The two-component system TtrRS boosts Vibrio parahaemolyticus colonization by exploiting sulfur compounds in host gut.

One of the greatest challenges encountered by enteric pathogens is responding to rapid changes of nutrient availability in host. However, the mechanisms by which pathogens sense gastrointestinal signals and exploit available host nutrients for proliferation remain largely unknown. Here, we identified a two-component system in Vibrio parahaemolyticus, TtrRS, which senses environmental tetrathionate and subsequently activates the transcription of the ttrRS-ttrBCA-tsdBA gene cluster to promote V. parahaemolyticus colonization of adult mice. We demonstrated that TsdBA confers the ability of thiosulfate oxidation to produce tetrathionate which is sensed by TtrRS. TtrRS autoregulates and directly activates the transcription of the ttrBCA and tsdBA gene clusters. Activated TtrBCA promotes bacterial growth under micro-aerobic conditions by inducing the reduction of both tetrathionate and thiosulfate. TtrBCA and TsdBA activation by TtrRS is important for V. parahaemolyticus to colonize adult mice. Therefore, TtrRS and their target genes constitute a tetrathionate-responsive genetic circuit to exploit the host available sulfur compounds, which further contributes to the intestinal colonization of V. parahaemolyticus.

The association between paced left ventricular activation time and cardiac reverse remodeling in heart failure patients with left bundle branch block.

INTRODUCTION: The association between paced LVAT and cardiac structure and function at baseline, as well as whether longer LVAT is associated with worse cardiac reverse remodeling in patients with heart failure (HF) and left bundle branch block (LBBB) has not been well investigated. The purpose of this study is to investigate the association between paced LVAT and baseline echocardiographic parameters and cardiac reverse remodeling at follow-up. METHODS: Patients with HF and LBBB receiving successful left bundle branch pacing (LBBP) from June 2018 to April 2023 were enrolled and grouped based on paced LVAT. NT-proBNP and echocardiographic parameters were recorded during routine follow-up. The relationships between paced LVAT and echocardiographic parameters at baseline and follow-up were analyzed. RESULTS: Eighty-three patients were enrolled (48 males, aged 65 ± 9.8, mean LVEF 32.1 ± 7.5%, mean LVEDD 63.0 ± 8.5 mm, median NT-proBNP 1057[513-3158] pg/mL). The paced QRSd was significantly decreased (177 ± 17.9 vs. 134 ± 18.5, p < .001) and median paced LVAT was 80[72-88] ms. After a median follow-up of 12[9-29] months, LVEF increased to 52.1 ± 11.2%, LVEDD decreased to 52.6 ± 8.8 mm, and NT-proBNP decreased to 215[73-532]pg/mL. Patients were grouped based on paced LVAT: LVAT < 80 ms (n = 39); 80 ≤ LVAT < 90 ms (n = 24); LVAT ≥ 90 ms (n = 20). Patients with longer LVAT had larger LVEDD and lower LVEF (LVEDDbaseline: p < .001; LVEFbaseline: p = .001). The difference in LVEF6M was statistically significant among groups (p < .001) and patients with longer LVAT had lower LVEF6M, while the difference in LVEF1Y was not seen (p = .090). There was no significant correlation between ΔLVEF6M-baseline, ΔLVEF1Y-6M and LVAT respectively (ΔLVEF6M-baseline: p = .261, r = -.126; ΔLVEF1Y-6M: p = .085, r = .218). CONCLUSION: Long paced LVAT was associated with worse echocardiographic parameters at baseline, but did not affect the cardiac reverse remodeling in patients with HF and LBBB. Those with longer LVAT required longer time to recover.

CD-MOF-1 Growth on Polysaccharide Gels through Only C2-OH/C3-OH or C5-O/C6-OH Group Formed Four-Coordinated K+ Ions for Developing Porous Biogels.

The γ-cyclodextrin (γ-CD) metal-organic frameworks (CD-MOF-1) consist of γ-CD and potassium (K+) ions through coordinating an eight-coordinated K+ ion with two C5-linked oxygen and C6-linked hydroxyl (C5-O/C6-OH) groups in the primary faces of adjacent γ-CD units and two C2- and C3-linked hydroxyl (C2-OH/C3-OH) groups in the secondary faces. Herein, we found polysaccharide gels with only C2-OH/C3-OH or C5-O/C6-OH groups in pyranoid rings can form four-coordinated K+ ions and then coordinate γ-CD in a KOH solution for CD-MOF-1 growth. Exposure of C2-OH/C3-OH or C5-O/C6-OH groups in polysaccharide gels is important to form active four-coordinated K+ ions. Mechanism supporting this work is that four-coordinated K+ ion sites are first formed after coordinating C2-OH/C3-OH groups in pectin and then coordinating C5-O/C6-OH groups in the primary faces of γ-CD units. Alternatively, four-coordinated K+ ions with C5-O/C6-OH groups in chitosan can coordinate the C2-OH/C3-OH groups in the secondary faces of γ-CD units. Mechanism of CD-MOF-1 growing on pectin and chitosan gels through the proposed four-coordinated K+ ions is also universally applicable to other polysaccharide gels with similar C2-OH/C3-OH or C5-O/C6-OH groups such as alginate gel. Based on this mechanism, we developed pectin and chitosan gel-based CD-MOF-1 composites and exemplified applications of them in antibacterial and organic dye removal. To help future research and applications of this mechanism, we share our theoretical assumption for further investigations that any matrices with an ortho-hydroxyl carbon chain or ortho-hydroxyl ether structures may form four-coordinated K+ ions for CD-MOF-1 growth. The proposed mechanism will broaden the development of novel CD-MOF-1 composites in various fields.

Predictors of functional mitral regurgitation improvement in patients with left bundle branch block treated with left bundle branch area pacing.

BACKGROUND: Functional mitral regurgitation (FMR) and its severity are associated with adverse outcomes in heart failure patients. This study aims to analyze the predictors of FMR improvement after successful left bundle branch area pacing (LBBAP) in patients with LVEF < 50% and complete left bundle branch block (CLBBB). METHODS: Consecutive patients with LVEF < 50% and CLBBB who underwent successful LBBAP from July 2018 to July 2023 were retrospectively identified. Significant MR was defined as regurgitation of moderate severity or greater. Patients with significant FMR were included in the analysis. FMR improvement (FMRI) was defined as a reduction of at least one grade in regurgitation severity compared to baseline at 3 months or longer follow-up. RESULTS: Among the 81 identified patients, 42 patients with significant FMR preoperatively were included. After LBBAP, QRS duration significantly shortened from 170.6 ± 18.8 ms to 114.5 ± 20.2 ms (p < .001). Significant FMR improves in approximately 76.2%, and the patients were divided into an FMRI group (n = 32) and a non-FMRI group (n = 10). Univariate analysis showed that absence of persistent atrial fibrillation, typical CLBBB, and left atrium diameter at baseline were associated with improvement of FMR after LBBAP. Of these variables, only absence of persistent atrial fibrillation remains an independent predictor in the multivariate model (OR 12.436, p = .009). CONCLUSION: LBBAP is able to improve FMR in heart failure patients who had CLBBB with LVEF < 50%. Meanwhile, the absence of persistent atrial fibrillation is an independent predictor of FMR improvement.

Novel algorithm for diagnosis of Arrhythmogenic cardiomyopathy and dilated cardiomyopathy: Key gene expression profiling using machine learning.

BACKGROUND: It is difficult to distinguish between arrhythmogenic cardiomyopathy (ACM) and dilated cardiomyopathy (DCM) because of their similar clinical manifestations. This study aimed to develop a novel diagnostic algorithm for distinguishing ACM from DCM. METHODS: Two public datasets containing human ACM and DCM myocardial samples were used. Consensus clustering, non-negative matrix factorization and principal component analysis were applied. Weighted gene co-expression network analysis and machine learning methods, including random forest and the least absolute shrinkage and selection operator, were used to identify candidate genes. Receiver operating characteristic curves and nomograms were performed to estimate diagnostic efficacy, and Spearman's correlation analysis was used to assess the correlation between candidate genes and cardiac function indices. RESULTS: Both ACM and DCM showed highly similar gene expression patterns in the clustering analyses. Hub gene modules associated with cardiomyopathy were obtained using weighted gene co-expression network analysis. Thirteen candidate genes were selected using machine learning algorithms, and their combination showed a high diagnostic value (area under the ROC curve = 0.86) for distinguishing ACM from DCM. In addition, TATA-box binding protein associated factor 15 showed a negative correlation with cardiac index (R = -0.54, p = 0.0054) and left ventricular ejection fraction (R = -0.48, p = 0.0015). CONCLUSIONS: Our study revealed an effective diagnostic model with key gene signatures, which indicates a potential tool to differentiate between ACM and DCM in clinical practice. In addition, we identified several genes that are highly related to cardiac function, which may contribute to our understanding of ACM and DCM.

Effects of environmental pollutant benzop[α]yrene on the innate immunity of Scylla paramamosain and its mechanism.

Benzo[α]pyrene (BaP), a polycyclic aromatic hydrocarbon, is present in the aquatic environment and may be harmful to aquatic animals. We exposed the mud crab Scylla paramamosain to BaP for 7 days, the of superoxide dismutase (SOD), catalase (CAT), phenoloxidase (PO), lysozyme (LZM), glutathione (GSH), glutathione-S-transferase (GST), and acid phosphatase (ACP) activities in the hemolymph of mud crab were reduced. Additionally, the reactive oxygen species content was increased in mud crabs after exposed to BaP. When BaP concentration was increased, the total hemocyte count (THC), the survival rate of hemocytes and their proliferation were decreased. Histopathology analysis revealed damaged hepatopancreas cells, which indicating that BaP exposure is cytotoxic to crab hemocytes. However, the degree of DNA damage did not worsen with increasing BaP concentration. The expression levels of p53, MCM7, Caspase-3, and Myosin were changed with increasing concentration of BaP, which indicated that BaP exposure may affect apoptosis and phagocytosis in mud crabs. As BaP concentration was increased, the apoptosis rate of hemocytes was increased and the phagocytosis was decreased. These results confirmed that BaP exposure inhibited the innate immune response of mud crabs. A possible explanation for this effect is that BaP reduces the antioxidant enzyme activity and increases the reactive oxygen species content in mud crabs, thereby oxidizing and damaging hemocytes, which stimulates phagocytosis and apoptosis and negatively affects the innate immunity of S. paramamosain.

The effect of reactive oxygen species (ROS) in immunity and WSSV infection of Scylla paramamosain.

Reactive oxygen species (ROS) are typically regarded as being generated by the cellular respiratory chain or by cells under pathological damage, which play a crucial role as signaling molecules in promoting hemocytes circulation and normal cellular physiological functions. In this study, the antioxidant N-acetylcysteine (NAC) was used to reduce ROS in vivo and in vitro, which to analyze the effect of ROS on innate immunity and viral infection of mud crab. The total hemocyte count (THC), phenoloxidase (PO), superoxide dismutase (SOD) activity, immune-relative genes were analyzed, respectively. Moreover, the effect of ROS on WSSV infection was analyzed by THC and hemocytes apoptosis. The data showed that NAC could effectively remove and inhibit intracellular ROS. The THC of NAC group was reduced at 12 h and 24 h compared with that of control. And the inhibition of ROS by NAC could increase the SOD activity with control group, while increased the PO activity caused by early WSSV infection. And NAC could up-regulate the expression of MCM7, JAK, TLR and proPO significantly, while down-regulate the expression of Astakine, proPO, caspase and p53. Similarly, NAC could inhibit WSSV-induced apoptosis of S. paramamosain hemocytes. The data illustrated that ROS participates in the interaction between hemocytes and virus infection by regulating innate immunity. Especially, after NAC inhibited ROS, the expression of hemocytes proliferation gene Astakine was also inhibited, which may indicate that ROS is related to the process of hemocytes proliferation. The data will show a preliminary exploration on the regulatory role of ROS in crustacean immune system.

Left Bundle Branch Pacing for Bradycardia in Non-obstructive Hypertrophic Cardiomyopathy Patients: Feasibility, Safety, and Effect.

PURPOSE: Left bundle branch pacing (LBBP) is as an innovative physiological pacing approach. The research on LBBP in non-obstructive hypertrophic cardiomyopathy (NOHCM) patients is scarce. This study aimed to assess the feasibility, safety, and effect of LBBP in bradycardia NOHCM patients with permanent pacemaker (PPM) implantation indication. METHODS: Thirteen consecutive patients with NOHCM who received LBBP were retrospectively enrolled as a hypertrophic cardiomyopathy (HCM) group. Following 1:3 matching, 39 patients without HCM were randomly matched as a control group. Echocardiographic index and pacing parameters were collected. RESULTS: The successful LBBP was achieved in 96.2% of all cases (50/52), and the success rate of the HCM group was 92.3% (12/13). In the HCM group, the paced QRS duration (from the pacing stimulus to QRS end) was 145.6±20.8 ms. The stimulus to left ventricular activation time (s-LVAT) was 87.4±15.2 ms. In the control group, the paced QRS duration was 139.4±17.2 ms, and the s-LVAT was 79.9±14.1 ms. During the implantation, R-wave sensing and the pacing threshold of the HCM group were significantly higher than the control group (20.2±10.5 vs 12.5±5.9 mV, P < 0.05; 0.8±0.3 vs 0.6±0.2V/0.4 ms, P < 0.05). In addition, the fluoroscopic duration and procedural duration were longer in the HCM group (14.8±8.3 vs 10.3±6.6min, P = 0.07; 131.8±50.5 vs 101.4±41.6 min, P < 0.05). The lead insertion depth was 15±2 mm in the HCM group, and no procedure-related complications occurred. During the 12-month follow-up, pacing parameters remained stable and were of no significance in the two groups. The cardiac function did not deteriorate, and the left ventricular outflow tract gradient (LVOTG) did not increase in the follow-up. CONCLUSION: LBBP might be feasible and safe for NOHCM patients with conventional bradycardia pacing indication, and there is no deterioration in cardiac function and LVOTG of patients with NOHCM.

Dietary quercetin protects Cherax quadricarinatus against white spot syndrome virus infection.

Quercetin is a plant flavonoid with a molecular formula C15H10O7. It has antioxidant, anti-inflammatory, antibacterial, and anti-apoptotic effects in animals. We used red claw crayfish (Cherax quadricarinatus) infected with white spot syndrome virus (WSSV) to investigate quercetin's effects on innate immunity of crustaceans. Quercetin supplementation significantly reduced the mortality of crayfish caused by WSSV infection and the number of VP28 copies in WSSV-infected crayfish. Quantitative real-time PCR analysis showed that dietary quercetin supplementation increased the expression of immune-related genes, like JAK, STAT and ALF. Quercetin supplementation affected the activity of six immune-related enzymes and increased the total number of hemocytes in crayfish. It also significantly reduced the rate of hemocyte apoptosis in both WSSV-infected and uninfected crayfish. These results demonstrate the potential for commercial use of quercetin for the prevention of WSSV disease in crustaceans.

Coumarin protects Cherax quadricarinatus (red claw crayfish) against white spot syndrome virus infection.

Coumarin is a natural compound from plants with the molecular formula C9H6O2. Cherax quadricarinatus (red claw crayfish) is an aquaculture species exhibiting high economic efficiency and quality that is mainly distributed and cultivated in the southeast provinces in China. In order to identify an effective herbal immunopotentiator against white spot syndrome virus (WSSV) infection, this study examined the effect of coumarin as a feed additive in protecting C. quadricarinatus against WSSV infection. The expression of immune-related genes and WSSV copies were analyzed by Q-PCR. Challenge experiments were conducted to analyze the survival rate and determine the optimal concentration of coumarin. The Phenoloxidase activity (PO), Acid phosphatase (ACP) and superoxide dismutase activity (SOD) activity and lysozyme activity were also analyzed. Total hemocyte count (THC) and apoptosis rate were determined by flow cytometry. The WSSV challenge results showed that 40 mg/kg coumarin reduced the mortality of C. quadricarinatus and delayed the WSSV infection process. Further investigation showed that coumarin treatment had a positive effect on the important immunity-related parameters THC, ACP activity, SOD activity, LZM and PO activity. Coumarin up-regulated the expression of proPO, JAK, STAT, ALF, Hsp70 and down-regulated the expression of caspase at the mRNA level. After WSSV infection, the hemocyte apoptosis rate was lower in the 40 mg/kg coumarin + WSSV group compared with the WSSV only group. These data illustrate that coumarin enhances innate immunity in C. quadricarinatus and exhibits a protective effect against WSSV infection by reducing the number of WSSV copies and slowing the process of infection, which provides a potential theoretical basis for studies of coumarin as a new aquatic feed additive in crustacean aquaculture.

Dietary glycerol monolaurate protects Cherax quadricarinatus against white spot syndrome virus infection.

Glycerol monolaurate (GML), one of the medium-chain fatty acid esters, is often used as an emulsifier or preservative. Its biological functions include antibacterial and antiviral activities. In this study, we examined the effects of dietary GML on the resistance of the red claw crayfish to WSSV infection. Crayfish fed with 4 g/kg GML showed higher survival rate and lower WSSV copy numbers than the control after WSSV infection. A RT-qPCR analysis showed that GML supplementation enhanced the expression of immune-related genes, especially JAK and caspase. Our data indicate that GML affects the immune parameters of crayfish, including the total hemocyte counts and phenoloxidase, acid phosphatase, superoxide dismutase, lysozyme, and peroxidase activities. After treatment with GML, the apoptosis of hemocytes increased significantly in both WSSV-infected and uninfected crayfish. In summary, GML reduced the mortality of WSSV-infected crayfish, perhaps by modulating the innate immunity of the crayfish. Our study shows that GML can be used to induce the innate immunity and enhance the immune protection of the red claw crayfish against WSSV infection, either therapeutically or as a preventive measure.

Two homologous Salmonella serogroup C1-specific genes are required for flagellar motility and cell invasion.

BACKGROUND: Salmonella is a major bacterial pathogen associated with a large number of outbreaks of foodborne diseases. Many highly virulent serovars that cause human illness belong to Salmonella serogroup C1, and Salmonella ser. Choleraesuis is a prominent cause of invasive infections in Asia. Comparative genomic analysis in our previous study showed that two homologous genes, SC0368 and SC0595 in Salmonella ser. Choleraesuis were unique to serogroup C1. In this study, two single-deletion mutants (Δ0368 and Δ0595) and one double-deletion mutant (Δ0368Δ0595) were constructed based on the genome. All these mutants and the wild-type strain were subjected to RNA-Seq analysis to reveal functional relationships of the two serogroup C1-specific genes. RESULTS: Data from RNA-Seq indicated that deletion of SC0368 resulted in defects in motility through repression of σ28 in flagellar regulation Class 3. Consistent with RNA-Seq data, results from transmission electron microcopy (TEM) showed that flagella were not present in △0368 and △0368△0595 mutants resulting in both swimming and swarming defects. Interestingly, the growth rates of two non-motile mutants △0368 and △0368△0595 were significantly greater than the wild-type, which may be associated with up-regulation of genes encoding cytochromes, enhancing bacterial proliferation. Moreover, the △0595 mutant was significantly more invasive in Caco-2 cells as shown by bacterial enumeration assays, and the expression of lipopolysaccharide (LPS) core synthesis-related genes (rfaB, rfaI, rfaQ, rfaY, rfaK, rfaZ) was down-regulated only in the △0368△0595 mutant. In addition, this study also speculated that these two genes might be contributing to serotype conversion for Salmonella C1 serogroup based on their apparent roles in biosynthesis of LPS and the flagella. CONCLUSION: A combination of biological and transcriptomic (RNA-Seq) analyses has shown that the SC0368 and SC0595 genes are involved in biosynthesis of flagella and complete LPS, as well as in bacterial growth and virulence. Such information will aid to revealing the role of these specific genes in bacterial physiology and evolution within the serogroup C1.

Left bundle branch pacing for cardiac resynchronization therapy: A systematic literature review and meta-analysis.

BACKGROUND: Left bundle branch pacing (LBBP) recently has been suggested as an alternative modality to deliver cardiac resynchronization therapy (CRT). Data on LBBP for CRT are limited to small sample reports, and clinical benefits and risks have not been systematically assessed. We sought to systematically examine published studies of LBBP for CRT and quantify the feasibility and efficacy of the therapy. METHODS: Cochrane Library, PubMed, Web of Science, and Embase databases were searched from inception to September 30, 2020 to identify relevant studies evaluating LBBP in patients for CRT. Clinical outcomes of interest included implant success rate, QRS duration (QRSd), pacing threshold, left ventricular (LV) function at baseline and follow-up, heart failure-related hospitalization, and mortality. Data were extracted and summarized. RESULTS: A total of six studies (two single-arm studies and four comparative studies) involving 174 patients were included. The results showed that the average age of patients was 64.9 years and all were implanted for CRT. The procedural success rate was only reported in two studies (97% and 81.1%, respectively). LBBP resulted in a narrow of mean QRSd from 172.7 ± 4.8 to 115.1 ± 7.6 ms. LV function, including LV ejection fraction and LV end-diastolic dimension improved at follow-up. During a mean follow-up of 8.1 months, 1.3% of patients experienced heart failure-related hospitalization and no patients died. CONCLUSION: LBBP is a feasible strategy with significant efficacy and safety for CRT candidates.

Molecular Characterization of Cephalosporin-Resistant Salmonella Enteritidis ST11 Isolates Carrying blaCTX-M from Children with Diarrhea.

Salmonella Enteritidis is an important foodborne pathogen with high prevalence of resistance to cephalosporins, imposing a serious threat to public health. Therefore, a total of 162 Salmonella Enteritidis isolates collected from child patients in China from 2007 to 2017 were characterized for their resistance to cephalosporins and investigated the transmission characteristics of cephalosporin resistance gene. We found that 15 (9.26%) isolates were all resistant to cefalotin (minimum inhibitory concentration [MIC] ≥512 µg/mL), ceftazidime (MIC 16-128 µg/mL), ceftriaxone (MIC 64 to ≥512 µg/mL), ceftiofur (MIC 64-256 µg/mL), and cefotaxime (MIC 64 to ≥512 µg/mL) with the possession of cephalosporin resistance genes blaCTX-M-55 (n = 13), blaCTX-M-101 (n = 1), and blaCTX-M-153 (n = 1). Molecular typing further revealed that these 15 isolates belonged to sequence type ST11 and shared close pulsed-field gel electrophoresis patterns, suggesting the possibility of clonal spread in Salmonella Enteritidis interspecies. Furthermore, conjugation experiments were successfully performed in 13 of 15 isolates, and blaCTX-M-55 was present on conjugative plasmids with sizes ranging from 54.7 to 173.4 kb. Compared with recipient Escherichia coli C600, transconjugants conferred elevated MICs for cephalosporins ranging from 2- to 2048-fold. The genetic structure surrounding of blaCTX-M-55 gene in transconjugants were ΔISEcp1-blaCTX-M-55-orf477 (n = 8) and ISEcp1-blaCTX-M-55-orf477 (n = 3), respectively. Taken together, blaCTX-M on the plasmids might contribute to cephalosporin resistance in Salmonella Enteritidis, and conjugative transfer of blaCTX-M-55 might facilitate the spread of cephalosporin resistance in Salmonella Enteritidis. Hence, effective mitigation measurements are needed to reduce the threat caused by cephalosporin-resistant Salmonella Enteritidis to public health.

PRAP: Pan Resistome analysis pipeline.

BACKGROUND: Antibiotic resistance genes (ARGs) can spread among pathogens via horizontal gene transfer, resulting in imparities in their distribution even within the same species. Therefore, a pan-genome approach to analyzing resistomes is necessary for thoroughly characterizing patterns of ARGs distribution within particular pathogen populations. Software tools are readily available for either ARGs identification or pan-genome analysis, but few exist to combine the two functions. RESULTS: We developed Pan Resistome Analysis Pipeline (PRAP) for the rapid identification of antibiotic resistance genes from various formats of whole genome sequences based on the CARD or ResFinder databases. Detailed annotations were used to analyze pan-resistome features and characterize distributions of ARGs. The contribution of different alleles to antibiotic resistance was predicted by a random forest classifier. Results of analysis were presented in browsable files along with a variety of visualization options. We demonstrated the performance of PRAP by analyzing the genomes of 26 Salmonella enterica isolates from Shanghai, China. CONCLUSIONS: PRAP was effective for identifying ARGs and visualizing pan-resistome features, therefore facilitating pan-genomic investigation of ARGs. This tool has the ability to further excavate potential relationships between antibiotic resistance genes and their phenotypic traits.

Beneficial Effects of Sacubitril/Valsartan at Low Doses in an Asian Real-World Heart Failure Population.

This study aimed at analyzing the clinical profile of real-world patients with heart failure with reduced ejection fraction (HFrEF) and evaluating the safety and efficacy of sacubitril/valsartan among Asian patients in daily practice. We conducted a single-center prospective observational cohort study of HFrEF patients treated with sacubitril/valsartan from September 2017 to September 2018 with a follow-up of 6 months. The mean (SD) age of the 110 patients enrolled was 59.7 ± 13.3, 85 (77.3%) were men and 41 (37.3%) had ischemic cardiomyopathy. Thirty-one (27.2%) patients with low systolic blood pressure initiated sacubitril/valsartan on a tiny dose of 12/13 mg. Despite the low mean daily dose achieved in real world mainly because of hypotension, left ventricular ejection fraction increased significantly from 35.4 ± 8.9% at baseline to 43.0 ± 12.2% after 6-month follow-up (P < 0.001). We also observed a significant improvement in a 6-minute walk test (6-MWT) distance and N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration reduction. No severe adverse event was recorded. Low dose sacubitril/valsartan induces beneficial cardiac reverse remodeling and improves clinical functional performance in real-world HFrEF patients without severe adverse effect. A tiny initial dose may enhance tolerability and reduce discontinuation rate by minimizing hypotension events in patients with low systolic blood pressure. These data further support using low-dose sacubitril/valsartan among eligible patients with HFrEF in Asia.

Typical BBB morphology and implantation depth of 3830 electrode predict QRS correction by left bundle branch area pacing.

AIM: Strict criteria of typical left bundle branch block (LBBB) can help with the prediction for cardiac resynchronization therapy response. The aim of this study is to determine whether the use of strict criteria for both LBBB and right bundle branch block (RBBB) predicts successful QRS correction (≤130 ms) by left bundle branch area pacing (LBBAP). METHODS: Consecutive patients with pacemaker indications according to the present guideline who also underwent LBBAP implantation were retrospectively assessed. Inclusion criteria were patients with BBB and the baseline QRSd > 130 ms. Baseline characteristics and pacing parameters were compared between typical and atypical BBB groups. Multivariate logistic regression was used to adjust for covariates that were found in univariate analyses for successful QRS correction by LBBAP. RESULTS: Seventy-three patients were enrolled. Among them, 10 (13.6%) had atypical BBB (5 LBBB and 5 RBBB) and 63 (86.4%) had typical BBB (30 LBBB and 33 RBBB). The rate of successful QRS correction was higher in typical-BBB patients (52/63; 82.5%) than that in atypical-BBB patients (3/10; 30%), P < .001. Paced QRSd was obviously narrower in patients with typical BBB than that in patients with atypical-BBB (118 ± 14 vs 133 ± 14 ms, P = .003). In multivariate logistic regression, only typical BBB morphology and the implantation depth of 3830 pacing electrode in the ventricular septum were independent predictors for successful QRS correction. CONCLUSION: This study demonstrates that patients with typical-BBB morphology benefit more from LBBAP for QRS correction. Typical BBB morphology together with deep penetration of 3830 ventricular electrode in the interventricular septum predicts the success of QRS correction by LBBAP.

Reversion of cardiac memory during left bundle branch pacing.

Cardiac memory (CM) is identified as an altered T wave when normal ventricular activation resumes after an abnormal myocardial activation period. We present a case who initially underwent temporary right ventricular apex (RVA) pacing for one week which induced typical pseudo-primary T wave changes. The T wave inversion was observed after the end of RVA pacing when left bundle branch pacing (LBBP) was initiated, and the abnormal T waves gradually return to almost normal repolarization during LBBP 40 days later.

Prevalence and Characterization of Antimicrobial Resistance in Salmonella enterica Isolates from Retail Foods in Shanghai, China.

This study characterized the prevalence and antimicrobial resistance characteristics of foodborne Salmonella isolates from March 2016 to February 2017 in Shanghai, China. A total of 147 (14.2%) nonduplicate foodborne Salmonella isolates were obtained from 1035 food samples. The Salmonella isolates were most frequently identified in fresh meat samples (28.0%), followed by ready-to-eat foods (9.0%), frozen convenience foods (7.1%), and fresh produce (4.5%). The top 3 serovars were Salmonella Enteritidis (46.3%; 68/147), Salmonella Typhimurium (32.7%; 48/147), and Salmonella Derby (6.8%; 10/147). The majority of isolates were resistant to sulfisoxazole (93.9%; 138/147) and trimethoprim/sulfamethoxazole (61.2%; 90/147). Interestingly, frozen convenience food isolates exhibited an extremely high multidrug resistance rate (86.7%; resistant to ≥3 classes of antimicrobials). Among 81 quinolone-resistant isolates, aac(6')-Ib-cr (100%), oqxAB (84.0%), qnrS1 (23.5%), D87Y (49.4%), and D87N (33.3%) mutations in GyrA, and T57S in ParC (12.3%) were observed. The ß-lactamase genes blaTEM-1 (100%) were present in 63 ampicillin-resistant isolates. Polymerase chain reaction-based plasmid replicon typing revealed that 147 isolates represented 6 plasmid incompatibility groups (IncFIIs, IncHI2, IncI1, IncP, IncFIC, and IncA/C), among which, IncFIIs (59.2%) and IncHI2 (26.5%) were predominant. The genetic relationship of isolates was elucidated using multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). MLST results indicated that ST34 and ST11 were predominate types in Salmonella Typhimurium (56.3%; 27/48) and Salmonella Enteritidis (95.6%; 65/68), respectively. Importantly, 96.3% (26/27) of ST34 Salmonella Typhimurium isolates possessed the ACSSuT resistance pattern (ampicillin, chloramphenicol, streptomycin, sulfamethoxazole, and tetracycline). PFGE analysis of ST34 isolates showed clonal dissemination across all four types of retail foods. Our findings highlight the high prevalence of antimicrobial-resistant Salmonella isolates in retail foods in Shanghai, especially the clonal expansion of ST34 isolates with MDR-ACSSuT resistance, which might pose a public health threat.

Quantification of Acute Myocardial Damage Secondary to Implantation of Electrodes for the Left Bundle Branch Area Pacing.

BACKGROUND: Different from the traditional right ventricular pacing, the left bundle branch area pacing (LBBAP) is accomplished with deeper lead implantation and more attempts. However, myocardial damage is unclear in LBBAP. OBJECTIVE: The objective of the study was to observe the change of troponin T and explore possible factors associated with greater myocardial damage in LBBAP. METHODS: Patients with an indication for pacemaker implantation underwent attempts for LBBAP by transventricular septal method. Levels of troponin T were determined before operation, 12 h and 1 week after the operation. Parameters of intraoperation and follow-up were recorded and analyzed. RESULTS: In total, successful LBBAP was achieved in 126 patients. The levels of troponin T increased significantly at 12 h after the operation compared with those before operation (96.45 ± 11.07 [69.06] vs. 16.59 ± 1.84 [11.92] ng/L, p < 0.001), while there were no significant differences between pre- and post-operative levels at 1 week. Correlation and regression analysis showed that only the number of attempts was an independent factor related to the change of troponin T. During 1 year of follow-up, LBBAP was safe and feasible with few complications. CONCLUSIONS: Myocardial damage of LBBAP was clinically significant. The number of attempts was an independent factor related to the myocardial damage.