Long‐Range Cationic Disordering Induces two Distinct Degradation Pathways in Co‐Free Ni‐Rich Layered Cathodes

Ni-rich layered oxides are one of the most attractive cathode materials in high-energy-density lithium-ion batteries, their degradation mechanisms are still not completely elucidated. Herein, we report a strong dependence of degradation pathways on the long-range cationic disordering of Co-free Ni-rich Li1−m(Ni0.94Al0.06)1+mO2 (NA). Interestingly, a disordered layered phase with lattice mismatch can be easily formed in the near-surface region of NA particles with very low cation disorder (NA-LCD, m≤0.06) over electrochemical cycling, while the layered structure is basically maintained in the core of particles forming a “core–shell” structure. Such surface reconstruction triggers a rapid capacity decay during the first 100 cycles between 2.7 and 4.3 V at 1 C or 3 C. On the contrary, the local lattice distortions are gradually accumulated throughout the whole NA particles with higher degrees of cation disorder (NA-HCD, 0.06≤m≤0.15) that lead to a slow capacity decay upon cycling

Pathways to optimising antibiotic use in rural China:Identifying key determinants in community and clinical settings, a mixed methods study protocol

Paul I. Kadetz - ORCID: 0000-0002-2824-1856 https://orcid.org/0000-0002-2824-1856Item not available in this repository.Introduction This study aims to investigate patterns of antibiotic treatment-seeking, describe current levels of and drivers for antibiotic use for common infections (respiratory tract and urinary tract infections) and test the feasibility of determining the prevalence and epidemiology of antimicrobial resistance (AMR) in rural areas of Anhui province, in order to identify potential interventions to promote antibiotic stewardship and reduce the burden of AMR in China. Methods and analysis We will conduct direct observations, structured and semistructured interviews in retail pharmacies, village clinics and township health centres to investigate treatment-seeking and antibiotic use. Clinical isolates from 1550 sputum, throat swab and urine samples taken from consenting patients at village and township health centres will be analysed to identify bacterial pathogens and ascertain antibiotic susceptibilities. Healthcare records will be surveyed for a subsample of those recruited to the study to assess their completeness and accuracy. Ethics and dissemination The full research protocol has been reviewed and approved by the Biomedical Ethics Committee of Anhui Medical University (reference number: 20170271). Participation of patients and doctors is voluntary and written informed consent is sought from all participants. Findings from the study will be disseminated through academic routes including peerreviewed publications and conference presentations, via tailored research summaries for health professionals, health service managers and policymakers and through an end of project impact workshop with local and regional stakeholders to identify key messages and priorities for action.This work was supported by the Newton Fund (UK Research and Innovation (UKRI) and the National Natural Science Foundation of China (NSFC)) under the UK-China AMR Partnership Initiative, grant number MR/P00756/1. RMK, CC, MH and IO all acknowledge support from the NIHR Health Protection Research Unit in Evaluation of Interventions at the University of Bristol.http://dx.doi.org/10.1136/bmjopen-2018-0278199pubpub

Establishment of a Novel Detection Platform for Clostridioides difficile Toxin Genes Based on Orthogonal CRISPR

ABSTRACT Clostridioides difficile is one of the leading pathogens causing nosocomial infection. The infection can range from mild to severe, and rapid identification is pivotal for early clinical diagnosis and appropriate treatment. Here, a genetic testing platform for toxins, referred to as OC-MAB (orthogonal CRISPR system combined with multiple recombinase polymerase amplification [RPA]), was developed to detect the C. difficile toxin genes tcdA and tcdB. While recognizing the amplified products of the tcdA gene and the tcdB gene, Cas13a and Cas12a could activate their cleavage activities to cut labeled RNA and DNA probes, respectively. The cleaved products were subsequently identified by dual-channel fluorescence using a quantitative PCR (qPCR) instrument. Finally, they could also be combined with labeled antibodies on immunochromatographic test strips to achieve visual detection. The OC-MAB platform exhibited ultrahigh sensitivity in detecting the tcdA and tcdB genes at levels of as low as 102 to 101 copies/mL. When testing 72 clinical stool samples, the sensitivity (95% confidence interval [CI], 0.90, 1) and specificity (95% CI, 0.84, 1) of the single-tube method based on the fluorescence readout was 100%, with a positive predictive value (PPA) value of 100% (95% CI, 0.90, 1) and a negative predictive value (NPA) value of 100% (95% CI, 0.84, 1), compared to the results of qPCR. Likewise, the sensitivity of the 2-step method based on the test strip readout was 100% (95% CI, 0.90, 1), while the specificity was 96.3% (95% CI, 0.79, 0.99), with a PPA of 98% (95% CI, 0.87, 0.99) and an NPA of 100% (95% CI, 0.90, 1). In short, orthogonal CRISPR technology is a promising tool for the detection of C. difficile toxin genes. IMPORTANCE C. difficile is currently the primary causative agent of hospital-acquired antibiotic-induced diarrhea, and timely and accurate diagnosis is crucial for hospital-acquired infection control and epidemiological investigation. Here, a new method for the identification of C. difficile was developed based on the recently popular CRISPR technology, and an orthogonal CRISPR dual system was utilized for the simultaneous detection of toxin genes A and B. It also uses a currently rare CRISPR dual-target lateral flow strip with powerful color-changing capabilities, which is appropriate for point-of-care testing (POCT)

Role of the Outer Membrane Protein OprD2 in Carbapenem-Resistance Mechanisms of Pseudomonas aeruginosa.

We investigated the relationship between the outer membrane protein OprD2 and carbapenem-resistance in 141 clinical isolates of Pseudomonas aeruginosa collected between January and December 2013 from the First Affiliated Hospital of Anhui Medical University in China. Agar dilution methods were employed to determine the minimum inhibitory concentration of meropenem (MEM) and imipenem (IMP) for P. aeruginosa. The gene encoding OprD2 was amplified from141 P. aeruginosa isolates and analyzed by PCR and DNA sequencing. Differences between the effects of IMPR and IMPS groups on the resistance of the P. aeruginosa were observed by SDS-poly acrylamide gel electrophoresis (SDS-PAGE). Three resistance types were classified in the 141 carbapenem-resistant P. aeruginosa (CRPA) isolates tested, namely IMPRMEMR (66.7%), IMPRMEMS (32.6%), and IMPRMEMS (0.7%). DNA sequencing revealed significant diverse gene mutations in the OprD2-encoding gene in these strains. Thirty-four strains had large fragment deletions in the OprD2gene, in 6 strains the gene contained fragment inserts, and in 96 resistant strains, the gene featured small fragment deletions or multi-site mutations. Only 4 metallo-β-lactamase strains and 1 imipenem-sensitive (meropenem-resistant) strain showed a normal OprD2 gene. Using SDS-PAGE to detect the outer membrane protein in 16 CRPA isolates, it was found that 10 IMPRMEMR strains and 5 IMPRMEMS strains had lost the OprD2 protein, while the IMPSMEMR strain contained a normal 46-kDa protein. In conclusion, mutation or loss of the OprD2-encoding gene caused the loss of OprD2, which further led to carbapenem-resistance of P. aeruginosa. Our findings provide insights into the mechanism of carbapenem resistance in P. aeruginosa

The efficacy and safety of tigecycline for the treatment of bloodstream infections: a systematic review and meta-analysis

Abstract Patients with bloodstream infections (BSI) are associated with high mortality rates. Due to tigecycline has shown excellent in vitro activity against most pathogens, tigecycline is selected as one of the candidate drugs for the treatment of multidrug-resistant organisms infections. The purpose of this study was to evaluate the effectiveness and safety of the use of tigecycline for the treatment of patients with BSI. The PubMed and Embase databases were systematically searched, to identify published studies, and we searched clinical trial registries to identify completed unpublished studies, the results of which were obtained through the manufacturer. The primary outcome was mortality, and the secondary outcomes were the rate of clinical cure and microbiological success. 24 controlled studies were included in this systematic review. All-cause mortality was lower with tigecycline than with control antibiotic agents, but the difference was not significant (OR 0.85, [95% confidence interval (CI) 0.31–2.33; P = 0.745]). Clinical cure was significantly higher with tigecycline groups (OR 1.76, [95% CI 1.26–2.45; P = 0.001]). Eradication efficiency did not differ between tigecycline and control regimens, but the sample size for these comparisons was small. Subgroup analyses showed good clinical cure result in bacteremia patients with CAP. Tigecycline monotherapy was associated with a OR of 2.73 (95% CI 1.53–4.87) for mortality compared with tigecycline combination therapy (6 studies; 250 patients), without heterogeneity. Five studies reporting on 398 patients with Klebsiella pneumoniae carbapenemase-producing K. pneumoniae BSI showed significantly lower mortality in the tigecycline arm than in the control arm. The combined treatment with tigecycline may be considered the optimal option for severely ill patients with BSI

OprD₂ gene sequencing results of 141 CRPA strains.

<p>OprD₂ gene sequencing results of 141 CRPA strains.</p

OprD₂ outer membrane protein quantification in 18 <i>P</i>. <i>aeruginosa</i> strains.

<p>* Determined using Quantity One image analysis software.</p><p>* *+fragment missing or inserted, -normal sequence.</p><p>^# The mean value of strains 1∼15.</p><p>^## The mean value of strains 16–18.</p><p>OprD₂ outer membrane protein quantification in 18 <i>P</i>. <i>aeruginosa</i> strains.</p

PCR amplification of the OprD₂ gene shown for 10 selected <i>P</i>. <i>aeruginosa</i> strains.

<p>The electrophoresis results of strains 1, 2, 5, and 8 were negative, demonstrating that those strains had large fragment deletions. Strains 3, 4, 6, 7, 9, and 10 were positive, without any OprD₂ gene mutations, lack of small fragments, or inserted fragments. M: Marker DL2000.</p

SDS-PAGE for the OprD₂ protein in <i>Pseudomonas aeruginosa</i> strains.

<p>M = standard marker protein, lane 1–3 = IMP^RMEM^R strains, lane 4–5 = IMP^RMEM^S strains, lane 6 = IMP^SMEM^R strains, lane 7 = for IMP^SMEM^S strains, 8 = PAO1. The expected band size of 46 kDa was detected for the OprD₂ protein in the two IMP^S strains and the PAO1 strain (6–8), while the size decreased in the IMP^R strains 1–5.</p

National Surveillance of Legionnaires’ Disease, China, 2014–2016

We report national surveillance of Legionnaires’ disease in China. Urine samples from 11 (3.85%) of 286 patients with severe pneumonia of unknown cause were positive for the Legionella pneumophila serogroup 1 antigen. We isolated Legionella strains from 7 patients. Improved diagnostic testing is needed for this underestimated disease in China