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.

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.

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.

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..

Blood flow volume of left atrial appendage measured by magnetic resonance imaging is improved after radiofrequency catheter ablation of atrial fibrillation.

INTRODUCTION: Hemodynamics of left atrial appendage (LAA) is an important factor for future risk of ischemic stroke in atrial fibrillation (AF) patients. Velocity encoded cardiac magnetic resonance imaging (VENC-MRI) can evaluate blood flow volume of LAA without any invasive procedures. We aimed to evaluate the association between radiofrequency catheter ablation (RFCA) and LAA hemodynamics measured by MRI. METHODS AND RESULTS: Consecutive RFCA cases in a single arrhythmia center were retrospectively analyzed. A total of 3120 AF patients who underwent first RFCA were analyzed. Among these patients 360 patients had both pre- and post-RFCA VENC-MRI evaluation. Atrial fibrillation was non-paroxysmal in 174 (48.3%) patients. Mean VENC-MRI (ml/sec) was significantly improved after RFCA with 49.93 ± 32.92 and 72.00 ± 34.82 for pre- and post-RFCA, respectively. Patients with non-paroxysmal AF (∆VENC-MRI = 14.63 ± 40.67 vs. 30.03 ± 35.37; p < .001) and low pre-RFCA VENC-MRI (∆VENC-MRI = 17.19 ± 38.35 vs. 50.35 ± 29.12; p < .001) had significantly higher improvement in VENC-MRI. Those who experienced late recurrence before post-RFCA MRI had significantly less improvement in LAA flow volume (∆VENC-MRI = 15.55 ± 41.41 vs. 26.18 ± 36.77; p = .011). Late recurrence and pre-RFCA VENC-MRI were significantly associated with ∆VENC-MRI after adjusting covariates. Patients who were AF before RFCA but maintained sinus rhythm after RFCA showed greatest improvement in VENC-MRI. CONCLUSION: Effective rhythm control through RFCA can be associated with significant improvement in LAA hemodynamics. Low pre-RFCA VENC-MRI and absence of late recurrence were associated with greater improvement in LAA hemodynamics.

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.

Coralmycin Derivatives with Potent Anti-Gram Negative Activity Produced by the Myxobacteria Corallococcus coralloides M23.

Seven new coralmycin derivatives, coralmycins C (1), D (2), E (3), F (4), G (5), H (6), and I (7), along with three known compounds, cystobactamids 891-2 (8), 905-2 (9), and 507 (10), were isolated from a large-scale culture of the myxobacteria Corallococcus coralloides M23. The structures of these compounds, including their relative stereochemistries, were elucidated by interpretation of their spectroscopic and CD data. The structure-activity relationships of their antibacterial and DNA gyrase inhibitory activities indicated that the para-nitrobenzoic acid unit is critical for the inhibition of DNA gyrase and bacterial growth, while the nitro moiety of the para-nitrobenzoic acid unit and the isopropyl chain at C-4 could be important for permeability into certain Gram-negative bacteria, including Pseudomonas aeruginosa and Klebsiella pneumoniae, and the ß-methoxyasparagine moiety could affect cellular uptake into all tested bacteria. These results could facilitate the chemical optimization of coralmycins for the treatment of multidrug-resistant Gram-negative bacteria.

Enzymatic synthesis of avermectin B1a glycosides for the effective prevention of the pine wood nematode Bursaphelenchus xylophilus.

Avermectin produced by Streptomyces avermitilis is an anti-nematodal agent against the pine wood nematode Bursaphelenchus xylophilus. However, its potential usage is limited by its poor water solubility. For this reason, continuous efforts are underway to produce new derivatives that are more water soluble. Here, the enzymatic glycosylation of avermectin was catalyzed by uridine diphosphate (UDP)-glycosyltransferase from Bacillus licheniformis with various UDP sugars. As a result, the following four avermectin B1a glycosides were produced: avermectin B1a 4″-ß-D-glucoside, avermectin B1a 4″-ß-D-galactoside, avermectin B1a 4″-ß-L-fucoside, and avermectin B1a 4″-ß-2-deoxy-D-glucoside. The avermectin B1a glycosides were structurally analyzed based on HR-ESI MS and 1D and 2D nuclear magnetic resonance spectra, and the anti-nematodal effect of avermectin B1a 4″-ß-D-glucoside was found to exhibit the highest activity (IC50 = 0.23 µM), which was approximately 32 times greater than that of avermectin B1a (IC50 = 7.30 µM), followed by avermectin B1a 4″-ß-2-deoxy-D-glucoside (IC50 = 0.69 µM), avermectin B1a 4″-ß-L-fucoside (IC50 = 0.89 µM), and avermectin B1a 4″-ß-D-galactoside (IC50 = 1.07 µM). These results show that glycosylation of avermectin B1a effectively enhances its in vitro anti-nematodal activity and that avermectin glycosides can be further applied for treating infestations of the pine wood nematode B. xylophilus.

Daphnane and Phorbol Diterpenes, Anti-neuroinflammatory Compounds with Nurr1 Activation from the Roots and Stems of Daphne genkwa.

The methanol extract of the roots and stems of Daphne genkwa and its constituents yuanhuacin (1) and genkwanine N were previously reported to have Nurr1 activating effects and neuroprotective effects in an animal model of Parkinson's disease (PD). In this study, four more daphnane-type diterpenes (acutilonine F (2), wikstroemia factor M1 (3), yuanhuadine (5), and yuanhuatine (6)) and two phorbol-type diterpenes (prostratin Q (4) and 12-O-n-deca-2,4,6-trienoyl-phorbol-(13)-acetate (7)) were isolated as Nurr1 activating compounds from the D. genkwa extract. Consistent with their higher Nurr1 activating activity, compounds 1, 4, 5, and 7 exhibited higher inhibitory activity on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in murine microglial BV-2 cells with an IC50 (µM) of 1-2, which was 15-30 times more potent than that of minocycline (29.9 µM), a well-known anti-neuroinflammatory agent. Additionally, these diterpenes reduced expression and transcription of LPS-induced pro-inflammatory cytokines in BV-2 cells. Thus, the daphnane-type and phorbol-type diterpenes had anti-neuroinflammatory activity with Nurr1 activation and could be responsible for the anti-PD effect of the roots and stems of D. genkwa.

Generation of New Complestatin Analogues by Heterologous Expression of the Complestatin Biosynthetic Gene Cluster from Streptomyces chartreusis AN1542.

The heterologous expression of the biosynthetic gene cluster (BGC) of natural products enables the production of complex metabolites in a well-characterized host, and facilitates the generation of novel analogues by the manipulation of the genes. However, the BGCs of glycopeptides such as vancomycin, teicoplanin, and complestatin are usually too large to be directly cloned into a single cosmid. Here, we describe the heterologous expression of the complestatin BGC. The 54.5 kb cluster was fully reconstituted from two overlapping cosmids into one cosmid by λ-RED recombination-mediated assembly. Heterologous expression of the assembled gene cluster in Streptomyces lividans TK24 resulted in the production of complestatin. Deletion of cytochrome P450 monooxygenase genes (open reading frames 10 and 11) and heterologous expression of the modified clusters led to the production of two new monocyclic and linear derivatives, complestatins M55 and S56.

Characteristic anatomical conformation of the vertebral artery causing vascular compression against the root exit zone of the facial nerve in patients with hemifacial spasm.

BACKGROUND: Hemifacial spasm (HFS) is caused by tortuous offending vessels near the facial nerve root exit zone. However, the definitive mechanism of offending vessel formation remains unclear. We hypothesized that vascular angulation and tortuosity, probably caused by uneven vertebral artery blood flow, result in vascular compression of the facial nerve root exit zone. METHODS: The authors observed two anatomical characteristics of the vertebrobasilar arterial system in 120 subjects in the surgical group and 188 controls. The presence of the dominant vertebral artery (DVA) and laterality of the vertebrobasilar junction (VBJ) were observed. We also analyzed the morphological characteristics of the surgical group showing the presence of DVA. The morphological characteristics were classified into three types: type I had the VBJ and DVA on the same side, type II had the VBJ within 2 mm of the midline, and type III had the VBJ opposite the DVA. RESULT: The DVA was more prevalent in the surgical group than in the control group (71 % versus 54 %, P < 0.05). The surgical group patients with HFS on the left were more likely to have a DVA on the left (P < 0.05) and with HFS on the right were more likely to have a DVA on the right (P < 0.01) compared with controls. The direction of the VBJ was more common on the same side as the DVA, which corresponds with the laterality of the HFS. In the surgical group with the DVA and HFS on the same side, type I was predominant, but in the surgical group with a contralateral DVA and HFS, type III was predominant. CONCLUSION: The presence of a DVA and shifting of the VBJ on the same side plays a role in the angulation and tortuosity of vessels in the perivertebrobasilar junction, resulting in neurovascular compression of the facial nerve root exit zone and thereby causing HFS.

Tyrosol blocks E. coli anaerobic biofilm formation via YbfA and FNR to increase antibiotic susceptibility.

Bacteria within mature biofilms are highly resistant to antibiotics than planktonic cells. Oxygen limitation contributes to antibiotic resistance in mature biofilms. Nitric oxide (NO) induces biofilm dispersal; however, low NO levels stimulate biofilm formation, an underexplored process. Here, we introduce a mechanism of anaerobic biofilm formation by investigating the antibiofilm activity of tyrosol, a component in wine. Tyrosol inhibits E. coli and Pseudomonas aeruginosa biofilm formation by enhancing NO production. YbfA is identified as a target of tyrosol and its downstream targets are sequentially determined. YbfA activates YfeR, which then suppresses the anaerobic regulator FNR. This suppression leads to decreased NO production, elevated bis-(3'-5')-cyclic dimeric GMP levels, and finally stimulates anaerobic biofilm formation in the mature stage. Blocking YbfA with tyrosol treatment renders biofilm cells as susceptible to antibiotics as planktonic cells. Thus, this study presents YbfA as a promising antibiofilm target to address antibiotic resistance posed by biofilm-forming bacteria, with tyrosol acting as an inhibitor.

Long-term outcome of surgical treatment of patients with intractable epilepsy associated with schizencephaly.

BACKGROUND: Schizencephaly is a developmental anomaly of the brain that is sometimes associated with intractable seizures. Patients that suffer from medically refractory seizures may be considered for surgical treatment. METHOD: Five patients with intractable epilepsy associated with schizencephaly were studied. Evaluation methods included medical history assessment, neurological examination, magnetic resonance imaging (MRI) with three-dimensional (3D) surface rendering, positron emission tomography (PET), video-electroencephalogram (EEG) monitoring with surface electrodes and subdural grid electrodes, sodium amobarbital test, and neuropsychological assessments. Topectomy was performed close to the schizencephalic cleft in two patients, and at an area distant from the cleft in one under the guidance of electrocorticography (ECoG). Temporal lobectomy was performed in two patients. RESULTS: MRI revealed unilateral schizencephaly in all five patients. Video-EEG monitoring recorded simple partial seizures in two patients and complex partial seizures in three patients. The epileptogenic zone was localized close to the schizencephalic cleft in two patients, distant to the cleft in one patient, and in the temporal lobe in two patients. Postoperatively, one of two patients with temporal lobectomy and one of three patients with topectomy were seizure-free at 1-year follow-up. Three patients experienced marked seizure reduction but were not seizure-free at 1 year; however, at the follow-up periods of 2.5 years and 6.5 years, two of these three patients were seizure free. One patient who underwent temporal lobectomy began to have very brief losses of consciousness lasting 1-3 s (3-4 times per year). Neurological complications included temporary upper monoparesis in one and hemiparesis in one. CONCLUSIONS: The abnormal cortex lining schizencephalic clefts and cortical tissues near the cleft may be epileptogenic. Areas distant to the cleft may also be the source of seizures. Careful evaluation should be performed to define the epileptogenic zone in patients with intractable epilepsy associated with schizencephaly, and meticulous resection of the epileptogenic zone can lead to good seizure control.

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.

Hemimasticatory spasm treated with microvascular decompression of the trigeminal nerve.

Hemimasticatory spasm is a very rare disorder of the trigeminal nerve characterized by paroxysmal involuntary contraction of the jaw-closing muscles. The mechanisms leading to hemimasticatory spasm are still unclear. Recently, injection of botulinum toxin has become the treatment of choice due to its excellent results. We report a case of a successful treatment of hemimasticatory spasm via microvascular decompression of the motor branch of the trigeminal nerve.

Independent predictors for recurrence of chronic subdural hematoma.

BACKGROUND: Chronic subdural hematoma is characterized by blood in the subdural space that evokes an inflammatory reaction. Numerous factors potentially associated with recurrence of chronic subdural hematoma have been reported, but these factors have not been sufficiently investigated. In this study, we evaluated the independent risk factors of recurrence. METHODS: We analyzed data for 420 patients with chronic subdural hematoma treated by the standard surgical procedure for hematoma evacuation at our institution. RESULTS: Ninety-two (21.9 %) patients experienced at least one recurrence of chronic subdural hematoma during the study period. We did not identify any significant differences between chronic subdural hematoma recurrence and current antiplatelet therapy. The recurrence rate was 7 % for the homogeneous type, 21 % for the laminar type, 38 % for the separated type, and 0 % for the trabecular type. The rate of recurrence was significantly lower in the homogeneous and trabecular type than in the laminar and separated type. We performed a multivariate logistic regression analysis and found that postoperative midline shifting (OR, 3.6; 95 % CI, 1.618-7.885; p = 0.001), diabetes mellitus (OR, 2.2; 95 % CI, 1.196-3.856; p = 0.010), history of seizure (OR, 2.6; 95 % CI, 1.210-5.430; p = 0.014), width of hematoma (OR, 2.1; 95 % CI, 1.287-3.538; p = 0.003), and anticoagulant therapy (OR, 2.7; 95 % CI, 1.424-6.960; p = 0.005) were independent risk factors for the recurrence of chronic subdural hematoma. CONCLUSIONS: We have shown that postoperative midline shifting (≥5 mm), diabetes mellitus, preoperative seizure, preoperative width of hematoma (≥20 mm), and anticoagulant therapy were independent predictors of the recurrence of chronic subdural hematoma. According to internal architecture of hematoma, the rate of recurrence was significantly lower in the homogeneous and the trabecular type than the laminar and separated type.

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.

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.

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.