Sex Differences in Quality of Life and Clinical Outcomes in Patients with Heart Failure

Background: Heart failure (HF) is generally associated with poor quality of life (QoL). Limited data are available characterizing health-related QoL (HRQL) in Chinese patients with HF. Methods: We used the Minnesota Living with Heart Failure Questionnaire (MLHFQ) to record QoL in 4082 patients with HF from China who were followed up over 12 months in the Heart Failure Registry of Patient Outcomes (HERO) study. Baseline HRQL and differences in QoL between women and men with heart failure were compared. We used multivariable Cox regression with adjustment for variables to assess the association between MLHFQ summary scores and a composite of all-cause mortality and HF hospitalization. Result: At baseline, the mean MLHFQ in the overall population was 42.9 ± 19.57; the scores for physical and emotional domains were 22.0 ± 8.69 and 8.66 ± 6.08, respectively. Women had a higher (poorer) MLHFQ summary score (44.27 ± 19.13) than men (41.63 ± 19.90) (P<0.001). Female patients also had higher MLHFQ physical and emotional scores than male patients (P<0.001). The specific scores of the questionnaire were higher in women than men. NYHA class was the strongest independent predictor of MLHFQ score (β=6.12 unit increment; P<0.001). Sex was not independently associated with higher MLHFQ scores after multivariable adjustments. The 12-month mortality in the overall cohort was 19.6%, the hospitalization rate was 24.4%, and the composite endpoint was 40.15%. A 10-point increase in MLHFQ score was associated with higher risk of mortality (female and male HRs=1.19 [95% CI 1.12–1.26]; P<0.001 and 1.18 [95% CI 1.12–1.24]; P<0.001, respectively) and composite outcomes (HRs=1.08 [95% CI 1.04–1.13]; P<0.001 and 1.11 [95% CI 1.07–1.14]; P<0.001, respectively). Females did not show a significant association between HRQL and hospitalization (HR=1.04 [95% CI 0.99–1.09]; P=0.107). Conclusion: Quality of life was largely poorer in women than men, but was similar between sexes in terms of physical burden and emotional limitation. HRQL is an independent predictor of all-cause death and HF hospitalization in patients with HF

Why Is a High Temperature Needed by Thermus thermophilus Argonaute During mRNA Silencing: A Theoretical Study

Thermus thermophiles Argonaute (TtAgo) is a complex, which is consisted of 5′-phosphorylated guide DNA and a series of target DNA with catalytic activities at high temperatures. To understand why high temperatures are needed for the catalytic activities, three molecular dynamics simulations and binding free energy calculations at 310, 324, and 338K were performed for the TtAgo-DNA complex to explore the conformational changes between 16-mer guide DNA/15-mer target DNA and TtAgo at different temperatures. The simulation results indicate that a collapse of a small β-strand (residues 507–509) at 310 K caused Glu512 to move away from the catalytic residues Asp546 and Asp478, resulting in a decrease in catalytic activity, which was not observed in the simulations at 324 and 338 K. The nucleic acid binding channel became enlarged at 324 and 338K, thereby facilitating the DNA to slide in. Binding free energy calculations and hydrogen bond occupancy indicated that the interaction between TtAgo and the DNA was more stable at 324K and 338K than at 310 K. The DNA binding pocket residues Lys575 and Asn590 became less solvent accessible at 324 and 338K than at 310 K to influence hydrophilic interaction with DNA. Our simulation studies shed some light on the mechanism of TtAgo and explained why a high temperature was needed by TtAgo during gene editing of CRISPR

Identification and characterization of a novel β-lactamase gene, blaAMZ–1, from Achromobacter mucicolens

BackgroundAchromobacter is a genus of gram-negative bacteria that can act as opportunistic pathogens. Recent studies have revealed that some species of Achromobacter show inherent resistance to β-lactams, but the resistance mechanisms of Achromobacter mucicolens have rarely been reported.MethodThe bacterium was isolated using standard laboratory procedures. The agar dilution method was used to determine the minimum inhibitory concentrations (MICs). Genome sequencing was performed using the PacBio RS II and Illumina HiSeq 2500 platforms, and the Comprehensive Antibiotic Resistance Database (CARD) was used to annotate the drug resistance genes. The localization of the novel β-lactamase AMZ-1 was determined, and its characteristics were determined via molecular cloning and enzyme kinetic analysis. The phylogenetic relationship and comparative genomic analysis of the resistance gene-related sequences were also analyzed.ResultAchromobacter mucicolens Y3, isolated from a goose on a farm in Wenzhou, showed resistance to multiple antibiotics, including penicillins and cephalosporins. BlaAMZ–1 showed resistance to amoxicillin, penicillin G, ampicillin, cephalothin and cefoxitin, and the resistance activity could be inhibited by β-lactamase inhibitors. Enzyme kinetic analysis results showed that AMZ-1 has hydrolytic activity against a wide range of substrates, including cephalothin, amoxicillin, penicillin G, and cefoxitin but not ampicillin. The hydrolytic activity of AMZ-1 was greatly inhibited by avibactam but much more weakly inhibited by tazobactam. Mobile genetic elements could not be found around the blaAMZ–1-like genes, which are conserved on the chromosomes of bacteria of the genus Achromobacter.ConclusionIn this study, a novel AmpC gene, blaAMZ–1, from the animal-origin bacterium A. mucicolens Y3 was identified and characterized. It conferred resistance to some penicillins and first- and second-generation cephalosporins. The identification of this novel resistance gene will be beneficial for the selection of effective antimicrobials to treat associated infections

Identification and characterization of a novel chromosomal aminoglycoside 3’-O-phosphotransferase, APH(3′)-Id, from Kluyvera intermedia DW18 isolated from the sewage of an animal farm

BackgroundAminoglycosides, as important clinical antimicrobials, are used as second-line drugs for treating multidrug-resistant tuberculosis or combined with β-lactam drugs for treating severe infections such as sepsis. Aminoglycoside-modifying enzyme (AME) is the most important mechanism of aminoglycoside resistance and deserves more attention.MethodsThe bacterium Kluyvera intermedia DW18 was isolated from the sewage of an animal farm using the conventional method. The agar dilution method was used to determine the minimum inhibitory concentrations (MICs) of antimicrobials. A novel resistance gene was cloned, and the enzyme was expressed. The kinetic parameters were measured by a SpectraMax M5 multifunctional microplate reader. Bioinformatic analysis was performed to reveal the genetic context of the aph(3′)-Id gene and its phylogenetic relationship with other AMEs.ResultsA novel aminoglycoside 3′-O-phosphotransferase gene designated aph(3′)-Id was identified in K. intermedia DW18 and shared the highest amino acid identity of 77.49% with the functionally characterized aminoglycoside 3′-O-phosphotransferase APH(3′)-Ia. The recombinant plasmid carrying the novel resistance gene (pMD19-aph(3′)-Id/E. coli DH5α) showed 1,024-, 512-, 128- and 16-fold increased MIC levels for kanamycin, ribostamycin, paromomycin and neomycin, respectively, compared with the reference strain DH5α. APH(3′)-Id showed the highest catalytic efficiency for ribostamycin [kcat/Km of (4.96 ± 1.63) × 105 M−1/s−1], followed by paromomycin [kcat/Km of (2.18 ± 0.21) × 105 M−1/s−1], neomycin [kcat/Km of (1.73 ± 0.20) × 105 M−1/s−1], and kanamycin [kcat/Km of (1.10 ± 0.18) × 105 M−1/s−1]. Three conserved functional domains of the aminoglycoside phosphotransferase family and ten amino acid residues responsible for the phosphorylation of kanamycin were found in the amino acid sequence of APH(3′)-Id. No mobile genetic element (MGE) was discovered surrounding the aph(3′)-Id gene.ConclusionIn this work, a novel aminoglycoside 3’-O-phosphotransferase gene designated aph(3′)-Id encoded in the chromosome of the environmental isolate Kluyvera intermedia DW18 was identified and characterized. These findings will help clinicians select effective antimicrobials to treat infections caused by pathogens with this kind of resistance gene

Family Socio-Economic Status and Children’s Play Behaviors: The Mediating Role of Home Environment

Family socio-economic status (SES) is a significant predictor of children’s early learning performance, while little is known about the relationship between family SES and children’s play. This study aimed to examine how family SES was related to different aspects of children’s play behaviors and whether the home environment served as a mediator in this relationship. A total of 844 mothers of children aged three to six (Nboys = 431) from different SES backgrounds (Nlow-SES = 123, Nmedium-SES = 322, Nhigh-SES = 399) reported the situation of the home environment and their children’s play behaviors with self-developed questionnaires. Results of regression analyses showed that family SES significantly predicted the level of Imagination, Approaches to Learning, and Emotion Expression in children’s play and that the home environment partially mediated such relationships. The results indicate SES-related differences in children’s play behaviors and offer the possibility of narrowing such discrepancies by establishing a child-friendly home environment

The effect of an axial mean temperature gradient on communication between one-dimensional acoustic and entropy waves

This work performs a theoretical and numerical analysis of the communication between one-dimensional acoustic and entropy waves in a duct with a mean temperature gradient. Such a situation is highly relevant to combustor flows where the mean temperature drops axially due to heat losses. A duct containing a compact heating element followed by an axial temperature gradient and choked end is considered. The proposed jump conditions linking acoustic and entropy waves on either side of the flame show that the generated entropy wave is generally proportional to the mean temperature ratio across the flame and the ratio ( F - 1 ) , where F is the flame transfer function. It is inversely proportional to the Mach number immediately downstream of the flame M 2 . The acoustic and entropy fields in the region of axial mean temperature gradient are calculated using four approaches: (1) using the full three linearised Euler equations as the reference; (2) using two linearised Euler equations in which the acoustic and entropy waves are assumed independent (thus allowing the extent of communication between the acoustic and entropy wave to be evaluated); (3) using a Helmholtz solver which neglects mean flow effects and (4) using a recently developed analytical solution. It is found that the communication between the acoustic and entropy waves is small at low Mach numbers; it rises with increasing Mach number and cannot be neglected when the mean Mach number downstream of the heating element exceeds 0.1. Predictions from the analytical method generally match those from the full three linearised Euler equations, and the Helmholtz solver accurately determines the acoustic field when M 2 ≤ 0 . 1

Open-Circuit Fault Diagnosis of Wind Power Converter Using Variational Mode Decomposition, Trend Feature Analysis and Deep Belief Network

The power converter is a significant device in a wind power system. The wind turbine will be shut down and off grid immediately with the occurrence of the insulated gate bipolar transistor (IGBT) module open-circuit fault of the power converter, which will seriously impact the stability of grid and even threaten personal safety. However, in the existing diagnosis strategies for the power converter there are few single and double IGBT module open-circuit fault diagnosis methods producing negative results, including erroneous judgment, omissive judgment and low accuracy. In this paper, a novel method to diagnose the single and double IGBT modules open-circuit faults of the permanent magnet synchronous generator (PMSG) wind turbine grid-side converter (GSC) is proposed: Primarily, by collecting the three-phase current varying with a wind speed of 22 states, including a normal state and 21 failure states of PMSG wind turbine GSC as the original signal data. Afterward, the original signal data are decomposed by using variational mode decomposition (VMD) to obtain the mode coefficient series, which are analyzed by the proposed method base on fault trend feature for extracting the trend feature vectors. Finally, the trend feature vectors are utilized as the input of the deep belief network (DBN) for decision-making and obtaining the classification results. The simulation and experimental results show that the proposed method can diagnose the single and double IGBT modules open-circuit faults of GSC, and the accuracy is higher than the benchmark models