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RNS60 is a physically modified saline solution hypothesized to contain oxygen nanobubbles. It has been reported to reduce ischemia/reperfusion injury in a pig model of acute myocardial infarction. We investigated the effects of RNS60 during cardiac hypoxia in mice and as an additive to cardioplegic solution in rat hearts. ApoE−/−LDLr−/− mice were treated by intravenous injection of RNS60 or saline as a control while monitoring the ECG and post-hypoxic serum release of troponin T and creatine kinase activity. Hearts infused with Custodiol containing 10% RNS60 or saline as the control were subjected to 4 h of 4 °C preservation, followed by an assessment of myocardial metabolites, purine release, and mechanical function. RNS60 attenuated changes in the ECG STU area during hypoxia, while the troponin T concentration and creatine kinase activity were significantly higher in the serum of the controls. During reperfusion after 4 h of cold ischemia, the Custodiol/RNS60-treated hearts had about 30% lower LVEDP and better dp/dtmax and dp/dtmin together with a decreased release of purine catabolites vs. the controls. The myocardial ATP, total adenine nucleotides, and phosphocreatine concentrations were higher in the RNS60-treated hearts. This study indicates that RNS60 enhances cardioprotection in experimental myocardial hypoxia and under conditions of cardioplegic arrest. Improved cardiac energetics are involved in the protective effect, but complete elucidation of the mechanism requires further study.

Adenosine is a small molecule directly involved in maintaining homeostasis under pathological and stressful conditions. Due to its rapid metabolism, delivery vehicles capable of exhibiting extended release of adenosine are of paramount interest. Herein, we demonstrate a superior long-term (9 days) release profile of adenosine from biocompatible MOFs in a physiologically relevant environment. The key to the biocompatibility of MOFs is their stability under biologically relevant conditions. This study additionally highlights the interplay between the chemical stability of prototypal MOFs, assessed under physiological conditions, and their cytotoxicity profiles. Cytotoxicity of the prototypal Zn-based MOF (ZIF-8) and three Zr-based MOFs (UiO-66, UiO-66-NH

Understanding the penetrance of pathogenic variants identified as secondary findings (SFs) is of paramount importance with the growing availability of genetic testing. We estimated penetrance through large-scale analyses of patients referred for diagnostic sequencing for hypertrophic cardiomyopathy (HCM; 10,400 cases, 1,340 variants) and dilated cardiomyopathy (DCM; 2,564 cases, 665 variants), using a cross-sectional approach comparing allele frequencies against reference populations (293,226 participants from UK Biobank and gnomAD). We generated updated prevalence estimates for HCM (1:543) and DCM (1:220).In aggregate, the penetrance by late adulthood of rare, pathogenic variants (23% for HCM, 35% for DCM) and likely pathogenic variants (7% for HCM, 10% for DCM) was substantial for dominant CM. Penetrance was significantly higher for variant subgroups annotated as loss of function or ultra-rare, and for males compared to females for variants in HCM-associated genes.We estimated variant-specific penetrance for 316 recurrent variants most likely to be identified as SFs (51% HCM and 17% DCM cases). 49 variants were observed at least ten times (14% of cases) in HCM-associated genes. Median penetrance was 14.6% (±14.4% SD). We explore estimates of penetrance by age, sex, and ancestry, and simulate the impact of including future cohorts.This dataset is the first to report penetrance of individual variants at scale and will inform the management of individuals undergoing genetic screening for SFs. While most variants had low penetrance and the costs and harms of screening are unclear, some carriers of highly penetrant variants may benefit from SFs.Graphical AbstractA flowchart of the estimated penetrance for dominant cardiomyopathy by late adulthood for a variant of interest. The estimates of penetrance in this study are for carriers identified from unselected populations (e.g., consumer-initiated elective genomic testing or as secondary (2°) findings in clinical settings). If the variant is ultra-rare (i.e., identified once or less in population datasets), only estimates by variant subgroup in aggregate are available. If the variant is identified multiple times in both case and population datasets, variant-specific penetrance estimates may be available. If the variant is curated as a variant of uncertain significance (VUS), the penetrance estimate is low. If the variant is a likely pathogenic predicted loss of function (pLoF) variant and is identifiable multiple times in cases and population cohorts, penetrance estimates vary by gene (Figure 2). High aggregate penetrance represents an estimate of >25%; moderate aggregate penetrance represents 10%-25%, and low penetrance represents

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.

Calcific aortic valve disease affects the aortic side of the valve, exposed to low magnitude multidirectional ("disturbed) blood flow, more than it affects the ventricular side, exposed to high magnitude uniaxial flow. Overt disease is preceded by endothelial dysfunction and inflammation. Here we investigate the potential role of the transforming growth factor-β (TGF-β) receptor ALK5 in this process. Although ECs are always subject to shear stress due to blood flow, and their responses to shear stress are important in healthy valve development and homeostasis, low magnitude multidirectional flow can induce pathophysiological changes. Previous work has shown ALK5 to be an important mechanosensor. ALK5 transduces mechanically sensed signals via the activation of the SMAD2/3 transcriptional modulators. However, it is currently unclear precisely how ALK5-mediated shear stress responses translate into pathological changes under conditions of chronically disturbed flow. Here, we demonstrate that ALK5 mechanosensory signalling influences flow-induced endothelial leukocyte adhesion and paracellular permeability. Low magnitude multidirectional flow resulted in downregulation of the receptor, accompanied by increased SMAD2 phosphorylation, in human umbilical vein endothelial cell (HUVEC) monolayers. These changes correlated with elevated monocyte adhesion and significantly increased transendothelial transport of an albumin-sized tracer. These effects were abolished by inhibition of ALK5 kinase activity. Analysis of ALK5 expression patterns in porcine aortic valve tissue corroborated the findings from cell-based experiments. Together, these results suggest that ALK5 has a role in shear stress-associated cardiovascular disease pathology, emphasising the importance of further mechanistic investigations and supporting it as a potential therapeutic target.

Cystic lesions found in and around the peritoneal cavity can often be challenging to diagnose owing to significant overlap in imaging appearance between the different entities. When the cystic lesion can be recognized to arise from one of the solid abdominal organs, the differential considerations can be more straightforward; however, many cystic lesions, particularly when large, cannot be clearly associated with one of the solid organs. Cystic lesions arising from the mesentery and peritoneum are less commonly encountered and can be caused by relatively rare entities or by a variant appearance of less-rare entities. The authors provide an overview of the classification of cystic and cystic-appearing lesions and the basic imaging principles in evaluating them, followed by a summary of the clinical, radiologic, and pathologic features of various cystic and cystic-appearing lesions found in and around the peritoneal cavity, organized by site of origin. Emphasis is given to lesions arising from the mesentery, peritoneum, or gastrointestinal tract. Cystic lesions arising from the liver, spleen, gallbladder, pancreas, urachus, adnexa, or soft tissue are briefly discussed and illustrated with cases to demonstrate the overlap in imaging appearance with mesenteric and peritoneal cystic lesions. When approaching a cystic lesion, the key imaging features to assess include cyst content, locularity, wall thickness, and presence of internal septa, solid components, calcifications, or any associated enhancement. While definitive diagnosis is not always possible with imaging, careful assessment of the imaging appearance, location, and relationship to adjacent structures can help narrow the differential diagnosis. Online supplemental material is available for this article. (©)RSNA, 2021

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.

LVAD therapy is an effective rescue in acute and especially chronic cardiac failure. In several scenarios, it provides a platform for regeneration and sustained myocardial recovery. While unloading seems to be a key element, pharmacotherapy may provide powerful tools to enhance effective cardiac regeneration. The synergy between LVAD support and medical agents may ensure satisfying outcomes on cardiomyocyte recovery followed by improved quality and quantity of patient life. This review summarizes the previous and contemporary strategies for combining LVAD with pharmacotherapy and proposes new therapeutic targets. Regulation of metabolic pathways, enhancing mitochondrial biogenesis and function, immunomodulating treatment, and stem-cell therapies represent therapeutic areas that require further experimental and clinical studies on their effectiveness in combination with mechanical unloading.

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.

Locoregional therapies can be offered to hepatocellular carcinoma patients as a bridge to transplant, to downstage disease burden for transplant eligibility, or for disease control to prolong survival. Systemic therapies also play a large role in HCC treatment, occasionally in conjunction with other methods. This manuscript reviews the various treatment options for HCC with a historically noncurative intent.

Artificial Intelligence (AI) continues to shape the practice of radiology, with imaging of hepatocellular carcinoma (HCC) being of no exception. This article prepared by members of the LI-RADS Treatment Response (TR LI-RADS) work group and associates, presents recent trends in the utility of AI applications for the volumetric evaluation and assessment of HCC treatment response. Various topics including radiomics, prognostic imaging findings, and locoregional therapy (LRT) specific issues will be discussed in the framework of HCC treatment response classification systems with focus on the Liver Reporting and Data System treatment response algorithm (LI-RADS TRA).

The COVID-19 pandemic has disrupted the radiology reading room with a potentially lasting impact. This disruption could introduce the risk of obviating the need for the reading room, which would be detrimental to many of the roles of radiology that occur in and around the reading room. This disruption could also create the opportunity for accelerated evolution of the reading room to meet the strategic needs of radiology and health care through thoughtful re-design of the virtual reading room. In this article, we overview the impact of the COVID-19 pandemic on radiology in our institution and across the country, specifically on the dynamics of the radiology reading room. We introduce the concept of the virtual reading room, which is a redesigned alternative to the physical reading room that can serve the diverse needs of radiology and healthcare during and beyond the pandemic.

Recently, laser radiation and nanomaterials have been utilized to improve biogas yield via anaerobic digestion of herd’s manure through biostimulating methanogenic bacteria. Yet, laser irradiation and nanomaterials as anaerobic bacteria stimulant could have environmental impacts that have not been assessed or known. The aim of the current research was to understand and evaluate variable laser doses in the presence of nickel nanoparticles (Ni NPs) and their environmental impacts during the production of biogas from treated manure. A life cycle assessment scheme was employed to achieve this aim. The used laser doses were 0.5 h, 1 h and 2 h and correlated to 1-h incandescent light exposure, where all treatments received 2 g/m3 Ni NPs. The outcomes were conferred in the pattern of specific influences for the biogas utilization and production as an energy source. The studied impacts were global warming, greenhouse gas emissions mitigation, acidification, eutrophication, ozone layer depletion, freshwater ecotoxicity and prospective human toxicity. Results revealed that laser irradiation with the addition of Ni NPs during the biostimulation of anaerobic digestion has the least environmental adverse effects when compared to the control group.

Mitral stenosis (MS) is associated with left atrial (LA) functional and morphological changes as a result of chronic increase in LA pressure. Relieving the mitral obstruction via balloon mitral valvuloplasty (BMV) might be associated with LA structural and functional remodeling. To study alterations of LA volume and functions 1 year following successful BMV in patients with isolated rheumatic severe mitral stenosis. Thirty patients (median age 33 years, 22 women) with severe rheumatic MS were included in the study. Using biplane method, trans-thoracic 2D echocardiography was used to estimate LA volume indexed to body surface area (BSA). Maximal, minimal and pre-A left atrial volumes were measured and indexed to BSA. LA volumetric functions were then assessed and the measurements were repeated 6 months and 1 year after successful valvuloplasty. At baseline, median mitral valve area (MVA) was 0.9 (0.6–1.3) cm2 measured by planimetry with a mean pressure gradient of 12.5 (8–24) mmHg. Following BMV, a significant regression of left atrial volume index was noticed at 6 months compared to baseline (51 vs. 60 ml/m2, p = 0.001) with a further decrease at 1 year (48 vs. 51 ml/m2, p = 0.03). At 6 months, volumetric assessment of left atrial functions showed a significant improvement in LA total emptying fraction (42% vs 30%, p = 0.001) as well as in LA passive emptying fraction (26% vs 14%, p = 0.033) and LA active emptying fraction (20% vs. 18%, p = 0.016). All these indices showed further improvement at 1 year [47% (P = 0.02), 29% (p = 0.03) and 31% (p = 0.001) respectively]. In patients with isolated rheumatic MS, mitral valvuloplasty was associated with a significant decline of LA volume accompanied by a significant improvement of its volumetric functions.

Aims Dilated cardiomyopathy (DCM) is associated with mutations in many genes encoding sarcomere proteins. Truncating mutations in the titin gene TTN are the most frequent. Proteomic and functional characterizations are required to elucidate the origin of the disease and the pathogenic mechanisms of TTN-truncating variants. Methods and results We isolated myofibrils from DCM hearts carrying truncating TTN mutations and measured the Ca2+ sensitivity of force and its length dependence. Simultaneous measurement of force and adenosine triphosphate (ATP) consumption in skinned cardiomyocytes was also performed. Phosphorylation levels of troponin I (TnI) and myosin binding protein-C (MyBP-C) were manipulated using protein kinase A and λ phosphatase. mRNA sequencing was employed to overview gene expression profiles. We found that Ca2+ sensitivity of myofibrils carrying TTN mutations was significantly higher than in myofibrils from donor hearts. The length dependence of the Ca2+ sensitivity was absent in DCM myofibrils with TTN-truncating variants. No significant difference was found in the expression level of TTN mRNA between the DCM and donor groups. TTN exon usage and splicing were also similar. However, we identified down-regulation of genes encoding Z-disk proteins, while the atrial-specific regulatory myosin light chain gene, MYL7, was up-regulated in DCM patients with TTN-truncating variants. Conclusion Titin-truncating mutations lead to decreased length-dependent activation and increased elasticity of myofibrils. Phosphorylation levels of TnI and MyBP-C seen in the left ventricles are essential for the length-dependent changes in Ca2+ sensitivity in healthy donors, but they are reduced in DCM patients with TTN-truncating variants. A decrease in expression of Z-disk proteins may explain the observed decrease in myofibril passive stiffness and length-dependent activation., Graphical Abstract

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.

To determine preferences of clinicians and surgeons regarding radiology reporting of liver observations in patients at risk for hepatocellular carcinoma (HCC). Members of the American College of Radiology Liver Imaging and Data Reporting System (LI-RADS) Outreach & Education Group (30 members) as well as Society of Abdominal Radiology Disease-Focused Panel on HCC diagnosis (27 members) created and distributed an 18-question survey to clinicians and surgeons, with focus on preferences regarding radiology reporting of liver observations in patients. The survey questions were directed to physician demographics, current use of LI-RADS by their local radiologists, their opinions about current LI-RADS and potential improvements. A total of 152 physicians responded, 66.4% (101/152) from North America, including 42 surgeons, 81 physicians and 29 interventional radiologists. Participants were predominantly from academic centers 83% (126/152), while 13.8% (21/152) worked in private/community centers and 3.2% (5/152) worked in a hybrid practice. Almost 90% (136/152) of participants preferred the use of LI-RADS (compared to nothing or other standardized reporting systems; OPTN and AASLD) to communicate liver-related observations. However, only 28.5% (43/152) of participants input was sought at the time of implementing LI-RADS in their institutions. Fifty-eight percent (88/152) of all participants found standardized LI-RADS management recommendations in radiology reports to be clinically helpful. However, a subgroup analysis of surgeons in academic centers showed that 61.8% (21/34) prefer not to receive standardized LI-RADS recommendations. Most participants preferred the use LI-RADS in reporting CT and MRI examination. When considering inclusion of management recommendations, radiologists should consult with their referring physicians, as preference may differ.

OBJECTIVES Following the Ross operation, the pulmonary autograft undergoes structural changes (remodelling). We sought to determine the extent, nature and possible determinants of long-term remodelling in the different components of the pulmonary autograft. METHODS Ten pulmonary autografts and 12 normal control valves (6 pulmonary and 6 aortic) were examined by conventional histology, immunocytochemistry and electron microscopy. The structural changes were quantified by morphometry. RESULTS The leaflets from free-standing root replacement valves demonstrated thickening to levels comparable to the normal aortic leaflets, largely due to the addition of a thin layer of ‘neointima’ formed of radial elastic fibres, collagen bundles and glycoaminoglycans, on the ventricular aspect of the leaflets. The leaflets of valves from sub-coronary implantation demonstrated a significantly thicker fibroelastic layer on the ventricularis and calcium deposition in the fibrosa. The media of the explanted valves showed increased number of lamellar units to levels comparable to normal aortic roots. Electron microscopy of valves inserted as free-standing roots showed increased organization into continuous layers. However, intralamellar components showed varying degrees of ‘disorganization’ in comparison to those in the normal aortic media. In addition, there was a marked increase in the number of vasa vasorum with thickened arteriolar wall in the outer media and adventitia. CONCLUSIONS Following the Ross operation, in the very long term, all components of the autograft showed varying degrees of remodelling, which was judged to be largely adaptive. Defining the type, determinants and possible functional effects of remodelling could help in understanding and optimizing the results of the Ross operation.

OBJECTIVE. The objective of this article is to assess the impact of integrating peer review in PACS on the reporting of discrepancies. Our hypothesis is that a PACS-integrated machine-randomized an...

Ten competition periods as treatments (T1-10) could be valuable for predicting increase productivity (W) T1 to T5 were allowed to infest the crop and (WF) T6 to T10 was kept weed free, weed competition periods for W and WFi.e. 3, 6, 9, 12 Weeks after emergence (WAE) and up to harvest. So, two field experiments were conducted season 2018 and 2019. Critical Periods for Weed Control (CPWC) was determined based on relative percentage yield ton/h-1 (SY %) of weed free as a check by fitting curves regression models (linear and non-linear, which recommended losing yield value 10%. with seed yield reduction t/h-1 declined from 2.3, 2.28 WF to 0.39- 0.36 W as a checked treatment for 1st, 2nd seasons, respectively about 83.33%, 85% due to relative seed yield. Gompertz as a non linear regression equation recorded 0.99* The effects of treatment classified into 3 groups where A involved 5 superior treatments (T1, T7, T8, T9 and T10). However, T4 and T5 described inferior treatments which located in group C. Low of weed density and increasing of weed index (WI %) 80% observed for 1st season of T4 but T5 was translocated with increasing both weeds number and severed for weed index. It could be summarized that it should be keeping crop weed-free during stages 2nd week and continue until 8th week after crop emergence, which is providing maximum seed yield of soybean.

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.

Objective: We have previously reported that human calcified aortic cusps have abundant expression of smooth muscle (SM) markers and co-activators. We hypothesised that cells in bicuspid aortic valve (BAV) cusps and those affected by rheumatic heart valve (RHV) disease may follow a similar phenotypic transition into smooth muscle cells, a process that could be regulated by transforming growth factors (TGFs). Aims: Cusps from 8 patients with BAV and 7 patients with RHV were analysed for ealy and late SM markers and regulators of SM gene expression by immunocytochemistry and compared to healthy aortic valves from 12 unused heart valve donors. The ability of TGFs to induce these markers in valve endothelial cells (VECs) on two substrates was assessed. Results: 7 out of 8 BAVs and all the RHVs showed an increased and atypical expression of early and late SM markers α-SMA, calponin, SM22 and SM-myosin. The SM marker coactivators were aberrantly expressed in 6 of the BAV and 6 of the RHV, in a similar regional pattern to the expression of SM markers. Additionally, regions of VECs, and endothelial cells lining the vessels within the cusps were found to be positive for SM markers and coactivators in 3 BAV and 6 RHV. Both BAVs and RHVs were significantly thickened and HIF1α expression was prominent in 4 BAVs and 1 RHV. The ability of TGFβs to induce the expression of SM markers and myocardin was greater in VECs cultured on fibronectin than on gelatin. Fibronectin was shown to be upregulated in BAVs and RHVs, within the cusps as well as in the basement membrane. Conclusion: BAVs and RHVs expressed increased numbers of SM marker-positive VICs and VECs. Concomittantly, these cells expressed MRTF-A and myocardin, key regulators of SM gene expression. TGFβ1 was able to preferentially upregulate SM markers and myocardin in VECs on fibronectin, and fibronectin was found to be upregulated in BAVs and RHVs. These findings suggest a role of VEC as a source of cells that express SM cell markers in BAVs and RHVs. The similarity between SM marker expression in BAVs and RHVs with our previous study with cusps from patients with aortic stenosis suggests the existance of a common pathological pathway between these different pathologies. Abbreviations: BAV, bicuspid aortic valve; RHV, rheumatic heart valve; SM, smooth muscle; TGF, transforming growth factor; MRTF-A, myocardin related transcription factor A; VIC, valve interstitial cell; VEC, valve endothelial cell; PCNA, proliferating nuclear cell antigen; HIF1α, hypoxia inducible factor 1α.

The lungs are the primary target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, with severe hypoxia being the cause of death in the most critical cases. Coronavirus disease 2019 (COVID-19) is extremely heterogeneous in terms of severity, clinical phenotype and, importantly, global distribution. Although the majority of affected patients recover from the acute infection, many continue to suffer from late sequelae affecting various organs, including the lungs. The role of the pulmonary vascular system during the acute and chronic stages of COVID-19 has not been adequately studied. A thorough understanding of the origins and dynamic behaviour of the SARS-CoV-2 virus and the potential causes of heterogeneity in COVID-19 is essential for anticipating and treating the disease, in both the acute and the chronic stages, including the development of chronic pulmonary hypertension. Both COVID-19 and chronic pulmonary hypertension have assumed global dimensions, with potential complex interactions. In this Review, we present an update on the origins and behaviour of the SARS-CoV-2 virus and discuss the potential causes of the heterogeneity of COVID-19. In addition, we summarize the pathobiology of COVID-19, with an emphasis on the role of the pulmonary vasculature, both in the acute stage and in terms of the potential for developing chronic pulmonary hypertension. We hope that the information presented in this Review will help in the development of strategies for the prevention and treatment of the continuing COVID-19 pandemic., In this Review, the authors discuss the potential causes of the heterogeneity of COVID-19 and summarize the pathobiology of the disease, with an emphasis on the role of the pulmonary vasculature in the acute stage and the potential for developing chronic pulmonary hypertension., Key points A thorough understanding of the dynamic behaviour of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential to understanding its heterogeneous effects on the pulmonary vasculature in patients with coronavirus disease 2019 (COVID-19).The severity and clinical phenotype of COVID-19 are influenced by host factors, including socioeconomic factors and genetics.Silent hypoxia is a major and independent cause of lung damage in COVID-19; the use of modern imaging techniques is proving to be very valuable in identifying silent hypoxia.The pulmonary vascular system has a major role in the pathobiology of COVID-19.Both COVID-19 and chronic pulmonary hypertension are global diseases with a complex interaction.

Despite numerous therapeutic advances in pulmonary arterial hypertension, patients continue to suffer high morbidity and mortality, particularly considering a median age of 50 years. This article explores whether early, robust reduction of right ventricular afterload would facilitate substantial improvement in right ventricular function and thus whether afterload reduction should be a treatment goal for pulmonary arterial hypertension. The earliest clinical studies of prostanoid treatment in pulmonary arterial hypertension demonstrated an important link between lowering mean pulmonary arterial pressure (or pulmonary vascular resistance) and improved survival. Subsequent studies of oral monotherapy or sequential combination therapy demonstrated smaller reductions in mean pulmonary arterial pressure and pulmonary vascular resistance. More recently, retrospective reports of initial aggressive prostanoid treatment or initial combination oral and parenteral therapy have shown marked afterload reduction along with significant improvements in right ventricular function. Some data suggest that reaching threshold levels for pressure or resistance (components of right ventricular afterload) may be key to interrupting the self-perpetuating injury of pulmonary vascular disease in pulmonary arterial hypertension and could translate into improved long-term clinical outcomes. Based on these clues, the authors postulate that improved clinical outcomes might be achieved by targeting significant afterload reduction with initial oral combination therapy and early parenteral prostanoids.

Background Inflammatory bowel disease(IBD) is a lifelong illness that mainly affects patients of working age with a significant impact on their professional life. In fact, the maintenance and promotion of employees is one of the important social goals and can be considered as a determinants of health for IBD patients. The aim of the study was to analyze the impact of disease on the working life among IBD patients and to characterize the breadth of challenges they experience in their workplace. Methods We conducted a cross-sectional study including working patients followed for IBD, over a 9-months period. We collected sociodemographic, clinico-biological and evolutionary data. We performed a survey among these patients using a self-report questionnairy on employment status, IBD-related difficulties at work and sick leave. Results We included 45 patients: 80% Crohn disease and 20% ulcerative colitis. The mean age was 44 years [20-72], the sex-ratio M/F was 0.7 and the average of follow-up was 9 years [1-18]. Civil servants represented 33% of the total population, those in the private sector 47%, and those in the liberal profession 20%. The most important socio-professional category was manual workers with 51%. Thirty-seven patients(82%) developed their disease after being employed with a mean delay of 142 months[2-648]. The average number of working hours per week was 38.84 [9-60]. The majority of the employees worked full time(84%), only seven subjects worked part-time, two of them because of their IBD. One in three patients claimed to have been exposed to at least one harmful agent during their professional career. The main complaint reported by the patients during the daily work was about physical fatigue (69%). The digestive symptoms were mainly abdominal pain(53%) evaluated according to VAS with a mean intensity of 2.8 [0 - 10], subocclusive syndrome(40%), presence of diarrhea(38%), incontinence and fecal impaction(22%) which was worsened by the absence of accessible restrooms(33%). Psychological repercussions such as anxiety and depression were mentioned in 27% of cases. The average absenteeism during the last twelve months was 49.6 days [0-240] and the average number of hospitalization days was 30.7 [0-150]. Twenty patients(44%) claimed that they were subject to a salary restriction because of their illness. Only five people had alreadỳ benefited from a contact with the occupational medicine and health service. Conclusion IBD has a negative impact on the working life of patients, due to uncomfortable symptoms, days of absenteeism, and unadapted workplaces, which can affect career plans, professional achievement, and income. Appropriate supports and accommodations to the workplace are needed in order to improve their working experience.

Background Inflammatory bowel disease(IBD) is a chronic disease usually diagnosed in early adulthood and characterized by unpredictable flare-ups and debilitating symptoms that can interfere with the patient's ability to work and perform daily activities. In fact, since work disability is difficult to quantify, several scores have been developed for this purpose. The Work Ability Index(WAI) is a validated practical tool to measure the work capacity of patients. The objective of this study was to assess work performance in patients followed for IBD using the WAI psychometric tool, and to identify predictive factors of work disability. Methods We conducted a cross-sectional study including working patients followed for IBD, over a 9-months period. We collected sociodemographic, clinico-biological and evolutionary data. Quality of life was assessed by the IBDQ questionnairy. Work capacity was assessed using the WAI, a short 7-item questionnairy, which classified work performance into four categories: poor (score between 7-27), moderate(28-36), good(37-43) and excellent(44-49). Results We included 45 patients: 80% Crohn disease and 20% ulcerative colitis. The mean age was 44 years[20-72], the sex-ratio M/F was 0.7, and the mean of follow-up time was 9 years[1-18]. The average number of working hours per week was 38.84 [9-60]. The mean absenteeism during the last twelve months was 49.6 days [0-240] and the average number of hospitalization days was 30.7 [0-150]. The mean WAI value was 32.58, which corresponds to a moderate work performance. Assessment of work performance according to the WAI questionnaire showed that 38% of patients (N=17) had poor work ability, 24% (N=11) moderate work ability, 33% (N=15) good work ability and only two patients had an excellent work ability. In univariate and multivariate study, predictive factors of disability at work in IBD patients were: Furthermore, the assessment of health-related quality of life by the IBDQ questionnairy showed a mean IBDQ value of 160.78 which corresponds to a moderate score relating a quality of life; 224 being the maximum score obtainable reflecting an optimal quality of life. In the analytical study and using Spearman's test, a statistically significant correlation was found between the WAI and IBDQ with a p-value Conclusion In our study, one third of patients had poor work capacity. Risk factors for poor performance were disease severity, presence of osteoarticular extraintestinal manifestation, and patients with children. The only protective factor identified was a high level of education. Thus, the Work Ability Index can be used as a screening tool to identify the need for rehabilitation.

The success of tissue-engineered heart valves rely on a balance between polymer degradation, appropriate cell repopulation, and extracellular matrix (ECM) deposition, in order for the valves to continue their vital function. However, the process of remodeling is highly dynamic and species dependent. The carbon fibers have been well used in the construction industry for their high tensile strength and flexibility and, therefore, might be relevant to support tissue-engineered hearts valve during this transition in the mechanically demanding environment of the circulation. The aim of this study was to assess the suitability of the carbon fibers to be incorporated into tissue-engineered heart valves, with respect to optimizing their cellular interaction and mechanical flexibility during valve opening and closure. The morphology and surface oxidation of the carbon fibers were characterized by scanning electron microscopy (SEM). Their ability to interact with human adipose-derived stem cells (hADSCs) was assessed with respect to cell attachment and phenotypic changes. hADSCs attached and maintained their expression of stem cell markers with negligible differentiation to other lineages. Incorporation of the carbon fibers into a stand-alone tissue-engineered aortic root, comprised of jet-sprayed polycaprolactone aligned carbon fibers, had no negative effects on the opening and closure characteristics of the valve when simulated in a pulsatile bioreactor. In conclusion, the carbon fibers were found to be conducive to hADSC attachment and maintaining their phenotype. The carbon fibers were sufficiently flexible for full motion of valvular opening and closure. This study provides a proof-of-concept for the incorporation of the carbon fibers into tissue-engineered heart valves to continue their vital function during scaffold degradation.

Computations of fractional flow reserve, based on CT coronary angiography and computational fluid dynamics (CT-based FFR) to assess the severity of coronary artery stenosis, was introduced around a decade ago and is now one of the most successful applications of computational fluid dynamic modelling in clinical practice. Although the mathematical modelling framework behind this approach and the clinical operational model vary, its clinical efficacy has been demonstrated well in general. In this review, technical elements behind CT-based FFR computation are summarised with some key assumptions and challenges. Examples of these challenges include the complexity of the model (such as blood viscosity and vessel wall compliance modelling), whose impact has been debated in the research. Efforts made to address the practical challenge of processing time are also reviewed. Then, further application areas – myocardial bridge, renal stenosis and lower limb stenosis – are discussed along with specific challenges expected in these areas.