum levels of adipokines were measured. Total EAT volume was significantly higher in CAD patients than in control group. Serum resistin showed significant correlation with EAT volume (r = 0.69, P0.001). Analysis of 256 coronary segments showed larger sEAT volume with increasing luminal stenosis of the corresponding segment (mild: 8.2 cm(3); moderate: 11 cm(3); severe: 11.8 cm(3), P0.001). sEAT volume was larger in segments with mixed than those with calcified or non-calcified plaques (12.1 vs. 10.2 vs. 9.5 cm(3), respectively, P = 0.015). sEAT volume was larger in segments with low CT attenuation non-calcified plaques compared with non-calcified plaques with CT attenuation30 HU (10.5 vs. 8.2 mm(3), P0.001).Peri-coronary epicardial adipose tissue volume is significantly associated with the extent and severity of coronary atherosclerosis and may be a determinant of plaque vulnerability.

Left ventricular assist devices (LVADs) were developed as a means of temporary circulatory support, but the mechanical unloading they offer also results in significant reverse remodelling. In selected patients, these improvements are sufficient to allow ultimate device explantation without requiring transplantation; this represents a fundamental shift in our understanding of heart failure. Like heart failure itself, LVADs influence multiple biological systems. The transverse tubules are a system of membrane invaginations in ventricular cardiomyocytes which allow rapid propagation of the action potential throughout the cell. Through their dense concentration of L-type Ca2+ channels in close proximity to intracellular ryanodine receptors, the t-tubules enable synchronous Ca2+ release throughout the cell. The t-tubules’ structure appears to be specifically regulated by mechanical load, such that either the overload of heart failure (or the spontaneously hypertensive rat model) or the profound unloading in a chronically unloaded heart result in impaired t-tubule structure, with ineffective Ca2+ release. While there are multiple molecular pathways which underpin t-tubule regulation, Telethonin (Tcap) appears to be important in regulating the effect of altered loading on the t-tubule system.

Mutations in the gene coding for cardiac myosin binding protein-C (cMyBP-C), a multi-domain (C0-C10) protein, are a major causative factor for inherited hypertrophic cardiomyopathy. Patients carrying mutations in this gene have an extremely heterogeneous clinical course, with some progressing to end-stage heart failure. The cause of this variability is unknown. We here describe molecular modeling of a double mutation in domains C1 (E258K) and C2 (E441K) in a patient with severe HCM phenotype. The three-dimensional structure for the C1-motif-C2 complex was constructed with double and single mutations being introduced. Molecular dynamic simulations were performed for 10 ns under physiological conditions. The results showed that both E258K and E441K in isolation can predominantly affect the native domain as well as the nearby motif via conformational changes and result in an additive effect when they coexist. These changes involve important regions of the motif such as phosphorylation and potential actin-binding sites. Moreover, the charge reversal mutations altered the surface electrostatic properties of the complex. In addition, we studied protein expression, which showed that the mutant proteins were expressed and we can suppose that the severe phenotype was not due to haploinsufficiency. However, additional studies on human gene expression will need to confirm this hypothesis. The double mutation affecting the regulatory N-terminal of cMyBP-C have the potential of synergistically interfering with the binding to neighbouring domains and other sarcomeric proteins. These effects may account for the severe phenotype and clinical course observed in the complex cMyBP-C genotypes.

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

Detailed assessment of the tricuspid valve using two-dimensional echocardiography is always challenging, as only two of three leaflets can be seen at a time. Three-dimensional echocardiography can provide the enface view of the tricuspid valve that allows simultaneous visualization of all of the three leaflets. In a 42-year-old male patient scheduled for pulmonary endarterectomy, 3DTEE showed that the tricuspid valve is bileaflet, with one septal and another lateral leaflet. There were two commissures, one of them is anteriorly positioned and the other one is posterior. Our findings were confirmed intra-operatively by direct surgical visualization of the tricuspid valve.

peer-reviewed Representative compounds from three classes of microporous solids, namely metal-organic frameworks (MOFs), hybrid ultramicroporous materials (HUMs) and porous-organic polymers (POPs), were investigated for their nitric oxide gas uptake and release behavior. Low pressure sorption studies indicated strong chemisorption of NO on the free amine groups decorating the MOF UiO-66-NH2 when compared to its non-amine functionalized parent. The HUMs demonstrated reversible physisorption within the low pressure regime but interestingly in one case there was evidence for chemisorption following pressurization with NO at 10 bar. Significant release of chemisorbed NO from the UiO-66-NH2 and one of the HUMs was triggered by addition of acid to the medium, a pH change from 7.4 to 5.4 being sufficient to trigger NO release. An imidazole-based POP exhibited chemisorption of NO at high pressure wherein the ring basicity facilitated both NO uptake and spontaneous release upon contact with the aqueous release medium.

Objectives Valve-conserving operations for aneurysms of the ascending aorta and root offer many advantages, and their use is steadily increasing. Optimizing the results of these operations depends on providing the best conditions for normal function and durability of the new root. Methods Multimodality imaging including 2-dimensional echocardiography, multislice computed tomography, and cardiovascular magnetic resonance combined with image processing and computational fluid dynamics were used to define geometry, dynamism and aortic root function, before and after the remodeling operation. This was compared with 4 age-matched controls. Results The size and shape of the ascending aorta, aortic root, and its component parts showed considerable changes postoperatively, with preservation of dynamism. The postoperative size of the aortic annulus was reduced without the use of external bands or foreign material. Importantly, the elliptical shape of the annulus was maintained and changed during the cardiac cycle (Δ ellipticity index was 15% and 28% in patients 1 and 2, respectively). The "cyclic" area of the annulus changed in size (Δarea: 11.3% in patient 1 and 13.1% in patient 2). Functional analysis showed preserved reservoir function of the aortic root, and computational fluid dynamics demonstrated normalized pattern of flow in the ascending aorta, sinuses of Valsalva, and distal aorta. Conclusions The remodeling operation results in near-normal geometry of the aortic root while maintaining dynamism of the aortic root and its components. This could have very important functional implications; the influence of these effects on both early- and long-term outcomes needs to be studied further.

Kawasaki disease (KD) is a rare vascular disease that, if left untreated, can result in irreparable cardiac damage in children. While the symptoms of KD are well-known, as are best practices for treatment, the etiology of the disease and the factors contributing to KD outbreaks remain puzzling to both medical practitioners and scientists alike. Recently, a fungus known as Candida , originating in the farmlands of China, has been blamed for outbreaks in China and Japan, with the hypothesis that it can be transported over long ranges via different wind mechanisms. This paper provides evidence to understand the transport mechanisms of dust at different geographic locations and the cause of the annual spike of KD in Japan. Candida is carried along with many other dusts, particles or aerosols, of various sizes in major seasonal wind currents. The evidence is based upon particle categorization using the Moderate Resolution Imaging Spectrometer (MODIS) Aerosol Optical Depth (AOD), Fine Mode Fraction (FMF) and Angstrom Exponent (AE), the Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO) attenuated backscatter and aerosol subtype, and the Aerosol Robotic Network’s (AERONET) derived volume concentration. We found that seasonality associated with aerosol size distribution at different geographic locations plays a role in identifying dominant abundance at each location. Knowing the typical size of the Candida fungus, and analyzing aerosol characteristics using AERONET data reveals possible particle transport association with KD events at different locations. Thus, understanding transport mechanisms and accurate identification of aerosol sources is important in order to understand possible triggers to outbreaks of KD. This work provides future opportunities to leverage machine learning, including state-of-the-art deep architectures, to build predictive models of KD outbreaks, with the ultimate goal of early forecasting and intervention within a nascent global health early-warning system.

[first paragraph of article]In spite of the growing discoveries in cardiac surgery, perioperative bleeding remains one of the most common causes of morbidity and mortality. Around 50-60% of cardiac surgery patients receive blood transfusions, which are harmful and strongly associated with increased morbidity, mortality, hospital stay, and hospital cost. Patients taken back to the OR for re-exploration and control of bleeding after cardiac surgery, have a four-fold increase in the incidence of sternal infection and mortality.

Congenital cardiac defects continue to be a major cause of death and suffering in the low/middle-income countries.1 This stems from the larger burden of congenital heart defects in these countries,2 coupled with the paucity of specialised centres and the reported worse outcome of operations in the existing centres. These facts have stimulated concerted efforts to establish new sustainable centres3 and, importantly, developing strategies to improve outcome in the existing centres. The Heart paper by Khan and colleagues4 is a welcome addition to the literature as it highlights the advantages, as well …

8 p., Background Most data on mortality and prognostic factors in patients with heart failure come from North America and Europe, with little information from other regions. Here, in the International Congestive Heart Failure (INTERCHF) study, we aimed to measure mortality at 1 year in patients with heart failure in Africa, China, India, the Middle East, southeast Asia and South America; we also explored demographic, clinical, and socioeconomic variables associated with mortality. Methods We enrolled consecutive patients with heart failure (3695 [66%] clinic outpatients, 2105 [34%] hospital in patients) from 108 centres in six geographical regions. We recorded baseline demographic and clinical characteristics and followed up patients at 6 months and 1 year from enrolment to record symptoms, medications, and outcomes. Time to death was studied with Cox proportional hazards models adjusted for demographic and clinical variables, medications, socioeconomic variables, and region. We used the explained risk statistic to calculate the relative contribution of each level of adjustment to the risk of death. Findings We enrolled 5823 patients within 1 year (with 98% follow-up). Overall mortality was 16·5%: highest in Africa (34%) and India (23%), intermediate in southeast Asia (15%), and lowest in China (7%), South America (9%), and the Middle East (9%). Regional differences persisted after multivariable adjustment. Independent predictors of mortality included cardiac variables (New York Heart Association Functional Class III or IV, previous admission for heart failure, and valve disease) and non-cardiac variables (body-mass index, chronic kidney disease, and chronic obstructive pulmonary disease). 46% of mortality risk was explained by multivariable modelling with these variables; however, the remainder was unexplained. Interpretation Marked regional differences in mortality in patients with heart failure persisted after multivariable adjustment for cardiac and non-cardiac factors. Therefore, variations in mortality between regions could be the result of health-care infrastructure, quality and access, or environmental and genetic factors. Further studies in large, global cohorts are needed. Funding The study was supported by Novartis.

Purpose The purpose of this study was to report early outcomes and assess the learning curve in a new MRI-based cervical brachytherapy program. Methods We accrued 33 patients prospectively, and only patients with ≥3 months' followup (n = 27) were assessed for disease control and toxicity. Eras were defined as first half and second half for the intracavitary (IC)-only era (n = 13 each), and the intracavitary/interstitial (IC/IS) era was separated by difference in applicator availability (n = 7). Dose to 90% of the high-risk clinical target volume (D90 HR-CTV) and minimum dose to the maximally irradiated 2 cubic centimeters (D2cc) to organs at risk were used to assess dosimetry. Statistics were performed with t tests and Kaplan–Meier method. Results Median followup was 14.7 months. Median treatment duration was 50.5 vs. 57 days for patients treated with external beam radiation therapy at our institution vs. an outside institution (p = 0.03). One-year local control, noncervical pelvic control, distant metastasis–free rate, and overall survival were 84.0%, 96.0%, 78.5%, and 91.3%, respectively. When comparing the first half and second half eras of IC only, there were no differences in median D90 HR-CTV or D2cc of the bladder, rectum, or sigmoid. Comparing the entire IC era to the IC/IS era, median D90 HR-CTV trended higher from 88.0 Gy to 92.9 Gy (p = 0.11). D2cc rectum decreased from 69.3 Gy to 62.6 Gy (p = 0.01), and D2cc bladder trended lower from 87.5 Gy to 83.6 Gy (p = 0.09). Conclusions There was no significant difference between the first half and second half eras with IC-only MRI-based brachytherapy. Incorporation of an IC/IS applicator generated the greatest dosimetric improvement. Early results of the MRI-based brachytherapy program are favorable.

The pathogenesis of pulmonary arterial hypertension remains undefined. Changes in the expression and effects mediated by a number of vasoactive factors have been implicated to play a role in the onset and progression of the disease. The source of many of these mediators, such as nitric oxide (NO), prostacyclin and endothelin-1 (ET-1), is the pulmonary endothelium. This article focus in the role of nitric oxide in PAH, reviewing the evidence for its involvement in regulation of pulmonary a vascular tone under physiological conditions, the mechanisms by which it can contribute to the pathological changes seen in PAH and strategies for the use of NO as a therapy for treatment of the disease.

The ability of cells to secrete extracellular matrix proteins is an important property in the repair, replacement, and regeneration of living tissue. Cells that populate tissue-engineered constructs need to be able to emulate these functions. The motifs, KTTKS or palmitoyl-KTTKS (peptide amphiphile), have been shown to stimulate production of collagen and fibronectin in differentiated cells. Molecular modeling was used to design different forms of active peptide motifs to enhance the efficacy of peptides to increase collagen and fibronectin production using terminals KTTKS/SKTTK/SKTTKS connected by various hydrophobic linkers, V4A3/V4A2/A4G3. Molecular dynamic simulations showed SKTTKS-V4A3-SKTTKS (P3), with palindromic (SKTTKS) motifs and SKTTK-V4A2-KTTKS (P5), maintained structural integrity and favorable surface electrostatic distributions that are required for functionality. In vitro studies showed that peptides, P3 and P5, showed low toxicity to human adipose-derived stem cells (hADSCs) and significantly increased the production of collagen and fibronectin in a concentration-dependent manner compared with the original active peptide motif. The 4-day treatment showed that stem cell markers of hADSCs remained stable with P3. The molecular design of novel peptides is a promising strategy for the development of intelligent biomaterials to guide stem cell function for tissue engineering applications.

Purpose Using a combination of magnetic resonance imaging of the prostate and prostate specific antigen density, we aim to determine which men on active surveillance are at risk of being upstaged, and which men could avoid repeat biopsy while remaining on surveillance. Methods We reviewed 110 men on active surveillance with Gleason 6 disease who underwent magnetic resonance imaging followed by Uronav-fusion biopsy. Using univariable and multivariable logistic regression analyses, we examined the effect of age, race, prostate specific antigen, prostate specific antigen density, prostate volume, Prostate Imaging - Reporting and Data System (PI-RADS) score, number and size of target lesions, and time on surveillance to determine the likelihood of upstaging to Gleason ≥7 disease. Results A total of 33 men, or 30%, were upstaged. On multivariable analysis, prostate specific antigen density and PI-RADS score were significant predictors of upstaging with adjusted odds ratios of 3.97 for prostate specific antigen density of ≥0.16 (CI 1.31-12.00, p Conclusion A combination of PI-RADS score and prostate specific antigen density predicts patients at risk of being upstaged at surveillance biopsy. Conversely, this combination may help determine which men may safely forgo biopsy.

PURPOSE To demonstrate that optimized pulse sequence parameters for a T2-weighted (T2w) fast spin echo acquisition reduced artifacts from a titanium brachytherapy applicator compared to conventional sequence parameters. METHODS AND MATERIALS Following Institutional Review Board approval and informed consent, seven patients were successfully imaged with both standard sagittal T2w fast spin echo parameters (voxel size of 0.98 × 0.78 × 4.0 mm3; readout bandwidth of 200 Hz/px; repetition time of 2800 ms; echo time of 91 ms; echo train length of 15; 36 slices; and imaging time of 3:16 min) and an additional optimized T2w sequence (voxel size of 0.98 × 0.98 × 4.0 mm3; readout bandwidth of 500 Hz/px; repetition time of 3610 ms; echo time of 91 ms; echo train length of 25; 18-36 slices; and imaging time of 1:15-2:30 min), which had demonstrated artifact reduction in prior phantom work. Visualized intracavitary tandem was hand-segmented by two of the authors. Three body imaging radiologists assessed image quality and intraobserver agreement scores were analyzed. RESULTS The average segmented volume of the intracavitary applicator significantly (p < 0.05) decreased with the experimental pulse sequence parameters as compared to the standard pulse sequence. Comparison of experimental and standard T2w sequence qualitative scores for each reviewer showed no significant differences between the two techniques. CONCLUSIONS This study demonstrated that pulse sequence parameter optimization can significantly reduce distortion artifact from titanium applicators while maintaining image quality and reasonable imaging times.