Validity of SOFA score as a prognostic tool for critically ill elderly patients with acute infective endocarditis.

The prognostic value of the sequential organ failure assessment (SOFA) score for critically ill elderly patients with acute infective endocarditis (IE) remains unknown. From January 2015 to December 2019, 111 elderly (≥65 years) patients with acute IE were consecutively included and divided into a low SOFA (<6) group (n = 71) and a high SOFA (≥6) group (n = 40). Endpoints included in-hospital and long-term (12-36 month) mortality. A high SOFA score was related to higher incidence of in-hospital mortality (30.0%) with an area under the curve (AUC) of 0.796. In multivariate analysis, age [odds ratio (OR) = 2.21, 95% confidence intervals (CI), 1.16-6.79, p = 0.040], SOFA ≥6 (OR = 6.38, 95% CI, 1.80-16.89, p = 0.004) and surgical treatment (OR = 0.21, 95% CI, 0.05-0.80, p = 0.021) were predictive of in-hospital mortality. A Cox proportional-hazards model identified age [Hazard ratios (HR)= 2.85, 95% CI, 1.11-7.37, p = 0.031], diabetes mellitus (HR = 3.99, 95% CI, 1.35-11.80, p = 0.013), SOFA ≥6 (OR = 3.38, 95% CI, 1.26-9.08, p = 0.001) and surgical treatment (HR = 0.24, 95% CI, 0.08-0.68, p = 0.021) as predictors of long-term mortality. A high SOFA score predicts a poor outcome including in-hospital and long-term mortality in critically ill elderly patients with acute IE.

Development of the computational antibiotic screening platform (CLASP) to aid in the discovery of new antibiotics.

Bacterial colonization of biotic and abiotic surfaces and antibiotic resistance are grand challenges with paramount societal impacts. However, in the face of increasing bacterial resistance to all known antibiotics, efforts to discover new classes of antibiotics have languished, creating an urgent need to accelerate the antibiotic discovery pipeline. A major deterrent in the discovering of new antibiotics is the limited permeability of molecules across the bacterial envelope. Notably, the Gram-negative bacteria have nutrient specific protein channels (or porins) that restrict the permeability of non-essential molecules, including antibiotics. Here, we have developed the Computational Antibiotic Screening Platform (CLASP) for screening of potential drug molecules through the porins. The CLASP takes advantage of coarse grain (CG) resolution, advanced sampling techniques, and a parallel computing environment to maximize its performance. The CLASP yields comprehensive thermodynamic and kinetic output data of a potential drug molecule within a few hours of wall-clock time. Its output includes the potential of mean force profile, energy barrier, the rate constant, and contact analysis of the molecule with the pore-lining residues, and the orientational analysis of the molecule in the porin channel. In our first CLASP application, we report the transport properties of six carbapenem antibiotics-biapenem, doripenem, ertapenem, imipenem, meropenem, and panipenem-through OccD3, a major channel for carbapenem uptake in Pseudomonas aeruginosa. The CLASP is designed to screen small molecule libraries with a fast turnaround time to yield structure-property relationships to discover antibiotics with high permeability. The CLASP will be freely distributed to enable accelerated antibiotic drug discovery.

Multivariate Analysis of Individual Bacterial Outer Membrane Vesicles Using Fluorescence Microscopy.

Gram-negative bacteria produce outer membrane vesicles (OMVs) that play a critical role in cell-cell communication and virulence. OMVs have emerged as promising therapeutic agents for various biological applications such as vaccines and targeted drug delivery. However, the full potential of OMVs is currently constrained by inherent heterogeneities, such as size and cargo differences, and traditional ensemble assays are limited in their ability to reveal OMV heterogeneity. To overcome this issue, we devised an innovative approach enabling the identification of various characteristics of individual OMVs. This method, employing fluorescence microscopy, facilitates the detection of variations in size and surface markers. To demonstrate our method, we utilize the oral bacterium Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) which produces OMVs with a bimodal size distribution. As part of its virulence, A. actinomycetemcomitans secretes leukotoxin (LtxA) in two forms: soluble and surface associated with the OMVs. We observed a correlation between the size and toxin presence where larger OMVs were much more likely to possess LtxA compared to the smaller OMVs. In addition, we noted that, among the smallest OMVs (<100 nm diameter), the fractions that are toxin positive range from 0 to 30%, while the largest OMVs (>200 nm diameter) are between 70 and 100% toxin positive.

The Emulsifying Properties, In Vitro Digestion Characteristics and Storage Stability of High-Pressure-Homogenization-Modified Dual-Protein-Based Emulsions.

The droplet size, zeta potential, interface protein adsorption rate, physical stability and microrheological properties of high-pressure-homogenization (HPH)-modified, dual-protein-based whey-soy (whey protein isolate-soy protein isolate) emulsions containing different oil phase concentrations (5%, 10% and 15%; w/w) were compared in this paper. The in vitro digestion characteristics and storage stability of the dual-protein emulsions before and after HPH treatment were also explored. The results show that with an increase in the oil phase concentration, the droplet size and interface protein adsorption rate of the untreated dual-protein emulsions increased, while the absolute value of the zeta potential decreased. When the oil phase concentration was 10% (w/w), HPH treatment could significantly reduce the droplet size of the dual-protein emulsion, increase the interface protein adsorption rate, and improve the elasticity of the emulsion. Compared with other oil phase concentrations, the physical stability of the dual-protein emulsion containing a 10% (w/w) oil phase concentration was the best, so the in vitro digestion characteristics and storage stability of the emulsions were studied. Compared with the control group, the droplet size of the HPH-modified dual-protein emulsion was significantly reduced after gastrointestinal digestion, and the in vitro digestibility and release of free amino groups both significantly increased. The storage stability results show that the HPH-modified dual-protein emulsion showed good stability under different storage methods, and the storage stability of the steam-sterilized dual-protein emulsion stored at room temperature was the best. These results provide a theoretical basis for the development of new nutritional and healthy dual-protein liquid products.

The Effect of High Pressure Homogenization on the Structure of Dual-Protein and Its Emulsion Functional Properties.

It has been proven that high-pressure homogenization (HPH) could improve the functional properties of proteins by modifying their structure. This study researched the effect of HPH on the structural and functional properties of whey-soy dual-protein (Soy Protein Isolation-Whey Protein Isolation, SPI-WPI). Different protein solution samples were treated with HPH at 30, 60, 90, 120 and 150 MPa, and the structure changed under different pressures was analyzed by measuring particle size, zeta potential, Fourier infrared spectrum (FTIR), fluorescence spectrum and scanning electron microscope (SEM). The results showed that HPH significantly reduced the particle size of SPI-WPI, changed the secondary and tertiary structures and improved the hydrophobic interaction between molecules. In addition, HPH significantly improved the solubility and emulsification of all proteins, and the improvement effect on SPI-WPI was significantly better than SPI and WPI. It was found that SPI-WPI treated with 60 MPa had the best physicochemical properties. Secondly, we researched the effect of HPH by 60 MPa on the emulsion properties of SPI-WPI. In this study, the SPI-WPI had the lowest surface tension compared to a single protein after HPH treatment. The emulsion droplet size was obviously decreased, and the elastic properties and physical stability of SPI-WPI emulsion were significantly enhanced. In conclusion, this study will provide a theoretical basis for the application of HPH in modifying the structure of dual-protein to improve its development and utilization in liquid specialty food.

Retrograde recanalization of radial artery occlusion via the distal transradial artery: A single-center experience.

Background: Radial artery occlusion (RAO) often occurs after catheterization when using a transradial artery approach. Objective: This prospective study assessed the success and feasibility of accessing the distal transradial artery (dTRA) for retrograde recanalization of RAO. Methods: From June 2019 to December 2021, 44 consecutive patients who had undergone cardiac catheterization resulting in RAO were given retrograde recanalization via the dTRA. According to the result of the procedure (primary endpoint), patients' cases were analyzed as successful or failed. Rates of post-operative patency and adverse events were calculated up to 12 months. Results: The procedural success rate was 88.6%. Compared with the successful group, a significantly higher percentage of patients in the failed group were current smokers and/or suffered from diabetes mellitus (each, 80.0% cf. 33.3%, P = 0.046); had undergone at least 3 previous cardiac catheterizations (60.0% cf. 12.8%, P = 0.011), lower rate of anticoagulation (30.77% cf. 0%, P = 0.048) and exhibited chronic total occlusion (100.0% cf. 51.28%, P = 0.041). In each group, one patient each had minor bleeding at the access site and hematoma. The patency rates in the successful group at postoperative 3, 6, and 12 months were 48.7, 43.6, and 35.9%, respectively. Conclusion: The dTRA approach for retrograde recanalization of RAO showed a high procedural success rate, but with patency rates of <50% at follow-up.

Applications of Catechins in the Treatment of Bacterial Infections.

Tea is the second most commonly consumed beverage worldwide. Along with its aromatic and delicate flavors that make it an enjoyable beverage, studies report numerous health advantages in tea consumption, including applications in antimicrobial therapy. The antimicrobial properties of tea are related to catechin and its derivatives, which are natural flavonoids that are abundant in tea. Increasing evidence from in vitro studies demonstrated antimicrobial effects of catechins on both gram-positive and gram-negative bacteria, and proposed direct and indirect therapeutic mechanisms. Additionally, catechins were reported to be effective anti-virulence agents. Furthermore, a number of studies presented evidence that catechins display synergistic effects with certain antibiotics, thus potentiating the activity of antibiotics in resistant bacteria. Despite their numerous beneficial properties, catechins face many challenges in their development as therapeutic agents, including poor absorption, low bioavailability, and rapid degradation. The introduction of nanobiotechnology provides target-based and stable delivery, which enhances catechin bioavailability and optimizes drug efficacy. As further research continues to focus on overcoming the unresolved challenges, catechins are likely to see additional promising applications in our continual fight against bacterial infections.

Mouse bone marrow derived mesenchymal stem cells-secreted exosomal microRNA-125b-5p suppresses atherosclerotic plaque formation via inhibiting Map4k4.

BACKGROUND: Accumulating evidence has reported the role of microRNA (miR) on atherosclerosis (AS), while it is unclear about the relationship between microRNA-125b-5p (miR-125b-5p) and AS. Thus, the object of this study was to investigate the impact of exosomal miR-125b-5p targeting mitogen-activated protein 4 kinase 4 (Map4k4) on AS plaque formation. METHODS: The AS model was established using a high fat diet in ApoE-/- mice. Mouse bone marrow-derived mesenchymal stem cells (BMSCs) were selected and BMSC-exosomes (BMSC-EXO) were extracted and then identified. The targeted relationship between miR-125b-5p and Map4k4 was tested. BMSC-EXO were modified with miR-125b-5p- and Map4k4-related sequences to interfere with AS mice. MiR-125b-5p and Map4k4 expression in AS tissues were tested. The inflammation-related indices, blood lipid, plaque area, apoptosis index, MMP-9 and α-SMA expression in mice with AS were measured. RESULTS: BMSCs and BMSC-EXO were successfully isolated. MiR-125b-5p was down-regulated and Map4k4 was up-regulated in aorta tissues from ApoE-/- mice after AS modeling, verses those from C57BL/6 mice without modeling. MiR-125b-5p targeted Map4k4. BMSC-EXO increased miR-125b-5p expression and decreased Map4k4 expression. BMSC-EXO/up-regulated miR-125b-5p and down-regulated Map4k4 in exosomes decreased inflammatory reaction, blood lipid, plaque area, MMP-9 expression and increased α-SMA expression, as well as inhibited apoptosis index of AS mice. CONCLUSION: Functional studies revealed that exosomal miR-125b-5p from BMSCs suppresses atherosclerotic plaque formation via inhibiting Map4k4 expression.

Comparison of Pharmacological Treatment Effects on Long-Time Outcomes in Heart Failure With Preserved Ejection Fraction: A Network Meta-analysis of Randomized Controlled Trials.

Beneficial effects of therapeutic drugs are controversial for heart failure with preserved ejection fraction (HFpEF). This meta-analysis aimed to evaluate and compare the interactive effects of different therapeutic drugs and placebo in patients with HFpEF. A comprehensive search was conducted using PubMed, Google Scholar, and Cochrane Central Register to identify related articles published before March 2021. The primary outcome was all-cause mortality. Secondary outcomes were cardiovascular mortality, heart failure (HF) hospitalization, and worsening HF events. A total of 14 randomized controlled trials, comprising 19,573 patients (intervention group, n = 9,954; control group, n = 9,619) were included in this network meta-analysis. All-cause mortality, cardiovascular mortality, and worsening HF events among therapeutic drugs and placebo with follow-up of 0.5-4 years were not found to be significantly correlated. The angiotensin receptor neprilysin inhibitor (ARNI) and angiotensin-converting enzyme inhibitor (ACEI) significantly reduced the HF hospitalizations compared with placebo (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.60-0.87 and HR 0.64, 95% CI 0.43-0.96, respectively), without heterogeneity among studies. The ARNI was superior to angiotensin receptor blocker (ARB) in reducing HF hospitalizations (HR 0.80, 95% CI 0.71-0.91), and vericiguat 10 mg ranked worse than beta-blockers for reducing all-cause mortality in patients with HFpEF (HR 3.76, 95% CI 1.06-13.32). No therapeutic drugs can significantly reduce mortality, but the ARNI or ACEI is associated with the low risk of HF hospitalizations for patients with HFpEF. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021247034.

Sympathectomy versus conventional treatment for refractory coronary artery spasm.

BACKGROUND: There is no clear consensus on the potential efficacy and indications for sympathectomy to prevent recurrence of vasospasm in patients with refractory coronary artery spasm (CAS). OBJECTIVE: To compare the clinical outcomes of sympathectomy with those of conventional treatment in patients with refractory CAS. PATIENTS AND METHODS: Patients with refractory CAS were randomly assigned to sympathectomy group (n = 37) or conventional treatment group (n = 42). The primary end point was a composite of major adverse cardiac event (MACE) episodes (including cardiac death, nonfatal myocardial infarction, unstable angina, heart failure, and life-threatening arrhythmia), and the secondary end point was death from any cause within 24 months after randomization. RESULTS: During the follow-up period of 24 months, the incidence of MACE in the sympathectomy and conventional treatment groups was 16.22 and 61.90%, respectively (P = 0.0001). All-cause death as the secondary end point occurred in zero and six (14.29%) patients, respectively (P = 0.0272). The Kaplan-Meier curve for MACE and all-cause death showed a significant between-group difference (log-rank test, P = 0.0013 and 0.0176, respectively). CONCLUSION: Compared with conventional treatment, sympathectomy significantly reduced the composite end point of MACE episodes and death from any cause in patients with refractory CAS by effectively preventing recurrence of vasospasm.

Effect of cadmium on oxidative stress and immune function of common carp (Cyprinus carpio L.) by transcriptome analysis.

Cadmium (Cd) is an increasingly important environmental pollutant which causes irreversible toxicity to fish. To understand how Cd impacts the immune response and oxidative stress in common carp, we performed transcriptomic profiles for head kidney, the immune organ of common carp which were underwent Cd exposure. Totally there are 42,489,124 and 48,562,526 high quality clean reads obtained from the Cd exposure groups, and 44,677,578 and 44,106,696 clean reads from the control groups. Among them, 308 genes were differently expressed, including 101 upregulated and 207 down-regulated genes. The identified genes were enriched using databases of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Antioxidant systems and immune function genes and pathways were identified and validated by quantitative real-time RT-PCR. Our results showed that Cd exposure leads to oxidative stress and immunosuppression in head kidney of common carp. These results provide new insights for unveiling the biological effects of Cd in common carp.