Melatonin Enhances the Tolerance and Recovery Mechanisms in Brassica juncea (L.) Czern. Under Saline Conditions.

Melatonin has been recently known to stimulate plant growth and induce protective responses against different abiotic stresses. However, the mechanisms behind exogenous melatonin pretreatment and restoration of plant vigor from salinity stress remain poorly understood. The present study aimed to understand the effects of exogenous melatonin pretreatment on salinity-damaged green mustard (Brassica juncea L. Czern.) seedlings in terms of oxidative stress regulation and endogenous phytohormone production. Screening of several melatonin concentrations (0, 0.1, 1, 5, and 10 µM) on mustard growth showed that the 1 µM concentration revealed an ameliorative increase of plant height, leaf length, and leaf width. The second study aimed at determining how melatonin application can recover salinity-damaged plants and studying its effects on physiological and biochemical parameters. Under controlled environmental conditions, mustard seedlings were irrigated with distilled water or 150 mM of NaCl for 7 days. This was followed by 1 µM of melatonin application to determine its recovery impact on the damaged plants. Furthermore, several physiological and biochemical parameters were examined in stressed and unstressed seedlings with or without melatonin application. Our results showed that plant height, leaf length/width, and stem diameter were enhanced in 38-day-old salinity-stressed plants under melatonin treatment. Melatonin application obviously attenuated salinity-induced reduction in gas exchange parameters, relative water content, and amino acid and protein levels, as well as antioxidant enzymes, such as superoxide dismutase and catalase. H2O2 accumulation in salinity-damaged plants was reduced by melatonin treatment. A decline in abscisic acid content and an increase in salicylic acid content were observed in salinity-damaged seedlings supplemented with melatonin. Additionally, chlorophyll content decreased during the recovery period in salinity-damaged plants by melatonin treatment. This study highlighted, for the first time, the recovery impact of melatonin on salinity-damaged green mustard seedlings. It demonstrated that exogenous melatonin supplementation significantly improved the physiologic and biochemical parameters in salinity-damaged green mustard seedlings.

Status of international normalized ratio control and treatment patterns in patients with nonvalvular atrial fibrillation taking vitamin K antagonist with or without antiplatelet therapy: Results from KORAFII registry.

BACKGROUND: Studies have shown that the concomitant use of a vitamin K antagonist (VKA) and an antiplatelet (APL) drug increased the bleeding risk and was less effective at preventing ischemic events. This study aimed to investigate the control status of international normalized ratio (INR) and the discontinuation rate of a VKA in patients taking VKA plus an APL drug compared with those taking a VKA alone. METHODS: Data were extracted from the KORean Atrial Fibrillation Investigation II registry, a multicenter noninterventional prospective observational study. Nonvalvular atrial fibrillation (NVAF) patients with CHADS 2 scores ≥ 1 who newly started (within 3 months) a VKA were enrolled and followed up for 1 year. RESULTS: A total of 866 NVAF patients (mean age, 67.7 years; 60.3% men) without a bleeding history were divided into the VKA+APL (n = 229) and VKA alone (n = 637) groups. During follow-up, mean INR level was lower in the VKA+APL group than in the VKA alone group (1.7 ± 0.8 vs 1.9 ± 0.9, P = 0.0005). INR levels were poorly controlled in both groups (66.1% and 64.7%, respectively). Patients in the VKA+APL group more frequently discontinued VKA than patients in the VKA alone group (28.8% vs 24.2%, P = 0.045). Major causes of VKA discontinuation were uncontrolled INR level and patient dissatisfaction or concerns. CONCLUSIONS: The conditions of NVAF patients were inadequately controlled with VKA with or without an APL. These findings suggest that other antithrombotic treatment options are warranted in NVAF patients to achieve INR control.

Clinical and Echocardiographic Risk Factors Predict Late Recurrence after Radiofrequency Catheter Ablation of Atrial Fibrillation.

The benefits of radiofrequency catheter ablation (RFCA) for patients with atrial fibrillation (AF) significantly decrease with late recurrence (LR). We aimed to develop a scoring system to identify patients at high and low risk for LR following RFCA, based on a comprehensive evaluation of multiple risk factors for AF recurrence, including echocardiographic parameters. We studied 2,352 patients with AF undergoing first-time RFCA in a single institution. The LR-free survival rate up to 5 years was measured using a Kaplan-Meier analysis. The influence of clinical and echocardiographic parameters on LR was calculated with a Cox-regression analysis. Duration of AF ≥4 years (hazard ratio [HR] = 1.75; p < 0.001), non-paroxysmal AF (HR = 3.18; p < 0.001), and diabetes (HR = 1.34; p = 0.015) were associated with increased risk of LR. Left atrial (LA) diameter ≥45 mm (HR = 2.42; p < 0.001), E/e' ≥ 10 (HR = 1.44; p < 0.001), dense SEC (HR = 3.30; p < 0.001), and decreased LA appendage flow velocity (≤40 cm/sec) (HR = 2.35; p < 0.001) were echocardiographic parameters associated with increased risk of LR following RFCA. The LR score based on the aforementioned risk factors could be used to predict LR (area under curve = 0.717) and to stratify the risk of LR (HR = 1.45 per 1 point increase in the score; p < 0.001). In conclusion, LR after RFCA is affected by multiple clinical and echocardiographic parameters. This study suggests that combining these multiple risk factors enables the identification of patients with AF at high or low risk for having arrhythmia recurrence.

Electrophysiological features and radiofrequency catheter ablation of supraventricular tachycardia in patients with persistent left superior vena cava.

BACKGROUND: The electrophysiological features and roles of persistent left superior vena cava (PLSVC) in supraventricular tachycardia (SVT) are not known. OBJECTIVE: The purpose of this study was to elucidate the electrophysiological features and roles of PLSVC in patients with SVT. METHODS: We included 37 patients with PLSVC (mean age 43.5 ± 17.1 years; 35.1% men) and 510 patients without PLSVC (mean age 43.9 ± 18.8 years; 48.2% men) who underwent an electrophysiology study for SVT. The number of induced tachycardias, location of the slow pathway (SP) or accessory pathway (AP), and radiofrequency catheter ablation (RFCA) outcomes were compared between patients with and without PLSVC. During RFCA of the left AP, a coronary sinus (CS) catheter was placed into the left superior vena cava (left superior vena cava group) or the great cardiac vein (great cardiac vein group). The RFCA outcomes were compared between the groups. RESULTS: In patients with PLSVC, 40 tachycardias were induced: atrioventricular nodal reentrant tachycardia (AVNRT) (n = 19), atrioventricular reentrant tachycardia (n = 17), and focal atrial tachycardia (n = 4). Among patients with AVNRT, an SP in the CS was significantly more frequent in patients with PLSVC than in those without PLSVC (47.4% vs 3.8%; P < .001). In patients with the left AP, the number of RFCA attempts and recurrence were lower in the great cardiac vein group than in the left superior vena cava group. CONCLUSION: An SP in the CS is prevalent in patients with AVNRT and PLSVC. It is useful to place a CS catheter into the great cardiac vein in patients with a left AP and PLSVC.

Different Responses of Left Atrium and Left Atrial Appendage to Radiofrequency Catheter Ablation of Atrial Fibrillation: a Follow Up MRI study.

Atrial fibrillation (AF) is known to cause adverse remodeling of left atrium (LA). Radiofrequency catheter ablation (RFCA) of AF is associated with decrease in LA volume. However, the impact of RFCA on left atrial appendage (LAA) volume and hemodynamic function is not fully understood. We analyzed 123 patients who underwent cardiac magnetic resonance imaging (MRI) evaluation before and after RFCA in Korea University Anam Hospital. LA and LAA volume were measured before and after RFCA based on cardiac MRI. Baseline LA volume was 99.5 ± 38.4 cm3 and decreased to 74.6 ± 28.5 cm3 after RFCA (p < 0.001). LA diameter measured with transthoracic echocardiography was also decreased after RFCA (43.3 ± 6.2 mm at baseline and 39.9 ± 5.9 mm at follow up; p < 0.001). However, LAA volume was significantly increased after RFCA (19.4 ± 8.5 cm3 at baseline and 23.7 ± 13.3 cm3 at follow up; p < 0.001). Total ablation time and additional substrate modification was associated with change in LA volume. After RFCA, average LAA velocity measured by transesophageal echocardiography was increased to 51.0 cm/sec from 41.1 cm/sec (p < 0.001). In conclusion, LAA volume was increased after RFCA in contrast to LA volume. Our data raise a concern about worsening hemodynamics of LA and LAA following RFCA and long term clinical significance of enlarged LAA after RFCA needs further evaluation.

Long-Term Clinical Comparison of Procedural End Points After Pulmonary Vein Isolation in Paroxysmal Atrial Fibrillation: Elimination of Nonpulmonary Vein Triggers Versus Noninducibility.

BACKGROUND: Pulmonary vein isolation (PVI) is effective for maintenance of sinus rhythm in 50% to 75% of patients with paroxysmal atrial fibrillation, and it is not uncommon for patients to require additional ablation after PVI. We prospectively evaluated the relative effectiveness of 2 post-PVI ablation strategies in paroxysmal atrial fibrillation. METHODS AND RESULTS: A total of 500 patients (mean age, 55.7±11.0 years; 74.6% male) were randomly assigned to undergo ablation by 2 different strategies after PVI: (1) elimination of non-PV triggers (group A, n=250) or (2) stepwise substrate modification including complex fractionated atrial electrogram or linear ablation until noninducibility of atrial tachyarrhythmia was achieved (group B, n=250). During a median follow-up of 26.0 months, 75 (32.2%) patients experienced at least 1 episode of recurrent atrial tachyarrhythmia after the single procedure in group A compared with 105 (43.8%) patients in group B (P value in log-rank test of Kaplan-Meier analysis: 0.012). Competing risk analysis showed that the cumulative incidence of atrial tachycardia was significantly higher in group B compared with group A (P=0.007). With the exception of total ablation time, there were no significant differences in fluoroscopic time or procedure-related complications between the 2 groups. CONCLUSIONS: Elimination of triggers as an end point of ablation in patients with paroxysmal atrial fibrillation decreased long-term recurrence of atrial tachyarrhythmia compared with a noninducibility approach achieved by additional empirical ablation. The post-PVI trigger test is thus a better end point of ablation for paroxysmal atrial fibrillation.

Non-vitamin K antagonist oral anticoagulants versus warfarin for the prevention of spontaneous echo-contrast and thrombus in patients with atrial fibrillation or flutter undergoing cardioversion: A trans-esophageal echocardiography study.

Spontaneous echo-contrast (SEC) and thrombus observed in trans-esophageal echocardiography (TEE) is known as a strong surrogate marker for future risk of ischemic stroke in patients with atrial fibrillation (AF) or atrial flutter (AFL). The efficacy of non-vitamin K antagonist oral anticoagulants (NOAC) compared to warfarin to prevent SEC or thrombus in patients with AF or AFL is currently unknown. AF or AFL patients who underwent direct current cardioversion (DCCV) and pre-DCCV TEE evaluation from January 2014 to October 2016 in a single center were analyzed. The prevalence of SEC and thrombus were compared between patients who received NOAC and those who took warfarin. NOAC included direct thrombin inhibitor and factor Xa inhibitors. Among 1,050 patients who were considered for DCCV, 424 patients anticoagulated with warfarin or NOAC underwent TEE prior to DCCV. Eighty patients who were anticoagulated for less than 21 days were excluded. Finally, 344 patients were included for the analysis (180 warfarin users vs. 164 NOAC users). No significant difference in the prevalence of SEC (44.4% vs. 43.9%; p = 0.919), dense SEC (13.9% vs. 15.2%; p = 0.722), or thrombus (2.2% vs. 4.3%; p = 0.281) was observed between the warfarin group and the NOAC group. In multivariate analysis, there was no association between NOAC and risk of SEC (odds ratio [OR]: 1.4, 95% CI: 0.796-2.297, p = 0.265) or thrombus (OR: 3.4, 95% CI: 0.726-16.039, p = 0.120). In conclusion, effectiveness of NOAC is comparable to warfarin in preventing SEC and thrombus in patients with AF or AFL undergoing DCCV. However, numerical increase in the prevalence of thrombus in NOAC group warrants further evaluation.

Value of adenosine test to reveal dormant conduction or adenosine-induced atrial fibrillation after pulmonary vein isolation.

BACKGROUND: Recent studies investigating the implications of additional ablation guided by dormant pulmonary vein (PV) conduction testing using adenosine showed conflicting results, and the data about atrial fibrillation (AF) recurrence after trigger site elimination in adenosine-induced AF are still lacking. METHODS: Of 846 patients with paroxysmal AF (PAF) who underwent PV isolation (PVI), adenosine test after PVI was performed in 148 patients. RESULTS: PVI was successfully achieved in 846 patients. We excluded 58 patients due to loss to the follow-up. A higher rate of AF recurrence was found in the group without adenosine test (136/644, 21%) compared to the group with adenosine test (20/144, 13%, log-rank P=0.047). In multivariate analysis model for AF freedom during the follow-up period, the only significant clinical predictor of AF freedom was adenosine test (hazard ratio [HR] 1.97; 95% confidence interval [CI]: 1.2-3.23; P=0.007).Among 148 patients with adenosine test, 114 (77%) patients showed neither dormant conductions nor AF-induced, 22 (15%) showed positive dormant conductions only, and 12 (8%) revealed adenosine-induced AF (6 of them also showed dormant conduction). After additional ablation in positive dormant conduction group and adenosine-induced AF group, AF recurrence was noted in 4/21 (19%) patients in positive dormant conduction group and 2/11 (18%) patients in adenosine-induced AF group, which was not different from that of patients in negative dormant conduction/ no AF-induced group (14/112, 12%, log-rank P=0.67). CONCLUSIONS: Adenosine test after PVI to confirm the absence of dormant conduction and triggers initiating AF is beneficial to improve the outcomes after catheter ablation of PAF.

Humanized mutant FUS drives progressive motor neuron degeneration without aggregation in 'FUSDelta14' knockin mice.

Mutations in FUS are causative for amyotrophic lateral sclerosis with a dominant mode of inheritance. In trying to model FUS-amyotrophic lateral sclerosis (ALS) in mouse it is clear that FUS is dosage-sensitive and effects arise from overexpression per se in transgenic strains. Novel models are required that maintain physiological levels of FUS expression and that recapitulate the human disease-with progressive loss of motor neurons in heterozygous animals. Here, we describe a new humanized FUS-ALS mouse with a frameshift mutation, which fulfils both criteria: the FUS Delta14 mouse. Heterozygous animals express mutant humanized FUS protein at physiological levels and have adult onset progressive motor neuron loss and denervation of neuromuscular junctions. Additionally, we generated a novel antibody to the unique human frameshift peptide epitope, allowing specific identification of mutant FUS only. Using our new FUSDelta14 ALS mouse-antibody system we show that neurodegeneration occurs in the absence of FUS protein aggregation. FUS mislocalization increases as disease progresses, and mutant FUS accumulates at the rough endoplasmic reticulum. Further, transcriptomic analyses show progressive changes in ribosomal protein levels and mitochondrial function as early disease stages are initiated. Thus, our new physiological mouse model has provided novel insight into the early pathogenesis of FUS-ALS.

Self-Aligned Multichannel Graphene Nanoribbon Transistor Arrays Fabricated at Wafer Scale.

We present a novel method for fabricating large-area field-effect transistors (FETs) based on densely packed multichannel graphene nanoribbon (GNR) arrays using advanced direct self-assembly (DSA) nanolithography. The design of our strategy focused on the efficient integration of the FET channel and using fab-compatible processes such as thermal annealing and chemical vapor deposition. We achieved linearly stacked DSA nanopattern arrays with sub-10 nm half-pitch critical dimensions (CD) by controlling the thickness of topographic Au confinement patterns. Excellent roughness values (∼10% of CD) were obtained, demonstrating the feasibility of integrating sub-10 nm GNRs into commercial semiconductor processes. Based on this facile process, FETs with such densely packed multichannel GNR arrays were successfully fabricated on 6 in. silicon wafers. With these high-quality GNR arrays, we achieved FETs showing the highest performance reported to date (an on-to-off ratio larger than 10(2)) for similar devices produced using conventional photolithography and block-copolymer lithography.

Successful Recanalization of Native Coronary Chronic Total Occlusion Is Not Associated With Improved Long-Term Survival.

OBJECTIVES: The purpose of this study was to evaluate long-term clinical outcomes after drug-eluting stent-supported percutaneous coronary intervention (PCI) for native coronary total occlusion (CTO). BACKGROUND: The benefit of successful recanalization of CTO on prognosis remains uncertain. METHODS: Between March 2003 and May 2014, 1,173 consecutive patients with CTO of native coronary vessels requiring PCI were enrolled. Drug-eluting stent implantation was performed in all successful procedures (1,004 patients, 85.6%). RESULTS: During a median follow-up of 4.6 years, the adjusted risks of all-cause mortality (hazard ratio [HR]: 1.04; 95% confidence interval [CI]: 0.53 to 2.04; p = 0.92) and the composite of death or myocardial infarction (HR: 1.05; 95% CI: 0.56 to 1.94; p = 0.89) were found to be comparable between patients with successful and failed CTO-PCI, whereas the adjusted risk of target vessel revascularization (HR: 0.15; 95% CI: 0.10 to 0.25; p < 0.001) and coronary artery bypass grafting (HR: 0.02; 95% CI: 0.006 to 0.06, p < 0.001) was significantly higher in patients with failed CTO-PCI. Among patients (n = 879) in whom complete revascularization for non-CTO vessels was performed, the risk of death or the composite of death or myocardial infarction were not found to differ between patients who underwent successful recanalization of the remaining CTO and patients who did not. This finding was consistent regardless of whether the patient had a multivessel disease including CTO or only had a single CTO disease. CONCLUSIONS: Successful CTO-PCI compared with failed PCI was not associated with a lesser risk for mortality. However, successful CTO-PCI was associated with significantly less subsequent coronary artery bypass grafting.

A case of scrub typhus requiring maintenance hemodialysis.

Renal failure caused by scrub typhus is known to be reversible. In most cases, renal function is almost fully restored after appropriate antibiotic treatment. A 71-year-old man was diagnosed with scrub typhus complicated by renal failure. A renal biopsy revealed histopathologic findings consistent with acute tubulointerstitial nephritis. Renal function did not improve 18 months after discharge and the patient required continuous hemodialysis. Although severe renal failure requiring dialysis is a rare complication of scrub typhus, we describe a case of scrub typhus requiring maintenance hemodialysis. To the best of our knowledge, this is the first such report.

Mechanisms of adipose tissue redistribution with rosiglitazone treatment in various adipose depots.

Treatment with thiazolidinediones (TZDs) improves glucose homeostasis by increasing insulin sensitivity, but it also leads to weight gain. Our hypothesis was that, in individual adipose depots, there is depot specificity for lipid storage and energy expenditure genes after TZD treatment. After 5 weeks of rosiglitazone treatment on Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes mellitus with obesity, and Long-Evans Tokushima Otsuka rats as controls, we measured changes in lipid storage and energy expenditure gene expression in various adipose depots, such as mesenteric and nonmesenteric adipose tissues (subcutaneous, epididymal, and retroperitoneal). Mesenteric fat masses did not change after TZD treatment in OLETF rats, but nonmesenteric fat masses increased. Messenger RNA expression of lipid storage genes increased in nonmesenteric fat, but energy expenditure gene expression increased in mesenteric fat after rosiglitazone treatment. In conclusion, our findings suggest that TZD treatment may be associated with the depot-specific effects of lipid storage and energy expenditure genes on fat redistribution in individual adipose tissues in OLETF rats.

Identification of the nuclear localization motif in the ETV6 (TEL) protein.

ETV6, or Translocation-Ets-Leukemia (TEL), is an ETS family transcriptional repressor that is essential for establishing hematopoiesis in neonatal bone marrow, and is frequently a target of chromosomal translocations in human cancer. ETV6 is predominantly a nuclear phosphoprotein that represses transcription by binding directly to the promoters of target genes. The nuclear localization mechanism of ETV6, however, is not well understood. In this report, we provide evidence that a nuclear localization signal (NLS) exists in the C-terminal region of ETV6. ETV6 proteins with mutations outside of amino acids 332-452 localize to the nucleus, whereas proteins with mutations within amino acids 332-452 remain in the cytoplasm. Furthermore, when a fragment of ETV6 comprised of amino acids 332-452 was fused to cytoplasmic beta-galactosidase protein, the fusion protein was able to enter the nucleus. These results strongly indicate that residues 332-452 mediate nuclear localization of ETV6.

Isolation of a novel plasmid, pNi15, from Enterobacter sp. Ni15 containing a nickel resistance gene.

We isolated nickel-resistant bacterium from soil in order to identify a novel nickel resistance determinant. Using 16S rRNA gene sequencing, an isolate was identified as Enterobacter sp. Ni15. This species showed a medium-level (resistant to up to 10 mM) nickel resistance in nutrient-rich media. Enterobacter sp. Ni15 has a novel plasmid, pNi15, and an increased nickel resistance to Escherichia coli DH5alphain trans. To isolate the nickel resistance gene from pNi15, the plasmid was digested with XbaI and its fragments were cloned into pBluescriptIISK(+). The clones were transferred into E. coli DH5alpha. The nickel resistance of the clones was then assayed. From these results, a pNi15100 isolate containing a 5,328 bp XbaI fragment of pNi15 was identified and sequenced. The E. coli DH5alpha harboring the pNi15100 showed a resistance to up to 7 mM nickel. Using a subcloning analysis, we were able to identify the novel nickel resistance determinant: the nrp gene encoding the putative proteins NrpA and NrpB.

Somatostatin (SRIF) receptor subtype 2 and 5 gene expression in growth hormone-secreting pituitary adenomas: the relationship with endogenous srif activity and response to octreotide.

To investigate the potential pathophysiologic role of human SRIF receptor gene expression in GH-secreting adenomas in acromegalic patients, we studied the relationship between the SRIF receptor gene expression, endogenous SRIF activity and exogenous response to octreotide in 16 acromagalic patients. Hypothalamic somatostatinergic activity (HSA) was assessed by glucose-induced suppression of TRH-stimulated TSH secretion. As an indicator of somatotrope sensitivity to HSA, glucose-induced suppression of TRH-stimulated GH secretion was determined. For the acute octreotide response, a 100 microg bolus of octreotide was injected intravenously and GH was measured hourly for 6 hr. Pituitary tumor SRIF receptor subtype 2 and 5 (sst2 and sst5) mRNA levels were measured by real-time RT-PCR. Gsp oncogene was also detected by direct PCR sequencing. Sst2 and sst5 mRNA levels were detected in all tumors. Sst2 mRNA levels positively correlated with that of sst5. Sst2 and sst5 mRNA levels did not show any correlation with basal GH values (nadir or peak). Expression of sst2, but not sst5, showed a positive correlation with the GH response to HSA, while the octreotide response positively correlated with the sum of sst2 and sst5 mRNA levels. Individuals with gsp-positive tumors were more responsive to octreotide than those with gsp-negative tumors but sst2 and sst5 mRNA levels did not differ between these two groups. These results suggest common transcriptional and/or post-transcriptonal regulatory mechanisms for these SRIF receptor subtypes within GH-secreting pituitary adenomas. The functional observations suggest that the degree (or level) of sst2 and sst5 expression is critical for the ultimate GH response of somatotropinomas to endogenous SRIF tone and exogenous SRIF analogue therapy. However, sst2 and sst5 mRNA levels are not the only factors mediating the response to SRIF.