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Extracellular vesicles (EV) in the tumor microenvironment have emerged as crucial mediators that promote proliferation, metastasis, and chemoresistance. However, the role of circulating small EVs (csEV) in cancer progression remains poorly understood. In this study, we report that csEV facilitate cancer progression and determine its molecular mechanism. csEVs strongly promoted the migration of cancer cells via interaction with phosphatidylserine of csEVs. Among the three TAM receptors, TYRO3, AXL, and MerTK, TYRO3 mainly interacted with csEVs. csEV-mediated TYRO3 activation promoted migration and metastasis via the epithelial–mesenchymal transition and stimulation of RhoA in invasive cancer cells. Additionally, csEV–TYRO3 interaction induced YAP activation, which led to increased cell proliferation and chemoresistance. Combination treatment with gefitinib and KRCT-6j, a selective TYRO3 inhibitor, significantly reduced tumor volume in xenografts implanted with gefitinib-resistant non–small cell lung cancer cells. The results of this study show that TYRO3 activation by csEVs facilitates cancer cell migration and chemoresistance by activation of RhoA or YAP, indicating that the csEV/TYRO3 interaction may serve as a potential therapeutic target for aggressive cancers in the clinic. Significance: These findings demonstrate that circulating extracellular vesicles are a novel driver in migration and survival of aggressive cancer cells via TYRO3 activation.

Background/Aims S-isomer (S) pantoprazole is more bioavailable and less dependent on cytochrome 2C19 than is racemic pantoprazole. We aim to evaluate the efficacy and safety of 10 mg S-pantoprazole for treatment of non-erosive reflux disease (NERD). Methods In this phase 3, double-blind, randomized placebo controlled, multicenter study, 174 NERD patients were randomized to one of both treatment groups: 10 mg S-pantoprazole, or placebo once daily for 4 weeks. Symptoms and safety were assessed. The efficacy endpoints were complete relief of symptoms, > 50% improvement of all reflux symptoms and recurrence. Results Eighty-eight patients were assigned to the S-pantoprazole group (25 males, mean 43.7 years old) and 86 to the placebo group (32 males, mean 43.0 years old), and 163 patients were subjected to full Analysis Set. A higher proportion of patients in the S-pantoprazole group had complete symptom relief (42.0 % [34/81] vs 17.1% [14/82], P 50% symptom responses (66.0% vs 50.0%, P = 0.010 for heartburn; 64.2% vs 28.0%, P = 0.010 for acid regurgitation; and 51.9% vs 30.5%, P = 0.03 for epigastric discomfort) compared to the placebo group. The factors associated with poor responsiveness to PPI were older age, female, greater body mass index, and severe baseline symptoms. Conclusions Low dose of S-pantoprazole (10 mg) for 4 weeks was more efficacious than placebo in providing reflux symptom relief in patients with NERD, especially acid regurgitation. More doses or longer periods of treatment with S-pantoprazole would be needed to completely eliminate symptoms. (J Neurogastroenterol Motil 2021;27:223-230)

The goal of this study was to test whether ischemia-mediated contractile dysfunction underlying the mitral valve affects functional mitral regurgitation (FMR) and the prognostic impact of FMR.FMR results from left ventricular (LV) remodeling, which can stem from myocardial tissue alterations. Stress cardiac magnetic resonance can assess ischemia and infarction in the left ventricle and papillary muscles; relative impact on FMR is uncertain.Vasodilator stress cardiac magnetic resonance was performed in patients with known or suspected coronary artery disease at 7 sites. Images were centrally analyzed for MR etiology/severity, mitral apparatus remodeling, and papillary ischemia.A total of 8,631 patients (mean age 60.0 ± 14.1 years; 55% male) were studied. FMR was present in 27%, among whom 16% (n = 372) had advanced (moderate or severe) FMR. Patients with ischemia localized to subpapillary regions were more likely to have advanced FMR (p = 0.003); those with ischemia localized to other areas were not (p = 0.17). Ischemic/dysfunctional subpapillary myocardium (odds ratio: 1.24/10% subpapillary myocardium; confidence interval: 1.17 to 1.31; p 0.001) was associated with advanced FMR controlling for infarction. Among a subgroup with (n = 372) and without (n = 744) advanced FMR matched (1:2) on infarct size/distribution, patients with advanced FMR had increased adverse mitral apparatus remodeling, paralleled by greater ischemic/dysfunctional subpapillary myocardium (p 0.001). Although posteromedial papillary ischemia was more common with advanced FMR (p = 0.006), subpapillary ischemia with dysfunction remained associated (p 0.001), adjusting for posteromedial papillary ischemia (p = 0.074). During follow-up (median 5.1 years), 1,473 deaths occurred in the overall cohort; advanced FMR conferred increased mortality risk (hazard ratio: 1.52; 95% confidence interval: 1.25 to 1.86; p 0.001) controlling for left ventricular ejection fraction, infarction, and ischemia.Ischemic and dysfunctional subpapillary myocardium provides a substrate for FMR, which predicts mortality independent of key mechanistic substrates.

Background/Aims: Ulcerative colitis (UC) is an inflammatory bowel disease for which new serological markers are required. The purpose of this study was to assess the role of the mucosa-associated epithelial chemokine CCL28 in UC. Methods: The study included 50 patients; of these, 25 were patients with UC, and 25 were healthy controls. The levels of serum CCL28 were analyzed using enzyme-linked immunosorbent assay. CCL28 expression was analyzed by immunohistochemistry (IHC) in 15 representative colon tissues biopsied based on disease activity (UC patients with severe activity, five samples; UC patients with mild activity, five samples; healthy controls, five samples). Results: The serum CCL28 levels were remarkably higher (p

Objective It is unclear if stopping treatment with dabigatran, a new oral anticoagulant (NOAC), induces a paradoxical rebound prothrombotic state. We investigated if short-term (1-3 days) dabigatran cessation is associated with a higher thrombus volume than expected from a simple reversal of the anticoagulant effect. Methods Ten-week-old C57Bl/6 mice (n=338) received one of the following oral treatments: phosphate-buffered saline (PBS), dabigatran for 7 days with or without 1-4 day cessation, and aspirin in either a single dose or daily for 7 days. Some of the animals that ceased dabigatran for 1-3 days received single-dose aspirin. Thereafter, we induced FeCl3 -mediated carotid thrombosis in 130 mice, after which we performed microCT thrombus imaging. The other 208 mice underwent coagulation assays or platelet function tests. As an explorative pilot study, we reviewed the medical records of 18 consecutive patients with NOAC cessation-related cerebral infarction in a large acute stroke cohort. Results We observed a higher volume of carotid thrombus after dabigatran cessation at 1-3 days than after vehicle treatment and showed that this effect could be prevented by single-dose aspirin pretreatment. Dabigatran cessation unduly increased platelet aggregability for 2 days after drug cessation, an effect mediated through arachidonic acid or thrombin, which effect was significantly attenuated by single-dose aspirin pretreatment. In patients, short-term (≤3 day) cessation of NOAC therapy, compared with longer-term (≥5 days) cessation, tended to be associated with relatively high stroke severity. Interpretation We provide the first preclinical evidence that a rebound prothrombotic state follows short-term cessation of dabigatran therapy. This article is protected by copyright. All rights reserved.

Background Coronavirus disease 2019 (COVID-19) is a growing pandemic that confers augmented risk for right ventricular (RV) dysfunction and dilation; the prognostic utility of adverse RV remodeling in COVID-19 patients is uncertain. Objectives The purpose of this study was to test whether adverse RV remodeling (dysfunction/dilation) predicts COVID-19 prognosis independent of clinical and biomarker risk stratification. Methods Consecutive COVID-19 inpatients undergoing clinical transthoracic echocardiography at 3 New York City hospitals were studied; images were analyzed by a central core laboratory blinded to clinical and biomarker data. Results In total, 510 patients (age 64 ± 14 years, 66% men) were studied; RV dilation and dysfunction were present in 35% and 15%, respectively. RV dysfunction increased stepwise in relation to RV chamber size (p = 0.007). During inpatient follow-up (median 20 days), 77% of patients had a study-related endpoint (death 32%, discharge 45%). RV dysfunction (hazard ratio [HR]: 2.57; 95% confidence interval [CI]: 1.49 to 4.43; p = 0.001) and dilation (HR: 1.43; 95% CI: 1.05 to 1.96; p = 0.02) each independently conferred mortality risk. Patients without adverse RV remodeling were more likely to survive to hospital discharge (HR: 1.39; 95% CI: 1.01 to 1.90; p = 0.041). RV indices provided additional risk stratification beyond biomarker strata; risk for death was greatest among patients with adverse RV remodeling and positive biomarkers and was lesser among patients with isolated biomarker elevations (p ≤ 0.001). In multivariate analysis, adverse RV remodeling conferred a >2-fold increase in mortality risk, which remained significant (p, Central Illustration

The detection of spontaneous coronary artery dissection (SCAD) causing myocardial infarction is integral in pursuing the appropriate management. Our case posed a diagnostic challenge, with Takotsubo cardiomyopathy and coronary embolism among the potential differential diagnoses upon the initial presentation. Extensive propagation of spontaneous coronary artery dissection subsequently resulted in a significant challenge to management requiring surgical revascularization. (Level of Difficulty: Intermediate.), Graphical abstract, The detection of spontaneous coronary artery dissection (SCAD) causing myocardial infarction is integral in pursuing the appropriate management. Our case posed a diagnostic challenge…

Background Presentation of life-threatening arrhythmias concomitantly with a new-onset non-ischaemic cardiomyopathy raises concern for an inflammatory cardiomyopathy such as cardiac sarcoidosis or cardiac manifestations of connective tissue disease. Comprehensive workup for specific aetiologies may be unrevealing except for signs of myocardial inflammation identified on cardiac positron emission tomography (PET). Here, we present five cases of such subjects and their clinical course. Case summary We collected clinical, imaging, pathological, and follow-up data of five subjects presenting with arrhythmias and unexplained new-onset cardiomyopathy. Mean age was 56.2 ± 5.8 years. Three subjects presented with ventricular tachycardia and two with atrial arrhythmias. Echocardiography showed a mean left ventricular ejection fraction of 37 ± 9%. Significant coronary artery disease was ruled out in all cases as the cause of the cardiomyopathy. All patients underwent cardiac magnetic resonance imaging (MRI) and PET scan at presentation and follow-up. In all patients, cardiac MRI revealed hyperenhancement in epicardial and mid-myocardial pattern in a non-coronary distribution, while PET scan revealed fluorodeoxyglucose (FDG) mismatch defects in multiple foci in a non-coronary distribution. Right ventricular biopsy was obtained in all patients and revealed interstitial fibrosis and cardiomyocyte hypertrophy. On median follow-up of 210 days, all subjects had improvement in both heart failure symptoms and arrhythmias and repeat PET in four out of five patients showed decreased inflammation. Discussion A high level of suspicion for inflammatory cardiomyopathy is needed in patients presenting with new unexplained cardiomyopathy and arrhythmias. A cardiac FDG-PET should be considered for diagnosis if cardiac inflammation is in the differential. This can inform further decisions regarding targeted immunomodulation therapy that may be helpful in this cohort.

Biopsies with conventional forceps beyond the operating range are difficult and cumbersome. Thus, we developed a new bendable forceps for improved access to gastrointestinal lesions and evaluated its technical feasibility. A bendable forceps was constructed with two channels and a two-stage knob. The bending motion-related structures were designed to improve the range of motion. For the evaluation of the forceps, we used 2 gastrointestinal simulators: an ex vivo porcine model, and an in vivo porcine model with some difficult endoscopic biopsy cases. All evaluations were performed by 5 expert endoscopists and an expert pathologist. Compared with the conventional forceps, the bendable forceps had greater efficacy in the simulator (6.2 ± 0.4 vs. 1.96 ± 0.2, p

Purpose To use delayed enhancement cardiac magnetic resonance (DE-CMR) as a reference standard to evaluate the prevalence and predictors of right atrial (RA) thrombus. Methods In this retrospective study, 130 cancer patients with central venous catheters undergoing CMR from August 2012–January 2018 were included. CMR (cine-CMR and DE-CMR) and echocardiography were interpreted for RA thrombus blinded to other imaging results and clinical data. RA thrombus properties including the number of discrete masses, size, total thrombus area, and perimeter were also assessed. Cine-CMR was also used to quantify cardiac structure and function as markers of RA thrombus. Student's t-test was used to assess continuous variables; chi-square or Fisher's exact test were used to assess categorical variables. Results 31/130 (24%) patients had RA thrombus on DE-CMR. Echocardiography (attained in 64% of the study population) demonstrated moderate sensitivity and specificity (75%, 90% respectively) in relation to DE-CMR; cine-CMR performance was higher (sensitivity 90%, specificity 98%). Patients with and without RA thrombus had similar right-sided structure/function and cancer diagnosis. Catheter depth approached significance in patients with RA thrombus (p = 0.05). 13% of patients with RA thrombus had concomitant pulmonary embolism within 60 days of CMR vs. 2% of patients without RA thrombus (p = 0.03). Embolic events were independent of RA thrombus size (p = 0.66). Conclusion Morphologic imaging by cine-CMR and echocardiography provide limited diagnostic utility for RA thrombus as established by DE-CMR tissue characterization. Catheter-associated RA thrombus occurs independently of right-sided structure or function and is associated with clinical embolic events and catheter depth.

Purpose Echocardiography (echo) is widely used for right ventricular (RV) assessment. Current techniques for RV evaluation require additional imaging and manual analysis; machine learning (ML) approaches have the potential to provide efficient, fully automated quantification of RV function. Methods An automated ML model was developed to track the tricuspid annulus on echo using a convolutional neural network approach. The model was trained using 7791 image frames, and automated linear and circumferential indices quantifying annular displacement were generated. Automated indices were compared to an independent reference of cardiac magnetic resonance (CMR) defined RV dysfunction (RVEF

Background and aims Exercise training (ET) helps treat atherosclerosis. However, many patients stop regular ET for various reasons. The effect of detraining on atherosclerosis is not well studied. We examined the effects of ET vs. short-term detraining on atheromatous matrix-metalloproteinase (MMP) activity in preexisting plaque and circulating cytokines/lipids. Methods and results Eighteen-week-old apolipoprotein-E−/− mice (n = 56) on a Western diet underwent: 1) ET for 6-weeks (ET5+1), 2) ET for 5-weeks and detraining for 1-week (ET5+0), 3) ET for the last 1-week (ET0+1), or 4) no treadmill ET at all for 6-weeks (ET0+0). Atheromatous MMP-activity was visualized using molecular imaging with an MMP-2/9-activatable near-infrared-fluorescent probe. Compared with no ET (ET0+0), regular ET (ET5+1) decreased carotid atheromatous MMP activity, but this protective effect was significantly blunted by short-term detraining (ET5+0). Short-term detraining after longer-term ET showed a reduction in MMP-activity similar to short-term ET (ET0+1). Blood levels of lipids and cytokines paralleled the molecular imaging results: exercise caused higher levels of high-density lipoprotein, adiponectin, and interleukin-10 and lower levels of vascular cell adhesion molecule, monocyte chemoattractant protein-1, interleukin-1β, and low-density lipoprotein. However, this beneficial effect was short-lived, with the ET5+0 group being similar to the ET0+0 group, and the ET0+1 group being similar to the ET5+1 group. The effect of exercise can be modeled with an exponential-decay of the protective factor of about 15%/day. Conclusions Even short-term detraining reduces atheroprotective effects, and tips the balance towards atherosclerosis. This suggests that ET, to be effective, needs to be prolonged and regular, and that detraining should be avoided.

IMPORTANCE Detailed incidence data for cataract surgery in the general population are limited, yet important for determining the surgical needs of the community and formulation of healthcare policies. BACKGROUND To report incidence rates of cataract surgery in South Korea. DESIGN Nationwide, retrospective population-based study. PARTICIPANTS This study involved the entire population of South Korea (n = 47 990 761); 2 236 107 eyes of 1 591 176 patients confirmed as having cataract surgery from 1 January 2011 to 31 December 2015 were included. METHODS Data for all patients who underwent primary cataract surgery in South Korea were retrieved using Korean Electronic Data Interchange and Korean Standard Classification of Diseases-7 codes. Annual incidence rates were calculated and adjusted to the national population data for the corresponding year. MAIN OUTCOME MEASURES The average incidence of cataract surgery during the 5-year study period was estimated using population data from the 2010 Korean census. RESULTS The incidence of cataract surgery increased from 8.54/1000 person-years in 2011 to 9.67/1000 person-years in 2015. The probability of second-eye surgery within 12 months after the first-eye surgery increased from 42.98% in 2011 to 48.01% in 2015. In total, 85.72% of surgeries were performed in non-rural areas: 43.18% in individuals with a higher household income and 76.65% in primary healthcare centres. The rate of vitrectomy for posterior capsular rupture was 0.72%. CONCLUSIONS AND RELEVANCE The incidence of cataract surgery in South Korea is increasing over time. Our findings are expected to aid in the formulation of future healthcare policies concerning cataract surgery in South Korea.

Myeloproliferative neoplasm (MPN) has been associated with pulmonary hypertension (PH) on the basis of small observational studies, but the mechanism and clinical significance of PH in MPN are not well established. The aims of this study were to expand understanding of PH in a well-characterized MPN cohort via study of PH-related symptoms, mortality risk, and cardiac remodeling sequalae of PH using quantitative echocardiographic methods.The population comprised a retrospective cohort of patients with MPN who underwent transthoracic echocardiography: Doppler-derived pulmonary arterial systolic pressure applied established cutoffs for PH (≥35 mm Hg) and advanced PH (≥50 mm Hg); right ventricular (RV) performance was assessed via conventional indices (tricuspid annular plane systolic excursion [TAPSE], S') and global longitudinal strain. Symptoms and mortality were discerned via standardized review.Three hundred one patients were studied; 56% had echocardiography-demonstrated PH (20% advanced) paralleling a high prevalence (67%) among patients with invasively quantified PASP. PH was associated with adverse left ventricular (LV) remodeling indices, including increased myocardial mass and diastolic dysfunction (P ≤ .001 for all): LV mass and filling pressure (P .01) were associated with PH independent of LV ejection fraction. RV dysfunction by strain and TAPSE and S' increased in relation to PH (P ≤ .001) and was about threefold greater among patients with advanced PH compared with those without PH. Patients with RV dysfunction were more likely to report dyspnea, as were those with advanced PH (P .05). During median follow-up of 2.2 years, all-cause mortality was 27%. PH grade (hazard ratio, 1.9; 95% CI, 1.1-3.0; P = .012) and TAPSE- and S'-demonstrated RV dysfunction (hazard ratio, 3.3; 95% CI, 1.3-8.2; P = .01) were independently associated with mortality; substitution of global longitudinal strain for TAPSE and S' yielded similar associations of RV dysfunction with death (hazard ratio, 3.2; 95% CI, 1.5-6.7; P = .003) independent of PH.PH is highly prevalent in patients with MPN and is linked to LV diastolic dysfunction; echocardiography-quantified RV dysfunction augments risk for mortality independent of PH.

Background Echocardiography (echo) is widely used to guide therapeutic decision-making for patients being considered for MitraClip. Relative utility of two- (2D) and three-dimensional (3D) echo predictors of MitraClip response, and impact of MitraClip on mitral annular geometry, are uncertain. Methods The study population comprised patients with advanced (> moderate) MR undergoing MitraClip. Mitral annular geometry was quantified on pre-procedural 2D transthoracic echocardiography (TTE) and intra-procedural 3D transesophageal echocardiography (TEE); 3D TEE was used to measure MitraClip induced changes in annular geometry. Optimal MitraClip response was defined as ≤mild MR on follow-up (mean 2.7 ± 2.5 months) post-procedure TTE. Results Eighty patients with advanced MR underwent MitraClip; 41% had optimal response (≤mild MR). Responders had smaller pre-procedural global left ventricular (LV) end-diastolic size and mitral annular diameter on 2D TTE (both p ≤ 0.01), paralleling smaller annular area and circumference on 3D TEE (both p = 0.001). Mitral annular size yielded good diagnostic performance for optimal MitraClip response (AUC 0.72, p 2/m2 [CI 1.19–3.13], p = 0.007) and global LV end-diastolic volume on 2D TTE (OR 1.29 per 10 ml/m2 [CI 1.02–1.63], p = 0.03). Substitution of 2D TTE derived mitral annular diameter for 3D TEE data demonstrated a lesser association between pre-procedural annular size (OR 5.36 per cm/m2 [CI 0.95–30.19], p = 0.06) and sub-optimal MitraClip response. Matched pre- and post-procedural TEE analyses demonstrated MitraClip to acutely decrease mitral annular area and circumference (all p p mild MR) on followup TTE (p = 0.017); greater magnitude of device-induced annular reduction remained associated with sub-optimal MitraClip response even when normalized for pre-procedure annular circumference (p = 0.028). Conclusions MitraClip alters mitral annular geometry as quantified by intra-procedural 3D TEE. Pre-procedural mitral annular dilation and magnitude of device-induced reduction in mitral annular size on 3D TEE are each associated with sub-optimal therapeutic response to MitraClip.

Background/Aims Irsogladine maleate, an enhancer of gastric mucosal protective factors, has demonstrated its efficacy for various gastric mucosal injuries. The aim of this study was to evaluate the efficacy and safety of irsogladine for prevention of nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin-induced peptic ulcer and gastritis. Methods In this multicenter, randomized, double-blind, exploratory clinical trial, 100 patients over 50 years of age who needed continuous NSAIDs or aspirin for more than 8 weeks were randomly assigned to either test group (irsogladine maleate 2 mg, twice daily, 39 patients for full analysis) or placebo group (37 patients for full analysis). Primary outcomes were incidence of peptic ulcer and ratio of modified Lanza score (MLS) 2 to 4. Secondary outcome was the number of acute erosions confirmed by endoscopy at 8 weeks. Adverse effects were also compared. Results There were no significant differences in gastric protective effects between test and placebo groups. However, two cases of peptic ulcer in the placebo group but none in the test group were observed. These two cases of peptic ulcer were Helicobacter pylori-negative. In addition, H. pylori-negative group showed significant changes in MLS score (p = 0.0247) and edema score (p = 0.0154) after the treatment compared to those before treatment in the test group. There was no significant difference in adverse events between the two groups. Conclusions The efficacy of irsogladine maleate was found in H. pylori-negative group, suggesting its potential as a protective agent against NSAIDs or aspirin-induced peptic ulcer and gastritis.

Stimuli-responsive systems are attractive since their properties can be controlled by external stimuli and/or surrounding environment. Recently, more than one stimulus is utilized in order to enhance the performance of systems, or to bypass undesired effects. However, most of previous research on multi-stimuli has been focused on enhancing or inducing changes in one type of response. Herein, we developed a nanocomposite material with independent multi-states composed of photo-responsive polymer and quantum dots (QDs), in which its properties can independently be controlled by different wavelengths of light. More specifically, azobenzene-incorporated poly(dimethylsiloxane) (AzoPDMS) triggers photobending (PB) by 365 nm light and uniformly dispersed methylammonium lead bromide perovskite (MAPbBr3) QDs show photoluminescence (PL) by light below 500 nm. The PB and PL could be simultaneously and independently controlled by the wavelength of applied light creating multi-states. Our approach is novel in that it creates multiple independent states which can further be used to transfer information such as logic gates (00(2), 01(2), 10(2), 11(2)) and possibly widen its application to flexible and transparent opto-electric devices.

Objective Atrial cardiopathy without atrial fibrillation (AF) may be a potential cardiac source of embolic strokes of undetermined source (ESUS). Atrial volume is a feature of atrial cardiopathy, but the relationship between atrial volume and ESUS remains unclear. Methods We compared left atrial volume among ischemic stroke subtypes in the Cornell Acute Stroke Academic Registry (CAESAR), which includes all patients with acute ischemic stroke at our hospital since 2011. Stroke subtype was determined by neurologists per the TOAST classification and consensus ESUS definition. Left atrial volume index (LAVI) was obtained directly from our echocardiography image system (Xcelera, Philips Healthcare). We used t‐tests and analysis of variance for unadjusted comparisons and targeted minimum loss‐based estimation for comparisons adjusted for demographics and comorbidities. Results Among 2116 patients in CAESAR from 2011 to 2016, 1293 had LAVI measurements. LAVI varied across subtypes (P

Background: The short-term risk of ischemic stroke in patients with left ventricular (LV) thrombus identified via delayed-enhancement cardiac magnetic resonance (DE-CMR) imaging is uncertain. Methods: We performed a retrospective cohort study of patients who underwent DE-CMR for evaluation of LV systolic dysfunction at NewYork-Presbyterian Hospital/Weill Cornell between 2007 and 2016. We identified all hospitalized patients who had DE-CMR evidence of LV thrombus, and as controls, all hospitalized patients who had no DE-CMR evidence of LV thrombus; 2 control patients were randomly selected for each patient with LV thrombus. Our primary outcome was ischemic stroke prior to hospital discharge. Additionally, we compared the risk of stroke among patients with: (1) no LV thrombus, (2) LV thrombus by DE-CMR but not by echocardiography, and (3) LV thrombus by both DE-CMR and echocardiography. Results: We identified 33 patients with LV thrombus and 66 patients without LV thrombus on DE-CMR. Of the 33 patients with LV thrombus on DE-CMR, 13 had echocardiographic evidence of thrombus. Ischemic stroke occurred in 3 of 33 (9.1%; 95% CI, 1.9%-24.3%) patients with LV thrombus on DE-CMR. Ischemic stroke occurred in 0 of 66 (0%; 95% CI, 0%-5.4%) patients without LV thrombus on DE-CMR, 1 of 20 (5.0%; 95% CI, .1%-24.9%) patients with thrombus on DE-CMR but not echocardiogram, and 2 of 13 (15.4%; 95% CI, 1.9%-45.4%) patients with thrombus on both DE-CMR and echocardiogram (P value for comparison among groups, .02). Conclusions: We found a 9% short-term risk of ischemic stroke in patients with LV thrombus detected on DE-CMR.

(1) Background: Household humidifier disinfectant (HD) brands containing polyhexamethylene guanidine (PHMG) have been found to cause the most HD-associated lung injuries (HDLIs) in the Republic of Korea. Nevertheless, no study has attempted to characterize the potential association of the health effects, including HDLI, with the physicochemical properties of PHMG dissolved in different HD brands. This study aimed to characterize the molecular weight (MW) distribution, the number-average molecular weight (Mn), the weight-average molecular weight (Mw), and the structural types of PHMG used in HD products. (2) Methods: Quantitative measurements were made using matrix-assisted laser desorption/ionization–time-of-flight mass spectrometry (MALDI-TOF MS). The Mn, Mw, and MW distributions were compared among various HD products. (3) Results: The mean Mn and Mw were 542.4 g/mol (range: 403.0–692.2 g/mol) and 560.7 g/mol (range: 424.0–714.70 g/mol), respectively. The degree of PHMG oligomerization ranged from 3 to 7. The MW distribution of PHMG indicated oligomeric compounds regardless of the HD brands. (4) Conclusions: Based on the molecular weight distribution, the average molecular weight of PHMG, and the degree of polymerization, the PHMG collected from HDLI victims could be regarded as an oligomer. PHMG, as used in household humidifiers, should not be exempted from toxic chemical registration as a polymer. Further study is necessary to examine the association of PHMG oligomeric compounds and respiratory health effects, including HDLI.

Arthropod-borne infectious diseases cause many deaths and a major economic burden worldwide. Repellents play an important role in protecting people from infectious biting arthropods. The repellency of veratraldehyde, a known food additive, and the WJ-1041 formulation containing 10% veratraldehyde was tested against Aedes albopictus and Culex pipiens pallens females and Haemaphysalis longicornis nymphs using arm-in-cage, indoor or filter paper tests. Veratraldehyde exhibited repellency similar to or lower than that of n,n-diethyl-meta-toluamide (DEET) against A. albopictus, but in H. longicornis, the activity of veratraldehyde was better than that of DEET. The repellency of the 10% veratraldehyde solution was comparable to that of 20% DEET against the two mosquitoes. When comparing repellency between the WJ-1041 formulation (10% veratraldehyde) and 10% DEET against C. pipiens pallens, A. Albopictus and H. longicornis, the two showed similar repellency and complete protection time (CPT) values. However, there was a small difference depending on the tested insects. The absorption of veratraldehyde via skin was minimal, if at all. The pharmacokinetic parameters (Cmax and Tmax) of veratraldehyde in blood samples of rats were not different from those of the control group. Based on these results, veratraldehyde has high potential to be commercialized as a repellent agent against infectious disease-borne pests in the near future.

Stent migration is a significant obstacle to successful stent placement. There has been no investigation of the effect and quantitative interpretation of flaps attached to a plastic stent (PS) on antimigration. The antimigration effects of the number of flaps on a PS in a 3D-printed pancreatic phantom (3DP) and extracted porcine pancreas (EPP) were investigated. Four PS types were used in this study: stent without flaps (type 1), stent with two flaps (type 2), stent with four horizontally made flaps (type 3), and stent with four vertically made flaps (type 4). The stents were measured and compared for antimigration force (AMF) in the 3DP and EPP using a customized measuring method and an integrated measuring device. The mean maximum AMFs (MAMFs) in types 2, 3, and 4 were significantly higher than that in type 1 (all p &lt, 0.001). Moreover, the mean MAMFs in types 3 and 4 were significantly higher than that in type 2 (all p &lt, 0.001). When the flaps were removed from the pancreatic duct, the AMF decreased rapidly. As the number of flaps increased, the antimigration effects significantly increased in the 3DP and EPP. However, the direction of the flaps did not affect the MAMF. The position of the flaps attached to the surface of the stent affected the AMF.

BackgroundLate gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) is widely used to identify cardiac neoplasms, for which diagnosis is predicated on enhancement stemming from lesion vascularity: Impact of contrast-enhancement pattern on clinical outcomes is unknown. The objective of this study was to determine whether cardiac metastasis (CMET) enhancement pattern on LGE-CMR impacts prognosis, with focus on heterogeneous lesion enhancement as a marker of tumor avascularity.MethodsAdvanced (stage IV) systemic cancer patients with and without CMETmatched (1:1) by cancer etiology underwent a standardized CMR protocol. CMETwas identified via established LGE-CMR criteria based on lesion enhancement; enhancement pattern was further classified as heterogeneous (enhancing and non-enhancing components) or diffuse and assessed via quantitative (contrast-to-noise ratio (CNR); signal-to-noise ratio (SNR)) analyses. Embolic events and mortality were tested in relation to lesion location and contrast-enhancement pattern.Results224 patients were studied, including 112 patients with CMETand unaffected (CMET-) controls matched for systemic cancer etiology/stage. CMETenhancement pattern varied (53% heterogeneous, 47% diffuse). Quantitative analyses were consistent with lesion classification; CNR was higher and SNR lower in heterogeneously enhancing CMET(p MET(hazard ratio [HR] = 1.64 [CI 1.17–2.29], p = 0.004) compared to controls, but varied by contrast-enhancement pattern: Diffusely enhancing CMEThad equivalent mortality to controls (p = 0.21) whereas prognosis was worse with heterogeneous CMET(p = 0.005) and more strongly predicted by heterogeneous enhancement (HR = 1.97 [CI 1.23–3.15], p = 0.005) than lesion size (HR = 1.11 per 10 cm [CI 0.53–2.33], p = 0.79).ConclusionsContrast-enhancement pattern and location of CMETon CMR impacts prognosis. Embolic events vary by CMETlocation, with likelihood of PE greatest with right-sided lesions. Heterogeneous enhancement—a marker of tumor avascularity on LGE-CMR—is a novel marker of increased mortality risk.

BACKGROUND: Although the number of vascular surgeries performed is increasing, the incidence of complications associated with this surgery has not improved and re-operations are frequently required. Thrombosis in a vessel is the most hazardous postoperative complication. OBJECTIVE: The aim of this study was to evaluate the anti-thrombotic and anti-inflammatory effects of sulodexide compared to aspirin in a rat model. METHODS: We divided the animals into three groups (sham (saline), aspirin, and sulodexide). The abdominal aorta was surgically opened and closed, primarily with 8/0 Prolene sutures. Postoperatively, saline, aspirin, or sulodexide was administered by oral gavage for 14 days to the rats. The degree of neovascularization, thrombus, calcification, inflammatory infiltrates, and fibrosis were analyzed histopathologically by hematoxylin and eosin staining. RESULTS: There was no significant difference in the incidence of postoperative thrombogenesis, but less calcification and inflammatory infiltrates were observed in the sulodexide group compared to the aspirin group. Histopathologic score revealed less infiltration of inflammatory cells and mild calcification for the sulodexide group (0.17±0.41 and 1.33±0.52, respectively) compared to the aspirin group (0.67±0.52 and 1.67±0.52, respectively) at days 14. CONCLUSIONS: This study offers the possibility that sulodexide could be used as an aspirin substitute for the postoperative management of vascular patients, with low gastrointestinal discomfort. In addition, it may also offer reduced postoperative calcification and inflammation.

To discuss the epidemiology of pulmonary valve (PV) disorders, anatomy and pathology of the PV, and current treatment strategies for PV disorders with special attention to the patient with congenital heart disease. The focus will be on utilization of multimodality imaging methods including echocardiography, cardiac CT, and MRI in the evaluation and management of PV disorders. The PV is affected in a myriad of congenital and acquired conditions, leading to stenotic, regurgitant, or mixed lesions. In addition to echocardiography, imaging modalities such as cardiac magnetic resonance imaging (MRI) and cardiac computed tomography (CT) are used to identify PV abnormalities and their sequelae including right ventricular dilation and dysfunction. In conjunction with open-heart surgery, transcatheter PV interventions offer outstanding therapeutic options with high success and low-risk profiles. PV disorders can range from benign to complex cyanotic congenital lesions. In the present era, many of these conditions are successfully treated by transcatheter interventions or surgery. Multimodality imaging techniques provide useful information for the diagnosis and management of these conditions.

Tricuspid regurgitation (TR) is a failure in right-sided AV valve function which, if left untreated, leads to marked cardiac shape changes and heart failure. However, the specific right ventricular shape changes resulting from TR are unknown. The goal of this study is to characterize the RV shape changes of patients with severe TR. RVs were segmented from CINE MRI images. Using particle-based shape modeling (PSM), a dense set of homologous landmarks were placed with geometric consistency on the endocardial surface of each RV, via an entropy-based optimization of the information content of the shape model. Principal component analysis (PCA) identified the significant modes of shape variation across the population. These modes were used to create a patient-prediction model. 32 patients and 6 healthy controls were studied. The mean RV shape of TR patients demonstrated increased sphericity relative to controls, with the three most dominant modes of variation showing significant widening of the short axis of the heart, narrowing of the base at the RV outflow tract (RVOT), and blunting of the RV apex. By PCA, shape changes based on the first three modes of variation correctly identified patient vs. control hearts 86.5% of the time. The shape variation may further illuminate the mechanics of TR-induced RV failure and recovery, providing potential targets for therapies including novel devices and surgical interventions.

Following our report that A(3) adenosine receptor (AR) antagonist 1 exhibited a polypharmacological profile as a dual modulator of peroxisome proliferator-activated receptor (PPAR)γ/δ, we discovered a new template, 1′-homologated adenosine analogues 4a–4t, as dual PPARγ/δ modulators without AR binding. Removal of binding affinity to A(3)AR was achieved by 1′-homologation, and PPARγ/δ dual modulation was derived from the structural similarity between the target nucleosides and PPAR modulator drug, rosiglitazone. All the final nucleosides were devoid of AR-binding affinity and exhibited high binding affinities to PPARγ/δ but lacked PPARα binding. 2-Cl derivatives exhibited dual receptor-binding affinity to PPARγ/δ, which was absent for the corresponding 2-H derivatives. 2-Propynyl substitution prevented PPARδ-binding affinity but preserved PPARγ affinity, indicating that the C2 position defines a pharmacophore for selective PPARγ ligand designs. PPARγ/δ dual modulators functioning as both PPARγ partial agonists and PPARδ antagonists promoted adiponectin production, suggesting their therapeutic potential against hypoadiponectinemia-associated cancer and metabolic diseases.

Chronic Obstructive Pulmonary Diseases (COPD) is a complex disease with considerable variability affecting about 65 million individuals [1]. We therefore performed a genome-wide association study (GWAS) of COPD severity. Thirty-four genetic variants were identified $(P\lt 1.0\times 10^{-5})$, and were located in intron and upstream/downstream regions. In conclusion, these genetic markers could provide insight into the understanding the pathological process of COPD.

Yeasts are promising industrial hosts for sustainable production of fuels and chemicals. Apart from efficient bioethanol production, yeasts have recently demonstrated their potential for biodiesel production from renewable resources. The fuel-oriented product profiles of yeasts are now expanding to include non-native chemicals with the advances in synthetic biology. In this review, current challenges and opportunities in yeast engineering for sustainable production of non-native chemicals will be discussed, with a focus on the comparative evaluation of a bioethanol-producing Saccharomyces cerevisiae strain and a biodiesel-producing Yarrowia lipolytica strain. Synthetic pathways diverging from the distinctive cellular metabolism of these yeasts guide future directions for product-specific engineering strategies for the sustainable production of non-native chemicals on an industrial scale.

Intestinal fibrosis induced by chronic and recurrent colitis, which is exacerbated by bowel stenosis, stricture, and obstruction, is challenging to treat. Toll-like receptor 4 (TLR4) stimulates innate and acquired immunity in response to specific microbial components, but the role of TLR4 in intestinal fibrosis is largely unknown. We investigated its role in intestinal fibrosis using not only a murine fibrosis model but also human myofibroblasts and intestinal epithelial cells. Colon fibrosis was induced in TLR4-deficient (TLR4−/−) mice and its wild-type counterparts with 3% dextran sulfate sodium. Absence of TLR4 gene attenuated chronic inflammation and colonic macrophages infiltration; intestinal fibrosis and collagen deposition were suppressed. Also, the production of tumor necrosis factor-α, interleukin-12p40, and transforming growth factor-β was reduced in TLR4-deficient peritoneal macrophages. TLR4 was silenced in CCD-18Co cells by small interfering RNA (siRNA), and matrix metalloproteinase-1, tissue inhibitor of metalloproteinase, and collagen α1 expression was evaluated. Role of TLR4 in epithelial-mesenchymal transition (EMT) was evaluated in HCT116 cells. Suppression of TLR4 transcription by siRNAs affected myofibroblasts activity, collagen synthesis, and EMT in the human cancer cell line. Thus, we suggest that TLR4 can be an essential mediator in intestinal chronic inflammation and fibrosis, indicating that TLR4 signaling is a potential therapeutic target for intestinal fibrosis.

This study aimed to quantify both chloromethylisothiazolinone (CMIT) and methylisothiazolinone (MIT) dissolved in different product brands and to characterize the exposure to these chemicals among humidifier disinfectant-associated lung injury (HDLI) patients. Both CMIT and MIT dissolved in different humidifier disinfectant (HD) products were quantified using gas chromatography&ndash, mass spectrometry. The inhalation level of CMIT and MIT was estimated based on HD-associated factors as reported by HDLI patients. A total of eleven HD products marketed until the end of 2011 were found to contain CMIT and/or MIT. The level of combined CMIT and/or MIT dissolved in these HD products ranged from 12 to 353 ppm. The level varied among HD products and the year of manufacture. The average inhalation levels were estimated to be 7.5, 4.1, and 3.2 &mu, g/m3 for the definite, probable, and possible groups, respectively. If probable and possible groups were collapsed together, the inhalation level of the collapsed group was significantly different from that of the definite group (p &lt, 0.001). All HDLI patients responded as having used HD not only while sleeping, but also as having a humidifier treated with HD within close proximity every day in insufficiently ventilated spaces. These HD use characteristics of patients may be directly/indirectly linked to the HDLI development.

Right ventricular hypertrophy (RVH) provides a key remodeling index alterable by pulmonary hypertension. Although echocardiography commonly integrates linear wall thickness and chamber dimensions to quantify left ventricular remodeling, the utility of an equivalent right ventricular (RV)-based approach is unknown.This was a retrospective analysis of 200 patients undergoing transthoracic echocardiography and cardiac magnetic resonance (CMR) within 30 days (median = 3 days; interquartile range, 15 days), stratified by echocardiography-quantified pulmonary artery systolic pressure (35, 35 to55, 55 to75, or ≥75 mm Hg). Echocardiographic assessment included RV linear dimensions in parasternal long-axis and apical four-chamber views and wall thicknesses in parasternal long-axis, four-chamber, and subcostal views. Subcostal wall thickness was integrated with chamber diameters to calculate RV mass, which was tested in relation to CMR-quantified RV mass and all-cause mortality.Echocardiography-based quantification of all linear dimensions was feasible in 95% of patients (190 of 200). RV wall thicknesses in all orientations increased in relation to pulmonary artery systolic pressure (P .001) and was greater among patients with, versus those without, CMR-evidenced RVH (P .001 for all). Correlations between echocardiography and CMR were greatest for RV basal diameter (r = 0.73), RV subcostal wall thickness (r = 0.71), and global RV mass (r = 0.82; P .001 for all). Echocardiography-derived global RV mass cutoffs were established in a derivation cohort and tested in a validation cohort. Results demonstrated good sensitivity and specificity (75.5% and 74.0%, respectively) in relation to CMR-quantified RVH. During follow-up (median, 4.2 years), 18% of patients (n = 36) died. Echocardiography-evidenced RVH (hazard ratio, 1.98; 95% CI, 1.09-3.88; P = .048) conferred similar mortality risk compared with RVH on CMR (hazard ratio, 2.41; 95% CI, 1.22-4.78; P = .01).Echocardiography-quantified RV parameters provide a robust index of RV afterload. Global RV mass calculated using a novel echocardiographic formula based on readily available linear indices yields good diagnostic performance for CMR-evidenced RVH and confers increased mortality risk.

Rapid advancements in technology and electronic medical record systems have given rise to massive amounts of cardiac imaging data with the potential to alter medical practices. The rise of machine learning (ML) and radiomics – the concept that images contain invaluable data regarding disease processes beyond what the eyes can see – promises increased precision and accuracy to the current standard of care. Recent advancements in major cardiac imaging modalities, such as echocardiography, cardiac CT and cardiac MRI, have uncovered promising diagnostic and prognostic information through the application of ML. In echocardiography, ML has been successfully applied to identify views, make right- and left-sided heart measurements, and detect certain diseases like hypertrophic cardiomyopathy. Application of ML in cardiac CT has seen success in quantifying coronary plaque burden, identifying significant coronary stenosis, and predicting mortality in coronary artery disease (CAD). In cardiac MRI, efforts have been made to automatize segmentation for chamber measurements and detecting fibrosis. For nuclear imaging, ML has been applied to not only make measurements like the left ventricular ejection fraction, but also to identify perfusion abnormalities and predict obstructive CAD. While there are many milestones still to be reached before ML can be widely integrated to current clinical practices, there is optimism for ML to advance the field of cardiovascular imaging through enhanced image analysis and improved efficiency.

OBJECTIVES Aortic valve replacement (AVR) potentially can modify pulse-wave propagation to the distal aorta. Echo-derived global circumferential strain (GCS) was used to test whether AVR for aortic stenosis (AS) or aortic insufficiency (AI) resulted in differential aortic biomechanics in the descending thoracic aorta. DESIGN This was a prospective observational study of patients who underwent cardiac surgery between 2016 and 2019. SETTING Weill Cornell Medicine, a single large academic medical center. PARTICIPANTS The population comprised 48 patients undergoing AVR (62 ± 15 y/o, 79% male; 22 with AI and 26 with AS) and 11 patients undergoing coronary bypass surgery as controls. INTERVENTIONS Elective cardiac surgery, transesophageal echocardiography (TEE), pulmonary artery catheter. MEASUREMENTS AND MAIN RESULTS Pre- and postprocedural TEEs were collected. Descending aorta short-axis images were analyzed for GCS, time-to-peak strain, aortic end-diastolic, end-systolic area, and fractional area changes. Pulse pressure (PP) and stroke volume were quantified. Preprocedural GCS significantly differed between patients with AI and AS, with AI patients having greater GCS (median/interquartile range, 9.6 95.3,13.6) than patients with AS (4.3 [3.4-5.1]). After AVR, in AI patients, strain significantly decreased (5.5 [3.8,8.2], p = 0.001), along with PP (mean ± standard deviation) (66.4 ± 0.8 to 54.1 ± 13.7, p < 0.001), and PP corrected strain did not (GCS/PP = 14.8 [6.9-19.9] v 12.7[8.2-18.6], p = 0.34). In AS patients, GCS significantly increased after AVR to (5.45 [4.2-6.8], p = 0.003), as did PP-corrected strain (6.9 [5.8-9.2] v 9.7 [6.5-13.4], p = 0.016). Surgical AVR produced decrements in time-to-peak strain in AI and AS groups (both p < 0.001). CONCLUSIONS After AVR for AI and AS, the direction of change in distal aortic strain from baseline depends on valve pathology. This finding may have important clinical implications in terms of indication for surgery and postoperative surveillance, especially in patients with aortopathies.

There is currently no governmental body in South Korea resembling the type of poison center (PC) recommended by the World Health Organization (WHO). All Organization for Economic Cooperation and Development (OECD) member countries except for South Korea maintain such a PC tasked with both preventing poisoning accidents and supporting the prompt treatment of poisoned patients. Such a PC could very possibly have allowed the country to more promptly recognize the widespread wave of humidifier disinfectant (HD) associated health effects, including fatal lung injury and death, that lasted started roughly in 2000 and continued through 2011. Despite this chemical poisoning tragedy, South Korea still lacks a surveillance system to monitor health effects caused by the use and consumption of materials that include products containing chemicals, foodborne pathogens, drugs, pesticides, etc. There have been no legal procedures for examining the potential risk of products or materials manufactured by industry. The reporting of national poisoning data or causes of poisoning, which is near ubiquitous in advanced countries with a PC, has not taken place We recommend that a PC should be established within the Korea Disease Control and Prevention Agency (KDCA). In addition, in order to perform surveillance of poisoning cases across the country, a certain number of regional PCs, including at large hospitals, will also be necessary.

OBJECTIVES: The aims of this study were to test the magnitude of agreement between echocardiography- (echo) and cardiac magnetic resonance (CMR)-derived left atrial (LA) strain and to study their relative diagnostic performance in discriminating diastolic dysfunction (DD) and predicting atrial fibrillation (AF). BACKGROUNDS: Peak atrial longitudinal strain (PALS) is a novel performance index. Utility of echo-quantified LA strain has yet to be prospectively tested in relation to current DD guidelines or compared to CMR. METHODS: The study population comprised 257 post-myocardial infarction (MI) patients undergoing echo and CMR, including prospective derivation (n = 157) and clinical validation (n = 100) cohorts. DD was graded on echo using established consensus guidelines blinded to strain results. RESULTS: PALS on both echo and CMR was nearly 2-fold lower among patients with versus no DD (p < 0.001) and was significantly different in those with mild versus no DD (p < 0.01). In contrast, LA geometric parameters including echo- and CMR-derived volumes were significantly different between advanced versus no DD groups (p < 0.001) but not between groups with mild versus no DD (all p > 0.05). Echo and CMR PALS yielded small differences irrespective of orientation and similar diagnostic performance for DD in the derivation (area under the curve: 0.70 to 0.78) and validation (area under the curve 0.75 to 0.78) cohorts. Impaired PALS on both modalities was independently associated with MI size (p < 0.001). During 4.4 ± 3.8 years of follow-up in the derivation cohort, 8% developed AF. Both 2-chamber echo- and CMR-derived PALS stratified arrhythmic risk (p = 0.004 and p = 0.02, respectively), including a 4-fold difference among patients in the Lowest versus remainder of quartiles of echo-derived PALS (24% vs. 6%). Similarly, echo and CMR PALS were Lower (both p < 0.05) among patients with subsequent heart failure hospitalizations. CONCLUSIONS: Echo-derived PALS parallels results of CMR, yields incremental diagnostic utility versus LA geometry for stratifying presence and severity of DD, and improves prediction of AF and congestive heart failure after MI.

Objective: The automation of insulin treatment is the most challenge aspect of glucose management for type 1 diabetes owing to unexpected exogenous events (e.g., meal intake). In this article, we propose a novel reinforcement learning (RL) based artificial intelligence (AI) algorithm for a fully automated artificial pancreas (AP) system. Methods: A bioinspired RL designing method was developed for automated insulin infusion. This method has reward functions that imply the temporal homeostatic objective and discount factors that reflect an individual specific pharmacological characteristic. The proposed method was applied to a training method using an RL algorithm and was evaluated in virtual patients from the FDA approved UVA/Padova simulator with unannounced meal intakes. Results: For a single-meal experiment with preprandial fasting, the trained policy demonstrated fully automated regulation in both the basal and postprandial phases. In the in silico trial with a variation of insulin sensitivity and dawn phenomenon, the policy achieved a mean glucose of 124.72 mg/dL and percentage time in the normal range of 89.56%. The layer-wise relevance propagation provides interpretable information on AI-driven decision for robustness to sensor noise, automated postprandial regulation, and insulin stacking avoidance. Conclusion: The AP algorithm based on the bioinspired RL approach enables fully automated blood glucose control with unannounced meal intake. Significance: The proposed framework can be extended to other drug-based treatments for systems with significant uncertainties.

Objective Revascularization via coronary artery bypass grafting (CABG) remains a common therapy for coronary artery disease. CABG-based revascularization is most commonly performed via either single arterial graft (SAG) or multiple arterial grafting (MAG) strategies. Echo-derived global and regional longitudinal strain was used to test where SAG or MAG results in immediate differences in left ventricular (LV) function after CABG. Materials and methods Pre- and postprocedural intraoperative transesophageal echos were prospectively collected. Two-dimensional LV images were analyzed for global and regional longitudinal strain (GLS), LV ejection fraction, end-diastolic volume, end-systolic volume, and stroke volume (SV). Results Twenty patients underwent open, on-pump CABG (63.9 ± 10 years old, 85% male; 10 with SAG and 10 with MAG. Preprocedural GLS significantly differed between patients with SAG and MAG, with patients with MAG having greater GLS (mean [standard deviation, SD], 20.41 [5.54]) than patients with SAG (16.28 [3.48]). After CABG, in patients with MAG, LV strain decreased both globally (-1.13 [3.15]) and regionally in the anterior-lateral (-1.22 [3.84]) and inferior-lateral regions (-1.32 [5.69]), along with LVEF. In patients with SAG, LV strain increased after CABG globally (1.34 [2.73]) and regionally in the anterior-lateral (1.20 [6.49]) and inferior-lateral regions (0.39 [7.26]), as did LVEF and SV. Postprocedure, more patients with MAG were given vasopressor (100% vs 60%) and inotrope infusions (70% vs 40%) than patients with SAG. Conclusions After CABG, LV function quantified through GLS changes both globally and regionally increased after SAG and decreased after MAG. This finding may have important clinical implications in terms of optimizing intraoperative management for patients with CABG and have the potential to guide the improvement of clinical outcomes.

OBJECTIVES To assess impact of left ventricular (LV) chamber remodeling on MitraClip (MClp) response. BACKGROUND MitraClip is the sole percutaneous therapy approved for mitral regurgitation (MR) but response varies. LV dilation affects mitral coaptation; determinants of MClp response are uncertain. METHODS LV and mitral geometry were quantified on pre- and post-procedure two-dimensional (2D) transthoracic echocardiography (TTE) and intra-procedural three-dimensional (3D) transesophageal echocardiography (TEE). Optimal MClp response was defined as ≤mild MR at early (1-6 month) follow-up. RESULTS Sixty-seven degenerative MR patients underwent MClp: Whereas MR decreased ≥1 grade in 94%, 39% of patients had optimal response (≤mild MR). Responders had smaller pre-procedural LV end-diastolic volume (94 ± 24 vs. 109 ± 25 mL/m2 , p = 0.02), paralleling smaller annular diameter (3.1 ± 0.4 vs. 3.5 ± 0.5 cm, p = 0.002), and inter-papillary distance (2.2 ± 0.7 vs. 2.5 ± 0.6 cm, p = 0.04). 3D TEE-derived annular area correlated with 2D TTE (r = 0.59, p

Background/objectives This study examined the association between refined grain consumption by subtype and the incidence of hypertension from the Korean Genome and Epidemiology Study data. Subjects/methods In total, 5,018 participants (2,439 men and 2,579 women) from 40 to 69 years without hypertension were recruited at the beginning (2001-2002). Blood pressure and antihypertensive medication use were assessed biennially for the incidence of hypertension during the 8-year follow-up period (2009-2010). Hypertension was diagnosed as systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg or antihypertensive medication use. Dietary intake including refined grains was assessed by a food frequency questionnaire at baseline and the follow-up (2005-2006). A multivariate Cox proportional hazard model was used to examine hazard ratios (HRs) and 95% confidence intervals (CIs) for incident hypertension according to refined-grain consumption. Results A total of 1,377 cases of hypertension (710 men and 667 women) were newly ascertained. Frequent noodle consumers (≥ 5 servings/week) among the women had a 2.3-fold higher risk of hypertension than infrequent noodle consumers after adjustment for potential confounders (HR = 2.31, 95% CI = 1.33-4.01, P for trend = 0.0001). However, no significant association was found among the men. The intake of other refined grain products such as white rice and breads was not associated with the incidence of hypertension. Conclusions Frequent noodle consumption was positively associated with a risk of incident hypertension in South Korean women.

Global longitudinal strain (GLS) has emerged as a valuable diagnostic and prognostic tool for evaluating left ventricular (LV) function. GLS has been shown to be a more sensitive marker of LV dysfunction than LV ejection fraction alone and have prognostic impact in non-surgical cardiac populations. GLS, is validated, reproducible, and easily obtained from 2-dimensional speckle- tracking echocardiography. While there is strong evidence for using GLS in clinical decision- making in non-surgical populations, there is less summarized evidence on using GLS in the cardiac surgical population. This review combines the evidence on the implications of using baseline transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) GLS in cardiac surgical populations including ischemic and structural heart disease to determine surgical outcomes. We found that results seem promising on the prognostic utility of LV strain in cardiac surgical populations. However due to the variability of study populations and outcomes, and modalities (TTE versus TEE), further research on normal versus abnormal values for different surgical populations, as well potential treatment options that may modify and potentially decrease surgical risk for those with abnormal GLS are needed.

CRT is a cornerstone of therapy for patients with heart failure and reduced ejection fraction. By restoring left ventricular (LV) electrical and mechanical synchrony, CRT can reduce mortality, improve LV function and reduce heart failure symptoms. Since its introduction, many advances have been made that have improved the delivery of and enhanced the response to CRT. Improving CRT outcomes begins with proper patient selection so CRT is delivered to all populations that could benefit from it, and limiting the implantation of CRT in those with a small chance of response. In addition, advancements in LV leads and delivery technologies coupled with multimodality imaging and electrical mapping have enabled operators to place coronary sinus leads in locations that will optimise electrical and mechanical synchrony. Finally, new pacing strategies using LV endocardial pacing or His bundle pacing have allowed for CRT delivery and improved response in patients with poor coronary sinus anatomy or lack of response to traditional CRT.

BACKGROUND Whereas cardiac magnetic resonance (CMR) imaging provides high temporal resolution imaging of aortic distensibility (strain), transesophageal echocardiography (TEE) is widely used for intra-operative aortic imaging and provides a clinical alternative for aortic assessment. We tested intra-operative global circumferential aortic strain (GCS) measured on TEE in relation to the reference of CMR-derived strain among patients undergoing surgical graft repair of ascending aortic aneurysms. METHODS CMR (3T) was prospectively performed in patients scheduled for aortic repair. TEE was performed intra-operatively; images were co-localized with MRI. GCS on CMR and TEE was quantified independently, blinded to results of the other modality. RESULTS 25 patients (54 ± 10 year-old, 88% male) were studied, inclusive of 13 genetically mediated and 12 degenerative aneurysms: CMR and TEE were performed within 12 ± 9 days. Pulse pressure (PP)-adjusted descending aortic TEE-derived GCS strongly correlated with cine-CMR-derived GCS (r = .75, P = .002) though absolute GCS and PP-adjusted values were slightly lower (5.40 ± 1.11 vs 6.49 ± 1.43% and 11.55 ± 3.04 vs 13.99 ± 4.53%, respectively). Similarly, TEE yielded slightly lower end-diastolic area (EDA [5.1 ± 1.7 cm2 vs 5.8 ± 1.3 cm2 , P = .004]) and end-systolic area (ESA [6.1 ± 1.9 cm2 vs 6.5 ± 1.7 cm2 , P = .10]), with significant correlations between the two modalities (r = .73, .76, P

Our study examines the power of language in shaping immigrants’ engagement in occupations during their integration into a host society. Beyond serving as a means of communication, language is under...

This paper proposes a deep learning approach to learning and predicting network-wide vehicle movement patterns in urban networks. Inspired by recent success in predicting sequence data using recurrent neural networks (RNN), specifically in language modeling that predicts the next words in a sentence given previous words, this research aims to apply RNN to predict the next locations in a vehicle’s trajectory, given previous locations, by viewing a vehicle trajectory as a sentence and a set of locations in a network as vocabulary in human language. To extract a finite set of “locations,” this study partitions the network into “cells,” which represent subregions, and expresses each vehicle trajectory as a sequence of cells. Using large amounts of Bluetooth vehicle trajectory data collected in Brisbane, Australia, this study trains an RNN model to predict cell sequences. It tests the model’s performance by computing the probability of correctly predicting the next [Formula: see text] consecutive cells. Compared with a base-case model that relies on a simple transition matrix, the proposed RNN model shows substantially better prediction results. Network-level aggregate measures such as total cell visit count and intercell flow are also tested, and the RNN model is observed to be capable of replicating real-world traffic patterns.

Innate immune cells recruited to inflammatory sites have short life spans and originate from the marrow, which is distributed throughout the long and flat bones. While bone marrow production and release of leukocyte increases after stroke, it is currently unknown whether its activity rises homogeneously throughout the entire hematopoietic system. To address this question, we employed spectrally resolved in vivo cell labeling in the murine skull and tibia. We show that in murine models of stroke and aseptic meningitis, skull bone marrow-derived neutrophils are more likely to migrate to the adjacent brain tissue than cells that reside in the tibia. Confocal microscopy of the skull–dura interface revealed myeloid cell migration through microscopic vascular channels crossing the inner skull cortex. These observations point to a direct local interaction between the brain and the skull bone marrow through the meninges.

We enzymatically prepared structured monogalactosydiacylglycerols (MGDGs) enriched in pinolenic acid (PLA). PLA-enriched free fatty acids (FFAs) containing ∼86 mol % PLA were produced from an FFA fraction obtained from pine nut oil (PLA content, ∼13 mol %) by urea crystallization. Commercial MGDGs (5 mg) were acidolyzed with PLA-enriched FFAs using four commercial immobilized lipases as biocatalysts. The reaction was performed in acetone (4 mL) in a stirred-batch reactor. Lipozyme RM IM (immobilized Rhizomucor miehei lipase) was the most effective biocatalyst for the reaction. Structured MGDGs containing 42.1 mol % PLA were obtained under optimal reaction conditions: temperature, 25 °C; substrate molar ratio, 1:30 (MGDGs/PLA-enriched FFAs); enzyme loading, 20 wt % of total substrates; and reaction time, 36 h. The structured MGDGs were separated from the reaction products at a purity of 96.6 wt % using silica column chromatography. The structured MGDGs could be possibly used as emulsifiers with appetite-suppression effects.

Therapy for moderate ischemic mitral regurgitation remains unclear. Determination of myocardial viability, a necessary prerequisite for an improvement in regional contractility, is a likely key factor in determining response to revascularization alone. Myocardial strain has been proposed as a viability measure but has not been compared with late gadolinium enhancement (LGE) cardiac magnetic resonance imaging. We hypothesized that abnormal strain overestimates nonviable left ventricular (LV) segments measured with LGE and that ischemia and mechanical tethering by adjacent transmural myocardial infarction (TMI) also decreases strain in viable segments.Sixteen patients with mild or greater ischemic mitral regurgitation and 7 healthy volunteers underwent cardiac magnetic resonance imaging with noninvasive tags (complementary spatial modulation of magnetization [CSPAMM]), LGE, and stress perfusion. CSPAMM images were post-processed with harmonic phase and circumferential and longitudinal strains were calculated. Viability was defined as the absence of TMI on LGE (hyperenhancement50% of wall thickness). The borderzone was defined as any segment bordering TMI. Abnormal strain thresholds (±1 to 2.5 SDs from normal mean) were compared with TMI, ischemia, and borderzone.7.4% of LV segments had TMI on LGE, and more than 14.5% of LV segments were nonviable by strain thresholds (p0.005). In viable segments, ischemia impaired longitudinal strain (least perfused one-third of LV segments: -0.18 ± 0.08 versus most perfused: -0.22 ± 0.1, p = 0.01) and circumferential strain (-0.12 ± 0.1 versus -0.16 ± 0.08, p0.05). In addition, infarct proximity impaired longitudinal strain (-0.16 ± 0.11 borderzone versus -0.18 ± 0.09 remote, p = 0.05).Impaired LV strain overestimates nonviable myocardium compared with TMI on LGE. Ischemia and infarct proximity also decrease strain in viable segments.

Fibroblastic reticular cells (FRCs) are stromal cells in secondary lymphoid organs, the major sites for HIV-1 infection of CD4+ T cells. Although FRCs regulate T cell survival, proliferation, and migration, whether they play any role in HIV-1 spread has not been studied. Here, we show that FRCs enhance HIV-1 spread via trans-infection in which FRCs capture HIV-1 and facilitate infection of T cells that come into contact with FRCs. FRCs mediate trans-infection in both two- and three-dimensional culture systems and in a manner dependent on the virus producer cells. This producer cell dependence, which was also observed for virus spread in secondary lymphoid tissues ex vivo, is accounted for by CD44 incorporated into virus particles and hyaluronan bound to such CD44 molecules. This virus-associated hyaluronan interacts with CD44 expressed on FRCs, thereby promoting virus capture by FRCs. Overall, our results reveal a novel role for FRCs in promoting HIV-1 spread., Fibroblastic reticular cells (FRCs) are important regulators of T cell survival, proliferation, and migration in secondary lymphoid organs, but their role in HIV infection isn’t studied. Here, Murakami et al. show that FRCs enhance HIV spread via CD44- and hyaluronan-mediated trans-infection.