A Fluorogenic Assay: Analysis of Chemical Modification of Lysine and Arginine to Control Proteolytic Activity of Trypsin.

The chemical modification of amino acids plays an important role in the modulation of proteins or peptides and has useful applications in the activation and stabilization of enzymes, chemical biology, shotgun proteomics, and the production of peptide-based drugs. Although chemoselective modification of amino acids such as lysine and arginine via the insertion of respective chemical moieties as citraconic anhydride and phenyl glyoxal is important for achieving desired application objectives and has been extensively reported, the extent and chemoselectivity of the chemical modification of specific amino acids using specific chemical agents (blocking or modifying agents) has yet to be sufficiently clarified owing to a lack of suitable assay methodologies. In this study, we examined the utility of a fluorogenic assay method, based on a fluorogenic tripeptide substrate (FP-AA1-AA2-AA3) and the proteolytic enzyme trypsin, in determinations of the extent and chemoselectivity of the chemical modification of lysine or arginine. As substrates, we used two fluorogenic tripeptide probes, MeRho-Lys-Gly-Leu(Ac) (lysine-specific substrate) and MeRho-Arg-Gly-Leu(Ac) (arginine-specific substrate), which were designed, synthesized, and evaluated for chemoselective modification of specific amino acids (lysine and arginine) using the fluorogenic assay. The results are summarized in terms of half-maximal inhibitory concentrations (IC50) for the extent of modification and ratios of IC50 values (IC50arginine/IC50lysine and IC50lysine/IC50arginine) as a measure of the chemoselectivity of chemical modification for amino acids lysine and arginine. This novel fluorogenic assay was found to be rapid, precise, and reproducible for determinations of the extent and chemoselectivity of chemical modification.

Triglyceride glucose index is a useful marker for predicting subclinical coronary artery disease in the absence of traditional risk factors.

BACKGROUND: Atherosclerotic cardiovascular (CV) events commonly occur in individuals with a low CV risk burden. This study evaluated the ability of the triglyceride glucose (TyG) index to predict subclinical coronary artery disease (CAD) in asymptomatic subjects without traditional CV risk factors (CVRFs). METHODS: This retrospective, cross-sectional, and observational study evaluated the association of TyG index with CAD in 1250 (52.8 ± 6.5 years, 46.9% male) asymptomatic individuals without traditional CVRFs (defined as systolic/diastolic blood pressure ≥ 140/90 mmHg; fasting glucose ≥126 mg/dL; total cholesterol ≥240 mg/dL; low-density lipoprotein cholesterol ≥160 mg/dL; high-density lipoprotein cholesterol < 40 mg/dL; body mass index ≥25.0 kg/m2; current smoking; and previous medical history of hypertension, diabetes, or dyslipidemia). CAD was defined as the presence of any coronary plaque on coronary computed tomographic angiography. The participants were divided into three groups based on TyG index tertiles. RESULTS: The prevalence of CAD increased with elevating TyG index tertiles (group I: 14.8% vs. group II: 19.3% vs. group III: 27.6%; P < 0.001). Multivariate logistic regression models showed that TyG index was associated with an increased risk of CAD (odds ratio [OR] 1.473, 95% confidence interval [CI] 1.026-2.166); especially non-calcified (OR 1.581, 95% CI 1.002-2.493) and mixed plaques (OR 2.419, 95% CI 1.051-5.569) (all P < 0.05). The optimal TyG index cut-off for predicting CAD was 8.44 (sensitivity 47.9%; specificity 68.5%; area under the curve 0.600; P < 0.001). The predictive value of this cut-off improved after considering the non-modifiable factors of old age and male sex. CONCLUSIONS: TyG index is an independent marker for predicting subclinical CAD in individuals conventionally considered healthy.

Three-Dimensional Computed Tomographic Analysis of Normal and Aneurysmal Aortic Roots: Is There a Specific Geometric Pattern in the Aortic Root?

Current knowledge of the aortic root geometric anatomy and its surgical implications remain limited. We analyzed multiple predefined parameters of the aortic root to increase our understanding of the geometric changes that occur in normal and aneurysmal transformations. Between November 2003 and September 2015, the aortic roots of 107 healthy subjects (control group) and 105 annuloaortic ectasia (AAE) patients (AAE group) were analyzed using multiplanar reformatted computed tomographic images. The intercommissural distance (ICD), sinus width (SW), and sinus volume (SV) of the left (LCS), right (RCS), and noncoronary sinuses (NCS) of Valsalva were adopted as study parameters. In the control group, all study parameters of the LCS were smaller than those of the RCS and the NCS. In the AAE group, all parameters of the LCS were significantly smaller than those of the RCS or NCS, but the RCS and NCS parameters were similar. Proportionately less LCS enlargement relative to either the RCS or NCS was observed in root aneurysm(AAE group) than in the control group. We observed a distinct aortic root geometric pattern which was characterized by the LCS being smaller than either the RCS or NCS, while the latter were similar. This geometric configuration was significantly accentuated in AAE patients due to the greater disproportionate disparity in the LCS relative to either the RCS or NCS than in the roots of normal control subjects. Clin. Anat. 32:117-123, 2019. © 2019 Wiley Periodicals, Inc.

Asymmetric and Reduced Xanthene Fluorophores: Synthesis, Photochemical Properties, and Application to Activatable Fluorescent Probes for Detection of Nitroreductase.

Xanthene fluorophores, including fluorescein, rhodol, and rhodamines, are representative classes of fluorescent probes that have been applied in the detection and visualization of biomolecules. "Turn on" activatable fluorescent probes, that can be turned on in response to enzymatic reactions, have been developed and prepared to reduce the high background signal of "always-on" fluorescent probes. However, the development of activity-based fluorescent probes for biological applications, using simple xanthene dyes, is hampered by their inefficient synthetic methods and the difficulty of chemical modifications. We have, thus, developed a highly efficient, versatile synthetic route to developing chemically more stable reduced xanthene fluorophores, based on fluorescein, rhodol, and rhodamine via continuous Pd-catalyzed cross-coupling. Their fluorescent nature was evaluated by monitoring fluorescence with variation in the concentration, pH, and solvent. As an application to activatable fluorescent probe, nitroreductase (NTR)-responsive fluorescent probes were also developed using the reduced xanthene fluorophores, and their fluorogenic properties were evaluated.

Machine learning assessment of myocardial ischemia using angiography: Development and retrospective validation.

BACKGROUND: Invasive fractional flow reserve (FFR) is a standard tool for identifying ischemia-producing coronary stenosis. However, in clinical practice, over 70% of treatment decisions still rely on visual estimation of angiographic stenosis, which has limited accuracy (about 60%-65%) for the prediction of FFR < 0.80. One of the reasons for the visual-functional mismatch is that myocardial ischemia can be affected by the supplied myocardial size, which is not always evident by coronary angiography. The aims of this study were to develop an angiography-based machine learning (ML) algorithm for predicting the supplied myocardial volume for a stenosis, as measured using coronary computed tomography angiography (CCTA), and then to build an angiography-based classifier for the lesions with an FFR < 0.80 versus ≥ 0.80. METHODS AND FINDINGS: A retrospective study was conducted using data from 1,132 stable and unstable angina patients with 1,132 intermediate lesions who underwent invasive coronary angiography, FFR, and CCTA at the Asan Medical Center, Seoul, Korea, between 1 May 2012 and 30 November 2015. The mean age was 63 ± 10 years, 76% were men, and 72% of the patients presented with stable angina. Of these, 932 patients (assessed before 31 January 2015) constituted the training set for the algorithm, and 200 patients (assessed after 1 February 2015) served as a test cohort to validate its diagnostic performance. Additionally, external validation with 79 patients from two centers (CHA University, Seongnam, Korea, and Ajou University, Suwon, Korea) was conducted. After automatic contour calibration using the caliber of guiding catheter, quantitative coronary angiography was performed using the edge-detection algorithms (CAAS-5, Pie-Medical). Clinical information was provided by the Asan BiomedicaL Research Environment (ABLE) system. The CCTA-based myocardial segmentation (CAMS)-derived myocardial volume supplied by each vessel (right coronary artery [RCA], left anterior descending [LAD], left circumflex [LCX]) and the myocardial volume subtended to a stenotic segment (CAMS-%Vsub) were measured for labeling. The ML for (1) predicting vessel territories (CAMS-%LAD, CAMS-%LCX, and CAMS-%RCA) and CAMS-%Vsub and (2) identifying the lesions with an FFR < 0.80 was constructed. Angiography-based ML, employing a light gradient boosting machine (GBM), showed mean absolute errors (MAEs) of 5.42%, 8.57%, and 4.54% for predicting CAMS-%LAD, CAMS-%LCX, and CAMS-%RCA, respectively. The percent myocardial volumes predicted by ML were used to predict the CAMS-%Vsub. With 5-fold cross validation, the MAEs between ML-predicted percent myocardial volume subtended to a stenotic segment (ML-%Vsub) and CAMS-%Vsub were minimized by the elastic net (6.26% ± 0.55% for LAD, 5.79% ± 0.68% for LCX, and 2.95% ± 0.14% for RCA lesions). Using all attributes (age, sex, involved vessel segment, and angiographic features affecting the myocardial territory and stenosis degree), the ML classifiers (L2 penalized logistic regression, support vector machine, and random forest) predicted an FFR < 0.80 with an accuracy of approximately 80% (area under the curve [AUC] = 0.84-0.87, 95% confidence intervals 0.71-0.94) in the test set, which was greater than that of diameter stenosis (DS) > 53% (66%, AUC = 0.71, 95% confidence intervals 0.65-0.78). The external validation showed 84% accuracy (AUC = 0.89, 95% confidence intervals 0.83-0.95). The retrospective design, single ethnicity, and the lack of clinical outcomes may limit this prediction model's generalized application. CONCLUSION: We found that angiography-based ML is useful to predict subtended myocardial territories and ischemia-producing lesions by mitigating the visual-functional mismatch between angiographic and FFR. Assessment of clinical utility requires further validation in a large, prospective cohort study.

Association between non-alcoholic fatty liver disease and subclinical coronary atherosclerosis: An observational cohort study.

BACKGROUND & AIMS: There are limited data on the association between non-alcoholic fatty liver disease (NAFLD) and subclinical coronary atherosclerosis. This study investigated the influence of NAFLD on subclinical coronary atherosclerosis as detected by coronary computed tomography angiography (CCTA) in an asymptomatic population. METHODS: A total of 5,121 consecutive asymptomatic individuals with no prior history of coronary artery disease or significant alcohol intake voluntarily underwent abdominal ultrasonography and CCTA as part of a general health examination. Fatty liver was assessed by ultrasonography examination. The fatty liver index and NAFLD fibrosis score were also calculated. Coronary atherosclerotic plaques on CCTA were evaluated. The association between NAFLD and subclinical coronary atherosclerosis was determined by logistic regression analysis. RESULTS: Of the study participants, 1,979 (38.6%) had ultrasonography-diagnosed NAFLD. After adjustment for cardiovascular risk factors, there were no statistically significant differences in the adjusted odds ratios of NAFLD for calcified plaque (1.03; 95% CI 0.89-1.20; p = 0.673) and mixed plaque (1.15; 95% CI 0.93-1.42; p = 0.214). However, adjusted odds ratios for any atherosclerotic plaque (1.18; 95% CI 1.03-1.35; p = 0.016) and non-calcified plaque (1.27; 95% CI 1.08-1.48; p = 0.003) were significantly higher in NAFLD. In addition, there was a significant association of fatty liver index ≥30 with non-calcified plaque (1.37; 95% CI 1.14-1.65; p = 0.001) and NAFLD fibrosis score ≥-1.455 with non-calcified plaque (1.20; 95% CI 1.08-1.42; p = 0.030). CONCLUSIONS: In this large cross-sectional study of asymptomatic individuals undergoing CCTA, NAFLD was consistently associated with non-calcified plaque, suggesting an increased cardiovascular risk. LAY SUMMARY: In asymptomatic individuals, non-alcoholic fatty liver disease (NAFLD) was an independent risk factor for non-calcified plaque, which has been known as a vulnerable plaque associated with sudden and unexpected cardiac events. Therefore, appropriate medical therapy for NAFLD was required to reduce future cardiac events.

Coronary CT angiography characteristics of OCT-defined thin-cap fibroatheroma: a section-to-section comparison study.

OBJECTIVES: To evaluate whether plaque characteristics as assessed by coronary computed tomography angiography (CCTA) were associated with the presence of a thin-cap fibroatheroma (TCFA)-a precursor of plaque rupture-defined by optical coherence tomography (OCT) in a section-to-section-level comparison. METHODS: From 28 symptomatic patients, 31 coronary lesions were evaluated on 727 cross-sections co-registered by both CCTA and OCT. CCTA plaque characteristics included low attenuation plaque (LAP, <30 HU), napkin ring sign (NRS), positive remodelling (PR, remodelling index ≥1.10), and spotty calcification and plaque area and plaque burden. By OCT, presence of TCFA, lumen area and arc of lipid were determined. RESULTS: OCT revealed a TCFA in 69 (9.4%) sections from 19 (61.2 %) lesions. In per-section analysis, OCT-TCFA showed higher frequency of CCTA-detected LAP (58.0% vs. 18.5%), NRS (31.9% vs. 8.8%) and PR (68.1% vs. 48.0%) and greater plaque burden (70.6% vs. 61.9%) as compared to sections without OCT-TCFA (all p < 0.05). In multivariable analysis, LAP (odds ratio [OR] 4.05, p < 0.001) and NRS (OR 2.47, p = 0.005) were associated with OCT-TCFA. CCTA-measured lumen area correlated well with OCT-measured lumen area (R = 0.859, limits of agreement -0.5 ± 3.7 mm2). CONCLUSIONS: LAP and NRS in CCTA were associated with the presence of OCT-defined TCFA in a section-to-section comparison. KEY POINTS: • CT-defined LAP and NRS were associated with OCT-defined TCFA • OCT-TCFA showed higher frequency of LAP, NRS, PR and greater plaque burden • Non-calcified plaque area was correlated with OCT-measured lipid arc.

Intravascular ultrasound-derived morphological predictors of myocardial ischemia assessed by stress myocardial perfusion computed tomography.

BACKGROUND: Although ischemia-guided revascularization improves clinical outcomes, morphological determinants of clinically relevant myocardial ischemia have not been studied. To identify intravascular ultrasound (IVUS)-derived anatomical parameters for predicting myocardial perfusion defect and its extent. METHODS: A total of 103 patients (88 stable and 15 unstable angina) with 153 lesions (angiographic diameter stenosis of 30-80%) underwent stress myocardial perfusion computed tomography (CT) and IVUS pre-procedure. The volume of CT perfusion defect and %CT perfusion defect in the target vessel territories were measured. RESULTS: The CT perfusion defect was seen in 76 (50%) lesions. The independent determinants for the presence of CT perfusion defect were IVUS-minimal lumen area (MLA) (adjusted OR = 0.56, 95% CI = 0.38-0.82), plaque burden (adjusted OR = 1.07, 95% CI = 1.02-1.11) and involvement of left main or left anterior descending artery (adjusted OR = 4.13, 95% CI = 1.75-9.78, all P < 0.05). The CT perfusion defect was predicted by IVUS-MLA <2.28mm2 (sensitivity 74%, specificity 82%) and plaque burden >77% (sensitivity 79%, specificity 78%) as thresholds. The independent determinants for the volume of CT perfusion defect were the involvement of left main or left anterior descending artery (ß = 16.43, standard errors = 4.387, P = 0.020) and a greater plaque burden (ß = 0.56, standard errors = 0.163, P = 0.026). CONCLUSIONS: IVUS-derived morphological parameters were useful to predict the presence of CT perfusion defect and the size of myocardial ischemia that were primarily determined by lesion severity and subtended myocardial territory. © 2016 Wiley Periodicals, Inc.

Myocardial segmentation based on coronary anatomy using coronary computed tomography angiography: Development and validation in a pig model.

OBJECTIVES: To validate a method for performing myocardial segmentation based on coronary anatomy using coronary CT angiography (CCTA). METHODS: Coronary artery-based myocardial segmentation (CAMS) was developed for use with CCTA. To validate and compare this method with the conventional American Heart Association (AHA) classification, a single coronary occlusion model was prepared and validated using six pigs. The unstained occluded coronary territories of the specimens and corresponding arterial territories from CAMS and AHA segmentations were compared using slice-by-slice matching and 100 virtual myocardial columns. RESULTS: CAMS more precisely predicted ischaemic area than the AHA method, as indicated by 95% versus 76% (p < 0.001) of the percentage of matched columns (defined as percentage of matched columns of segmentation method divided by number of unstained columns in the specimen). According to the subgroup analyses, CAMS demonstrated a higher percentage of matched columns than the AHA method in the left anterior descending artery (100% vs. 77%; p < 0.001) and mid- (99% vs. 83%; p = 0.046) and apical-level territories of the left ventricle (90% vs. 52%; p = 0.011). CONCLUSIONS: CAMS is a feasible method for identifying the corresponding myocardial territories of the coronary arteries using CCTA. KEY POINTS: • CAMS is a feasible method for identifying corresponding coronary territory using CTA • CAMS is more accurate in predicting coronary territory than the AHA method • The AHA method may underestimate the ischaemic territory of LAD stenosis.

Stress Myocardial Perfusion CT in Patients Suspected of Having Coronary Artery Disease: Visual and Quantitative Analysis-Validation by Using Fractional Flow Reserve.

PURPOSE: To assess the diagnostic accuracy of stress myocardial perfusion computed tomography (CT) by using visual and quantitative analytic methods in patients with coronary artery disease, with fractional flow reserve (FFR) as a reference standard. MATERIALS AND METHODS: The institutional review board approved the study, and written informed consent was obtained from all patients. The diagnostic accuracy of myocardial perfusion CT was assessed for 75 patients who underwent myocardial perfusion CT and conventional coronary angiography with reference to hemodynamically significant stenosis, defined as the presence of an FFR of 0.8 or less or an angiographically severe (≥90%) stenosis. Results of quantitative analysis of myocardial perfusion CT data were compared with those of visual analysis by using areas under the receiver operating characteristic curve (AUCs). RESULTS: Among the 75 patients and 210 epicardial arteries, 61 patients (81%) with 86 arteries (41%) had hemodynamically significant stenosis. The per-patient sensitivity and specificity of the visual assessment of myocardial perfusion CT data for all patients were 89% and 86%, respectively. At per-vessel analysis, the sensitivities and specificities, respectively, of myocardial perfusion CT were 80% and 95% for all vessels, 85% and 100% for 63 vessels with severe coronary calcification (defined as an Agatston score > 400), and 76% and 91% for 56 vessels in patients with multivessel disease. In severely calcified vessels, visual assessment of myocardial perfusion CT data in combination with CT angiography provided incremental value over CT angiography alone for the detection of myocardial ischemia (integrated discrimination improvement index, 0.38; P < .001). Quantitative assessment of transmural perfusion ratio had a lower AUC than visual analysis of myocardial perfusion CT (0.759 vs 0.877, P = .002). CONCLUSION: Stress myocardial perfusion CT provides incremental value over CT angiography in patients with a high calcium score for the detection of myocardial ischemia as defined by FFR.

Subprosthetic Pannus after Aortic Valve Replacement Surgery: Cardiac CT Findings and Clinical Features.

PURPOSE: To investigate the cardiac computed tomographic (CT) findings and clinical implications of subprosthetic pannus in patients who have undergone aortic valve replacement. MATERIALS AND METHODS: The institutional review board approved this retrospective study, and the need to obtain written informed consent was waived. From April 2011 to March 2012, 88 patients (mean age, 63 years; 45 men) with a prosthetic aortic valve who underwent cardiac CT were retrospectively selected. Dynamic cardiac CT images were analyzed by using a multiplanar reformatted technique. The presence or absence of subprosthetic pannus and its extent were evaluated at cardiac CT. The geometric orifice area and the effective orifice area of each prosthetic valve were measured to enable analysis of the pannus encroachment ratio in the systolic phase. Hemodynamic parameters at echocardiography, including mean transprosthetic pressure gradient (MTPG), were compared between patients with and those without pannus. The encroachment ratio and the MTPG were correlated by using the Spearman test to evaluate the relationship between the two variables. RESULTS: Seventeen patients (19%) had subprosthetic pannus at cardiac CT. In patients with subprosthetic pannus, MTPG, peak pressure gradient, transvalvular peak velocity, and left ventricular ejection fraction (LVEF) were significantly higher than in patients without pannus (MTPG: 28.1 mm Hg ± 19.8 [standard deviation] vs 14.0 mm Hg ± 6.5, P = .004; peak pressure gradient: 53.1 mm Hg ± 38.4 vs 26.1 mm Hg ± 11.4, P = .004; transvalvular peak velocity: 3.3 m/sec ± 1.3 vs 2.5 m/sec ± 0.5; and LVEF: 64.7% ± 7.4 vs 56.8% ± 10.5, P = .004). A high MTPG (≥40 mm Hg) was observed in four patients at echocardiography, and subprosthetic panni were identified at CT in all four patients. In patients with increased MTPGs, the encroachment ratio by subprosthetic pannus at CT was significantly higher than that in patients with MTPGs of less than 40 mm Hg (42.7 ± 13.3 vs 7.6 ± 3, P = .012). CONCLUSION: Cardiac CT revealed subprosthetic pannus to be a cause of the hemodynamic changes in patients who had undergone aortic valve replacement. By helping quantify the encroachment ratio by pannus, cardiac CT may help differentiate which subprosthetic panni might lead to substantial flow limitation over the prosthetic aortic valve.

Preoperative cardiac computed tomography for demonstration of congenital cardiac septal defect in adults.

OBJECTIVES: We aimed to evaluate the role of preoperative cardiac computed tomography (CT) for adults with congenital cardiac septal defect (CSD). METHODS: Sixty-five consecutive patients who underwent preoperative CT and surgery for CSD were included. The diagnostic accuracy of CT and the concordance rate of the subtype classification of CSD were evaluated using surgical findings as the reference standard. Sixty-five patients without CSD who underwent cardiac valve surgery were used as a control group. An incremental value of CT over echocardiography was described retrospectively. RESULTS: Sensitivity and specificity of CT for diagnosis of CSD were 95 % and 100 %, respectively. The concordance rate of subtype classification was 91 % in CT and 92 % in echocardiography. The maximum size of the defect measured by CT correlated well with surgical measurement (r = 0.82), and the limit of agreement was -0.9 ± 7.42 mm. In comparison with echocardiography, CT was able to detect combined abnormalities in three cases, and exclusively provided correct subtype classification or clarified suspected abnormal findings found on echocardiography in seven cases. CONCLUSIONS: Cardiac CT can accurately demonstrates CSD in preoperative adult patients. CT may have an incremental role in preoperative planning, particularly in those with more complex anatomy. KEY POINTS: • Cardiac CT can demonstrate cardiac septal defect accurately in preoperative planning. • Cardiac CT can demonstrate combined abnormalities of cardiac septal defect. • Cardiac CT may have an incremental role over echocardiography in complex anatomy.

Impact of Metabolic Syndrome on Subclinical Atherosclerosis in Asymptomatic Individuals.

BACKGROUND: Little is known about subclinical atherosclerosis on coronary computed tomographic angiography (CCTA) in asymptomatic individuals with metabolic syndrome (MetS). METHODS AND RESULTS: We analyzed 5,213 asymptomatic individuals who underwent CCTA. A cardiac event was defined as a composite of all-cause death, myocardial infarction, unstable angina, or coronary revascularization. Of the study participants, 2,042 (39.2%) had MetS. MetS was an independent predictor of significant coronary artery disease (CAD) in at least 1 coronary artery (odds ratio [OR]=1.992, 95% confidence interval [CI]=1.623-2.445, P<0.001) and significant CAD in the left main (LM) or proximal left anterior descending (LAD) artery (OR=2.151, 95% CI=1.523-3.037, P<0.001). During the follow-up period (median 28.1 [interquartile range, 19.2-36.5] months), 111 individuals had 114 cardiac events. Individuals with MetS were significantly associated with more cardiac events than those without (RR [rate ratio]=1.67, 95% CI=1.15-2.43, P=0.007). In the MetS group, individuals with significant CAD had the majority of cardiac events (RR=64.33, 95% CI=29.17-141.88, P<0.001). Furthermore, in the MetS with significant CAD group, those with significant CAD in the LM or proximal LAD had more cardiac events (RR=2.63, 95% CI=1.51-4.59, P=0.001). CONCLUSIONS: MetS was associated with subclinical atherosclerosis on CCTA with subsequent high risk for cardiac events. These findings suggest the importance of reducing unfavorable metabolic conditions in asymptomatic individuals.

Association between C-reactive Protein and type of coronary arterial plaque in asymptomatic patients: assessment with coronary CT angiography.

PURPOSE: To determine whether C-reactive protein is associated with the type of coronary plaque seen at computed tomographic (CT) angiography. MATERIALS AND METHODS: The institutional review board approved this retrospective study, and the need for informed consent was waived. C-reactive protein levels were measured in 2653 asymptomatic subjects (mean age ± standard deviation, 54.7 years ± 9.2; 1811 men) who underwent self-referred coronary CT angiography as part of a general health checkup. The presence of coronary plaque, plaque type (calcified, mixed calcified, or noncalcified), stenosis degree, and number of involved segments were evaluated. Subjects with one type of plaque (calcified plaque, mixed plaque, and noncalcified plaque groups) and two or more types of plaque (multiple lesions group) were analyzed separately. Multivariate logistic regression analysis was used to evaluate the association between increasing C-reactive protein levels and plaque type. RESULTS: Coronary plaque was found in 1150 of the 2653 subjects (43.3%): calcified plaque (n = 604, 22.8%), mixed plaque (n = 67, 2.5%), noncalcified plaque (n = 208, 7.8%), and multiple lesions (n = 271, 10.2%). The C-reactive protein cutoff value of the fourth quartile was 1.2 mg/L (11.4 nmol/L), and all types of coronary plaque were increased in the higher quartile of the C-reactive protein levels. Multivariate logistic regression analysis showed that a higher C-reactive protein level was an independent predictor for the presence of noncalcified plaque (fourth vs first quartile group, odds ratio = 1.70, P = .025) and significant (50% and higher) coronary stenosis (odds ratio = 1.76, P = .020) after adjustment for traditional risk factors for coronary artery disease. CONCLUSION: C-reactive protein is associated with noncalcified coronary arterial plaque, as seen at coronary CT angiography in asymptomatic patients after adjustment for traditional risk factors.

Demonstration of mitral valve prolapse with CT for planning of mitral valve repair.

Mitral valve prolapse (MVP), the most frequent cause of severe nonischemic mitral regurgitation, often warrants surgical or interventional valve repair. The severity of mitral regurgitation positively correlates with the development of heart failure and death. Even in patients who are asymptomatic, severe mitral regurgitation causes higher rates of death, heart failure, and atrial fibrillation. Repair procedures for mitral regurgitation have progressed to include leaflet repair, chordal transfer, ring or band annuloplasty, and new percutaneous procedures. In planning for mitral valve repair, detection and localization of mitral valve abnormalities are important. The causes of mitral regurgitation include degenerative mitral valve (eg, prolapsed leaflet, myxomatous degeneration, and Barlow disease [excessive degenerated tissues with elongated chordae]). Cardiac computed tomography (CT) is helpful for depicting mitral valve abnormalities. It allows complete visualization of cardiac anatomic features, including the coronary arteries, paravalvular structures, and cardiac wall motion. This review addresses the role of cardiac CT in depicting anatomic features of the mitral valve, provides a practical method for localizing the exact site of MVP, and discusses the CT findings of various causes of mitral regurgitation. The first step in reconstructing CT images for MVP is to select the best cardiac phase for depicting the anatomic features of the mitral valve. Additional views of the mitral valve then show the specific mitral valve abnormality. This article provides technical tips for demonstrating MVP with CT, as well as imaging results for various causes of MVP and intraoperative findings. Online supplemental material is available for this article.

Current Health Data Standardization Project and Future Directions to Ensure Interoperability in Korea.

OBJECTIVES: The need for interoperability at the national level was highlighted in Korea, leading to a consensus on the importance of establishing national standards that align with international technological standards and reflect contemporary needs. This article aims to share insights into the background of the recent national health data standardization policy, the activities of the Health Data Standardization Taskforce, and the future direction of health data standardization in Korea. METHODS: To ensure health data interoperability, the Health Data Standardization Taskforce was jointly organized by the public and private sectors in December 2022. The taskforce operated three working groups. It reviewed international trends in interoperability standardization, assessed the current status of health data standardization, discussed its vision, mission, and strategies, engaged in short-term standardization activities, and established a governance system for standardization. RESULTS: On September 15, 2023, the notice of "Health Data Terminology and Transmission Standards" in Korea was thoroughly revised to improve the exchange of health information between information systems and ensure interoperability. This notice includes the Korea Core Data for Interoperability (KR CDI) and the Korea Core Data Transmission Standard (HL7 FHIR KR Core), which are outcomes of the taskforce's efforts. Additionally, to reinforce the standardized governance system, the Health-Data Standardization Promotion Committee was established. CONCLUSIONS: Active interest and support from medical informatics experts are needed for the development and widespread adoption of health data standards in Korea.

Targeting Heme Oxygenase 2 (HO2) with TiNIR, a Theragnostic Approach for Managing Metastatic Non-Small Cell Lung Cancer.

Despite notable advancements in cancer therapeutics, metastasis remains a primary obstacle impeding a successful prognosis. Our prior study has identified heme oxygenase 2 (HO2) as a promising therapeutic biomarker for the aggressive subsets within tumor. This study aims to systematically evaluate HO2 as a therapeutic target of cancer, with a specific emphasis on its efficacy in addressing cancer metastasis. Through targeted inhibition of HO2 by TiNIR (tumor-initiating cell probe with near infrared), we observed a marked increase in reactive oxygen species. This, in turn, orchestrated the modulation of AKT and cJUN activation, culminating in a substantial attenuation of both proliferation and migration within a metastatic cancer cell model. Furthermore, in a mouse model, clear inhibition of cancer metastasis was unequivocally demonstrated with an HO2 inhibitor administration. These findings underscore the therapeutic promise of targeting HO2 as a strategic intervention to impede cancer metastasis, enhancing the effectiveness of cancer treatments.

Fatigue Life Improvement of Weld Beads with Overlap Defects Using Ultrasonic Peening.

Welding defects are common during the production of large welded structures. However, few studies have explored methods of compensating for clear welding defects without resorting to re-welding. Here, an ultrasonic peening method to compensate for the deteriorated mechanical properties of overlap weld defects without repair welding was studied. We experimentally investigated changes in the mechanical properties of defective welds before and after ultrasonic peening. The weld specimen with an overlap defect contained a large cavity-type defect inside the weld bead, which significantly reduced the fatigue life. When the surface of the defective test piece was peened, the fatigue life of the weld plate was restored, resulting in an equivalent or higher number of cycles to failure, compared to a specimen with a normal weld. The recovery of mechanical properties was attributed to the effect of surface work hardening by ultrasonic peening and the change in stress distribution. Thus, ultrasonic peening could compensate for the deterioration of mechanical properties such as tensile strength, fatigue life, and elongation due to overlap defects, without resorting to repair welding.

Poly-L-Lactic Acid Fillers Improved Dermal Collagen Synthesis by Modulating M2 Macrophage Polarization in Aged Animal Skin.

Poly-L-lactic acid (PLLA) fillers correct cutaneous volume loss by stimulating fibroblasts to synthesize collagen and by augmenting the volume. PLLA triggers the macrophage-induced activation of fibroblasts that secrete transforming growth factor-ß (TGF-ß). However, whether M2 macrophage polarization is involved in PLLA-induced collagen synthesis via fibroblast activation in aged skin is not known. Therefore, we evaluated the effect of PLLA on dermal collagen synthesis via M2 polarization in an H2O2-induced cellular senescence model and aged animal skin. H2O2-treated macrophages had increased expression levels of the M1 marker CD80 and decreased expression levels of the M2 marker CD163, which were reversed by PLLA. The expression levels of interleukin (IL)-4 and IL-13, which mediate M2 polarization, were decreased in H2O2-treated macrophages and increased upon the PLLA treatment. CD163, IL-4, and IL-13 expression levels were decreased in aged skin, but increased after the PLLA treatment. The expression levels of TGF-ß, pSMAD2/SMAD2, connective tissue growth factor (CTGF), alpha-smooth muscle actin (α-SMA), collagen type 1A1 (COL1A1), and COL3A1 were also decreased in aged skin, but increased after the PLLA treatment. Moreover, PLLA upregulated phosphatidylinositol 3-kinase p85α (PI3-kinase p85α)/protein kinase B (AKT) signaling, leading to fibroblast proliferation. PLLA decreased the expression of matrix metalloproteinase (MMP) 2 and MMP3, which destroy collagen and elastin fibers in aged skin. The amount of collagen and elastin fibers in aged skin increased following the PLLA treatment. In conclusion, PLLA causes M2 polarization by increasing IL-4 and IL-13 levels and upregulating TGF-ß expression and collagen synthesis in aged skin.