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Oxidative stress is a primary contributor to human skin aging, while antioxidants are known to mitigate skin damage related to aging processes. In this study, we investigated the possible action of trifluoromethyl phenethyl mesalazine (TFM), an antioxidizing agent, on skin aging processes, including skin wrinkles and pigmentation. Our data revealed that TFM exerted a strong free radical scavenging capability and notably inhibited melanin production. Moreover, TFM downregulated the UV-induced production of matrix metalloproteinase-1 and interleukin-6 in cultured human skin fibroblasts. Furthermore, in a clinical study with 24 women, TFM significantly reduced skin wrinkles and improved skin brightness compared to a placebo. These findings highlight the previously unrecognized effects of TFM on skin health by mitigating skin aging processes associated with oxidative damage. [ABSTRACT FROM AUTHOR]

Understanding the changes in arterial wall viscoelasticity during the progression of vascular disease is crucial. Nonetheless, there has been a lack of comprehensive investigation into the assessment of viscoelastic parameters and their impact on radial wall motion. To address this gap, we analyzed the radius waveform by solving the viscoelastic constitutive equations of the standard linear model (SLM) based on a thin-wall tube assumption. Additionally, a finite element method (FEM) was applied to simulate radial wall motion for thicker walls. The analytic solution showed that a well-balanced SLM model with the time constant ( τ ε ) values smaller than 0.05 s could effectively simulate the dynamic response of radial wall motion in a human carotid artery. FEM result showed that increasing wall thickness led to a decrease in the amplitude of the radius waveform, while its effect on phase lag was marginal. To evaluate the clinical relevance of arterial wall viscoelasticity, the viscoelastic parameters of the SLM were estimated from the pressure and diameter waveforms of each patient using an optimization technique. The 105 patients were categorized according to their cardiovascular disease risk status, and statistical comparisons were made for viscoelastic parameters across the different groups. The results revealed that the high-risk group exhibited significantly higher wall elasticity than the low-risk group (p < 0.03), while the intermediate-risk group demonstrated higher wall viscosity than the low-risk group (p < 0.01). Therefore, arterial wall elasticity holds potential as a significant indicator for distinguishing between low-risk and high-risk groups, whereas viscosity shows promise as a significant indicator for distinguishing between low-risk and intermediate-risk groups. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative diseases, and they affect millions of people worldwide, particularly older individuals. Therefore, there is a clear need to develop novel drug targets for the treatment of age-related neurodegenerative diseases. Emerging evidence suggests that mitochondrial dysfunction and reactive oxygen species (ROS) generation play central roles in the onset and progression of neurodegenerative diseases. Mitochondria are key regulators of respiratory function, cellular energy adenosine triphosphate production, and the maintenance of cellular redox homeostasis, which are essential for cell survival. Mitochondrial morphology and function are tightly regulated by maintaining a balance among mitochondrial fission, fusion, biogenesis, and mitophagy. In this review, we provide an overview of the main functions of mitochondria, with a focus on recent progress highlighting the critical role of ROS−induced oxidative stress, dysregulated mitochondrial dynamics, mitochondrial apoptosis, mitochondria-associated inflammation, and impaired mitochondrial function in the pathogenesis of age-related neurodegenerative diseases, such as AD and PD. We also discuss the potential of mitochondrial fusion and biogenesis enhancers, mitochondrial fission inhibitors, and mitochondria-targeted antioxidants as novel drugs for the treatment of these diseases. [ABSTRACT FROM AUTHOR]

Ventricular hypertrophy is associated with diastolic dysfunction, resulting in increased left atrial (LA) pressure, enlargement, fibrosis, and decreased LA function. Hypertrophic cardiomyopathy (HCM) is characterized by myocyte disarray, myocardial fibrosis, and hypertrophy. Notably, a thickened and noncompliant LV results in the impairment of diastolic function. These conditions promote LA remodeling and enlargement, which contribute to developing and maintaining atrial fibrillation (AF). AF is an atrial arrhythmia that occurs frequently in HCM, and evaluating the morphology and physiology of the atrium and ventricle is important for treatment and prognosis determination in HCM patients with AF. In addition, it provides a clue that can predict the possibility of new AF, even in patients not previously diagnosed with AF. Cardiac magnetic resonance (CMR), which can overcome the limitations of transthoracic echocardiography (TTE), has been widely used traditionally and even enables tissue characterization; moreover, it has emerged as an essential imaging modality for patients with HCM. Here, we review the role of multimodal imaging in patients with HCM and AF. [ABSTRACT FROM AUTHOR]

This study aimed to assess the safety and effectiveness of the highly cross-linked hyaluronic acid—LBSA0103—in patients with knee osteoarthritis (OA) as per the prescribing information (PI) in South Korea. A total of 3,140 subjects aged ≥19 years were enrolled in this post-marketing surveillance (PMS) study from 2013 to 2019. The subjects received one or two injections of LBSA0103. The median duration of follow-up was 308 days. Adverse events (AEs), adverse drug reactions (ADRs), and serious AEs (SAEs) were monitored. Effectiveness was evaluated based on an index of effectiveness in accordance with the guidelines established by the Ministry of Food and Drug Safety and using a 100-mm visual analog scale (VAS) for weight-bearing pain. Overall, 250 subjects (7.96%) experienced 292 AEs and of these, unexpected AEs occurred in 114 subjects (3.63% [95% CI: 3.00–4.35]). Injection site pain was the most frequent AE reported by 81 subjects (2.58% [95% confidence intervals (CI): 2.05–3.20]). One hundred subjects experienced 108 ADRs (3.18% [95% CI: 2.60, 3.86]) and 15 unexpected ADRs were experienced by 13 subjects (0.41% [95% CI: 0.22–0.71]). Seventeen subjects experienced 22 SAEs (0.54% [95% CI: 0.32–0.87]) during the entire PMS period, and all were considered "unlikely" related to the study drug. Most AEs were mild in terms of severity and resolved during the study period. LBSA0103 was also effective in relieving symptomatic pain in knee OA patients. The condition in more than 80% of the subjects was considered to be improved when assessed by the investigators. LBSA0103 resulted in a significant reduction in the mean VAS score at 12 weeks after the first and second injections (24.79 (± 20.55) mm and 17.63 (±12.31) mm, respectively; p<0.0001). In conclusion, LBSA0103, used for the treatment of knee OA in a real-world setting, was well tolerated, with an acceptable safety profile and consistent therapeutic effect. [ABSTRACT FROM AUTHOR]

Aims A comprehensive nationwide study on the incidence and outcomes of COVID-19 vaccination-related myocarditis (VRM) is in need. Methods and results Among 44 276 704 individuals with at least 1 dose of COVID-19 vaccination, the incidence and clinical courses of VRM cases confirmed by the Expert Adjudication Committee of the Korea Disease Control and Prevention Agency were analyzed. COVID-19 VRM was confirmed in 480 cases (1.08 cases per 100 000 persons). Vaccination-related myocarditis incidence was significantly higher in men than in women (1.35 vs. 0.82 per 100 000 persons, P < 0.001) and in mRNA vaccines than in other vaccines (1.46 vs. 0.14 per 100 000 persons, P < 0.001). Vaccination-related myocarditis incidence was highest in males between the ages of 12 and 17 years (5.29 cases per 100 000 persons) and lowest in females over 70 years (0.16 cases per 100 000 persons). Severe VRM was identified in 95 cases (19.8% of total VRM, 0.22 per 100 000 vaccinated persons), 85 intensive care unit admission (17.7%), 36 fulminant myocarditis (7.5%), 21 extracorporeal membrane oxygenation therapy (4.4%), 21 deaths (4.4%), and 1 heart transplantation (0.2%). Eight out of 21 deaths were sudden cardiac death (SCD) attributable to VRM proved by an autopsy, and all cases of SCD attributable to VRM were aged under 45 years and received mRNA vaccines. Conclusion Although COVID-19 VRM was rare and showed relatively favorable clinical courses, severe VRM was found in 19.8% of all VRM cases. Moreover, SCD should be closely monitored as a potentially fatal complication of COVID-19 vaccination. [ABSTRACT FROM AUTHOR]

Aims: We compared diagnostic performance, costs, and association with major adverse cardiovascular events (MACE) of clinical coronary computed tomography angiography (CCTA) interpretation versus semiautomated approach that use artificial intelligence and machine learning for atherosclerosis imaging‐quantitative computed tomography (AI‐QCT) for patients being referred for nonemergent invasive coronary angiography (ICA). Methods: CCTA data from individuals enrolled into the randomized controlled Computed Tomographic Angiography for Selective Cardiac Catheterization trial for an American College of Cardiology (ACC)/American Heart Association (AHA) guideline indication for ICA were analyzed. Site interpretation of CCTAs were compared to those analyzed by a cloud‐based software (Cleerly, Inc.) that performs AI‐QCT for stenosis determination, coronary vascular measurements and quantification and characterization of atherosclerotic plaque. CCTA interpretation and AI‐QCT guided findings were related to MACE at 1‐year follow‐up. Results: Seven hundred forty‐seven stable patients (60 ± 12.2 years, 49% women) were included. Using AI‐QCT, 9% of patients had no CAD compared with 34% for clinical CCTA interpretation. Application of AI‐QCT to identify obstructive coronary stenosis at the ≥50% and ≥70% threshold would have reduced ICA by 87% and 95%, respectively. Clinical outcomes for patients without AI‐QCT‐identified obstructive stenosis was excellent; for 78% of patients with maximum stenosis < 50%, no cardiovascular death or acute myocardial infarction occurred. When applying an AI‐QCT referral management approach to avoid ICA in patients with <50% or <70% stenosis, overall costs were reduced by 26% and 34%, respectively. Conclusions: In stable patients referred for ACC/AHA guideline‐indicated nonemergent ICA, application of artificial intelligence and machine learning for AI‐QCT can significantly reduce ICA rates and costs with no change in 1‐year MACE. Key points: Software platform technology solutions now enable artificial intelligence guided and quantitative cardiac computed tomography angiography (CCTA) for coronary artery plaque quantification and characterization and vascular morphology assessment.As most patients referred for invasive coronary angiography (ICA) are found not to have actionable coronary artery disease, artificial intelligence guided CCTA measures of vascular morphology may allow for improved referral management to ICA in a manner that is safe and lower in costs. [ABSTRACT FROM AUTHOR]

Aims: Increased red cell distribution width (RDW) is a poor prognostic factor in patients with heart failure (HF). However, only a few large‐scale studies have identified the clinical utility of RDW after adjusting for covariates affecting RDW. Methods and results: From January 2010 to April 2021, we retrospectively enrolled patients diagnosed with HF from three referral hospitals with available RDW data (taken within 3 months of HF diagnosis) using an integrated clinical data system. Patients with an ejection fraction (EF) < 50% or HFA‐PEFF (Heart Failure Association Pre‐test assessment, Echocardiography and natriuretic peptide, Functional testing, Final aetiology) score ≥ 2 without severe valvular heart disease or coronary revascularization were enrolled. The primary endpoint was all‐cause mortality, and cardiovascular mortality was also collected. Multivariable Cox regression analysis and stabilized inverse probability of treatment weighting (IPTW) were used to identify any association between RDW and all‐cause death by balancing covariates or compounding factors. The global χ2 score was calculated and discrimination analysis was performed to evaluate the incremental value of RDW in predicting prognosis. Among the 6599 participants enrolled in this study, 1256 (19.0%) cases of all‐cause death occurred, and the median duration of follow‐up was 887 (interquartile range 351–1589) days. Elevated RDW at the initial diagnosis was associated with poor prognosis [cumulative incidence: 819 (30.2%) vs. 437 (11.2%), relative risk 1.58, 95% confidence interval (CI) 1.51–1.67, log‐rank P < 0.001]. Multivariable Cox analysis showed that elevated RDW was a poor prognostic factor for the primary endpoint [hazard ratio (HR) 1.11, 95% CI 1.06–1.16, P < 0.001], independent of clinical risk factors, N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), and EF, which was concordant with the stabilized IPTW (HR 1.29, 95% CI 1.10–1.49, P < 0.001). Adding RDW to model composed of traditional risk factors, NT‐proBNP, and echocardiographic parameters showed incremental prognostic value for predicting poor prognosis (area under the receiver operating characteristic curve, 0.799–0.826; P < 0.001). Conclusions: Increased RDW at the time of diagnosis is associated with poor prognosis in patients with HF, independent of clinical risk factors, such as NT‐proBNP, and echocardiographic parameters. Therefore, RDW may aid in the management of these patients beyond traditional risk factors. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to elucidate the relationship between premature ventricular complexes (PVCs) and right ventricular (RV) dysfunction, and the effects of radiofrequency catheter ablation (RFCA) on RV function. Methods: A total of 110 patients (age, 50.8 ± 14.4 years; 30 men) without structural heart disease who had undergone RFCA for RV outflow tract (RVOT) PVCs were retrospectively included. RV function was assessed using fractional area change (FAC) and global longitudinal strain (GLS) before and after RFCA. Clinical data were compared between the RV dysfunction (n = 63) and preserved RV function (n = 47) groups. The relationship between PVC burden and RV function was analyzed. Change in RV function before and after RFCA was compared between patients with successful and failed RFCA. Results: PVC burden was significantly higher in the RV dysfunction group than in the preserved RV function group (p <.001). FAC and GLS were significantly worse in proportion to PVC burden (p <.001 and p <.001, respectively). The risk factor associated with RV dysfunction was PVC burden [odds ratio (95% confidence interval), 1.092 (1.052–1.134); p <.001]. Improvement in FAC (13.0 ± 8.7% and –2.5 ± 5.6%, respectively; p <.001) and GLS (–6.8 ± 5.7% and 2.1 ± 4.2%, respectively; p <.001) was significant in the patients with successful RFCA, compared to the patients in whom RFCA failed. Conclusions: Frequent RVOT PVCs are associated with RV dysfunction. RV dysfunction is reversible by successful RFCA. [ABSTRACT FROM AUTHOR]

Background: To investigate the differential contribution of the left atrial (LA) function and left ventricular (LV) fibrosis to pulmonary arterial systolic pressure (PASP) in hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM) and reperfused acute myocardial infarction (AMI).Methods: Data of 370 patients with HCM (n = 133), DCM (n = 114) and reperfused AMI (n = 123) who underwent both echocardiography and cardiovascular magnetic resonance (CMR) were comprehensively reviewed. Phasic LA volumes, LA-global longitudinal strain (GLS), LA stiffness index, defined as E/e'/LA-GLS and extracellular volume fraction (ECV) of LV were measured using CMR.Results: E/e' was correlated with PASP in all groups; however, the predicted value was significantly attenuated after adjusting for LA volume and LA strain in HCM and DCM, but remained significant in AMI. The LA stiffness index was related to PASP in HCM (p = 0.01) and DCM (p = 0.03) independent of LA volume index and E/e', but not in AMI. In DCM, ECV was significantly related to PASP (p < 0.001) independent of LA volume index and E/e'. When subdivided according to the linear regression between PASP and E/e', patients in the discrepantly high PASP group had lower total emptying fraction and reservoir fraction of left atrium in HCM and DCM but not in AMI.Conclusions: The LA function in HCM and DCM and LV fibrosis in DCM correlated with PASP independent of E/e' and LA size, contrary to that in AMI. These results suggest the presence of LA dysfunction in non-ischemic cardiomyopathies and usefulness of ECV measurement in DCM for the comprehensive evaluation of LV diastolic function. [ABSTRACT FROM AUTHOR]

Background: Cardiac evaluation using transthoracic echocardiography before noncardiac surgery is common in real-world practice. However, evidence supporting preoperative echocardiography is lacking. This study aims to evaluate the additional benefit of preoperative echocardiography in predicting postoperative cardiovascular events (CVE) in noncardiac surgery.Methods: This study is designed as a multicenter, prospective study to assess the utility of preoperative echocardiography in patients undergoing intermediate- or high-risk noncardiac surgery. This trial comprises two studies: (1) a randomized controlled trial (RCT) for patients undergoing intermediate-risk surgery with fewer than three clinical risk factors from the revised cardiac risk index (intermediate-risk group) and (2) a prospective cohort study for patients undergoing intermediate-risk surgery with three or more clinical risk factors, or who undergo high-risk surgery regardless of the number of clinical risk factors (high-risk group). We hypothesize that the use of preoperative echocardiography will reduce postoperative CVEs in patients undergoing intermediate- to high-risk surgery through discovery of and further intervention for unexpected cardiac abnormalities before elective surgery. A total of 2330 and 2184 patients will be enrolled in the two studies. The primary endpoint is a composite of all-cause death; aborted sudden cardiac arrest; type I acute myocardial infarction; clinically diagnosed unstable angina; stress-induced cardiomyopathy; lethal arrhythmia, such as sustained ventricular tachycardia or ventricular fibrillation; and/or newly diagnosed or acutely decompensated heart failure within 30 days after surgery.Discussion: This study will be the first large-scale prospective study examining the benefit of preoperative echocardiography in predicting postoperative CVE. The PREOP-ECHO trial will help doctors identify patients at risk of postoperative CVE using echocardiography and thereby reduce postoperative CVEs.Trial Registration: The Clinical Research Information Service KCT0006279 for RCT and KCT0006280 for prospective cohort study. Registered on June 21, 2021. [ABSTRACT FROM AUTHOR]

Aims: Despite advances in contemporary cardiopulmonary therapies, cardiomyopathy remains the leading cause of death in patients with Duchenne muscular dystrophy (DMD). Also, the long‐term clinical outcomes of patients with DMD and cardiomyopathy is unknown. This study investigated long‐term clinical outcomes and their associated factors in patients with late‐stage DMD. Methods and results: A total of 116 patients with late‐stage DMD (age > 15 years) were enrolled in this retrospective study. All enrolled patients were followed up at a single tertiary referral hospital. LV systolic dysfunction was dichotomously defined as reduced [left ventricular ejection fraction (LVEF) ≤ 40%] vs. preserved [>40%] based on the initial echocardiographic result. The primary endpoint was all‐cause death. The secondary endpoint was a composite event defined as death or unexpected hospitalization due to cardiovascular reasons including chest pain, dyspnoea, and generalized oedema. The patients were divided into preserved (n = 84, 72.4%) and reduced LVEF groups (n = 32, 27.6%). The mean age was 20.8 ± 5.9 years, the mean disease duration, 8.8 ± 3.7 years, and the mean follow‐up duration, 1708 ± 659 days. For primary endpoint, the reduced LVEF group showed a lower rate of overall survival (Reduced LVEF vs. Preserved LVEF; 81.3% vs. 98.8%, log‐rank P = 0.005). In the multivariable Cox regression analysis, brain‐natriuretic peptide (BNP) level (adjusted hazard ratio [HR] 1.088, 95% confidence interval [CI] 1.019–1.162, P = 0.011) and diuretic use (adjusted HR 9.279, 95%CI 1.651–52.148, P = 0.011) were significant predictors of all‐cause death in patients with DMD. For the secondary endpoint, the reduced LVEF group had a lower rate of freedom from composite events than the preserved LVEF group (65.6% vs. 86.9%, log‐rank P = 0.005). In the multivariable Cox regression analysis, BNP level (adjusted HR 1.057, 95%CI 1.005–1.112, P = 0.032) and diuretic use (adjusted HR 4.189, 95% CI 1.704–10.296, P = 0.002) were significant predictors of the composite event in patients with DMD. Conclusions: Patients with DMD and reduced LVEF had worse clinical outcomes than those with preserved LVEF. BNP level and diuretic use were associated with adverse clinical outcomes in patients with late‐stage DMD, irrespective of LVEF. [ABSTRACT FROM AUTHOR]

The etiology of open-angle glaucoma (OAG) is yet unclear. This study investigated possible risk factors, such as the morphology of the border tissue that affect the pattern of visual field (VF) progression in eyes with OAG. 166 eyes of 166 OAG patients with an externally oblique border tissue (EOBT) at least in one direction were included. EOBT was obtained by analyzing enhanced depth imaging spectral-domain optical coherence tomography images. A pointwise linear regression was used to determine VF progression by measuring the deterioration rate of each point in the VF. The odds ratio of VF progression for each risk factor was estimated using logistic regression analysis. Seventy (42.2%) eyes showed VF deterioration. In multivariate analysis, longer follow-up period, higher baseline intraocular pressure (IOP), lower mean ocular perfusion pressure (MOPP), and smaller angular location of the longest EOBT were associated with VF progression (all p values were below 0.05). In the multivariate analysis, the location of the longest EOBT was significantly associated with inferior (p = 0.002) and central (p = 0.017) VF progression. In conclusion, VF progression pattern in OAG eyes is associated with the location of the longest EOBT as well as other known risk factors. [ABSTRACT FROM AUTHOR]

Improving predictive models for intensive care unit (ICU) inpatients requires a new strategy that periodically includes the latest clinical data and can be updated to reflect local characteristics. We extracted data from all adult patients admitted to the ICUs of two university hospitals with different characteristics from 2006 to 2020, and a total of 85,146 patients were included in this study. Machine learning algorithms were trained to predict in-hospital mortality. The predictive performance of conventional scoring models and machine learning algorithms was assessed by the area under the receiver operating characteristic curve (AUROC). The conventional scoring models had various predictive powers, with the SAPS III (AUROC 0.773 [0.766–0.779] for hospital S) and APACHE III (AUROC 0.803 [0.795–0.810] for hospital G) showing the highest AUROC among them. The best performing machine learning models achieved an AUROC of 0.977 (0.973–0.980) in hospital S and 0.955 (0.950–0.961) in hospital G. The use of ML models in conjunction with conventional scoring systems can provide more useful information for predicting the prognosis of critically ill patients. In this study, we suggest that the predictive model can be made more robust by training with the individual data of each hospital. [ABSTRACT FROM AUTHOR]

Purpose: Although rapid-acting insulins (RAIs) are used frequently in Korean clinical settings, evidence on their use is limited. This study explores the pattern and clinical effectiveness of the use of RAIs in Korean patients with type 2 diabetes mellitus (T2DM). Patients and Methods: This non-interventional, observational study enrolled patients (aged > 18 years) with T2DM who were prescribed RAIs. The pattern of use and effectiveness of RAI analogs were evaluated over 6 months. Results: A total of 299/451 patients were analyzed. Approximately 90% (n/N=270/299) of the patients received insulin glulisine, which significantly reduced their levels of glycated hemoglobin (HbA1c: n=270, mean± standard deviation [SD]; − 1.16± 6.02%, p=0.0017), fasting plasma glucose (n=40; mean±SD: − 54.9± 90.89 mg/dl, p=0.0005), and post prandial blood glucose (n=35, mean±SD: − 89.46± 105.68 mg/dl, p< 0.0001) at 6 months, with a corresponding increase in body weight (BW) (n=197, mean±SD:1.45± 3.64 kg, p< 0.0001). At 6 months, more patients receiving an intensive regimen (basal insulin+≥ 2 RAI injections/day) had HbA1c < 7% than those receiving a non-intensive regimen (basal insulin+1 RAI injection/day) (20.69% vs 7.46%; p=0.0333); the corresponding reduction in HbA1c was also higher in patients receiving the intensive regimen (p< 0.0001). About one-fourth patients (n/N=22/95) were switched to the intensive regimen (from 1 to ≥ 2 RAI injections/day), and only 4.41% (n/N=9/204) of the patients were switched to 1 RAI injection/day. The patients receiving the intensive regimen showed higher levels of HbA1c reductions (mean±SD: − 1.27± 1.96%) compared with the maintenance group-1 RAI injection/day (mean±SD: − 0.72± 1.66%) (p=0.0459), without a significant increase in BW and body mass index. Conclusion: The insulin glulisine intensification regimen showed glycemic target achievement and can be considered a therapeutic tool in the management of T2DM patients. [ABSTRACT FROM AUTHOR]

The frequency of non-invasive respiratory support use has increased in neonates of all gestational ages with respiratory distress (RD). However, the impact of delayed initiation of non-invasive respiratory support in outborn neonates remains poorly understood. This study aimed to identify the impact of the delayed initiation of non-invasive respiratory support in outborn, late-preterm, and term neonates. Medical records of 277 infants (gestational age of ≥ 35 weeks) who received non-invasive respiratory support as primary respiratory therapy < 24 h of age between 2016 and 2020 were retrospectively reviewed. Factors associated with respiratory adverse outcomes were investigated in 190 outborn neonates. Infants with RD were divided into two groups: mild (fraction of inspired oxygen [FiO2] ≤ 0.3) and moderate-to-severe RD (FiO2 > 0.3), depending on their initial oxygen requirements from non-invasive respiratory support. The median time for the initiation of non-invasive respiratory support at a tertiary center was 3.5 (2.2-5.0) h. Male sex, a high oxygen requirement (FiO2 > 0.3), high CO2 level, and respiratory distress syndrome were significant factors associated with adverse outcomes. Subgroup analysis revealed that in the moderate-to-severe RD group, delayed commencement of non-invasive respiratory support (≥ 3 h) was significantly associated with pulmonary air leakage (p = 0.033).Conclusion: Our study shows that outborn neonates with moderate-to-severe RD, who were treated with delayed non-invasive respiratory support, were associated with an increased likelihood of pulmonary air leakage. Additional prospective studies are required to establish the optimal timing and methods of non-invasive respiratory support for outborn, late-preterm, and term infants.What Is Known: • Non-invasive respiratory support is widely used in neonates of all gestational ages. • Little is known on the impact of delayed initiation of non-invasive respiratory support in outborn, late preterm, and term neonates.What Is New: • Male sex, high oxygen requirement (FiO2 >0.3), high initial CO2 level, and respiratory distress syndrome significantly correlated with adverse outcomes. • Outborn late-preterm and term neonates with high oxygen requirement who were treated with delayed non-invasive respiratory support indicated an increased likelihood of pulmonary air leakage. [ABSTRACT FROM AUTHOR]

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 (β = 0.26, p = .013) and self-management behaviour (β = 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. [ABSTRACT FROM AUTHOR]

Excessive activation of the ionotropic N-methyl-d-aspartate (NMDA) receptor has been shown to cause abnormally high levels of Ca2+ influx, thereby leading to excitotoxic neuronal death. In this study, exposure of mouse primary cortical neurons to NMDA resulted in the cleavage and activation of mammalian sterile 20-like kinase-1 (MST1), both of which were mediated by calpain 1. In vitro cleavage assay data indicated that calpain 1 cleaves out the autoinhibitory domain of MST1 to generate an active form of the kinase. Furthermore, calpain 1 mediated the cleavage and activation of wild-type MST1, but not of MST1 (G339A). Intriguingly, NMDA/calpain-induced MST1 activation promoted the nuclear translocation of the kinase and the phosphorylation of histone H2B in mouse cortical neurons, leading to excitotoxicity. Thus, we propose a previously unrecognized mechanism of MST1 activation associated with NMDA-induced excitotoxic neuronal death. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) has a heterogeneous pathophysiology according to individual patient characteristics. This study aimed to identify the effects of widely known risk factors on AF incidence according to age and to elucidate the clinical implications of these effects. Methods and results: We analyzed data from 501,668 subjects (≥18years old) without AF and valvular heart disease from the Korean National Health Insurance Service-National Sample Cohort. The total population was divided into two groups according to age, <60years and ≥60years. AF occurred in 0.7% of the overall population (3,416 of 501,668) during the follow-up period (mean 47.6 months). In Cox regression analysis, age, male sex, previous ischemic stroke, heart failure, and hypertension were related to increased risk of new-onset AF in both age groups. Especially in the <60years age group, risk of new-onset AF was increased by relatively modifiable risk factors: obesity (body mass index ≥25kg/m2; hazard ratio[HR] 1.37 [1.22–1.55], p<0.001, interaction p<0.001), and hypertension (HR 1.93[1.69–2.22], p<0.001, interaction p<0.001). Although interactions were not significant, chronic obstructive pulmonary disease (HR 1.41[1.24–1.60], p<0.001) and chronic kidney disease (HR 1.28[1.15–1.41], p<0.001) showed increased trends of the risk of new-onset AF in the ≥60years age group. Conclusion: The risk profile for new-onset AF was somewhat different between the <60years and the ≥60years age groups. Compared to the ≥60years group, relatively modifiable risk factors (such as obesity and hypertension) had a greater impact on AF incidence in the <60years age group. Different management strategies to prevent AF development according to age may be needed. [ABSTRACT FROM AUTHOR]

We evaluated the hemodynamic and geometric determinants of latent obstruction (LO, trans-left ventricular outflow tract (LVOT) gradient ≥30 mmHg with provocation) in patients with non-obstructive hypertrophic cardiomyopathy (HCMP). A total of 35 patients with non-obstructive HCMP underwent stepwise supine bicycle exercise echocardiography. Trans-LVOT pressure gradients, mitral geometric parameters, left ventricular ejection fractions (LVEF) and left ventricular end-systolic and diastolic dimensions (LVESD, LVEDD) were measured at each stage. The highest peak LVOT pressure gradient predominantly occurred immediately after exercise (n = 32, 91.3%) rather than during peak exercise (n = 3, 8.7%). Significant LO developed in nine patients (25%). No significant differences were found in resting echocardiographic parameters. Compared to the remaining patients, however, patients with LO had longer residual mitral leaflets (defined as residual portions of leaflets after coaptation; 4 ± 4 vs. 13 ± 4 mm, respectively; p = 0.001) and higher resting LVOT pressure gradients (7.4 ± 3.7 vs. 12.9 ± 5.8 mmHg, respectively; p = 0.001). Substantial decreases in mitral annular diameters from peak exercise to recovery after exercise were observed in the LO group, while mitral annular diameters increased after exercise in the non-LO group. In conclusion, the highest peak LVOT pressure gradient predominantly occurred immediately after exercise rather than during peak exercise, regardless of LO. Abrupt decrease of mitral annular diameter immediately after exercise, a longer residual mitral leaflet and a higher resting LVOT pressure gradient at rest might be related to LO. [ABSTRACT FROM AUTHOR]

Background: Although many controversies exist regarding the risk of red blood cell (RBC) transfusions, half of preterm infants born at <32 weeks of gestational age receive such transfusions because of anemia of prematurity. Because of the costs and risks associated with multiple transfusions, it has been suggested that a large transfusion volume reduces the number of transfusions. However, there have been persistent concerns that RBC transfusion might lead to volume overload. Methods: We examined the impacts of large (20 mL/kg) compared to standard volume (15 mL/kg) transfusions on the hemodynamic variables of stable, electively transfused, preterm infants, by serially measuring echocardiographic parameters and plasma B‐type natriuretic peptide levels. Results: A total of 39 infants born at <34 weeks of gestation and aged >2 weeks at the time of enrollment were randomly allocated to either a standard volume (15 mL/kg) or a large volume (20 mL/kg) group. Significant reductions in cardiac output and transient increases in plasma B‐type natriuretic peptide levels were found after RBC transfusion in both the standard and large volume (20 mL/kg) groups. However, these changes were not significantly different between the two groups. Conclusions: Large‐volume transfusions could be tolerable in stable preterm infants with anemia. [ABSTRACT FROM AUTHOR]

p62/SQSTM1 is known to act as a key mediator in the selective autophagy of protein aggregates, or aggrephagy, by steering ubiquitinated protein aggregates towards the autophagy pathway. Here, we use a yeast two-hybrid screen to identify the prefoldin-like chaperone UXT as an interacting protein of p62. We show that UXT can bind to protein aggregates as well as the LB domain of p62, and, possibly by forming an oligomer, increase p62 clustering for its efficient targeting to protein aggregates, thereby promoting the formation of the p62 body and clearance of its cargo via autophagy. We also find that ectopic expression of human UXT delays SOD1(A4V)-induced degeneration of motor neurons in a Xenopus model system, and that specific disruption of the interaction between UXT and p62 suppresses UXT-mediated protection. Together, these results indicate that UXT functions as an autophagy adaptor of p62-dependent aggrephagy. Furthermore, our study illustrates a cooperative relationship between molecular chaperones and the aggrephagy machinery that efficiently removes misfolded protein aggregates. p62/SQSTM1 acts as a key mediator in the selective autophagy of protein aggregates, or aggrephagy. Here the authors identify the prefoldin-like chaperone UXT as an autophagy adaptor of p62 dependent aggrephagy and show that ectopic UXT expression delays motor neuron degeneration in a Xenopus model. [ABSTRACT FROM AUTHOR]

Background: Several studies have suggested that adverse neurodevelopment could be induced by systemic inflammation in preterm infants. We aimed to investigate whether preterm infants with systemic inflammation would have impaired neurodevelopment and which biomarkers and neurophysiologic studies during inflammation are associated with poor neurodevelopment.Methods: This prospective cohort study enrolled infants born before 30 weeks of gestation or with birth weight < 1250 g. Infants were grouped according to the presence of systemic inflammation: Control (no inflammation, n = 49), I (systemic inflammation, n = 45). Blood and cerebrospinal fluid samples for markers of brain injury and inflammation were collected and amplitude-integrated electroencephalography (aEEG) was performed within 4 h of septic workup. We evaluated aEEG at 35 weeks postmenstrual age (PMA), head circumference at 36 weeks PMA, and brain MRI at discharge. The Bayley Scales of Infant and Toddler Development III (Bayley-III) was performed at a corrected age (CA) of 18 months.Results: The I group had more white matter injuries (2 vs. 26.7%, Control vs. I, respectively) at the time of discharge, lower brain functional maturation (9.5 vs. 8), and smaller head size (z-score - 1.45 vs. -2.12) at near-term age and poorer neurodevelopment at a CA of 18 months than the control (p < 0.05). Among the I group, the proportion of immature neutrophils (I/T ratios) and IL-1 beta levels in the CSF were associated with aEEG measures at the day of symptom onset (D0). Seizure spike on aEEG at D0 was significantly correlated with motor and social-emotional domains of Bayley-III (p < 0.05). The I/T ratio and CRP and TNF-α levels of blood at D0, white matter injury on MRI at discharge, head circumference and seizure spikes on aEEG at near-term age were associated with Bayley-III scores at a CA of 18 months.Conclusions: Systemic inflammation induced by clinical infection and NEC are associated with neurodevelopmental impairment in preterm infants. The seizure spike on aEEG, elevated I/T ratio, CRP, and plasma TNF-alpha during inflammatory episodes are associated with poor neurodevelopment. [ABSTRACT FROM AUTHOR]

Background: Myocardial fibrosis is an important prognostic factor in hypertrophic cardiomyopathy (HCM). However, the contribution from a wide spectrum of genetic mutations has not been well defined. We sought to investigate effect of sarcomere and mitochondria-related mutations on myocardial fibrosis in HCM. Methods: In 133 HCM patients, comprehensive genetic analysis was performed in 82 nuclear DNA (33 sarcomere-associated genes, 5 phenocopy genes, and 44 nuclear genes linked to mitochondrial cardiomyopathy) and 37 mitochondrial DNA. In all patients, cardiovascular magnetic resonance (CMR) was performed, including 16-segmental thickness, late gadolinium enhancement (LGE), native and post-T1, extracellular volume fraction (ECV), and T2, along with echo-Doppler evaluations. Results: Patients with sarcomere mutation (SM, n = 41) had higher LGE involved segment, % LGE mass, ECV and lower post-T1 compared to patients without SM (n = 92, all p < 0.05). When classified into, non-mutation (n = 67), only mitochondria-related mutation (MM, n = 24), only-SM (n = 36) and both SM and MM (n = 5) groups, only-SM group had higher ECV and LGE than the non-mutation group (all p < 0.05). In non-LGE-involved segments, ECV was significantly higher in patients with SM. Within non-SM group, patients with any sarcomere variants of uncertain significance had higher echocardiographic Doppler E/e' (p < 0.05) and tendency of higher LGE amount and ECV (p > 0.05). However, MM group did not have significantly higher ECV or LGE amount than non-mutation group. Conclusions: SMs are significantly related to increase in myocardial fibrosis. Although, some HCM patients had pathogenic MMs, it was not associated with an increase in myocardial fibrosis. [ABSTRACT FROM AUTHOR]

Pattern-recognition receptors including Toll-like receptors (TLRs) recognize invading pathogens and trigger an immune response in mammals. Here we show that mammalian ste20-like kinase 1/serine/threonine kinase 4 (MST1/STK4) functions as a negative regulator of lipopolysaccharide (LPS)-induced activation of the TLR4-NF-κB signaling pathway associated with inflammation. Myeloid-specific genetic ablation of MST1/STK4 increased the susceptibility of mice to LPS-induced septic shock. Ablation of MST1/STK4 also enhanced NF-κB activation triggered by LPS in bone marrow-derived macrophages (BMDMs), leading to increased production of proinflammatory cytokines by these cells. Furthermore, MST1/STK4 inhibited TRAF6 autoubiquitination as well as TRAF6-mediated downstream signaling induced by LPS. In addition, we found that TRAF6 mediates the LPS-induced activation of MST1/STK4 by catalyzing its ubiquitination, resulting in negative feedback regulation by MST1/STK4 of the LPS-induced pathway leading to cytokine production in macrophages. Together, our findings suggest that MST1/STK4 functions as a negative modulator of the LPS-induced NF-κB signaling pathway during macrophage activation. [ABSTRACT FROM AUTHOR]

Background: The age of candidates for device closure of atrial septal defect (ASD) has been increasing. Thus, concerns exist about dyspnea aggravation or atrial fibrillation development after device closure due to augmentation of left ventricular (LV) and left atrial (LA) preload. This study aimed to examine patterns and determinants of serial pulmonary arterial pressure and left ventricular filling pressure changes after device closure of ASD.Methods: Among the 86 consecutive patients who underwent percutaneous device closure of ASD, those with end-stage renal disease or those without pre- or postprocedural Doppler data were excluded. The clinical, transesophageal, and transthoracic echocardiographic findings of 78 patients were collected at baseline, one-day postprocedure, and one-year follow-up.Results: The mean age of study patients was 49.8 ± 15.0 years, and the average maximal defect diameter and device size were 20.2 ± 6.0 mm and 23.8 ± 6.4 mm. Four patients (5.6%) underwent new-onset atrial fibrillation, and five patients (6.4%) took diuretics within one-year after closure. Some patients (n = 21; 27%) exhibited paradoxically increased tricuspid regurgitant velocity (TRV) one-day postprocedure; they also were older with lower e', glomerular filtration rate, and LV ejection fraction and a higher LA volume index. However, even in these patients, TRV deceased below baseline levels one-year later. Both E/e' and LA volume index significantly increased immediately after device closure, but all decreased one-year later. Larger defect size and higher TRV were significantly correlated with immediate E/e' elevation.Conclusion: In older, renal, diastolic, and systolic dysfunctional patients with larger LA and scheduled for larger device implantation, peri-interventional preload reduction therapy would be beneficial. [ABSTRACT FROM AUTHOR]

Background: Left atrial (LA) enlargement and dysfunction are related to clinical course in patients with hypertrophic cardiomyopathy (HCM). We aimed to investigate genetic contribution to LA structural and functional remodeling.Methods: Two hundred twelve patients were consecutively enrolled, and echocardiography and extensive genetic analysis were performed. Cardiac magnetic resonance (CMR) was performed in 135 patients. Echocardiography was also performed in controls (n = 30).Results: Patients with HCM had lower late-diastolic mitral annular velocity (a') and higher LA volume index (LAVI) than controls. Patients with pathogenic or likely pathogenic sarcomere gene mutations (PSM, n = 67, 32%) had higher LAVI and lower CMR-derived LA total emptying fraction (37.0 ± 18.5 vs. 44.2 ± 12.4%, p = 0.025). In patients without AF (n = 187), the PSM had lower a' (6.9 ± 2.0 vs. 7.8 ± 1.9 cm/s, p = 0.004) than others. The PSM had higher prevalence and amount of late gadolinium enhancement (LGE) in the left ventricle (LV). In multivariate analysis, PSM was significantly related to lower a' independent of E/e', LV mass index, and LAVI. However, the relation significantly attenuated after adjustment for the extent of LGE in the LV, suggesting common myopathy in the LV and LA. In addition, PSM was significantly related to lower LA total emptying fraction independent of age, E/e', s', LV ejection fraction, LV myocardial global longitudinal strain and %LGE mass.Conclusions: PSM was related to LA dysfunction independent of LV filling pressure and LAVI, suggesting its contribution to atrial myopathy in HCM. [ABSTRACT FROM AUTHOR]

Screening for secondary hypertension (HTN) is recommended for early-onset HTN. However, there have been few studies on secondary HTN in young adults. We aimed to investigate the prevalence and risk factors for secondary HTN in young male military personnel. In this retrospective cross-sectional study, hypertensive men (age, 19-29 years) were identified using the electronic medical records (EMR) database between 2011 and 2017. Among them, patients with secondary HTN were confirmed through a review of the EMR. Using clinical characteristics and laboratory findings, independent predictors associated with secondary HTN were identified by binary logistic regression analysis. Secondary HTN was confirmed in 140 of 6373 participants (2.2%). Overall, the most common causes were polycystic kidney disease (n = 47, 0.74%) and renal parenchymal diseases (n = 24, 0.38%). The independent predictors of secondary HTN were abnormal thyroid function test (TFT) (odds ratio [OR]: 9.50, 95% confidence interval [CI]: 4.84-19.45, P < 0.001), proteinuria (≥ trace) (OR: 6.13, 95% CI: 2.97-12.99, P < 0.001), hematuria (≥ trace) (OR: 4.37, 95% CI: 2.15-9.01, P < 0.001), severe HTN (≥ 180/110 mmHg) (OR: 3.07, 95% CI: 1.42-6.65, P = 0.004), and non-overweight (OR: 3.03, 95% CI: 1.69-5.26, P < 0.001). However, there were no significant differences in the family history of HTN, headache, total cholesterol, and diabetes between patients with primary and secondary HTN. Therefore, to ensure cost-effectiveness, screening for secondary HTN in young hypertensive men should be performed selectively considering abnormal TFT, proteinuria, hematuria, severe HTN, and non-overweight. [ABSTRACT FROM AUTHOR]

It is necessary to understand the learning needs of heart failure (HF) patients to provide adequate patient education. It is necessary to identify what HF patients want to know and how this differs from the educational needs of healthcare providers. The aim of this descriptive and exploratory study was to evaluate and compare the learning needs priorities between HF patients and their healthcare providers. One hundred patients with HF and 20 healthcare providers were recruited from cardiovascular outpatient clinics at 2 large tertiary medical centers in South Korea. Learning needs were measured using a self-administered questionnaire with the Heart Failure Patients' Learning Needs Inventory. Data were analyzed using SPSS 23.0 program. Overall rank orders for 48 items were similar in both groups (Spearman rank order correlation 0.605, p <.001). The educational topics of medications and worsening signs and symptoms ranked highest in both groups. However, healthcare providers were more concerned with diet management than were the patients (mean score 4.18 vs. 3.62; p =.001). The study showed both similarities and differences between the assessments of the patients and healthcare providers of detailed educational learning needs. It is important to develop patient-centered educational materials considering HF patients' actual learning needs, and also to provide comprehensive and practical patient education based on a supportive understanding of healthcare provider needs. [ABSTRACT FROM AUTHOR]

Background: Machine learning (ML) is able to extract patterns and develop algorithms to construct data-driven models. We use ML models to gain insight into the relative importance of variables to predict obstructive coronary artery disease (CAD) using the Coronary Computed Tomographic Angiography for Selective Cardiac Catheterization (CONSERVE) study, as well as to compare prediction of obstructive CAD to the CAD consortium clinical score (CAD2). We further perform ML analysis to gain insight into the role of imaging and clinical variables for revascularization. Methods: For prediction of obstructive CAD, the entire ICA arm of the study, comprising 719 patients was used. For revascularization, 1,028 patients were randomized to invasive coronary angiography (ICA) or coronary computed tomographic angiography (CCTA). Data was randomly split into 80% training 20% test sets for building and validation. Models used extreme gradient boosting (XGBoost). Results: Mean age was 60.6 ± 11.5 years and 64.3% were female. For the prediction of obstructive CAD, the AUC was significantly higher for ML at 0.779 (95% CI: 0.672–0.886) than for CAD2 (0.696 [95% CI: 0.594–0.798]) (P = 0.01). BMI, age, and angina severity were the most important variables. For revascularization, the model obtained an overall area under the receiver-operation curve (AUC) of 0.958 (95% CI = 0.933–0.983). Performance did not differ whether the imaging parameters used were from ICA (AUC 0.947, 95% CI = 0.903–0.990) or CCTA (AUC 0.941, 95% CI = 0.895–0.988) (P = 0.90). The ML model obtained sensitivity and specificity of 89.2% and 92.9%, respectively. Number of vessels with ≥70% stenosis, maximum segment stenosis severity (SSS) and body mass index (BMI) were the most important variables. Exclusion of imaging variables resulted in performance deterioration, with an AUC of 0.705 (95% CI 0.614–0.795) (P <0.0001). Conclusions: For obstructive CAD, the ML model outperformed CAD2. BMI is an important variable, although currently not included in most scores. In this ML model, imaging variables were most associated with revascularization. Imaging modality did not influence model performance. Removal of imaging variables reduced model performance. [ABSTRACT FROM AUTHOR]

The balance between major DNA double-strand break (DSB) repair pathways is influenced by binding of the Ku complex, a XRCC5/6 heterodimer, to DSB ends, initiating non-homologous end joining (NHEJ) but preventing additional DSB end resection and homologous recombination (HR). However, the key molecular cue for Ku recruitment to DSB sites is unknown. Here, we report that FOXL2, a forkhead family transcriptional factor, directs DSB repair pathway choice by acetylation-dependent binding to Ku. Upon DSB induction, SIRT1 translocates to the nucleus and deacetylates FOXL2 at lysine 124, leading to liberation of XRCC5 and XRCC6 from FOXL2 and formation of the Ku complex. FOXL2 ablation enhances Ku recruitment to DSB sites, imbalances DSB repair kinetics by accelerating NHEJ and inhibiting HR, and thus leads to catastrophic genomic events. Our study unveils the SIRT1-(de)acetylated FOXL2-Ku axis that governs the balance of DSB repair pathways to maintain genome integrity. The Ku complex, formed by XRCC5/6 heterodimer, binds to double strand break (DSB) ends, initiating non homologous end joining (NHEJ) and preventing homologous recombination (HR). Here, the authors reveal that FOXL2, a forkhead family transcriptional factor, directs DSB repair pathway choice by acetylation-dependent binding to Ku. [ABSTRACT FROM AUTHOR]

The endothelial cilium is a microtubule‐based organelle responsible for blood flow‐induced mechanosensation and signal transduction during angiogenesis. The precise function and mechanisms by which ciliary mechanosensation occurs, however, are poorly understood. Although posttranslational modifications (PTMs) of cytoplasmic tubulin are known to be important in angiogenesis, the specific roles of ciliary tubulin PTMs play remain unclear. Here, we report that loss of centrosomal protein 41 (CEP41) results in vascular impairment in human cell lines and zebrafish, implying a previously unknown pro‐angiogenic role for CEP41. We show that proper control of tubulin glutamylation by CEP41 is necessary for cilia disassembly and that is involved in endothelial cell (EC) dynamics such as migration and tubulogenesis. We show that in ECs responding to shear stress or hypoxia, CEP41 activates Aurora kinase A (AURKA) and upregulates expression of VEGFA and VEGFR2 through ciliary tubulin glutamylation, as well as leads to the deciliation. We further show that in hypoxia‐induced angiogenesis, CEP41 is responsible for the activation of HIF1α to trigger the AURKA‐VEGF pathway. Overall, our results suggest the CEP41‐HIF1α‐AURKA‐VEGF axis as a key molecular mechanism of angiogenesis and demonstrate how important ciliary tubulin glutamylation is in mechanosense‐responded EC dynamics. Synopsis: CEP41 regulates cilia disassembly and angiogenesis through AURKA activation by modulating axonemal tubulin glutamylation in mammalian and zebrafish endothelial cells. CEP41‐mediated axonemal tubulin glutamylation is essential for endothelial cell dynamics during angiogenesis.CEP41 activates AURKA and upregulates VEGFA/VEGFR2 mRNAs to promote endothelia cellular deciliation under shear stress.CEP41 interacts with HIF1α and inhibits its UPS‐dependent degradation under hypoxia.CEP41 controls HIF1α activation to trigger AURKA‐VEGF pathway in hypoxia‐induced angiogenesis. [ABSTRACT FROM AUTHOR]

Background: Bilevel positive airway pressure (BiPAP) has recently been used in preterm infants with respiratory distress as an alternative to nasal continuous positive airway pressure (nCPAP) because, theoretically, BiPAP is thought to be more effective than nCPAP. However, the results of some studies comparing nCPAP with BiPAP as the initial respiratory support were controversial. The aim of this study is to compare the clinical effectiveness and safety of nCPAP with BiPAP at gestational ages of 30+0 to 34+6 weeks. Methods: A total of 93 infants with gestational ages of 30+0 to 34+6 weeks, who presented with respiratory distress within 24 h after birth, were randomized to the nCPAP group or the BiPAP group. The primary outcome was the incidence of treatment failure with these two non‐invasive respiratory support devices. Criteria for treatment failure included any of the following: respiratory acidosis (PaCO2 >65 mmHg with pH <7.2), hypoxia (FiO2 >0.4), or apnea (>2–3 episodes of apnea/h). Results: There was no statistically significant difference in treatment failure between the two groups (P = 0.576). The risk difference comparing treatment failure rate between nCPAP and BiPAP groups was −4.7% (95% CI: −21.5–11.9). Conclusions: Nasal continuous positive airway pressure is not inferior to BiPAP as an initial management of respiratory distress in these premature infants. We therefore conclude that nCPAP can be used as an initial management for preterm infants at gestational age of between 30 and 35 weeks as a substitute for BiPAP. [ABSTRACT FROM AUTHOR]

Acute myocardial infarction, acute myocarditis, and stress-induced cardiomyopathy must be differentiated in patients with acute chest pain and elevated troponin levels. 4041901 5 Jahnke C, Sinn M, Hot A et al (2023) Differentiation of acute non-ST elevation myocardial infarction and acute infarct-like myocarditis by visual pattern analysis: a head-to-head comparison of different CMR techniques. [Extracted from the article]

Although the risk of foot injuries during walking increases with the foot deformity, the dynamic mechanism is not clearly understood. This study aims at the investigation of dynamic change of center of pressure (COP) in different foot types. Contrasted by previous studies, this study analyzed COP in each gait phase, i.e., loading response, mid stance, terminal stance, and pre-swing. A total of 19 young males participated in this study and the resting calcaneal stance position (RCSP) angle was measured for the classification into three foot types. All participants performed level walking with shoes on. COP trajectory was normalized by foot width and length. In the loading response and mid stance phases COP of Pes Cavus located most laterally (p < 0. 0 5). No difference among foot types existed at terminal stance and pre-swing phases (p > 0. 0 5). Foot deformity is known to occur due to the abnormality of musculoskeletal system such as lower extremities muscles, bones, and ligaments. Because the role of musculoskeletal system differs between gait phases, this may have caused phase-dependent COP difference among different foot types. [ABSTRACT FROM AUTHOR]

One of the most frequent sitting styles of Asians in everyday life is a cross-legged sitting. The cross-legged sitting results in higher compression load in spine than sitting on a chair, so a proper sitting posture is more needed. The purpose of this study was to classify the spinal posture during cross-legged sitting from the seat pressure pattern for future usage in the posture monitoring system. Twenty young men participated in this study. The seat pressure was measured for three spinal postures of flat, slump, and lordosis when subjects were instructed to pose a certain posture while seated on the floor with legs crossed. The contact area was divided into feet and buttocks by using a filter with a pressure threshold ( th f ). A decision tree was developed for the classification of three postures, with a decision variable of feet to buttocks pressure ratio. The three spinal postures were classified by comparison of feet-buttocks ratio ( R f b) and thresholds ( th R 1 , th R 2 ): a slump posture with a greater R f b than th R 1 , a lordosis posture with a smaller R f b than th R 2 . Each threshold was calculated by adding or subtracting a certain percentage (α , β) to or from the R f b of flat posture and the classification accuracy was investigated with a range of thresholds. The accuracy of classification achieved 99.38% for certain ranges of thresholds. The developed algorithm showed the best performance when α and β were in the range of 2.85–5.67% and 1.58–2.20%, respectively. The feet-buttocks pressure ratio showed significant correlation with lumbar angle (r = 0. 6 7 , p < 0. 0 0 1). Anterior and posterior tilts of upper body in the slump and lordosis postures would result in more pressure concentration in the feet and buttocks, respectively, which was incorporated in the classification algorithm of this study. The result of this study could be extended to the real-time or offline monitoring of the sitting posture. [ABSTRACT FROM AUTHOR]

High amplitude of movements in the lower body during walking is attenuated in the upper body to stabilize the head, which serves as the platform of critical sensory systems (vestibular and visual). The upper body attenuation has been investigated on the linear acceleration, however, not on the angular motion. This study aimed to compare the attenuation of axial rotation in different age-groups. Methods: Thirty healthy men (15 young and 15 elderly) participated in this study. Subjects walked on a level surface with gyro sensors attached at four locations of the back (pelvis, thorax, shoulder, and head), from which the angular motion was derived. Outcome measures included the average peak-to-peak amplitude of axial rotation at all sensor locations and the phase delay at each location with reference to the pelvis. Results: Age-position interaction was significant for both the amplitude and phase delay. Post hoc test revealed that rotation amplitude was similar at pelvis, thorax and shoulder in the elderly, whereas it was significantly reduced at the thorax-shoulder section in the young. The elderly also showed smaller phase delay at shoulder and head than those of the young. Discussion: The results suggest that the attenuation by upper trunk was reduced and the shoulder and head motions were more tightly coupled to the pelvis in the elderly, i.e., the upper body moved more like a rigid body in the axial motion. [ABSTRACT FROM AUTHOR]