Dietary L-Methionine modulates the gut microbiota and improves the expression of tight junctions in an in vitro model of the chicken gastrointestinal tract.

BACKGROUND: The poultry industry encounters a number of factors that affect growth performance and productivity; nutrition is essential for sustaining physiological status and protecting against stressors such as heat, density, and disease. The addition of vitamins, minerals, and amino acids to the diet can help restore productivity and support the body's defense mechanisms against stress. Methionine (Met) is indispensable for poultry's energy metabolism, physiology, performance, and feed utilization capacity. Through this study, we aimed to examine the physiological effects of methionine supplementation on poultry as well as alterations of intestinal microbiome. METHODS: We utilized the DL- and L- form of methionine on Caenorhabditis elegans and the FIMM (Fermentor for intestine microbiota model) in-vitro digesting system. A genomic-analysis of the transcriptome confirmed that methionine supplementation can modulate growth-related physiological metabolic pathways and immune responses in the host poultry. The C. elegans model was used to assess the general health benefits of a methionine supplement for the host. RESULTS: Regardless of the type or concentration of methionine, supplementation with methionine significantly increased the lifespan of C. elegans. Feed grade L-Methionine 95%, exhibited the highest lifespan performance in C. elegans. Methionine supplementation increased the expression of tight junction genes in the primary intestinal cells of both broiler and laying hens, which is directly related to immunity. Feed grade L-Methionine 95% performed similarly or even better than DL-Methionine or L-Methionine treatments with upper doses in terms of enhancing intestinal integrity. In vitro microbial cultures of healthy broilers and laying hens fed methionine revealed changes in intestinal microflora, including increased Clostridium, Bacteroides, and Oscillospira compositions. When laying hens were given feed grade L-Methionine 95% and 100%, pathogenic Campylobacter at the genus level was decreased, while commensal bacteria were increased. CONCLUSIONS: Supplementation of feed grade L-Methionine, particularly L-Methionine 95%, was more beneficial to the host poultry than supplementing other source of methionine for maintaining intestinal integrity and healthy microbiome.

Dietary supplementation with probiotics promotes weight loss by reshaping the gut microbiome and energy metabolism in obese dogs.

Obesity and overweight among companion animals are significant concerns, paralleling the issues observed in human populations. Recent research has highlighted the potential benefits of various probiotics in addressing weight-related changes, obesity, and associated pathologies. In this study, we delved into the beneficial probiotic mechanisms in high-fat-induced obese canines, revealing that Enterococcus faecium IDCC 2102 (IDCC 2102) and Bifidobacterium lactis IDCC 4301 (IDCC 4301) have the capacity to mitigate the increase in body weight and lipid accumulation in obese canines subjected to a high-fat diet and hyperlipidemic Caenorhabditis elegans (C. elegans) strain VS29. Both IDCC 2102 and IDCC 4301 demonstrated the ability to reduce systemic inflammation and hormonal disruptions induced by obesity. Notably, these probiotics induced modifications in the microbiota by promoting lactic acid bacteria, including Lactobacillaceae, Ruminococcaceae, and S24-7, with concomitant activation of pyruvate metabolism. IDCC 4301, through the generation of bacterial short-chain fatty acids and carboxylic acids, facilitated glycolysis and contributed to ATP synthesis. Meanwhile, IDCC 2102 produced bacterial metabolites such as acetic acid and butyric acid, exhibiting a particular ability to stimulate dopamine synthesis in a canine model. This stimulation led to the restoration of eating behavior and improvements in glucose and insulin tolerance. In summary, we propose novel probiotics for the treatment of obese animals based on the modifications induced by IDCC 2102 and IDCC 4301. These probiotics enhanced systemic energy utilization in response to high caloric intake, thereby preventing lipid accumulation and restoring stability to the fecal microbiota. Consequently, this intervention resulted in a reduction in systemic inflammation caused by the high-fat diet.IMPORTANCEProbiotic supplementation affected commensal bacterial proliferation, and administering probiotics increased glycolysis and activated pyruvate metabolism in the body, which is related to propanate metabolism as a result of pyruvate metabolism activation boosting bacterial fatty acid production via dopamine and carboxylic acid specialized pathways, hence contributing to increased ATP synthesis and energy metabolism activity.

Change in the Gut Microbiota of Lactating Sows and Their Piglets by Inclusion of Dietary Spray-Dried Plasma in Sow Diets.

This study aimed to investigate the effects of dietary spray-dried plasma (SDP) on the gut microbiota of lactating sows and their piglets. A total of 12 sows were randomly assigned to one of two dietary treatment groups in a completely randomized design. The treatments were a sow diet based on corn and soybean meal (CON), and a CON diet with an added 1% SDP. The sows were fed the dietary treatments from d 30 before farrowing to weaning (d 28). The fecal samples of three sows from each treatment and two of their randomly selected piglets were collected to verify their fecal microbiota. There were no differences in the alpha diversity and distinct clustering of the microbial communities in the sows and their piglets when SDP was added to the sow diets from late gestation to weaning. The fecal microbiota of the lactating sows and their piglets showed a higher relative abundance of the phylum Bacteroidota and genus Lactobacillus and Ruminococcus and showed a lower relative abundance of the phylum Bacillota and genus Bacteroides, Escherichia/Shigella, and Clostridium in the sows fed the SDP diet than those fed the CON diet. Overall, these results show that the addition of SDP to the sow diet during lactation altered the gut environment with positive microbial composition changes. These results were similar in the nursing piglets, suggesting that the control of the sow diets during lactation may contribute to the intestinal health and growth in piglets after weaning.

Alleviation of DSS-induced colitis via bovine colostrum-derived extracellular vesicles with microRNA let-7a-5p is mediated by regulating Akkermansia and ß-hydroxybutyrate in gut environments.

IMPORTANCE: Even though studying on the possible involvement of extracellular vesicles (EVs) in host-microbe interactions, how these relationships mediate host physiology has not clarified yet. Our current findings provide insights into the encouraging benefits of dietary source-derived EVs and microRNAs (miRNAs) on organic acid production and ultimately stimulating gut microbiome for human health, suggesting that supplementation of dietary colostrum EVs and miRNAs is a novel preventive strategy for the treatment of inflammatory bowel disease.

Dietary effects of melatonin on growth performance by modulation of protein bioavailability and behavior in early weaned rats and pigs.

Melatonin, which is produced from tryptophan, exerts various biological functions, including the regulation of circadian rhythm, sedative agents, and antioxidant ability. Therefore, we conducted two experiments with early-weaned rats and pigs to investigate the antioxidant and sedative effects of melatonin. In the rat experiment, a total of 42 rats (21 days old) were used, and the antioxidant capacity was determined. Next, we used 120 early-weaned piglets (21 days old) to conduct a 5-week experiment to evaluate the reductive effect of melatonin on energy-wasting movement, including roaming and fight states. Dietary melatonin supplementation significantly improved growth in both rats and pigs compared to the control groups. Additionally, rats fed a melatonin-supplemented diet showed advanced antioxidant capacity with a decrease in hepatic malondialdehyde concentration compared to rats fed a basal diet. Moreover, dietary melatonin ingestion increased resting and feeding behaviors and reduced roaming and fight behaviors during Days 8-21 compared to the control diet group. Collectively, early weaned animals given dietary melatonin supplementation showed improved growth through upregulation of hepatic antioxidant capacity and minimization of energy-wasting behavior, including roaming and fight states, after pigs' social hierarchy establishment.

The Ingestion of Dietary Prebiotic Alternatives during Lactation Promotes Intestinal Health by Modulation of Gut Microbiota.

Palm kernel expeller (PKE), a by-product of palm oil extraction, contains higher amounts of fiber than corn and soybean meal, but offers low energy density, protein value, and amino acid (AA) composition, limiting its use for swine. Recently however, it was reported that dietary fiber has a positive effect on the gut microbiota of the host, and therefore it is necessary to study the effect of PKE feeding on the intestinal microbiota of swine. In this study, we investigated the effects of supplementation with PKE in lactation diets on the gut microbiota composition of lactating sows and their litters. A total of 12 sows were randomly assigned to two dietary treatment groups in a completely randomized design. The treatments were a diet based on corn-soybean meal (CON) and CON supplemented with 20% of PKE. Sow and piglet fecal samples were collected before farrowing, on days 7 and 28 (weaning) after farrowing, and on days 7 and 28 (weaning) after farrowing, respectively, to verify gut microbiota composition by pyrosequencing analysis. The beta-diversity result showed a significant difference only in weaning-stage piglets, but dietary PKE altered the gut microbiota in sows by increasing the abundance of Lactobacillus compared with CON. In piglets, dietary PKE decreased the abundance of opportunistic pathogen Proteus and increased the abundance of potentially beneficial bacteria, such as Prevotellaceae and Prevotella. Our results can be helpful in developing feeding strategies and support the beneficial effects of dietary PKE to improve the gut health of animals.

Modification of Gut Microbiota and Immune Responses via Dietary Protease in Soybean Meal-Based Protein Diets.

Plant-based protein sources such as soybean meal have low digestibility and are generally promoted accumulation of undigested proteins into the intestine by enzymatic treatments. Moreover, potential intestinal pathogens ferment undigested proteins, producing harmful substances, such as ammonia, amines and phenols, leading to an overactive immune response and diarrhea in weaned pigs. As a solution, dietary proteases hydrolyze soybean-based antinutritive factors, which negatively affect immune responses and gut microbiota. In this study, we investigated the effects of dietary proteases (PRO) in a low-crude protein (CP) commercial diet on the immune responses and gut microbiota of weaned pigs. The experimental design consisted of three dietary treatments: a commercial diet as a positive control (PC; phase1 CP = 23.71%; phase 2 CP: 22.36%), a lower CP diet than PC as negative control (NC; 0.61% less CP than PC), and NC diet supplement with 0.02% PRO. We found that PRO tended to decrease the frequency of diarrhea in the first two weeks after weaning compared with PC and NC. In addition, pigs fed PRO showed decreased TNF-α and TGF-ß1 levels compared with those fed PC and NC. The PRO group had a higher relative proportion of the genus Lactobacillus and lower levels of the genus Streptococcus than the PC and NC groups. In conclusion, the addition of PRO to a low CP commercial weaned diet attenuated inflammatory responses and modified gut microbiota in weaned pigs.

Effects of Dietary Carbohydrases on Fecal Microbiome Composition of Lactating Sows and Their Piglets.

Corn-soybean meal diets are commonly used in the pork industry as a primary source of energy and protein. However, such a diet generally contains non-starch polysaccharides (NSPs) which present a challenge in finding ways to improve their availability and digestibility. Dietary multi-carbohydrases (MCs) have been proposed as an efficient approach to utilize NSPs, and can result in improved growth performance and host intestinal fitness. In this study, we evaluated the effects of MC in lactation diets on gut microbiota composition of lactating sows and their litters. The experimental design contained two dietary treatments, a diet based on corn-soybean meal (CON), and CON supplemented with 0.01% multigrain carbohydrases (MCs). Sow and piglet fecal samples were collected on days 7 and 28 after farrowing. Based on the results from 16S rRNA gene amplicon sequencing, MC led to changes in species diversity and altered the microbial compositions in lactating sows and their piglets. Specifically, the MC treatment induced an increase in the proportions of Lactobacillus in piglets. Clostridium and Spirochaetaceae showed a significantly reduced proportion in MC-treated sows at day 28. Our results support the beneficial effects of dietary carbohydrases and their link with improved production due to better host fitness outcomes and gut microbiota composition.

Comparative analysis of background EEG activity in juvenile myoclonic epilepsy during valproic acid treatment: a standardized, low-resolution, brain electromagnetic tomography (sLORETA) study.

BACKGROUND: By definition, the background EEG is normal in juvenile myoclonic epilepsy (JME) patients and not accompanied by other developmental and cognitive problems. However, some recent studies using quantitative EEG (qEEG) reported abnormal changes in the background activity. QEEG investigation in patients undergoing anticonvulsant treatment might be a useful approach to explore the electrophysiology and anticonvulsant effects in JME. METHODS: We investigated background EEG activity changes in patients undergoing valproic acid (VPA) treatment using qEEG analysis in a distributed source model. In 17 children with JME, non-parametric statistical analysis using standardized low-resolution brain electromagnetic tomography was performed to compare the current density distribution of four frequency bands (delta, theta, alpha, and beta) between untreated and treated conditions. RESULTS: VPA reduced background EEG activity in the low-frequency (delta-theta) bands across the frontal, parieto-occipital, and limbic lobes (threshold log-F-ratio = ±1.414, p < 0.05; threshold log-F-ratio= ±1.465, p < 0.01). In the delta band, comparative analysis revealed significant current density differences in the occipital, parietal, and limbic lobes. In the theta band, the analysis revealed significant differences in the frontal, occipital, and limbic lobes. The maximal difference was found in the delta band in the cuneus of the left occipital lobe (log-F-ratio = -1.840) and the theta band in the medial frontal gyrus of the left frontal lobe (log-F-ratio = -1.610). CONCLUSIONS: This study demonstrated the anticonvulsant effects on the neural networks involved in JME. In addition, these findings suggested the focal features and the possibility of functional deficits in patients with JME.

Dietary effects of sophorolipids on nutrient bioavailability and intestinal microenvironments in broiler chickens.

Using antibiotics as growth promoter has been banned in poultry feed industry, thus various researchers try to seek an alternative to replace the growth-promoting antibiotics. In this study, we aimed to evaluate the growth performance via intestinal nutrient utilization and cecal microbial composition of broiler after dietary supplementation with most commonly using antibiotics, zinc bacitracin, and sophorolipid. A total of 180 1-day-old chicks were randomly assigned, and dietary treatment was as follow: CON, basal diet; ZB, 100 ppm of zinc bacitracin supplemented diet; and SPL, 250 ppm of sophorolipid supplemented diet. Their growth performance was evaluated and the samples of blood, small intestine, and ileal and cecal digesta were collected for biochemical, histological, and genomic analyses. The body weight and average daily gain of 7-day-old chicks were higher in ZB and those in overall experimental period were improved by ZB and SPL supplementation (p < 0.05). Their intestinal characteristics were not affected by dietary treatments in duodenum and ileum. Nonetheless, villus height was increased by SPL supplementation in jejunum (p < 0.05). Moreover, dietary SPL supplementation could down-regulate the expression level of pro-inflammatory cytokine, IL-1ß (p < 0.05). mRNA levels of lipid and protein transporters did not differ among the treatments, however, relative expression levels of carbohydrate transporters, GLUT2 and SGLT1 were increased in broiler chicken's jejumum fed zinc bacitracin and sophorolipid supplemented diets (p < 0.05). Dietary zinc bacitracin supplementation could increase the population of Firmicutes in phylum level, and the portion of Turiciacter in genus level. On the other hands, the portion of Faecalibacterium was increased by dietary SPL supplementation compared to the other treatments. Our findings suggest that SPL supplementation improves growth performance through enhanced carbohydrate utilization capacity via improvement of gut morphological status and modulation of the cecal microbial population of broilers.

Bacillus amyloliquefaciens SCGB1 Alleviates Dextran Sulfate Sodium-Induced Colitis in Mice Through Immune Regulation.

Probiotics, as living microorganisms, exert health benefits to the host by alleviating excess inflammation through modulating the immune system and establishing intestinal homeostasis. In this study, we evaluated the probiotic characteristics and inflammation alleviatory effects of Bacillus amyloliquefaciens isolated from traditional Korean fermented foods. The strains withstood the acidic environment of the digestive process, extended the lifespan of Caenorhabditis elegans, and enhanced pmk-1 expression. However, only B. amyloliquefaciens SCGB1 could attach to C. elegans in the intestines, which enhanced their survival upon exposure to Escherichia coli O157:H7. We also investigated the anti-inflammatory effect of SCGB1 using the RAW264.7 macrophage stimulated with lipopolysaccharide. The strain treatment enhanced anti-inflammatory cytokine interleukin (IL)-10 secretion and downregulated proinflammatory cytokine IL-6 expression in vitro. Next, we used a dextran sulfate sodium (DSS)-induced colitis mouse model to investigate whether SCGB1 can ameliorate gut inflammation in vivo. Compared to those in the DSS-induced mice, histological damage and IL-6 cytokine levels were significantly reduced in SCGB1-fed mice. These results suggest that B. amyloliquefaciens SCGB1 as potential probiotics may have health-promoting effects by reduction of inflammatory responses.

A synbiotic combination of Lactobacillus gasseri 505 and Cudrania tricuspidata leaf extract prevents hepatic toxicity induced by colorectal cancer in mice.

Colorectal cancer (CRC) is known to be a life-threatening disease and commonly leads to metastasis in the liver. Fermented milk acts as an effective carrier for probiotic strains, whose consumption improves host health. Our previous study indicated that fermented milk that included a synbiotic combination of Lactobacillus gasseri 505 (505) and Cudrania tricuspidata leaf extract (CT) resulted in significantly greater anti-oxidative effects than fermented milk without CT. Therefore, we hypothesized that fermented milk containing CT and 505 (FCT) could result in hepatoprotective effects against CRC-induced liver metastasis. Liver inflammation and CRC were induced in male C57BL/6J mice, using azoxymethane/dextran sodium sulfate, and 505, CT, and FCT were administered to the 3 sample-treated 505, CT, and FCT groups, respectively, for 10 wk. The results showed that FCT treatment significantly reduced serum aspartate aminotransferase and alanine aminotransferase concentrations and elevated albumin concentrations. Moreover, the results of histological analysis showed that hepatic steatosis was notably reduced in the FCT group. Among the 3 sample-treated groups, the expression of mRNA associated with enzymes showing anti-oxidative activities, such as superoxide dismutase, catalase, and glutathione reductase, was the highest in the FCT-treated mice. In addition, FCT administration resulted in the greatest anti-inflammatory activity, as inflammatory marker levels (i.e., tumor necrosis factor-α, cyclooxygenase-2, myeloperoxidase, and nuclear factor kappa-light-chain enhancer of activated B cells) were significantly downregulated at the mRNA level and the expression of proteins associated with the nuclear factor kappa-light-chain enhancer of activated B cells and mitogen-activated protein kinase signaling pathways was suppressed by FCT. Therefore, this study demonstrated that fermented milk containing novel synbiotics has the potential to prevent hepatic toxicity induced because of CRC owing to its enhanced anti-oxidative and anti-inflammatory activities.

The Electrical Isolation of the Left Atrial Posterior Wall in Catheter Ablation of Persistent Atrial Fibrillation.

OBJECTIVES: This study explored whether complete electrical isolation of the left atrial (LA) posterior wall improves the rhythm outcome of catheter ablation of persistent atrial fibrillation (AF). BACKGROUND: Although the STAR AF2 (Substrate and Trigger Ablation for Reduction of Atrial Fibrillation Trial Part II) proved no additional benefit of empirical extra-pulmonary vein (PV) LA ablation, the long-term recurrence rate after circumferential PV isolation (CPVI) alone remains high. METHODS: We randomly assigned 217 patients with persistent AF (83.1% men, age 58.7 ± 10.8 years, 73.3% long-standing persistent AF) to ablation with CPVI alone (CPVI group) or CPVI with a POsterior wall Box Isolation (POBI group). The endpoint of the POBI group was the elimination of the posterior atrial potentials by roof and posterior inferior lines and touch-up focal ablation. RESULTS: After a mean follow-up of 16.2 ± 8.8 months, the clinical recurrence rate did not significantly differ between the 2 groups (23.8% vs. 26.5%; p = 0.779) in the CPVI and POBI groups. The recurrence rate for atrial tachycardias (16.0% vs. 11.1%; p = 0.913) and cardioversion rates (6.7% vs. 13.7%; p = 0.093) to control clinical recurrences also did not significantly differ between the 2 groups. At the final follow-up, sinus rhythm was maintained without antiarrhythmic drug in 50.5% and 55.9% in the CPVI and POBI groups, respectively (p = 0.522). No significant difference was found in the major complication rates between the 2 groups, but the total ablation time was significantly longer in the POBI group (4,289 ± 1,837 s vs. 5,365 ± 2,358 s; p < 0.001). CONCLUSIONS: In patients with persistent AF, an empirical complete POBI did not improve the rhythm outcome of catheter ablation or influence the type of recurrent atrial arrhythmia. (Comparison of Circumferential Pulmonary Vein Isolation Alone Versus Linear Ablation in Addition to Circumferential Pulmonary Vein Isolation for Catheter Ablation in Persistent Atrial Fibrillation: Prospective Randomized Controlled Trial; NCT02721121).

Impact of persistent left superior vena cava on radiofrequency catheter ablation in patients with atrial fibrillation.

AIMS: The impact of persistent left superior vena cava (PLSVC) in atrial fibrillation (AF) patients undergoing radiofrequency catheter ablation (RFCA) is not well known. We performed this analysis to evaluate the electrophysiological characteristics of PLSVC and its role in triggering and maintaining AF. METHODS AND RESULTS: Patients with AF referred to two tertiary hospitals were screened and patients with PLSVC in pre-RFCA imaging studies were enrolled. Among 3967 patients, PLSVC was present in 36 patients (0.9%). There were four morphological types of PLSVC: type 1, atresia of the right superior vena cava (SVC) (n = 2); type 2A, dual SVCs with an anastomosis between right and left SVCs (n = 15); type 2B, dual SVCs without an anastomosis (n = 16); type 3, PLSVC draining into the left atrium (LA; n = 2); and unclassified in one patient. Thirty-two patients underwent RFCA and electrophysiology study focusing on PLSVC: PLSVC was the trigger of AF in 48.4% of patients and the driver of AF in 46.9% of patients. Cumulatively, PLSVC was a trigger or driver of AF in 22 patients (68.8%). Whether to ablate PLSVC was determined by the results of electrophysiology study, and no significant difference in the late recurrence rate was observed between patients who did and did not have either trigger or driver from PLSVC. CONCLUSION: Pre-RFCA cardiac imaging revealed PLSVC in 0.9% of AF patients. This study demonstrated that PLSVC has an important role in initiating and maintaining AF in substantial proportion of patients. Electrophysiology study focusing on PLSVC can help to decide whether to ablate PLSVC.

p53 expression status is associated with cancer-specific survival in stage III and high-risk stage II colorectal cancer patients treated with oxaliplatin-based adjuvant chemotherapy.

BACKGROUND: We attempted to elucidate whether p53 expression or TP53 mutation status was associated with cancer-specific survival in adjuvant FOLFOX-treated patients with stage III or high-risk stage II colorectal cancer (CRC). METHODS: We analysed CRCs (N = 621) for the presence of TP53 alterations and for p53 expression, using targeted resequencing and immunohistochemistry. CRCs were grouped into four subsets according to the p53 expression status, which included p53-no, mild, moderate and strong expression. RESULTS: The distributions of CRCs were 19.85, 11.05, 17.7% and 51.5% in the p53-no, mild, moderate and strong expression groups, respectively. Cases in the p53-mild to moderate expression group were associated with a more frequent proximal location, undifferentiated histology, lower N category, extraglandular mucin production, microsatellite instability, CIMP-P1, CK7 expression and decreased CDX2 expression compared with those of cases of the p53-no expression and p53-strong expression groups. According to survival analysis, the p53-mild expression group showed a poor 5-year relapse-free survival (hazard ratio (HR): 2.71, 95% confidence interval (CI) = 1.60-4.60, P < 0.001) and poor 5-year cancer-specific survival (HR: 2.90, 95% CI = 1.28-6.57, P = 0.011). CONCLUSIONS: p53-mild expression status was found to be an independent prognostic marker in adjuvant FOLFOX-treated patients with stage III and high-risk stage II CRC.

Comparison between linear and focal ablation of complex fractionated atrial electrograms in patients with non-paroxysmal atrial fibrillation: a prospective randomized trial.

AIMS: Findings regarding efficacy of substrate modification for non-paroxysmal atrial fibrillation (AF) are inconsistent. We prospectively compared clinical outcomes of complex fractionated atrial electrogram (CFAE)-guided focal ablation (CFA) and CFAE-guided linear ablation (CLA) in patients with non-paroxysmal AF. METHODS AND RESULTS: We randomized 150 patients with non-paroxysmal AF into CFA and CLA groups in a 1:1 ratio. Complex fractionated atrial electrogram distribution was evaluated using an automated algorithm of a three-dimensional mapping system. After pulmonary vein isolation (PVI), CFAE-guided ablation was performed in the left atrium and then in the right atrium (RA). When compared with conventional CFA, CLA was performed based on conventional lines, with additional lines. Atrial fibrillation was not induced after PVI alone or with cavotricuspid isthmus ablation in 20.7% of patients. To achieve the endpoint, additional CFAE-guided RA ablation was required in 42.7% and 36.0% of patients undergoing CFA and CLA, respectively (P = 0.403). Atrial fibrillation was terminated during CFAE-guided ablation in 72.9% and 75.0% of patients undergoing CFA and CLA, respectively (P = 0.792). Termination of atrial tachycardia (AT) or non-inducibility of AF/AT was achieved in 61.3% and 68.0% of patients undergoing CFA and CLA, respectively (P = 0.393). The CLA group showed decreased 1-year freedom from AF/AT recurrence (60.0%, CFA vs. 47.3%, CLA; log rank P = 0.085), but no significant difference throughout the follow-up (22.2 ± 21.0 months) (67.1%, CFA vs. 68.9%, CLA; log rank P = 0.298). CONCLUSION: Long-term efficacy of CFAE-guided ablation was unaffected by the ablation technique in patients with non-paroxysmal AF.

Activated Electron-Transport Layers for Infrared Quantum Dot Optoelectronics.

Photovoltaic (PV) materials such as perovskites and silicon are generally unabsorptive at wavelengths longer than 1100 nm, leaving a significant portion of the IR solar spectrum unharvested. Small-bandgap colloidal quantum dots (CQDs) are a promising platform to offer tandem complementary IR PV solutions. Today, the best performing CQD PVs use zinc oxide (ZnO) as an electron-transport layer. However, these electrodes require ultraviolet (UV)-light activation to overcome the low carrier density of ZnO, precluding the realization of CQD tandem photovoltaics. Here, a new sol-gel UV-free electrode based on Al/Cl hybrid doping of ZnO (CAZO) is developed. Al heterovalent doping provides a strong n-type character while Cl surface passivation leads to a more favorable band alignment for electron extraction. CAZO CQD IR solar cell devices exhibit, at wavelengths beyond the Si bandgap, an external quantum efficiency of 73%, leading to an additional 0.92% IR power conversion efficiency without UV activation. Conventional ZnO devices, on the other hand, add fewer than 0.01 power points at these operating conditions.

Korean mistletoe lectin enhances natural killer cell cytotoxicity via upregulation of perforin expression.

BACKGROUND: Natural killer (NK) cells are crucial components of the innate immune system, providing the first line of defense against pathogens. In a previous study, we demonstrated prophylactic activity of water extract of Korean mistletoe (Viscum album coloratum) on tumor metastasis. However, the leading compound from water extract of Korean mistletoe was not clearly addressed. OBJECTIVE: The purpose of this research was mainly focused on addressing the effect of Korean mistletoe lectin (KMLC) on NK cell cytotoxicity, and the ability of cytokine secretion as well as its signal transduction, mitogen-activated protein kinase (MAPK) pathway. METHODS: KMLC was used to test NK cell-mediated cytotoxicity in vitro and in vivo. Non-isotope cytotoxicity assay (bis-N,N,N',N'-tetraacetic acid (BATDA) release assay) was performed to test the cytotoxicity of NK cells against target tumor cells. Receptor expression was checked by flow cytometry analysis and MAPK signal molecules were analyzed by immunoblotting. RESULTS AND CONCLUSIONS: KMLC at 200 ng/mL increased the cytotoxicity of NK92 cells by 35% compared with untreated cells. KMLC-treated (at 100 ng/mL) mice splenocytes showed a 20% increase in cytotoxic activity. Also, the B chain, one of the subchains of KMLC, increases perforin expression. We demonstrated that the signal transduction controlling NK cell cytotoxicity was mediated by upregulation of the NKG2D receptor and expression of a cytotoxic effector molecule. These results suggested that KMLC possessed immunological activity, mediated by NK cell activation.

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.