14 research outputs found

    Resection arthroplasty for luxation of the manubrio-sternal joint in rheumatoid arthritis—a case report

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    Contains fulltext : 89408.pdf (publisher's version ) (Open Access)1 juni 201

    National laboratory-based surveillance system for antimicrobial resistance: a successful tool to support the control of antimicrobial resistance in the Netherlands

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    An important cornerstone in the control of antimicrobial resistance (AMR) is a well-designed quantitative system for the surveillance of spread and temporal trends in AMR. Since 2008, the Dutch national AMR surveillance system, based on routine data from medical microbiological laboratories (MMLs), has developed into a successful tool to support the control of AMR in the Netherlands. It provides background information for policy making in public health and healthcare services, supports development of empirical antibiotic therapy guidelines and facilitates in-depth research. In addition, participation of the MMLs in the national AMR surveillance network has contributed to sharing of knowledge and quality improvement. A future improvement will be the implementation of a new semantic standard together with standardised data transfer, which will reduce errors in data handling and enable a more real-time surveillance. Furthermore, the

    Feasibility of Cowpea chlorotic mottle virus-like particles as scaffold for epitope presentations

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    Within the last decade Virus-Like Particles (VLPs) have increasingly received attention from scientists for their use as a carrier of (peptide) molecules or as scaffold to present epitopes for use in subunit vaccines. To test the feasibility of Cowpea chlorotic mottle virus (CCMV) particles as a scaffold for epitope presentation and identify sites for epitope fusion or insertion that would not interfere with virus-like-particle formation, chimeric CCMV coat protein (CP) gene constructs were engineered, followed by expression in E. coli and assessment of VLP formation. Various constructs were made encoding a 6x-His-tag, or selected epitopes from Influenza A virus [IAV] (M2e, HA) or Foot and Mouth Disease Virus [FMDV] (VP1 and 2C). The epitopes were either inserted 1) in predicted exposed loop structures of the CCMV CP protein, 2) fused to the amino- (N) or carboxyl-terminal (C) ends, or 3) to a N-terminal 24 amino acid (aa) deletion mutant (NÂż24-CP) of the CP protein. Results High levels of insoluble protein expression, relative to proteins from the entire cell lysate, were obtained for CCMV CP and all chimeric derivatives. A straightforward protocol was used that, without the use of purification columns, successfully enabled CCMV CP protein solubilization, reassembly and subsequent collection of CCMV CP VLPs. While insertions of His-tag or M2e (7-23 aa) into the predicted external loop structures did abolish VLP formation, high yields of VLPs were obtained with all fusions of His-tag or various epitopes (13- 27 aa) from IAV and FMDV at the N- or C-terminal ends of CCMV CP or NÂż24-CP. VLPs derived from CCMV CP still encapsulated RNA, while those from CCMV CP-chimera containing a negatively charged N-terminal domain had lost this ability. The usefulness and rapid ease of exploitation of CCMV VLPs for the production of potential subunit vaccines was demonstrated with the synthesis of chimeric CCMV VLPs containing selected sequences from the G N and G C glycoproteins of the recently emerged Schmallenberg orthobunyavirus at both termini of the CP protein. Conclusions CCMV VLPs can be successfully exploited as scaffold for epitope fusions up to 31 aa at the N- and C-terminus, and at a N-terminal 24 amino acid (aa) deletion mutant (NÂż24-CP) of the CP protein

    Prevention of symptomatic thrombosis with short term (low molecular weight) heparin in patients with rheumatoid arthritis after hip or knee replacement

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    The need for prevention of venous thromboembolism (VTE) after total hip or knee replacement is obvious. However, the optimal regimen to achieve this remains to be defined. In patients with rheumatoid arthritis (RA) long term coumarins may not be necessary owing to the use of non-steroidal anti-inflammatory drugs (NSAIDs). 103 patients in whom 151 surgical procedures were performed (55( )hip and 96 knee prostheses) were treated only with short term subcutaneous heparin. NSAIDs were used daily in 85% of the patients, and they were continued after hospital discharge. Only one patient developed symptomatic deep venous thrombosis during one year follow up. Bleeding complications were seen in 20/151 (13%) of the surgical procedures, all clinically judged as minor, and recovery was not delayed except in one case. Short term (low molecular weight) heparin appears to be an adequate, simple, and safe method for prevention of symptomatic VTE in patients with RA after knee or hip replacement, though further studies are necessary to confirm these preliminary findings.


    H-NS-mediated repression of CRISPR-based immunity in Escherichia coli K12 can be relieved by the transcription activator LeuO

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    The recently discovered prokaryotic CRISPR/Cas defence system provides immunity against viral infections and plasmid conjugation. It has been demonstrated that in Escherichia coli transcription of the Cascade genes (casABCDE) and to some extent the CRISPR array is repressed by heat-stable nucleoid-structuring (H-NS) protein, a global transcriptional repressor. Here we elaborate on the control of the E. coli CRISPR/Cas system, and study the effect on CRISPR-based anti-viral immunity. Transformation of wild-type E. coli K12 with CRISPR spacers that are complementary to phage Lambda does not lead to detectable protection against Lambda infection. However, when an H-NS mutant of E. coli K12 is transformed with the same anti-Lambda CRISPR, this does result in reduced sensitivity to phage infection. In addition, it is demonstrated that LeuO, a LysR-type transcription factor, binds to two sites flanking the casA promoter and the H-NS nucleation site, resulting in derepression of casABCDE12 transcription. Overexpression of LeuO in E. coli K12 containing an anti-Lambda CRISPR leads to an enhanced protection against phage infection. This study demonstrates that in E. coli H-NS and LeuO are antagonistic regulators of CRISPR-based immunit

    Antibiotic Resistance and the Risk of Recurrent Bacteremia

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    Background Direct health effects of antibiotic resistance are difficult to assess. We quantified the risk of recurrent bacteremia associated with resistance. Methods We extracted antimicrobial susceptibility testing data on blood isolates from the Dutch surveillance system for antimicrobial resistance between 2008 and 2017. First and first recurrent (4-30 days) bacteremia episodes were categorized as susceptible, single nonsusceptible, or co-nonsusceptible to third-generation cephalosporins without or with carbapenems (Enterobacteriaceae), ceftazidime without or with carbapenems (Pseudomonas species), aminopenicillins without or with vancomycin (Enterococcus species), or as methicillin-sensitive/-resistant S. aureus (MSSA/MRSA). We calculated risks of recurrent bacteremia after nonsusceptible vs susceptible first bacteremia, estimated the crude population attributable effect of resistance for the Netherlands, and calculated risks of nonsusceptible recurrent bacteremia after a susceptible first episode. Results Risk ratios for recurrent bacteremia after a single- and co-nonsusceptible first episode, respectively, vs susceptible first episode, were 1.7 (95% confidence interval [CI], 1.5-2.0) and 5.2 (95% CI, 2.1-12.4) for Enterobacteriaceae, 1.3 (95% CI, 0.5-3.1) and 5.0 (95% CI, 2.9-8.5) for Pseudomonas species, 1.4 (95% CI, 1.2-1.7) and 1.6 (95% CI, 0.6-4.2) for Enterococcus species, and 1.6 (95% CI, 1.1-2.4) for MRSA vs MSSA. The estimated population annual number of recurrent bacteremias associated with nonsusceptibility was 40. The risk of nonsusceptible recurrent bacteremia after a susceptible first episode was at most 0.4% (Pseudomonas species). Conclusions Although antibiotic nonsusceptibility was consistently associated with higher risks of recurrent bacteremia, the estimated annual number of additional recurrent episodes in the Netherlands (40) was rather limited
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