Transmission of human-pet antibiotic resistance via aerosols in pet hospitals of Changchun.

In recent years, aerosols have been recognized as a prominent medium for the transmission of antibiotic-resistant bacteria and genes. Among these, particles with a particle size of 2 µm (PM2.5) can directly penetrate the alveoli. However, the presence of antibiotic-resistant genes in aerosols from pet hospitals and the potential risks posed by antibiotic-resistant bacteria in these aerosols to humans and animals need to be investigated. In this study, cefotaxime-resistant bacteria were collected from 5 representative pet hospitals in Changchun using a Six-Stage Andersen Cascade Impactor. The distribution of bacteria in each stage was analyzed, and bacteria from stage 5 and 6 were isolated and identified. Minimal inhibitory concentrations of isolates against 12 antimicrobials were determined using broth microdilution method. Quantitative Polymerase Chain Reaction was employed to detect resistance genes and mobile genetic elements that could facilitate resistance spread. The results indicated that ARBs were enriched in stage 5 (1.1-2.1 µm) and stage 3 (3.3-4.7 µm) of the sampler. A total of 159 isolates were collected from stage 5 and 6. Among these isolates, the genera Enterococcus spp. (51%), Staphylococcus spp. (19%), and Bacillus spp. (14%) were the most prevalent. The isolates exhibited the highest resistance to tetracycline and the lowest resistance to cefquinome. Furthermore, 56 (73%) isolates were multidrug-resistant. Quantitative PCR revealed the expression of 165 genes in these isolates, with mobile genetic elements showing the highest expression levels. In conclusion, PM2.5 from pet hospitals harbor a significant number of antibiotic-resistant bacteria and carry mobile genetic elements, posing a potential risk for alveolar infections and the dissemination of antibiotic resistance genes.

MR Uniformity Ratio Estimates to Evaluate Ventricular Mechanical Dyssynchrony and Prognosis After ST-Segment Elevation Myocardial Infarction.

BACKGROUND: The impact of left ventricular mechanical dyssynchrony (LVMD) on the long-term prognosis of ST-segment elevation myocardial infarction (STEMI) is unclear. HYPOTHESIS: MR uniformity ratio estimates (URE) can detect LVMD and assess STEMI prognosis. STUDY TYPE: Retrospective analysis of a prospective multicenter registry (EARLY-MYO trial, NCT03768453). POPULATION: Overall, 450 patients (50 females) with first-time STEMI were analyzed, as well as 40 participants without cardiovascular disease as controls. FIELD STRENGTH/SEQUENCE: 3.0-T, balanced steady-state free precession cine and late gadolinium enhancement imaging. ASSESSMENT: MRI data were acquired within 1 week of symptom onset. Major adverse cardiovascular events (MACEs), including cardiovascular death, nonfatal re-infarction, hospitalization for heart failure, and stroke, were the primary clinical outcomes. LVMD was represented by circumferential URE (CURE) and radial URE (RURE) calculated using strain measurements. The patients were grouped according to clinical outcomes or URE values. Patients' clinical characteristics and MR indicators were compared. STATISTICAL TESTS: The Student's t-test, Mann-Whitney U test, chi-square test, Fisher's exact test, receiver operating characteristic curve analysis with area under the curve, Kaplan-Meier analysis, Cox regression, logistic regression, intraclass correlation coefficient, c-index, and integrated discrimination improvement were used. P < 0.05 was considered statistically significant. RESULTS: CURE and RURE were significantly lower in patients with STEMI than in controls. The median follow-up was 60.5 months. Patients with both lower CURE and RURE values experienced a significantly higher incidence of MACEs by 3.525-fold. Both CURE and RURE were independent risk factors for MACEs. The addition of UREs improved diagnostic efficacy and risk stratification based on infarct size and left ventricular ejection fraction (LVEF). The indicators associated with LVMD included male sex, serum biomarkers (peak creatine phosphokinase and cardiac troponin I), infarct size, and LVEF. DATA CONCLUSION: CURE and RURE may be useful to evaluate long-term prognosis after STEMI. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Antimicrobial resistance in E. Coli of animal origin and discovery of a novel ICE mobile element in Northeast China.

BACKGROUND: Multidrug resistance in Enterobacteriaceae including resistance to quinolones is rising worldwide. The development of resistance may lead to the emergence of new transmission mechanisms. In this study, the collection of different E. coli was performed from animals and subjected to subsequent procedures including pulsed-field gel electrophoresis, micro-broth dilution method, polymerase chain reaction. Whole genome sequencing of E. coli C3 was performed to detect the affinity, antimicrobial resistance and major carriers of the isolates. RESULTS: A total of 66 E. coli were isolated and their antibiotic resistance genes, frequency of horizontal transfer and genetic environment of E. coli C3 were determined. The results showed there were both different and same types in PFGE typing, indicating clonal transmission of E. coli among different animals. The detection of antimicrobial resistance and major antibiotic resistance genes and the plasmid transfer results showed that strains from different sources had high levels of resistance to commonly used clinical antibiotics and could be spread horizontally. Whole-genome sequencing discovered a novel ICE mobile element. CONCLUSION: In summary, the antimicrobial resistance of E. coli in northeast China is a serious issue and there is a risk of antimicrobial resistance transmission. Meanwhile, a novel ICE mobile element appeared in the process of antimicrobial resistance formation.

Peak early diastolic strain rate improves prediction of adverse cardiovascular outcomes in patients with ST-elevation myocardial infarction.

BACKGROUND: The prognostic role of diastolic dysfunction measured by the circumferential peak early diastolic strain rate (PEDSR) on ST-elevation myocardial infarction (STEMI) is not completely established. OBJECTIVES: We aimed to investigate the prognostic value of diastolic function by measuring PEDSR within 1 week after STEMI. METHODS: The cardiac magnetic resonance (CMR) pictures of 420 subjects from a clinical registry study (NCT03768453) were analyzed and the composite major adverse cardiac events (MACEs) were followed up. RESULTS: The PEDSR of patients was significantly lower compared with that of control subjects (P < 0.001). Within the median follow-up period of 52 months, PEDSR of patients who experienced MACEs deceased more significantly than that of patients without MACEs (P < 0.001). After adjusting with clinical or CMR indexes, per 0.1/s reduction of PEDSR increased the risks of MACEs to 1.402 or 1.376 fold and the risk of left ventricular (LV) remodeling to 1.503 or 1.369 fold. When PEDSR divided by best cutoff point, significantly higher risk of MACEs (P < 0.001) and more remarkable LV remodeling (P < 0.001) occurred in patients with PEDSR ≤ 0.485/s. Moreover, when adding the PEDSR to the conventional prognostic factors such as LV ejection fraction and infarction size, better prognostic risk classification models were created. Finally, aging, tobacco use, remarkable LV remodeling, and a low LV ejection fraction were factors related with the reduction of PEDSR. CONCLUSIONS: Diastolic dysfunction has an important prognostic effect on patients with STEMI. Measurement of the PEDSR in the acute phase could serve as an effective index to predict the long-term risk of MACEs and cardiac remodeling.

Genetic characterization of MDR genomic elements carrying two aac(6')-aph(2″) genes in feline-derived clinical Enterococcus faecalis isolate.

Multidrug-resistant Enterococcus faecalis (E. faecalis) often cause intestinal infections in cats. The aim of this study was to investigate a multidrug-resistant E. faecalis isolate for plasmidic and chromosomal antimicrobial resistance and their genetic environment. E. faecalis strain ESC1 was obtained from the feces of a cat. Antimicrobial susceptibility testing was carried out using the broth microdilution method. Conjugation experiments were performed using Escherichia coli and Staphylococcus aureus as receptors. Complete sequences of chromosomal DNA and plasmids were generated by whole genome sequencing (WGS) and bioinformatics analysis for the presence of drug resistance genes and mobile elements. Multidrug-resistant E. faecalis ESC1 contained a chromosome and three plasmids. The amino acid at position 80 of the parC gene on the chromosome was mutated from serine to isoleucine, and hence the amino acid mutation at this site led to the resistance of ESC1 strain to fluoroquinolones. Eleven antibiotic resistance genes were located on two plasmids. We identified a novel composite transposon carrying two aminoglycoside resistance genes aac(6')-aph(2″). This study reported the coexistence of a novel 5.4 kb composite transposon and a resistance plasmid with multiple homologous recombination in an isolate of E. faecalis ESC1. This data provides a basis for understanding the genomic signature and antimicrobial resistance mechanisms of this pathogen.

Famotidine Enhances Rifampicin Activity against Acinetobacter baumannii by Affecting OmpA.

The development of novel antibiotic adjuvants is imminent because of the frequent emergence of resistance in Gram-negative bacteria, which severely restricts the efficiency and longevity of commonly used clinical antibiotics. It is reported that famotidine, a clinical inhibitor of gastric acid secretion, enhances the antibacterial activity of rifamycin antibiotics, especially rifampicin, against Gram-negative bacteria and reverses drug resistance. Studies have shown that famotidine disrupts the cell membrane of Acinetobacter baumannii and inhibits the expression of the outer membrane protein ompA gene, while causing a dissipation of the plasma membrane potential, compensatively upregulating the pH gradient and ultimately increasing the accumulation of reactive oxygen species by leading to increased bacterial mortality. In addition, famotidine also inhibited the efflux pump activity and the biofilm formation of A. baumannii. In the Galleria mellonella and mouse infection models, the combination of famotidine and rifampicin increased the survival rate of infected animals and decreased the bacterial load in mouse organs. In conclusion, famotidine has the potential to be a novel rifampicin adjuvant, providing a new option for the treatment of clinical Gram-negative bacterial infections. IMPORTANCE In this study, famotidine was discovered for the first time to have potential as an antibiotic adjuvant, enhancing the antibacterial activity of rifamycin antibiotics against A. baumannii and overcoming the limitations of drug therapy. With the discovery of novel applications for the guanidine-containing medication famotidine, the viability of screening prospective antibiotic adjuvants from guanidine-based molecules was further explored. In addition, famotidine exerts activity by affecting the OmpA protein of the cell membrane, indicating that this protein might be used as a therapeutic drug target to treat A. baumannii infections.

Citric Acid Confers Broad Antibiotic Tolerance through Alteration of Bacterial Metabolism and Oxidative Stress.

Antibiotic tolerance has become an increasingly serious crisis that has seriously threatened global public health. However, little is known about the exogenous factors that can trigger the development of antibiotic tolerance, both in vivo and in vitro. Herein, we found that the addition of citric acid, which is used in many fields, obviously weakened the bactericidal activity of antibiotics against various bacterial pathogens. This mechanistic study shows that citric acid activated the glyoxylate cycle by inhibiting ATP production in bacteria, reduced cell respiration levels, and inhibited the bacterial tricarboxylic acid cycle (TCA cycle). In addition, citric acid reduced the oxidative stress ability of bacteria, which led to an imbalance in the bacterial oxidation-antioxidant system. These effects together induced the bacteria to produce antibiotic tolerance. Surprisingly, the addition of succinic acid and xanthine could reverse the antibiotic tolerance induced by citric acid in vitro and in animal infection models. In conclusion, these findings provide new insights into the potential risks of citric acid usage and the relationship between antibiotic tolerance and bacterial metabolism.

Analysis of an IncR plasmid carried by carbapenem-resistant Klebsiella pneumoniae: A survey of swine Klebsiella pneumoniae in Jilin Province.

OBJECTIVES: This study was conducted in Jilin Province to investigate the mechanism involved in the antibiotic resistance and pathogenicity of Klebsiella pneumoniae. METHODS: Lung samples were collected from large-scale pig farms in Jilin Province. Antimicrobial susceptibility and mouse lethality assays were carried out. K. pneumoniae isolate JP20, with high virulence and antibiotic resistance, was chosen for whole-genome sequencing. The complete sequence of its genome was annotated, and the virulence and antibiotic resistance mechanism were analysed. RESULTS: A total of 32 K. pneumoniae strains were isolated and tested for antibiotic resistance and pathogenicity. Among them, the JP20 strain showed high levels of resistance to all tested antimicrobial agents and strong pathogenicity in mice (lethal dose of 1.35 × 1011 CFU/mL). Sequencing of the multidrug-resistant and highly virulent K. pneumoniae JP20 strain revealed that the antibiotic resistance genes were mainly carried by an IncR plasmid. We speculate that extended-spectrum ß-lactamases and loss of outer membrane porin OmpK36 play an important role in carbapenem antibiotic resistance. This plasmid contains a mosaic structure consisting of a large number of mobile elements. CONCLUSION: Through genome-wide analysis, we found that an lncR plasmid carried by the JP20 strain may have evolved in pig farms, possibly leading to multidrug resistance in the JP20 strain. It is speculated that the antibiotic resistance of K. pneumoniae in pig farms is mainly mediated by mobile elements (insertion sequences, transposons, and plasmids). These data provide a basis for monitoring the antibiotic resistance of K. pneumoniae and lay a foundation for an improved understanding of the genomic characteristics and antibiotic resistance mechanism of K. pneumoniae.

Nomograms referenced by cardiac magnetic resonance in the prediction of cardiac injuries in patients with ST-elevation myocardial infarction.

BACKGROUND: Evaluation of cardiac injuries is essential in patients with ST-elevation myocardial infarction (STEMI). Cardiac magnetic resonance (CMR) has become the gold standard for quantifying cardiac injuries; however, its routine application is limited. A nomogram is a useful tool for prognostic prediction based on the comprehensive utilization of clinical data. We presumed that the nomogram models established using CMR as a reference could precisely predict cardiac injuries. METHODS: This analysis included 584 patients with acute STEMI from a CMR registry study for STEMI (NCT03768453). The patients were divided into training (n = 408) and testing (n = 176) datasets. The least absolute shrinkage and selection operator method and multivariate logistic regression were used to construct nomograms for predicting left ventricular ejection fraction (LVEF) ≤40%, infarction size (IS) ≥ 20% on the LV mass, and microvascular dysfunction. RESULTS: The nomogram for predicting LVEF≤40%, IS≥20%, and microvascular dysfunction comprised 14, 10, and 15 predictors, respectively. With the nomograms, the individual risk probability of developing specific outcomes could be calculated, and the weight of each risk factor was demonstrated. The C-index of the nomograms in the training dataset were 0.901, 0.831, and 0.814, respectively, and were comparable in the testing set, showing good nomogram discrimination and calibration. The decision curve analysis demonstrated good clinical effectiveness. Online calculators were also constructed. CONCLUSIONS: With the CMR results as the reference standard, the established nomograms demonstrated good effectiveness in predicting cardiac injuries after STEMI and could provide physicians with a new option for individual risk stratification.

Antibiotic synergist OM19r reverses aminoglycoside resistance in multidrug-resistant Escherichia coli.

Introduction: The continued emergence and spread of multidrug-resistant (MDR) bacterial pathogens require a new strategy to improve the efficacy of existing antibiotics. Proline-rich antimicrobial peptides (PrAMPs) could also be used as antibacterial synergists due to their unique mechanism of action. Methods: Utilizing a series of experiments on membrane permeability, In vitro protein synthesis, In vitro transcription and mRNA translation, to further elucidate the synergistic mechanism of OM19r combined with gentamicin. Results: A proline-rich antimicrobial peptide OM19r was identified in this study and its efficacy against Escherichia coli B2 (E. coli B2) was evaluated on multiple aspects. OM19r increased antibacterial activity of gentamicin against multidrug-resistance E. coli B2 by 64 folds, when used in combination with aminoglycoside antibiotics. Mechanistically, OM19r induced change of inner membrane permeability and inhibited translational elongation of protein synthesis by entering to E. coli B2 via intimal transporter SbmA. OM19r also facilitated the accumulation of intracellular reactive oxygen species (ROS). In animal models, OM19r significantly improved the efficacy of gentamicin against E. coli B2. Discussion: Our study reveals that OM19r combined with GEN had a strong synergistic inhibitory effect against multi-drug resistant E. coli B2. OM19r and GEN inhibited translation elongation and initiation, respectively, and ultimately affected the normal protein synthesis of bacteria. These findings provide a potential therapeutic option against multidrug-resistant E. coli.

Transcriptomic Changes and satP Gene Function Analysis in Pasteurella multocida with Different Levels of Resistance to Enrofloxacin.

Pasteurella multocida (Pm) is one of the major pathogens of bovine respiratory disease (BRD), which can develop drug resistance to many of the commonly used antibiotics. Our earlier research group found that with clinical use of enrofloxacin, Pm was more likely to develop drug resistance to enrofloxacin. In order to better understand the resistance mechanism of Pm to enrofloxacin, we isolated PmS and PmR strains with the same PFGE typing in vitro, and artificially induced PmR to obtain the highly resistant phenotype, PmHR. Then transcriptome sequencing of clinically isolated sensitive strains, resistant and highly drug-resistant strains, treated with enrofloxacin at sub-inhibitory concentrations, were performed. The satP gene, of which the expression changed significantly with the increase in drug resistance, was screened. In order to further confirm the function of this gene, we constructed a satP deletion (ΔPm) strain using suicide vector plasmid pRE112, and constructed the C-Pm strain using pBBR1-MCS, and further analyzed the function of the satP gene. Through a continuously induced resistance test, it was found that the resistance rate of ΔPm was obviously lower than that of Pm in vitro. MDK99, agar diffusion and mutation frequency experiments showed significantly lower tolerance of ΔPm than the wild-type strains. The pathogenicity of ΔPm and Pm was measured by an acute pathogenicity test in mice, and it was found that the pathogenicity of ΔPm was reduced by about 400 times. Therefore, this study found that the satP gene was related to the tolerance and pathogenicity of Pm, and may be used as a target of enrofloxacin synergistic effect.

Immunization effect of recombinant Lactobacillus casei displaying Aeromonas veronii Aha1 with an LTB adjuvant in carp.

Aeromonas veronii is an important aquatic zoonotic, which elicits a range of diseases, such as haemorrhagic septicemia. To develop an effective oral vaccine against Aeromonas veronii infection in carp, the Aeromonas veronii adhesion (Aha1) gene was used as a target molecule to attach to intestinal epithelial cells. Two anchored recombinant. Lactic acid bacteria strains (LC-pPG-Aha1 1038 bp and LC-pPG-Aha1-LTB 1383 bp) were constructed by fusing them with the E. coli intolerant enterotoxin B subunit (LTB) gene and using Lactobacillus casei as antigen delivery vector to evaluate immune effects of these in carp. Western blotting and immunofluorescence were used to confirm that protein expression was successful. Additionally, levels of specific IgM in serum and the activities of ACP, AKP, SOD, LYS, C3, C4, and lectin enzymes-were assessed. Cytokines IL-10, IL-1ß, TNF-α, IgZ1, and IgZ2 were measured in the liver, spleen, kidney, intestines, and gills tissue by qRT-PCR, which showed an increasing trend compared with the control group (P < 0.05). A colonization assay showed that the two L. casei recombinants colonized the middle and hind intestines of immunized fish. When immunized carp were experimentally challenged with Aeromonas veronii the relative percentage protection of LC-pPG-Aha1 was 53.57%, and LC-pPG-Aha1-LTB was 60.71%. In conclusion, these results demonstrate that Aha1 is a promising candidate antigen when it is displayed on lactic acid bacteria (Lc-pPG-Aha1 and Lc-pPG-Aha1-LTB) seems promising for a mucosal therapeutic approach. We plan to investigate the molecular mechanism of the L. casei recombinant in regulating the intestinal tissue of carp in future studies.

Catheter Ablation of a Right Atrial Free Wall Diverticulum-Related Accessory Pathway Masquerading as a Septal One.

Epicardial right-sided accessory pathway (AP) ablation is challenging. In rare cases, the atrial insertion of the AP is related to unconventional sites and associated with repeated and complex ablation procedures. In this study, we report a case of right free wall diverticulum-related AP with a distinct surface electrocardiogram (ECG).A 45-year-old male patient with repetitive palpitation for 2 years was referred for an electrophysiological (EP) study. His resting surface ECG showed manifest ventricular preexcitation with a negative delta wave and a "QS" wave in precordial lead V1, which is most consistent with right mid-septal AP.In the EP study, orthodromic atrioventricular reentrant tachycardia could be easily induced with the earliest atrial activation at the right atrium (RA) free wall, but the AP failed to be blocked by ablating the earliest activation on the tricuspid annulus edge. An epicardial free wall AP was then suspected.Inadvertent catheter manipulation into a narrow and long chamber was noted on the RA geometry. Angiography via contrast injection from the ablation tip revealed a diverticulum extending from the RA to the right ventricle side. The epicardial AP was suspected to be related to this diverticulum. The earliest atrial activation, as shown through a detailed activation mapping, was located at the entrance of the diverticulum. Subsequent ablation at the atrial insertion site successfully abolished the antegrade and retrograde AP conduction without any complication. A postprocedural computed tomography scan proved the presence of a free wall diverticulum associated with the right atrial appendage.A diverticulum-related AP at RA free wall might exhibit surface ECGs mimicking that of an AP at the RA septum. The approach targeting the atrial insertion of the epicardial AP is effective and might be facilitated by clarification of structural malformations prior to the ablation procedure.

The predictive value of YAP-1 and POU2F3 for the efficacy of immuno-chemotherapy in extensive-stage SCLC patients.

INTRODUCTION: Recently, several clinical trials of immunotherapy for extensive-stage small-cell lung cancer (ES-SCLC) have shown limited benefits because of unselected patients. Thus, we aimed to explore whether YES-associated protein 1 (YAP-1) and POU domain class 2 transcription factor 3 (POU2F3) could identify SCLC patients with durable benefits from immunotherapy as potential biomarkers. METHODS: We performed IHC of YAP-1 and POU2F3, and RNA-seq on tissues of ES- SCLC patients. An open-source plugin based on IHC-profiler was conducted to calculate the expression levels of YAP-1 and POU2F3. RESULTS: Patients with ES-SCLC were retrospectively investigated in the Guangdong Provincial People's Hospital from January 2018 to July 2021, and 21 patients whoever received atezolizumab plus etoposide/carboplatin (ECT) regimen also had tissue samples reachable. The median IHC-score of YAP-1 in responders (CR/PR patients) was significantly lower than in nonresponders (SD/PD patients) at 13.97 (95% CI: 8.97-16.30) versus 23.72 (95% CI: 8.13-75.40). The IHC-score of YAP-1 and PFS showed a negative correlation by Spearman (r=-0.496). However, POU2F3 did not show a correlation with efficacy. Besides, patients with YAP-1 high expression had IL6, MYCN, and MYCT1 upregulated, while analysis of immune cell infiltration only showed that M0 macrophages were significantly higher. CONCLUSIONS: The expression of YAP-1 negatively correlated with the efficacy of ECT in ES-SCLC patients while POU2F3 did not reveal the predictive value. However, prospective investigations with a large sample size are needed.

An Integrated Algorithm for Differentiating Hypertrophic Cardiomyopathy From Hypertensive Heart Disease.

BACKGROUND: Differentiating hypertrophic cardiomyopathy (HCM) from hypertensive heart disease (HHD) is challenging. PURPOSE: To identify differences between HCM and HHD on a patient basis using MRI. STUDY TYPE: Retrospective. POPULATION: A total of 219 subjects, 148 in phase I (baseline data and algorithm development: 75 HCM, 33 HHD, and 40 controls) and 71 in phase II (algorithm validation: 56 HCM and 15 HHD). FIELD STRENGTH/SEQUENCE: Contrast-enhanced inversion-prepared gradient echo and cine-balanced steady-state free precession sequences at 3.0 T. ASSESSMENT: MRI parameters assessed included left ventricular (LV) ejection fraction (LVEF), LV end systolic and end diastolic volumes (LVESV and LVEDV), mean maximum LV wall thickness (MLVWT), LV global longitudinal and circumferential strain (GRS, GLS, and GCS), and native T1. Parameters, which were significantly different between HCM and HHD in univariable analysis, were entered into a principal component analysis (PCA). The selected components were then introduced into a multivariable regression analysis to model an integrated algorithm (IntA) for screening the two disorders. IntA performance was assessed for patients with and without LGE in phase I (development) and phase II (validation). STATISTICAL TESTS: Univariable regression, PCA, receiver operating curve (ROC) analysis. A P value <0.05 was considered statistically significant. RESULTS: Derived IntA formulation included LVEF, LVESV, LVEDV, MLVWT, and GCS. In LGE-positive subjects in phase l, the cutoff point of IntA ≥81 indicated HCM (83% sensitivity and 91% specificity), with the area under the ROC curve (AUC) of 0.900. In LGE-negative subjects, a higher possibility of HCM was indicated by a cutoff point of IntA ≥84 (100% sensitivity and 82% specificity), with an AUC of 0.947. Validation of IntA in phase II resulted in an AUC of 0.846 in LGE-negative subjects and 0.857 in LGE-positive subjects. DATA CONCLUSION: A per-patient-based IntA algorithm for differentiating HCM and HHD was generated from MRI data and incorporated FT, LGE and morphologic parameters. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2.

Antibacterial activity and cytotoxicity of a novel bacteriocin isolated from Pseudomonas sp. strain 166.

Pseudomonas sp. strain 166 was isolated from soil samples from Changbai Mountains. A novel bacteriocin PA166 from Pseudomonas sp. 166 was purified using ammonium sulfate, dextran gel chromatography column and Q-Sepharose column chromatography successively. The molecular mass of bacteriocin PA166 was found to be 49.38 kDa by SDS-PAGE and liquid chromatography-mass spectrometry (MS)/MS. Bacteriocin PA166 showed stability at a wide range of pH (2-10), and thermal stability (40, 60, 80 and 100°C). The bacteriocin PA166 antimicrobial activity was slightly inhibited by Ca2+ , K+ and Mg2+ . The minimum bactericidal concentrations of bacteriocin PA166 against five Pasteurella multocida strains ranged from 2 to 8 µg ml-1 . Bacteriocin PA166 showed low cytotoxicity and a higher treatment index (TI = 82.51). Fluorescence spectroscopy indicated that bacteriocin PA166 destroyed the cell membrane to exert antimicrobial activity. In summary, bacteriocin PA166 had strong antibacterial activity, high TI and low toxicity, and hence could serve as a potential clinical therapeutic drug.

A Systemic Mapping Approach for Right and Left Parahisian Ventricular Arrhythmias Ablation.

Background: Catheter ablation for parahisian ventricular arrhythmias (PHVA) is technically challenging and associated with increased risks of atrioventricular block (AVB). We developed a systemic mapping approach to improve the efficacy and safety of PHVA ablation. Methods: Forty-three patients (29 males; average age 65.8 ± 10.5 years) with PHVAs were enrolled. A systemic mapping approach comprising differential electrocardiogram, sequential mapping, and ablation beneath/above the septal leaflet of the tricuspid valve (SLTV) and at the neighboring/contralateral regions (the aortic root and sub-aortic valve region) was applied for PHVA. The effectiveness and safety of this approach was evaluated at 1 year's follow-up. Results: Sequential ablation beneath the SLTV (B-SLTV) succeeded in 24 (66.7 %) of 36 with right PHVA and ablation above the SLTV succeeded in 6 of the remaining 12 with failed B-SLTV ablation. Target-His bundle (HB) distance > 4.5 mm significantly predicted successful right PHVA ablation (OR 1.703; 95% CI 1.084-2.676, P = 0.02). "Seeming" right PHVA by electrocardiogram in 4 and apparent left PHVA in 3 was successfully ablated at the sub-aortic parahisian region. At 1 year's follow-up, 27 (75%) of 36 patients with right PHVA and 6 (85.7%) of 7 patients with left PHVA were free of PHVA recurrence off anti-arrhythmic drugs. The total success rate was 76.7% by using the systemic mapping approach for PHVA. One patient with A-SLTV ablation underwent pacemaker implantation due to complete AVB. Conclusions: The systemic mapping approach was effective and safe for treating PHVA. The target-HB distance was a significant predictor for right PHVA ablation.

Isolation and partial characterization of a novel bacteriocin from Pseudomonas azotoformans with antimicrobial activity against Pasterella multocida.

In this study, a bacteriocin PA996 isolated from Pseudomonas azotoformans (P. azotoformans) was purified to homogeneity by ammonium sulphate precipitation and SP-Sepharose column chromatography. P. azotoformans began to grow at 6 h, reached exponential phase at 12-18 h. Bacteriocin PA996 was produced at 18 h and reached a maximum level of 2400 AU/mL. The molecular mass of purified bacteriocin PA996 was estimated by SDS-PAGE and its molecular mass was approximately 50 kDa. By screening in vitro, the bacteriocin PA996 showed an antimicrobial activity against Pasteurella multocida (P. multocida). The bacteriocin PA996 showed antibacterial activity in the range of pH2-10 and it was heat labile. The inhibitory activities were diminished after treatment with proteinase K, trypsin and papain, respectively, while catalase treatment was ineffective. The minimal inhibitory concentration (MIC) and bactericidal kinetics curves showed that the bacteriocin PA996 had a good inhibitory ability against P. multocida. Our data indicate that bacteriocin PA996 could inhibit the growth of P. maltocida and it may have the potential to apply as an alternative therapeutic drug.

Macro-reentrant atrial tachycardia after tricuspid or mitral valve surgery: is there difference in electrophysiological characteristics and effectiveness of catheter ablation?

BACKGROUND: Macro-reentrant atrial tachycardias (MATs) are a common complication after cardiac valve surgery. The MAT types and the effectiveness of MAT ablation might differ after different valve surgery. Data comparing the electrophysiological characteristics and the ablation results of MAT post-tricuspid or mitral valve surgery are limited. METHODS: Forty-eight patients (29 males, age 56.1 ± 13.3 years) with MAT after valve surgery were assigned to tricuspid valve (TV) group (n = 18) and mitral valve (MV) group (n = 30). MATs were mapped and ablated guided by a three-dimensional navigation system. The one-year clinical effectiveness was compared in two groups. RESULTS: Nineteen MATs were documented in TV group, including 16 cavo-tricuspid isthmus (CTI)-dependent AFL and 3 other MATs at right atrial (RA) free wall, RA septum and left atrial (LA) roof. Thirty-nine MATs were identified in MV group, including15 CTI-dependent AFL, 8 RA free wall scar-related, 2 RA septum scar-related, 8 peri-mitral flutter, 3 LA roof-dependent, 2 LA anterior scar-related, and 1 right pulmonary vein-related MAT. Compared with TV group, MV group had significantly lower prevalence of CTI-dependent AFL (38.5% vs. 84.2%), higher prevalence of left atrial MAT (35.9 vs.5.3%) and higher proportion of patients with left atrial MAT (40 vs. 5.6%), P = 0.02, 0.01 and 0.01, respectively. The acute success rate of MAT ablation (100 vs. 93.3%) and the one-year freedom from atrial tachy-arrhythmias (72.2 vs. 76.5%) was comparable in TV and MV group. No predictor for recurrence was identified. CONCLUSION: Although the types of MATs differed significantly in patients with prior TV or MV surgery, the acute and mid-term effectiveness of MAT ablation was comparable in two groups. TRIAL REGISTRATION: This study was registered as a part of EARLY-MYO-AF clinical trial at the website ClinicalTrials. gov (NCT04512222).

Real-World Prevalence of Direct Oral Anticoagulant Off-Label Doses in Atrial Fibrillation: An Epidemiological Meta-Analysis.

Background: The use of direct oral anticoagulant (DOAC) off-label doses in atrial fibrillation (AF) patients may result in poor clinical outcomes. However, the true prevalence remains scarce. This study aims at estimating the prevalence of DOAC off-label doses in AF patients. Methods: Databases of MEDLINE, EMBASE, and COCHRANE were searched from inception through February 2020 for real-world studies that reported the off-label definition and prevalence data of AF patients using DOACs. The primacy outcomes were the overall prevalence of DOAC off-label doses and the corresponding underdose and overdose. The random-effects model was used for data synthesis. Variations on individual DOAC and different regions were examined by subgroup analyses. Results: A total of 23 studies involving 162,474 AF patients were finally included. The overall prevalence of DOAC off-label doses was 24% (95% CI, 19-28%), with 18% for dabigatran, 27% for rivaroxaban, 24% for apixaban, and 26% for edoxaban. The prevalence of underdosed DOACs was 20% (95% CI, 16-24%) with significant difference among individual anticoagulants (13% for dabigatran, 22% for rivaroxaban, 22% for apixaban, and 18% for edoxaban; P interaction =0.02). The prevalence of overdosed DOACs was 5% (95% CI, 3-7%), with the lowest prevalence observed in apixaban (2%). Subgroup analyses by regions demonstrated that the prevalence of DOAC off-label doses was higher in Asia (32%) than in North America (14%) and in Europe (22%), with underdose being predominant. Regardless of different regions, the prevalence of overdose was relatively low (4-6%). Conclusion: This study provides an estimation of DOAC off-label doses in the real-world setting. The prevalence rate of DOAC off-label doses in AF patients was relatively high, with underdose being predominant. Clinicians in Asia preferred to prescribe underdose of DOACs to AF patients. More evidence about the appropriateness of DOAC off-label doses in AF patients is urgently needed. Education programs concerning the appropriate prescription of DOACs within the drug labels and accepted guidelines are necessary to DOAC prescribers to ensure the safety and effectiveness of anticoagulation therapy for patients with AF.