Electrohydrodynamic Nanopatterning: A Novel Solvent-Assisted Technique for Unconventional Substrates.

Electrohydrodynamic (EHD)-driven patterning is a pioneering lithographic technique capable of replicating and modifying micro/nanostructures efficiently. However, this process is currently restricted to conventional substrates, as it necessitates a uniform and robust electric field over a large area. Consequently, the use of nontraditional substrates, such as those that are flexible, nonflat, or have high insulation, has been notably limited. In our study, we extend the applicability of EHD-driven patterning by introducing a solvent-assisted capillary peel-and-transfer method that allows the successful removal of diverse EHD-induced structures from their original substrates. Compared with the traditional route, our process boasts a success rate close to 100%. The detached structures can then be efficiently transferred to nonconventional substrates, overcoming the limitations of the traditional EHD process. Our method exhibits significant versatility, as evidenced by successful transfer of structures with engineered wettability and patterned structures composed of metals and metal oxides onto nonconventional substrates.

Associations between cooking self-efficacy, attitude, and behaviors among people living alone: A cross-sectional survey analysis.

Cooking-related literacy and attitudes may play important roles in preventing and reducing diet-related chronic diseases and nutrition disparities. People living alone are an under-researched but growing population who face above average food insecurity rates. This study's objectives were to 1) test how cooking self-efficacy and attitude are stratified demographically among a sample of people living alone, focusing on variations across gender, age, and food security, and 2) examine how cooking self-efficacy and attitude are associated with two indicators of cooking behavior - cooking frequency and convenience orientation. We draw from a cross-sectional survey analysis of 493 adults living alone in Illinois, USA with validated measures for cooking self-efficacy, attitude, frequency, convenience orientation, and demographic characteristics. Hierarchical linear regression models were used to examine demographic factors explaining variation in self-efficacy and attitude, with attention to interactions between gender, food insecurity, and age. Poisson and OLS linear regression models were used to examine associations between self-efficacy and attitude and cooking frequency and convenience orientation. We find cooking-related self-efficacy and attitude showed strong but distinct associations with cooking frequency and convenience orientation. Overall, food insecure groups had lower self-efficacy than those who were food secure; however, food insecure women had higher self-efficacy than men in similar positions, apart from older-adult women who held particularly low efficacy. Cooking attitudes varied in small ways, notably with food insecure younger and older women possessing more negative cooking attitudes than middle-aged women. This research highlights the importance of understanding the cooking-related orientations of single-living people, while demonstrating that this group's ability to prevent and manage food insecurity is not uniform. These results can inform targeted interventions around food and nutrition insecurity, cooking attitudes, and self-efficacy among single-living populations.

Impact of Trimetazidine on the Incident Heart Failure After Coronary Artery Revascularization.

ABSTRACT: Abnormal myocardial metabolism is a common pathophysiological process underlying ischemic heart disease and heart failure (HF). Trimetazidine is an antianginal agent with a unique mechanism of action that regulates myocardial energy metabolism and might have a beneficial effect in preventing HF in patients undergoing myocardial revascularization. We aimed to evaluate the potential benefit of trimetazidine in preventing incident hospitalization for HF after myocardial revascularization. Using the common data model, we identified patients without prior HF undergoing myocardial revascularization from 8 hospital databases in Korea. To compare clinical outcomes using trimetazidine, database-level hazard ratios (HRs) were estimated using large-scale propensity score matching for each database and pooled using a random-effects model. The primary outcome was incident hospitalization for HF. The secondary outcome of interest was major adverse cardiac events (MACEs). After propensity score matching, 6724 and 11,211 patients were allocated to trimetazidine new-users and nonusers, respectively. There was no significant difference in the incidence of hospitalization for HF between the 2 groups (HR: 1.08, 95% confidence interval [CI], 0.88-1.31; P = 0.46). The risk of MACE also did not differ between the 2 groups (HR: 1.07, 95% CI, 0.98-1.16; P = 0.15). In conclusion, the use of trimetazidine did not reduce the risk of hospitalization for HF or MACE in patients undergoing myocardial revascularization. Therefore, the role of trimetazidine in contemporary clinical practice cannot be expanded beyond its current role as an add-on treatment for symptomatic angina.

Endovascular treatment of Takayasu arteritis in a middle-aged woman with syncope and limb claudication: a case report.

Takayasu arteritis (TA) is a disease that causes inflammation and stenosis of medium to large blood vessels. We report a case of a 50-year-old female patient with newly developed hypertension, syncope, and claudication of the extremities. Total occlusion of the left subclavian artery at the origin was found and significant stenosis of the right common iliac artery was revealed by hemodynamic analysis. She was successfully treated with percutaneous angioplasty for multiple peripheral arterial diseases and was finally diagnosed with TA. In consultation with a rheumatologist, medical treatment for TA was initiated, the patient's hypertension disappeared, and her claudication symptoms improved.

Antibacterial Activity against Clinical Isolates and In Vivo Efficacy of Coralmycins.

Coralmycins, such as coralmycin A and DH-coralmycin A, have novel molecular skeletons and have been reported to exhibit potent antibacterial activity against standard Gram-positive bacterial strains. Here, the in vitro antibacterial activity against an extensive clinical isolate collection, time-kill kinetics, pharmacokinetics (PK), and in vivo efficacy of coralmycins were studied. Coralmycin A showed potent antibacterial activity with an MIC90 of 1 mg/L against 73 clinical methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococci isolates, which was 2-8 times higher than the corresponding activities of DH-coralmycin A, vancomycin, daptomycin, and linezolid, and against 73 vancomycin-resistant Enterococcus and Streptococcus pneumoniae isolates, which was 4-16 times higher than the corresponding activities of DH-coralmycin A, daptomycin, and linezolid. Pharmacokinetic analysis after i.v. injection showed that coralmycins have a moderate volume of distribution and moderate-to-high clearance in mice. The coralmycin A and DH-coralmycin A bioavailability values were 61.3% and 11.7%, respectively, after s.c. administration. In a mouse respiratory tract infection model, coralmycin A showed bacteriostatic and bactericidal in vivo efficacies at an s.c. administration of 4 and 100 mg/kg bid, respectively; these efficacies were similar to those of vancomycin at 4 and 20 mg/kg bid, respectively. The present findings indicate that coralmycin A has great potential as a new class of antibiotic for treating infections caused by multidrug-resistant Gram-positive bacteria.

Curvularin Isolated From Phoma macrostoma Is an Antagonist of RhlR Quorum Sensing in Pseudomonas aeruginosa.

Quorum sensing (QS) is an attractive target for the treatment of multidrug-resistant Pseudomonas aeruginosa, against which new antibiotics are urgently needed. Because LasR is at the top of the QS hierarchy controlling Rhl and PQS systems, most QS inhibitors have been targeted to LasR. However, it has recently been reported that in clinical isolates of P. aeruginosa, LasR is frequently mutated and nonfunctional, and RhlR independently acts to produce virulent factors that maintain toxicity. Thus, for effective treatment of chronic cystic fibrosis infections, RhlR antagonists is needed to prevent the LasR-independent Rhl system, but RhlR antagonists have rarely been reported. In this study, we found that curvularin, an aromatic compound with a cyclized alkyl side chain isolated from Phoma macrostoma, at a low micromolar concentration of 1-30 µM potently and selectively inhibited pyocyanin and rhamnolipid production without affecting the cell viability of P. aeruginosa. Only high concentration (more over 100 µM) curvularin negligibly inhibited biofilm formation and elastase production, suggesting that curvularin at low concentrations selectively inhibits RhlR. The QS antagonism by curvularin was investigated in experiments using QS competition and signaling molecules assays with QS gene expression analysis, and the results showed that, indeed, at low concentrations, curvularin selectively antagonized RhlR; in contrast, it negligibly antagonized LasR only when applied at a high concentration. The exclusive RhlR antagonizing activity of curvularin at low concentrations was confirmed using QS mutants; specifically, curvularin at low concentrations inhibited pyocyanin and rhamnolipid production by selectively antagonizing N-butanoyl homoserine lactone (BHL)-activated RhlR. Moreover, by targeting RhlR, curvularin reduced the in vivo virulence of wild-type P. aeruginosa as well as lasR mutants in Caenorhabditis elegans. Overall, low-concentration curvularin is a pure RhlR antagonist in P. aeruginosa, and to the best of our knowledge, this is the first report describing an RhlR antagonist from natural resources. Hence, curvularin has great potential for the development of chronic P. aeruginosa infection therapeutics and for the study of RhlR function in the complex QS system.

Sex-Related Differences in Left Atrial Low-Voltage Areas According to CHA2DS2-VA Scores among Patients with Atrial Fibrillation.

(1) Background: We hypothesized that female sex would have a differential impact on left atrial (LA) low-voltage areas (LVAs) according to CHA2DS2-VA scores. (2) Methods: This study included 553 patients who underwent radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF). LVAs were defined as regions with bipolar peak-to-peak voltages of <0.5 mV. The proportion of LVAs was calculated by dividing the total LVA by the LA surface area. (3) Results: There was no sex-related difference in LA LVAs among patients with a CHA2DS2-VA scores ≤ 2. The proportion of LVAs was significantly higher in females among patients with CHA2DS2-VA scores of 3 or 4 (10.1 (4.7−15.1)% vs. 15.8 (9.2−32.1)%; p = 0.027). Female sex was significantly associated with extensive LVAs (LVA proportion ≥ 30%). Females had odd ratios of 27.82 (95% confidence interval (CI) 3.33−756.8, p = 0.01), and 1.53 (95% CI 0.81−2.83, p = 0.184) for extensive LAVs in patients with CHA2DS2-VA scores ≥ 3 and CHA2DS2-VA scores < 3, respectively. In the multiple regression model, female patients with a CHA2DS2-VA ≥3 were significantly associated with a higher proportion of LVAs (ß = 8.52, p = 0.039). (4) Conclusions: Female sex was significantly associated with extensive LVAs, particularly when their CHA2DS2-VA scores were ≥3. This result suggests that female sex has a differential effect on the extent of LVAs based on the presence of additional risk factors.

Electrical Remodeling of Left Atrium Is a Better Predictor for Recurrence Than Structural Remodeling in Atrial Fibrillation Patients Undergoing Radiofrequency Catheter Ablation.

BACKGROUND AND OBJECTIVES: Recurrence rates after radiofrequency catheter ablation (RFCA) in atrial fibrillation (AF) patients are not low especially in non-paroxysmal AF. The diameter of left atrium (LA) has been widely used to predict the recurrence after RFCA for decades. However, LA diameter represents structural remodeling of LA and does not reflect electrical remodeling. We aimed to determine the predictive value of electrical remodeling of LA which is represented by the amount of low voltage zone (LVZ). METHODS: We performed a retrospective cohort analysis of AF patients who underwent de novo RFCA in a single-center. RESULTS: A total of 3,120 AF patients with de novo RFCA were analyzed. Among these patients, 537 patients underwent an electroanatomic mapping with bipolar voltage measurement of LA. The diameter of LA and flow velocity of LA appendage (LAA) differed significantly according to quartile group of LVZ area and percentage: patients with high LVZ had large LA diameter and low LAA flow velocity (p<0.001). Freedom from late recurrence (LR) was significantly lower in patients with high LVZ area and percentage (p<0.001). The diameter and surface area of LA had area under curve (AUC) of 0.592 and 0.593, respectively (p=0.002 for both). The predictive value of LVZ area (AUC, 0.676) and percentage (AUC, 0.671) were both superior compared with LA diameter (p=0.011 and 0.027 for each comparison). CONCLUSIONS: In conclusion, LVZ can predict freedom from LR after RFCA in AF patients. Predictive value was higher in parameters reflecting electrical rather than structural remodeling of LA.

Characteristics of amniotic mesenchymal stromal cells derived from term and preterm labor.

OBJECTIVE: Amniotic mesenchymal stromal cells (AMSCs) can be obtained from the mesoderm of human amniotic membrane. AMSCs derived from term baby show increased expression of genes associated with apoptosis and senescence. The objective of this study was to examine gene expression profiles of AMSCs derived from preterm (preterm AMSCs) and term labors (term AMSCs) and analyze common and different mechanisms. MATERIALS AND METHODS: We isolated and cultured AMSCs from 43 placentas: 27 from term labor and 16 from preterm labor. Microarray analysis and gene network analysis were performed to compare gene expression profile (GEP) of preterm (n = 6) with term AMSCs (n = 10). Senescence-associated gene (CDKN2A and CDKN2B) expression was also measured by reverse transcription quantitative PCR. RESULTS: GEP demonstrated that preterm AMSCs showed upregulation of nicotinamide adenine dinucleotide biosynthetic process and downregulation of extracellular matrix, cholesterol import and transport, lipid storage, and maintenance of location. CDKN2A and CDKN2B genes showed similar expression levels between term and preterm AMSCs. CDKN2A gene expression was correlated with CDKN2B expression and population doubling time. Compared to term AMSCs, preterm AMSCs showed significantly different expression of genes associated with inflammatory response which could be one of the major players in labor events. CONCLUSION: Increased CDKN2A expression in AMSCs is associated with placental membrane aging which participates in both preterm and term labor. To the best of our knowledge, this is the first report to demonstrate the association of AMSCs with labor.

Association of Depression With Atrial Fibrillation in South Korean Adults.

Importance: The risk of atrial fibrillation (AF) in people with depression is not fully known. Depression is associated with sympathetic activation and emotional stress, which might increase the risk of new-onset AF. Objective: To assess the incidence of new-onset AF in those with and without depression using data from a nationwide health care database. Design, Setting, and Participants: This cohort study obtained data from the Korean National Health Insurance Service database and enrolled people who underwent a nationwide health checkup in 2009. People younger than 20 years and those with a history of heart valve surgery, previous diagnosis of mitral stenosis, or who were diagnosed with AF between January 1, 2002 and December 31, 2008 were excluded. The risk of new-onset AF (occurring between 2009 and 2018) was compared in people who were and were not diagnosed with depression within a year before the 2009 nationwide health checkup. Data were analyzed between August 1, 2020 and October 31, 2020. Exposure: Previous diagnosis of depression. Main Outcomes and Measures: Cumulative incidence and risk of new-onset AF between 2009 and 2018 in participants with and without depression. Kaplan-Meier analysis was conducted to assess incidence of AF, and Cox proportional hazards regression was used to calculate adjusted and unadjusted hazard ratios (HRs) and 95% CIs. Results: A total of 5 031 222 individuals with a mean (SD) age of 46.99 (14.06) years (2 771 785 men [55.1%]) were included in the analysis; of these individuals, 148 882 (3.0%) had a diagnosis of depression in the year before the 2009 health checkup and 4 882 340 (97%) did not. People with depression vs those without depression were older (aged 56.7 vs 46.7 years) and more likely to be women (96 472 [64.8%] vs 2 162 965 [44.3%]). Prevalence of hypertension, diabetes, dyslipidemia, and heart failure was higher in the depression group. The cumulative incidence of new-onset AF was significantly higher in people with depression vs without depression in the Kaplan-Meier analysis and showed steady divergence throughout 10 years of follow-up (cumulative incidence, 4.44% vs 1.92%; log-rank P < .001). After adjusting for covariates, depression was associated with a 25.1% increased risk of new-onset AF (HR, 1.25; 95% CI, 1.22-1.29; P < .001). People with recurrent episodes of depression showed even higher risk of new-onset AF (HR, 1.32; 95% CI, 1.27-1.37; P < .001). Young age and female sex had significant interactions with depression, which suggests that young people and women with depression may have an increased risk of new-onset AF. Conclusions and Relevance: This study found that depression was associated with a significantly increased cumulative incidence and risk of new-onset AF. Recurrent episodes of depression were associated with even higher risk. These findings suggest the need for adequate screening for AF in people with depression, particularly in younger people and women.

Comparison of Point-of-Care versus Central Laboratory Testing of Electrolytes, Hemoglobin, and Bilirubin in Neonates.

OBJECTIVE: Electrolyte, hemoglobin, and bilirubin values are routinely reported with point-of-care (POC) testing for blood gases. Results are rapidly available and require a small blood volume. Yet, these results are underutilized due to noted discrepancies between central laboratory (CL) and POC testing. The study aimed to determine the correlation between POC and CL measurement of electrolytes, hemoglobin, and bilirubin in neonates. STUDY DESIGN: Electrolyte, hemoglobin, and bilirubin results obtained from capillary blood over a 4-month period were analyzed. Each CL value was matched with a POC value from the same sample or another sample less than 1-hour apart. Agreement was determined by measuring the mean difference (MD) between paired samples with 95% limits of agreement (LOA) and Lin's concordance correlation (LCC). RESULTS: There were 355-paired sodium/potassium, 139 paired hemoglobin, and 197 paired bilirubin values analyzed. POC sodium values were lower (133.5 ± 5.8 mmol/L) than CL (140.2 ± 5.8 mmol/L), p <0.00001 with poor agreement (LCC = 0.49; MD = 6.7; 95% LOA: -13.6 to 0.14). POC potassium values were lower (4.6 ± 0.98 mmol/L) than CL (4.98 ± 1.24mEq/L), p < 0.0001, but with better concordance and agreement. (LCC = 0.6; MD = 0.4; 95% LOA: -2.3 to 1.4). There were no differences in hemoglobin between POC (14.3 ± 3.2 g/dL) and CL (14.4 ± 3.1 g/dL), p = 0.2 with good LCC (0.93) and in bilirubin values between POC (6.0 ± 3.2 mg/dL) and CL (5.8 ± 3.0 mg/dL), MD = 0.18, and p = 0.07. CONCLUSION: POC Sodium values are lower than CL. POC potassium levels are also lower, but the differences may not be clinically important while hemoglobin and bilirubin levels are similar between POC and CL. As POC potassium, hemoglobin, and bilirubin levels closely reflect CL values, these results can be relied upon to make clinical judgments in neonates. KEY POINTS: · Electrolyte, hemoglobin, and bilirubin are available as POC.. · POC sodium and potassium values are lower than CL results.. · Hemoglobin and bilirubin values are similar between POC and CL..

Adrenocorticotropic hormone and ß-endorphin concentration as a prognostic factor in patients with subarachnoid hemorrhage due to aneurysmal rupture.

OBJECTIVE: Adrenocorticotropic hormone (ACTH) and ß-endorphin are pituitary neuro-peptides released by acute stress. We determined why the prognosis of patients with subarachnoid hemorrhages (SAH) due to aneurysmal rupture is not always dependent on the Hunt-Hess grading system (HHS) and delta-National Institutes of Health Stroke Scale (NIHSS), while studying endogenous neuropeptides, including ACTH and ß-endorphin. METHODS: We analyzed blood samples collected from patients with SAH (SAH group; n=37) and those with unruptured intracranial aneurysms (control group; n=37). Blood sampling was performed before any procedure or chemical agents administration. The results of ACTH and ß-endorphin measurements were compared using the delta-NIHSS and HHS. The data were analyzed using descriptive statistics, independent samples t-tests, and Pearson's correlations. RESULTS: Of the 18 patients with low-grade HHS, 13 had low delta-NIHSS and five showed high delta-NIHSS. Of the 19 patients with high-grade HHS, the delta-NIHSS was ≥14 in the other five patients. ACTH concentration was high (497.3 pg/mL) in five patients with high-grade HHS and high delta-NIHSS. ß-endorphin concentration was high (159.7 pg/mL) in 13 patients with low-grade HHS and low delta-NIHSS. CONCLUSIONS: High ACTH levels in patients with massive bleeding and poor neurological status suggests increasing ACTH secretion in response to bleeding stress, which may aggravate neurological status. Contrary to ACTH, high ß-endorphin levels in patients with low-grade HHS implied the involvement of additional factors in predicting fair outcomes related to low delta-NIHSS. These results may provide insight into the varying prognostic potential of HHS in SAH patients.

Arrhythmia and Heart Rate Variability during Long Interdialytic Periods in Patients on Maintenance Hemodialysis: Prospective Observational Cohort Study.

Sudden cardiac death among hemodialysis patients is related to the hemodialysis schedule. Mortality is highest within 12 h before and after the first hemodialysis sessions of a week. We investigated the association of arrhythmia occurrence and heart rate variability (HRV) using an electrocardiogram (ECG) monitoring patch during the long interdialytic interval in hemodialysis patients. This was a prospective observational study with 55 participants on maintenance hemodialysis for at least six months. A patch-type ECG monitoring device was applied to record arrhythmia events and HRV during 72 h of a long interdialytic period. Forty-nine participants with sufficient ECG data out of 55 participants were suitable for the analysis. The incidence of supraventricular tachycardia and ventricular tachycardia did not significantly change over time. The square root of the mean squared differences of successive NN intervals (RMSSD), the proportion of adjacent NN intervals differing by >50 ms (pNN50), and high-frequency (HF) increased during the long interdialytic interval. The gap in RMSSD, pNN50, HF, and the low-frequency/high-frequency (LF/HF) ratio between patients with and without significant arrhythmias increased significantly over time during the long interdialytic interval. The daily changes in RMSSD, pNN50, HF, and the LF/HF ratio were more prominent in patients without significant arrhythmias than in those with significant arrhythmias. The electrolyte fluctuation between post-hemodialysis and subsequent pre-hemodialysis was not considered in this study. The study results suggest that the decreased autonomic response during interdialytic periods in dialysis patients is associated with poor cardiac arrhythmia events.

Atrial fibrillation is associated with increased risk of lethal ventricular arrhythmias.

Atrial fibrillation (AF) is associated with various major adverse cardiac events such as ischemic stroke, heart failure, and increased overall mortality. However, its association with lethal ventricular arrhythmias such as ventricular tachycardia (VT), ventricular flutter (VFL), and ventricular fibrillation (VF) is controversial. We conducted this study to determine whether AF can increase the risk of VT, VFL, and VF. We utilized the Korean National Health Insurance Service database for this nationwide population-based study. This study enrolled people who underwent a nationwide health screen in 2009 for whom clinical follow-up data were available until December 2018. Primary outcome endpoint was the occurrence of VT, VFL, or VF in people who were and were not diagnosed with new-onset AF in 2009. We analyzed a total of 9,751,705 people. In 2009, 12,689 people were diagnosed with new-onset AF (AF group). The incidence (events per 1000 person-years of follow-up) of VT, VFL, and VF was 2.472 and 0.282 in the AF and non-AF groups, respectively. After adjustment for covariates, new-onset AF was associated with 4.6-fold increased risk (p < 0.001) of VT, VFL, and VF over 10 years of follow-up. The risk of VT, VFL, and VF was even higher if identification of AF was based on intensified criteria (≥ 2 outpatient records or ≥ 1 inpatient record; hazard ratio = 5.221; p < 0.001). In conclusion, the incidence of VT, VFL, and VF was significantly increased in people with new-onset AF. The potential risk of suffering lethal ventricular arrhythmia in people with AF should be considered in clinical practice.

Tuberous roots of transgenic sweetpotato overexpressing IbCAD1 have enhanced low-temperature storage phenotypes.

Lignin is associated with cell wall rigidity, water and solute transport, and resistance to diverse stresses in plants. Lignin consists of polymerized monolignols (p-coumaryl, coniferyl, and sinapyl alcohols), which are synthesized by cinnamyl alcohol dehydrogenase (CAD) in the phenylpropanoid pathway. We previously investigated cold-induced IbCAD1 expression by transcriptome profiling of cold-stored tuberous roots of sweetpotato (Ipomoea batatas [L.] Lam). In this study, we confirmed that IbCAD1 expression levels depended on the sweetpotato root type and were strongly induced by several abiotic stresses. We generated transgenic sweetpotato plants overexpressing IbCAD1 (TC plants) to investigate CAD1 physiological functions in sweetpotato. TC plants displayed lower root weights and lower ratios of tuberous roots to pencil roots than non-transgenic (NT) plants. The lignin contents in tuberous roots of NT and TC plants differed slightly, but these differences were not significant. By contrast, monolignol levels and syringyl (S)/guaiacyl (G) ratios were higher in TC plants than NT plants, primarily owing to syringyl unit accumulation. Tuberous roots of TC plants displayed enhanced low-temperature (4 °C) storage with lower malondialdehyde and H2O2 contents than NT plants. We propose that high monolignol levels in TC tuberous roots served as substrates for increased peroxidase activity, thereby enhancing antioxidation capacity against cold stress-induced reactive oxygen species. Increased monolignol contents and/or increased S/G ratios might contribute to pathogen-induced stress tolerance as a secondary chilling-damage response in sweetpotato. These results provide novel information about CAD1 function in cold stress tolerance and root formation mechanisms in sweetpotato.

Premature ventricular contraction increases the risk of heart failure and ventricular tachyarrhythmia.

Premature ventricular contraction (PVC), a common arrhythmia affecting 1-2% of the general population, has been considered to have a benign clinical course. However, people with PVC often develop heart failure and ventricular arrhythmias such as ventricular tachycardia. We aimed to clarify the risk of heart failure and lethal ventricular arrhythmias in people with PVC. The Korean National Health Insurance Service database was used for this study. People who underwent nationwide health check-ups in 2009 were enrolled in this study and clinical follow-up data until December 2018 were analyzed. Newly diagnosed PVC in 2009 (≥ 1 inpatient or outpatient claim) were identified and cumulative incidence of heart failure (≥ 1 inpatient claim) and ventricular arrhythmias (≥ 1 inpatient or outpatient claim) were compared. A total of 4515 people were first diagnosed with PVC in 2009 among 9,743,582 people without prior history of PVC, heart failure, or ventricular arrhythmias. People with newly diagnosed PVC in 2009 had a significantly higher incidence of heart failure compared to those without PVC [adjusted hazard ratio (HR) 1.371; 95% confidence interval (CI) 1.177-1.598; p < 0.001]. Significant interaction was observed between age and PVC with young age people at greater risk of developing heart failure for having PVC. The incidence of ventricular arrhythmia was also significantly increased in people with PVC (HR 5.588; 95% CI 4.553-6.859; p < 0.001). Age and chronic kidney disease had significant interactions with PVC. In conclusion, the incidence of heart failure and ventricular arrhythmia was significantly increased in people with PVC. Outpatient follow-up of people with PVC can be helpful to detect early signs of heart failure or advanced forms of ventricular arrhythmia.

Directed evolution of glycosyltransferase for enhanced efficiency of avermectin glucosylation.

Avermectin, produced by Streptomyces avermitilis, is an active compound protective against nematodes, insects, and mites. However, its potential usage is limited by its low aqueous solubility. The uridine diphosphate (UDP)-glycosyltransferase (BLC) from Bacillus licheniformis synthesizes avermectin glycosides with improved water solubility and in vitro antinematodal activity. However, enzymatic glycosylation of avermectin by BLC is limited due to the low conversion rate of this reaction. Thus, improving BLC enzyme activity is necessary for mass production of avermectin glycosides for field application. In this study, the catalytic activity of BLC toward avermectin was enhanced via directed evolution. Three mutants from the BLC mutant library (R57H, V227A, and D252V) had specific glucosylation activity for avermectin 2.0-, 1.8-, and 1.5-fold higher, respectively, than wild-type BLC. Generation of combined mutations via site-directed mutagenesis led to even further enhancement of activity. The triple mutant, R57H/V227A/D252V, had the highest activity, 2.8-fold higher than that of wild-type BLC. The catalytic efficiencies (Kcat/Km) of the best mutant (R57H/V227A/D252V) toward the substrates avermectin and UDP-glucose were improved by 2.71- and 2.29-fold, respectively, compared to those of wild-type BLC. Structural modeling analysis revealed that the free energy of the mutants was - 1.1 to - 7.1 kcal/mol lower than that of wild-type BLC, which was correlated with their improved activity. KEY POINTS: • Directed evolution improved the glucosylation activity of BLC toward avermectin. • Combinatorial site-directed mutagenesis led to further enhanced activity. • The mutants exhibited lower free energy values than wild-type BLC.

Non-genetic risk factors for atrial fibrillation are equally important in both young and old age: A nationwide population-based study.

AIMS: There are several non-genetic risk factors for new-onset atrial fibrillation, including age, sex, obesity, hypertension, diabetes, and alcohol consumption. However, whether these non-genetic risk factors have equal significance among different age groups is not known. We performed a nationwide population-based analysis to compare the clinical significance of non-genetic risk factors for new-onset atrial fibrillation in various age groups. METHODS AND RESULTS: A total of 9,797,409 people without a prior diagnosis of atrial fibrillation who underwent a national health check-up in 2009 were included. During 80,130,090 person-years of follow-up, a total of 196,136 people were diagnosed with new-onset atrial fibrillation. The impact of non-genetic risk factors on new-onset atrial fibrillation was examined in different age groups. Obesity, male sex, heavy alcohol consumption, smoking, hypertension, diabetes and chronic kidney disease were associated with an increased risk of new-onset atrial fibrillation. With minor variations, these risk factors were consistently associated with the risk of new-onset atrial fibrillation among various age groups. Using these risk factors, we created a scoring system to predict future risk of new-onset atrial fibrillation in different age groups. In receiver operating characteristic curve analysis, the predictive value of these risk factors ranged between 0.556 and 0.603, and no significant trends were observed. CONCLUSIONS: Non-genetic risk factors for new-onset atrial fibrillation may have a similar impact on different age groups. Except for sex, these non-genetic risk factors can be modifiable. Therefore, efforts to control non-genetic risk factors might have relevance for both the young and old.

Different Influence of Blood Pressure on New-Onset Atrial Fibrillation in Pre- and Postmenopausal Women: A Nationwide Population-Based Study.

[Figure: see text].

A novel predictive model for late recurrence after catheter ablation for atrial fibrillation using left appendage volume measured by cardiac computed tomography.

Larger left atrial appendage (LAA) volume is associated with a higher risk of late recurrence (LR) in patients undergoing radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF). However, it is unclear whether LAA volume predicts LR, independent of established risk factors. We sought to evaluate the value of LAA volume in predicting LR after RFCA for AF and to develop a score prediction model including LAA volume for these patients. We retrospectively studied 992 patients who underwent RFCA for AF and cardiac computed tomography before RFCA at a single center. At 3 years after RFCA, 362 patients (36.5 %) experienced recurrence. The multivariate Cox regression model showed that age ≥ 75 years (10 points), non-paroxysmal AF (9 points), diabetes mellitus (4 points), left atrial volume index (1 point per 10 ml/m2 rounded to the nearest integer), and the second (4.7 to < 7 ml/m2; 4 points) and third (≥ 7 ml/m2; 5 points) tertiles of the LAA volume index were independent risk factors LR. The above-mentioned risk factors were included in the integrated score model, and the C-index of the proposed score model was 0.715 (95 % confidence interval [CI] 0.679-0.752). LAA volume is an independent predictor of LR and the predictive model including LAA volume showed good discrimination power. These findings provide evidence for the inclusion of LAA volume in the risk stratification for AF recurrence in patients undergoing RFCA for AF.