Low- or standard-dose edoxaban versus antiplatelet therapy for leaflet thrombus and cerebral thromboembolism after TAVR: A prespecified analysis of randomized ADAPT-TAVR trial.

BACKGROUND: The risks of leaflet thrombosis and the associated cerebral thromboembolism are unknown according to different anticoagulation dosing after transcatheter aortic valve replacement (TAVR). The aim was to evaluate the incidence of leaflet thrombosis and cerebral thromboembolism between low-dose (30 mg) or standard-dose (60 mg) edoxaban and dual antiplatelet therapy (DAPT) after TAVR. METHODS: In this prespecified subgroup analysis of the ADAPT-TAVR trial, the primary endpoint was the incidence of leaflet thrombosis on 4-dimensional computed tomography at 6-months. Key secondary endpoints were new cerebral lesions on brain magnetic resonance imaging and neurological and neurocognitive dysfunction. RESULTS: Of 229 patients enrolled in this study, 118 patients were DAPT group and 111 were edoxaban group (43 [39.1%] 60 mg vs 68 [61.3%] 30 mg). There was a significantly lower incidence of leaflet thrombosis in the standard-dose edoxaban group than in the DAPT group (2.4% vs 18.3%; odds ratio [OR] 0.11; 95% confidence interval [CI], 0.01-0.55; P = .03). However, no significant difference was observed between low-dose edoxaban and DAPT (15.0% vs 18.3%; OR 0.79; 95% CI, 0.32-1.81; P = .58). Irrespective of different antithrombotic regiments, the percentages of patients with new cerebral lesions on brain MRI and worsening neurological or neurocognitive function were not significantly different. CONCLUSIONS: In patients without an indication for anticoagulation after TAVR, the incidence of leaflet thrombosis was significantly lower with standard-dose edoxaban but not with low-dose edoxaban, as compared with DAPT. However, this differential effect of edoxaban on leaflet thrombosis was not associated with a reduction of new cerebral thromboembolism and neurological dysfunction.

Long-term clinical impact of early recurrence of atrial tachyarrhythmia after cryoballoon ablation in patients with atrial fibrillation.

INTRODUCTION: The impact of early recurrence of atrial tachyarrhythmia (ERAT) within the 90-day blanking period on long-term outcomes in atrial fibrillation (AF) patients undergoing cryoballoon ablation (CBA) is controversial. This study aimed to assess the relationship between ERAT and late recurrence of atrial tachyarrhythmia (LRAT) post-CBA. METHODS: Utilizing data from a multicenter registry in Korea (May 2018 to June 2022), we analyzed the presence and timing of ERAT (<30, 30-60, and 60-90 days) and its association with LRAT risk after CBA. LRAT was defined as any recurrence of AF, atrial flutter, or atrial tachycardia lasting more than 30 s beyond the 90 days. RESULTS: Out of 2636 patients, 745 (28.2%) experienced ERAT post-CBA. Over an average follow-up period of 21.2 ± 10.3 months, LRAT was observed in 874 (33.1%) patients. Patients with ERAT had significantly lower 1-year LRAT freedom compared to those without ERAT (42.6% vs. 85.5%, p < .001). Multivariate analysis identified ERAT as a potential predictor of LRAT, with a hazard ratio (HR) of 3.98 (95% confidence interval [CI], 3.47-4.57). Significant associations were noted across all examined time frames (HR, 3.84; 95% CI, 3.32-4.45 in <30 days, HR, 5.53; 95% CI, 4.13-7.42 in 30-60 days, and HR, 4.29; 95% CI, 3.12-5.89 in 60-90 days). This finding was consistently observed across all types of AF. CONCLUSION: ERAT during the 90-day blanking period strongly predicts LRAT in AF patients undergoing CBA, indicating a need to reconsider the clinical significance of this period.

Heart Failure-Smart Life: a randomized controlled trial of a mobile app for self-management in patients with heart failure.

BACKGROUND: It is an important strategy for healthcare providers to support heart failure patients with comprehensive aspects of self-management. A practical alternative to a comprehensive and user-friendly self-management program for heart failure patients is needed. This study aimed to develop a mobile self-management app program for patients with heart failure and to identify the impact of the program. METHODS: We developed a mobile app, called Heart Failure-Smart Life. The app was to provide educational materials using a daily health check-up diary, Q & A, and 1:1 chat, considering individual users' convenience. An experimental study was employed using a randomized controlled trial to evaluate the effects of the program in patients with heart failure from July 2018 to June 2019. The experimental group (n = 36) participated in using the mobile app that provided feedback on their self-management and allowed monitoring of their daily health status by cardiac nurses for 3 months, and the control group (n = 38) continued to undergo their usual care. The differences in the physical, psychosocial, and behavioral factors between the two groups over time were analyzed using the analysis of covariance. RESULTS: After 3 months of intervention, significant differences between experimental and control groups were shown in the New York Heart Association functional class (p = 0.003) and cardiac diastolic function (p = 0.024). The improvements over time in the experimental group tended to be higher than those in the control group in considered variables. However, no changes in psychosocial and behavioral variables were observed between the groups over time. CONCLUSIONS: This study provides evidence that the mobile app program may provide benefits to its users, specifically improvements of symptom and cardiac diastolic function in patients with heart failure. Healthcare providers can effectively and practically guide and support patients with heart failure using comprehensive and convenient self-management tools such as smartphone apps.

Minifying photometric stereo via knowledge distillation-based feature translation.

Photometric stereo (PS) estimates the surface normals of an object by utilizing multiple images captured under different light conditions. To obtain accurate surface normals, a large number of input images is often required. Therefore, a huge effort is needed to capture images and calibrate light directions together with a heavy computational cost. Therefore, in this paper, we propose a robust photometric stereo method even when the number of input images is very small. To this end, we design a feature translation module (FTM) that enriches features having scarce information. In particular, we insert FTMs between the layers of the baseline backbone PS network. Then, activations of each FTM are supervised by distillation loss. For computing distillation loss, we utilize a teacher PS network trained by taking lots of images as inputs. As a result, our PS network requires very few input images but produces a similar quality of output surface normals with the teacher PS network. The proposed method is applicable to both calibrated and uncalibrated PS. We show the effectiveness of the proposed method not only when the number of input images is small but also in various input conditions.

Association between self-management behaviour and quality of life in people with heart failure: a retrospective study.

BACKGROUND: The purpose of this study was to investigate the variables that significantly associated with the quality of life in people with heart failure, and particularly, to identify the association between self-management behaviour and the quality of life. METHODS: This retrospective study used data from heart failure outpatient clinics at two large tertiary medical centres in Seoul and Suwon, South Korea. We enrolled 119 participants who completed echocardiography and stress tests and responded to questionnaires on self-management behaviour and quality of life. We collected more data on sociodemographic and clinical characteristics and anthropometric and serum blood test results through electronic medical record review. We analysed data using multiple linear regression and the classification and regression tree (CART) method to explore the associated factors with the quality of life in participants with heart failure. RESULTS: Participants' mean age was 74.61 years, and women represented 52.1% of the sample. It showed that cardiac systolic function (ß = 0.26, p = .013) and self-management behaviour (ß = 0.20, p = .048) were two major associated factors with the quality of life in participants with heart failure in the multiple linear regression analysis. Also, cardiac systolic function and self-management behaviour were shown to be the primary determinants for the quality of life in those with heart failure in the CART analysis. Therefore, self-management behaviour of the participants with heart failure was a significant modifiable factor that can improve their quality of life. CONCLUSIONS: Healthcare providers should be aware of the importance of self-management in people with heart failure and help promote their quality of life by enhancing their self-management behaviour as own efforts to properly maintain and monitor the health status and prevent further worsening of heart failure.

Predictive Model for Quality of Life in Patients With Heart Failure.

BACKGROUND: Although many studies have been conducted to examine predictors of quality of life (QoL), little information exists on the real-world application of Rector's conceptual model for QoL related to heart failure (HF). OBJECTIVES: In this study, we aimed to examine a hypothetical model of QoL based on Rector's conceptual model for QoL in relation to HF and the existing literature on patients with HF. METHODS: Using a cross-sectional survey, 165 patients with HF were recruited from an outpatient clinic in Korea. Data were collected based on Rector's model constructs, such as cardiac function, symptoms, functional limitation, depression, distress, and QoL. Left ventricular ejection fraction for cardiac function was measured using echocardiography. RESULTS: Functional limitation, depression, and distress, but not symptoms, had a direct effect on QoL (all Ps < .001). Cardiac function and symptoms directly affected functional limitation (ß = 0.186, P = .004, and ß = -0.488, P = < .001, respectively), whereas cardiac function, symptoms, and depression affected QoL through functional limitation and distress. CONCLUSIONS: These results confirm that the Rector's model is suitable for predicting QoL in patients with HF. These findings have potential to guide and inform intervention programs designed to alleviate symptoms in patients with HF, enhance their physical functioning, and moderate their psychological distress with the ultimate goal of improving their QoL.

Lightweight Depth Completion Network with Local Similarity-Preserving Knowledge Distillation.

Depth perception capability is one of the essential requirements for various autonomous driving platforms. However, accurate depth estimation in a real-world setting is still a challenging problem due to high computational costs. In this paper, we propose a lightweight depth completion network for depth perception in real-world environments. To effectively transfer a teacher's knowledge, useful for the depth completion, we introduce local similarity-preserving knowledge distillation (LSPKD), which allows similarities between local neighbors to be transferred during the distillation. With our LSPKD, a lightweight student network is precisely guided by a heavy teacher network, regardless of the density of the ground-truth data. Experimental results demonstrate that our method is effective to reduce computational costs during both training and inference stages while achieving superior performance over other lightweight networks.

Anti-Inflammatory and Neuroprotective Mechanisms of GTS-21, an α7 Nicotinic Acetylcholine Receptor Agonist, in Neuroinflammation and Parkinson's Disease Mouse Models.

Neuroinflammation is crucial in the progression of neurodegenerative diseases. Thus, controlling neuroinflammation has been proposed as an important therapeutic strategy for neurodegenerative disease. In the present study, we examined the anti-inflammatory and neuroprotective effects of GTS-21, a selective α7 nicotinic acetylcholine receptor (α7 nAChR) agonist, in neuroinflammation and Parkinson's disease (PD) mouse models. GTS-21 inhibited the expression of inducible nitric oxide synthase (iNOS) and proinflammatory cytokines in lipopolysaccharide (LPS)-stimulated BV2 microglial cells and primary microglia. Further research revealed that GTS-21 has anti-inflammatory properties by inhibiting PI3K/Akt, NF-κB, and upregulating AMPK, Nrf2, CREB, and PPARγ signals. The effects of GTS-21 on these pro-/anti-inflammatory signaling molecules were reversed by treatment with an α7 nAChR antagonist, suggesting that the anti-inflammatory effects of GTS-21 are mediated through α7 nAChR activation. The anti-inflammatory and neuroprotective properties of GTS-21 were then confirmed in LPS-induced systemic inflammation and MPTP-induced PD model mice. In LPS-injected mouse brains, GTS-21 reduced microglial activation and production of proinflammatory markers. Furthermore, in the brains of MPTP-injected mice, GTS-21 restored locomotor activity and dopaminergic neuronal cell death while inhibiting microglial activation and pro-inflammatory gene expression. These findings suggest that GTS-21 has therapeutic potential in neuroinflammatory and neurodegenerative diseases such as PD.

Oleuropein attenuates the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-perturbing effects on pancreatic ß-cells.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an endocrine disrupting compound and persistent organic pollutant that has been associated with diabetes in several epidemiological studies. Oleuropein, a major phenolic compound in olive fruit, is a superior antioxidant and radical scavenger. This study aimed to examine the effects of oleuropein against TCDD-induced stress response in a pancreatic beta cell line, INS-1 cells. Cells were pre-incubated with various concentrations of oleuropein and then stimulated with TCDD (10 nM) for 48 hrs. When treated with TCDD, INS-1 cells produced robust amounts of prostaglandin E2 (PGE2) compared to the untreated control, and this increase was inhibited by oleuropein treatment. TCDD increased Ca2+-independent phospholipase A2 (iPLA2ß) level, but had no effect on Group 10 secretory phospholipase A2 (PLA2G10) level, while oleuropein deceased the levels of iPLA2ß and PLA2G10 in the presence of TCDD. Cyclooxygenase-1 (COX-1) was significantly increased by TCDD treatment and attenuated with oleuropein pretreatment. Oleuropein decreased TCDD-mediated production of JNK, TNF-α, and ROS. In addition, oleuropein increased Akt and GLUT2 levels suppressed by TCDD in INS-1 cells. Thus, the results suggest that oleuropein prevents pancreatic beta cell impairment by TCDD.

Antiatherogenic Effect of Resveratrol Attributed to Decreased Expression of ICAM-1 (Intercellular Adhesion Molecule-1).

Objective- Increasing evidence shows that resveratrol has antiatherogenic effects, but its underlying mechanisms are unknown. Thus, we evaluated the molecular mechanisms underlying the antiatherogenic effect of resveratrol. Approach and Results- Using the previously established mouse atherosclerosis model of partial ligation of the left carotid artery, we evaluated the role of resveratrol in antiatherosclerosis. We attempted to determine the mechanisms associated with focal adhesions using vascular endothelial cells. The results showed that resveratrol stimulated focal adhesion kinase cleavage via resveratrol-increased expression of lactoferrin in endothelial cells. Furthermore, we found that an N-terminal focal adhesion kinase fragment cleaved by resveratrol contained the FERM (band 4.1, ezrin, radixin, and moesin)-kinase domain. Furthermore, resveratrol inhibited lipopolysaccharide-stimulated adhesion of THP-1 human monocytes by decreased expression of ICAM-1 (intercellular adhesion molecule-1). A decreased ICAM-1 level was also observed in the left carotid artery of mice treated with resveratrol. To understand the relationship between resveratrol-induced antiinflammation and focal adhesion disruption, endothelial cells were transfected with FERM-kinase. Ectopically expressed FERM-kinase, the resveratrol-cleaved focal adhesion kinase fragment, was found in the nuclear fraction and inhibited the transcription level of icam-1 via the Nrf2 (nuclear factor erythroid 2-related factor 2)-antioxidant response element complex. Finally, ectopically expressed FERM-kinase blocked tumor necrosis factor-α- or IL- (interleukin) stimulated monocytic binding to endothelial cells. Conclusions- Our results show that resveratrol inhibits the expression of ICAM-1 via transcriptional regulation of the FERM-kinase and Nrf2 interaction, thereby blocking monocyte adhesion. These suppressive effects on the inflammatory mechanism suggest that resveratrol delayed the onset of atherosclerosis.

The phosphodiesterase 10 inhibitor papaverine exerts anti-inflammatory and neuroprotective effects via the PKA signaling pathway in neuroinflammation and Parkinson's disease mouse models.

BACKGROUND: Neuroinflammation plays a pivotal role in the pathogenesis of Parkinson's disease (PD). Thus, the development of agents that can control neuroinflammation has been suggested as a promising therapeutic strategy for PD. In the present study, we investigated whether the phosphodiesterase (PDE) 10 inhibitor has anti-inflammatory and neuroprotective effects in neuroinflammation and PD mouse models. METHODS: Papaverine (PAP) was utilized as a selective inhibitor of PDE10. The effects of PAP on the expression of pro-inflammatory molecules were examined in lipopolysaccharide (LPS)-stimulated BV2 microglial cells by ELISA, RT-PCR, and Western blot analysis. The effects of PAP on transcription factors were analyzed by the electrophoretic mobility shift assay, the reporter gene assay, and Western blot analysis. Microglial activation and the expression of proinflammatory molecules were measured in the LPS- or MPTP-injected mouse brains by immunohistochemistry and RT-PCR analysis. The effect of PAP on dopaminergic neuronal cell death and neurotrophic factors were determined by immunohistochemistry and Western blot analysis. To assess mouse locomotor activity, rotarod and pole tests were performed in MPTP-injected mice. RESULTS: PAP inhibited the production of nitric oxide and proinflammatory cytokines in LPS-stimulated microglia by modulating various inflammatory signals. In addition, PAP elevated intracellular cAMP levels and CREB phosphorylation. Treatment with H89, a PKA inhibitor, reversed the anti-inflammatory effects of PAP, suggesting the critical role of PKA signaling in the anti-inflammatory effects of PAP. We verified the anti-inflammatory effects of PAP in the brains of mice with LPS-induced systemic inflammation. PAP suppressed microglial activation and proinflammatory gene expression in the brains of these mice, and these effects were reversed by H89 treatment. We further examined the effects of PAP on MPTP-injected PD model mice. MPTP-induced dopaminergic neuronal cell death and impaired locomotor activity were recovered by PAP. In addition, PAP suppressed microglial activation and proinflammatory mediators in the brains of MPTP-injected mice. CONCLUSIONS: PAP has strong anti-inflammatory and neuroprotective effects and thus may be a potential candidate for treating neuroinflammatory disorders such as PD.

Impact of new-onset diabetes on clinical outcomes after ST segment-elevated myocardial infarction.

Objective. Patients with diabetes have higher mortality rate than patients without diabetes after ST-segment elevated myocardial infarction (STEMI). Prognosis of patients with new onset diabetes (NOD) after STEMI remains unclear. The aim of this study was to evaluate the prognosis of patients with NOD compared to that of patients without NOD after STEMI. Design. This study was a retrospective observational study. We enrolled 901 STEMI patients. Patients were divided into diabetic and non-diabetic groups at index admission. Non-diabetic group was divided into NOD and non-NOD groups. Kaplan-Meier analysis and Cox's proportional hazard regression models were used to compare major adverse cardiac events (MACE) free survival rate and hazard ratio for MACE between NOD and non-NOD groups. Results. Mean follow-up period was 59 ± 28 months. Diabetes group had higher MACE than non-diabetes group (p = .038). However, MACE was not different between NOD and non-NOD groups (p = 1.000). After 1:2 propensity score matching, incidence of MACE was not different between the two groups. In Kaplan-Meier survival curves, MACE-free survival rates were not statistically different between NOD and non-NOD groups either (p = .244). Adjusted hazard ratios of NOD for MACE, all-cause of death, recurrent myocardial infarction, and target vessel revascularization were 0.697 (95% confidence interval [CI]: 0.362-1.345, p = .282), 0.625 (95% CI: 0.179-2.183, p = .461), 0.794 (95% CI: 0.223-2.835, p = .723), and 0.506 (95% CI: 0.196-1.303, p = .158), respectively. Conclusion. This retrospective observational study with a limited statistical power did not show a different prognosis in patients with and without NOD.

Sulforaphane rescues amyloid-ß peptide-mediated decrease in MerTK expression through its anti-inflammatory effect in human THP-1 macrophages.

BACKGROUND: Mer tyrosine kinase (MerTK) activity necessary for amyloid-stimulated phagocytosis strongly implicates that MerTK dysregulation might contribute to chronic inflammation implicated in Alzheimer's disease (AD) pathology. However, the precise mechanism involved in the regulation of MerTK expression by amyloid-ß (Aß) in proinflammatory environment has not yet been ascertained. METHODS: The objective of this study was to determine the underlying mechanism involved in Aß-mediated decrease in MerTK expression through Aß-mediated regulation of MerTK expression and its modulation by sulforaphane in human THP-1 macrophages challenged with Aß1-42. We used protein preparation, Ca2+ influx fluorescence imaging, nuclear fractionation, Western blotting techniques, and small interfering RNA (siRNA) knockdown to perform our study. RESULTS: Aß1-42 elicited a marked decrease in MerTK expression along with increased intracellular Ca2+ level and induction of proinflammatory cytokines such as IL-1ß and TNF-α. Ionomycin A and thapsigargin also increased intracellular Ca2+ levels and production of IL-1ß and TNF-α, mimicking the effect of Aß1-42. In contrast, the Aß1-42-evoked responses were attenuated by depletion of Ca2+ with ethylene glycol tetraacetic acid. Furthermore, recombinant IL-1ß or TNF-α elicited a decrease in MerTK expression. However, immunodepletion of IL-1ß or TNF-α with neutralizing antibodies significantly inhibited Aß1-42-mediated downregulation of MerTK expression. Notably, sulforaphane treatment potently inhibited Aß1-42-induced intracellular Ca2+ level and rescued the decrease in MerTK expression by blocking nuclear factor-κB (NF-κB) nuclear translocation, thereby decreasing IL-1ß and TNF-α production upon Aß1-42 stimulation. Such adverse effects of sulforaphane were replicated by BAY 11-7082, a NF-κB inhibitor. Moreover, sulforaphane's anti-inflammatory effects on Aß1-42-induced production of IL-1ß and TNF-α were significantly diminished by siRNA-mediated knockdown of MerTK, confirming a critical role of MerTK in suppressing Aß1-42-induced innate immune response. CONCLUSION: These findings implicate that targeting of MerTK with phytochemical sulforaphane as a mechanism for preventing Aß1-42-induced neuroinflammation has potential to be applied in AD therapeutics.

Anti-inflammatory and anti-oxidant mechanisms of an MMP-8 inhibitor in lipoteichoic acid-stimulated rat primary astrocytes: involvement of NF-κB, Nrf2, and PPAR-γ signaling pathways.

BACKGROUND: Recent evidence suggests that reactive astrocytes play an important role in neuroinflammation and neurodegenerative diseases. Thus, controlling astrocyte reactivity has been suggested as a promising strategy for treating neurodegenerative diseases. In the present study, we investigated whether a matrix metalloproteinase (MMP)-8 inhibitor, M8I, could control neuroinflammation in lipoteichoic acid (LTA)-stimulated rat primary astrocytes. METHODS: The effects of M8I on the expression of inducible nitric oxide synthase, cytokines, and MMPs were examined in LTA-stimulated rat primary astrocytes by ELISA, RT-PCR, and Western blot analysis. The effects of M8I on reactive oxygen species (ROS) generation and phase II antioxidant enzyme expression were examined by the DCF-DA assay, RT-PCR, and Western blot analysis. The detailed molecular mechanisms underlying the anti-inflammatory and antioxidant effects of M8I were analyzed by the electrophoretic mobility shift assay, the reporter gene assay, Western blot, and RT-PCR analysis. RESULTS: Treatment with LTA, a major cell wall component of Gram-positive bacteria, led to astrocyte activation and induced the expression of inflammatory molecules such as iNOS, COX-2, and pro-inflammatory cytokines. In addition, LTA induced the expression of MMPs such as MMP-1, MMP-3, MMP-8, MMP-9, and MMP-13 in rat primary astrocytes. Based on previous reports showing that MMP-8 plays a role as a proinflammatory mediator in microglia, we investigated whether MMP-8 is also involved in inflammatory reactions of reactive astrocytes. We found that treatment of astrocytes with M8I significantly inhibited LTA-induced expression of iNOS, TNF-α, IL-1ß, IL-6, and TLR-2. In addition, M8I inhibited LTA-induced NF-κB, MAP kinase, and Akt activities, while it increased the anti-inflammatory PPAR-γ activities. Moreover, M8I showed antioxidant effects by suppressing ROS production in LTA- or H2O2-stimulated astrocytes. Interestingly, M8I increased the expression of phase II antioxidant enzymes such as hemeoxygenase-1, NQO1, catalase, and MnSOD by modulating the Nrf2/ARE signaling pathway. CONCLUSIONS: The data collectively suggest the therapeutic potential of an MMP-8 inhibitor in neuroinflammatory disorders that are associated with astrocyte reactivity.

Myocardial Mass Contributes to the Discrepancy Between Anatomic Stenosis Severity Assessed by Intravascular Ultrasound and Fractional Flow Reserve in Intermediate Lesions of the Coronary Artery.

OBJECTIVES: The present study investigated the major contributors to the discrepancy between the minimal lumen area (MLA) and fractional flow reserve (FFR). BACKGROUND: There was considerable discrepancy between MLA or diameter stenosis (DS) and FFR. METHODS: We enrolled 744 patients with intermediate stenoses of the left anterior descending artery (LAD). Summed epicardial coronary artery length distal to the target stenosis was obtained from each longest view of the vessels on the coronary angiograms. Mismatching was defined as a lesion with FFR of >0.80 and MLA smaller than the best cut-off value (BCV) for predicting FFR of ≤0.80. Reverse mismatching was defined as a lesion with FFR of ≤0.80 and MLA larger than the BCV. RESULTS: Summed epicardial coronary artery length was longer at the lesions of proximal LAD than that of middle LAD (380 mm ± 82 mm vs. 341 mm ± 80 mm, P < 0.001). Reverse mismatching was found more frequently in the proximal than middle LAD (28.3% vs. 5.5%, P < 0.001). Independent predictors of FFR ≤ 0.80 were age, male, multi-vessel disease, proximal LAD lesion, MLA, DS, plaque burden at distal reference, lesion length and summed epicardial coronary artery length. Proximal LAD lesion was an independent predictor of reverse mismatching (hazard ratio 3.162, 1.858-5.382, P < 0.001). CONCLUSIONS: Myocardial mass subtended by a lesion is an important factor predicting FFR ≤0.80 and discrepancy between FFR and MLA. Myocardial mass subtended by a lesion should be considered when determining the revascularization therapy by intravascular ultrasound parameters. © 2017 Wiley Periodicals, Inc.

Normal reference values of diastolic strain rate in healthy individuals: Chronological trends and the comparison according to genders.

PURPOSE: Recently, the diastolic strain rate (DSR) utilizing speckle-tracking echocardiography has been proposed as a novel parameter for left ventricular diastolic function. We aimed to present normal reference data for those in a large-sized, selected group of healthy individuals. METHODS: The current study was a part of the Normal echOcardiogRaphic Measurements in KoreAn popuLation (NORMAL), a prospective nationwide survey from 23 centers in Korea. We analyzed 447 subjects (age 48 ± 15 years, 234 females) without any history of cardiovascular disease and presented the early and late DSRs (SRe and SRa , respectively) in a total and gender-/age-specified groups. RESULTS: Among the total subjects, the mean SRe and SRa were 1.6 ± 0.4 S-1 and 0.8 ± 0.3 S-1 , respectively. With increasing age, there were significant trends of decreasing SRe and increasing SRa . Although both gender groups showed comparable age, the female group presented significantly higher SRe compared to male subjects with age of 20-59 years, which diminished after the age of 60 years. However, the SRa was comparable between genders in all age groups. On multiple linear regression, age showed independent associations with both SRe (ß = -0.132, P = .010) and SRa (ß = 0.440, P < .001), whereas gender did not show any association with SRe or SRa . CONCLUSION: We present normal reference data of a novel parameter, DSR, in a large-sized selected group with healthy Korean subjects. Additionally, we present significant age-related changes both in SRe and SRa without the impact of their gender.

Suppression of neuroinflammation by matrix metalloproteinase-8 inhibitor in aged normal and LRRK2 G2019S Parkinson's disease model mice challenged with lipopolysaccharide.

Microglial priming is caused by aging and neurodegenerative diseases, and is characterized by an exaggerated microglial inflammatory response to secondary and sub-threshold challenges. In the present study, we examined the effects of the matrix metalloproteinase-8 (MMP-8) inhibitor (M8I) on the brain of aged normal and leucine-rich repeat kinase 2 (LRRK2) G2019S Parkinson's disease (PD) model mice systemically stimulated with lipopolysaccharide (LPS). The results indicated that Iba-1 positive microglia and GFAP-positive astrocytes, which were increased by LPS, significantly decreased by M8I in aged normal and PD model mice. M8I also decreased the expression of pro-inflammatory markers in the hippocampus and midbrain of aged normal and PD model mice challenged with LPS, while it also improved the motor coordination of aged normal mice after LPS challenge in rotor rod test and the general crossing locomotor activities of LPS-treated LRRK2G2019S PD mice after LPS challenge in open field test. To assess the effects of M8I in an in vitro priming model, BV2 microglia were pretreated with macrophage colony-stimulating factor (CSF)-1 or interleukin (IL)-34, and subsequently stimulated with LPS or polyinosinic-polycytidylic acid (poly[I:C]). M8I inhibited the LPS- or poly(I:C)-induced production of the tumor necrosis factor-α and nitric oxide, alone or in combination with CSF-1 or IL-34. Collectively, the data suggested that M8I has a therapeutic potential in treating neurodegenerative diseases that are aggravated by systemic inflammation.