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1.  Coordinate Hyperproduction of SmeZ and SmeJK Efflux Pumps Extends Drug Resistance in Stenotrophomonas maltophilia 
A Stenotrophomonas maltophilia mutant that coordinately hyper-expresses three resistance nodulation division-type efflux pump genes, smeZ, smeJ, and smeK, has been identified. SmeZ is responsible for elevating aminoglycoside MICs; SmeJ and SmeK are jointly responsible for elevating tetracycline, minocycline, and ciprofloxacin MICs and conferring levofloxacin resistance. One clinical isolate with this same phenotype was identified from a sample of six, and the isolate also coordinately hyper-expresses smeZ and smeJK, confirming the clinical relevance of our findings.
doi:10.1128/AAC.01020-12
PMCID: PMC3535947  PMID: 23147729
2.  Determinants of fracture risk in a UK-population-based cohort of older women: a cross-sectional analysis of the Cohort for Skeletal Health in Bristol and Avon (COSHIBA) 
Age and Ageing  2011;41(1):46-52.
Background: identification of individuals with high fracture risk from within primary care is complex. It is likely that the true contribution of falls to fracture risk is underestimated.
Methods: cross-sectional analysis of a population-based cohort of 3,200 post-menopausal women aged 73 ± 4 years. Self-reported data were collected on fracture, osteoporosis clinical risk factors and falls/mobility risk factors. Self-reported falls were compared with recorded falls on GP computerised records. Multivariable logistic regression was used to identify independent risk factors for fracture.
Results: a total of 838 (26.2%) reported a fracture after aged 50; 441 reported falling more than once per year, but 69% of these had no mention of falls on their computerised GP records. Only age [odds ratios (OR): 1.37 per 5 year increase, 95% confidence interval (CI): 1.23–1.53], height (1.02 per cm increase, 95% CI: 1.01–1.04), weight (OR: 0.99 per kg increase, 95% CI: 0.98–0.99) and falls (OR: 1.49 for more than once per year compared with less, 95% CI: 1.13–1.94) were independent risk factors for fracture. Falls had the strongest association.
Conclusion: when identifying individuals with high fracture risk we estimate that more than one fall per year is at least twice as important as height and weight. Furthermore, using self-reported falls data is essential as computerised GP records underestimate falls prevalence.
doi:10.1093/ageing/afr132
PMCID: PMC3234077  PMID: 22107913
fractures; falls; COSHIBA; FRAX; cohort study; elderly
3.  Patient-reported history of leg ulceration 12–16 years after total primary knee or hip replacement 
Acta Orthopaedica  2011;82(4):471-474.
Background and purpose
Deep vein thrombosis is common after total joint replacement. It is frequently asymptomatic, and it is unclear whether this leads to longer-term problems such as post-thrombotic syndrome and leg ulceration. We investigated whether the postoperative prevalence of ulceration in patients who had undergone primary total hip replacement (THR) or total knee replacement (TKR) was higher than that found in a control group who had not undergone total joint replacement.
Methods
The study group consisted of patients who had undergone THR or TKR at one orthopedic center 12–16 years previously without routine chemothromboprophylaxis, and who had not undergone revision surgery. The control group was recruited via primary care. All participants were recruited by post and asked to complete a questionnaire. Age- and sex-adjusted prevalence of self-reported leg ulceration was calculated, and logistic regression was used to determine whether there were any associations between THR or TKR and leg ulceration.
Results
Completed questionnaires were received from 441 THR patients (54% response rate), 196 TKR patients (48%) and 967 control participants (36%). No statistically significant differences in age- and sex-adjusted prevalence of ulceration were found between the groups, for either lifetime prevalence or prevalence over the previous 15 years.
Interpretation
Patients who undergo THR and TKR without chemothromboprophylaxis are unlikely to be at a higher risk of long-term venous ulceration than the normal population.
doi:10.3109/17453674.2011.596064
PMCID: PMC3237039  PMID: 21751860
4.  The complete genome, comparative and functional analysis of Stenotrophomonas maltophilia reveals an organism heavily shielded by drug resistance determinants 
Genome Biology  2008;9(4):R74.
The complete Stenotrophomonas maltophilia genome sequence suggests that it can act as a reservoir of antibiotic resistance determinants.
Background
Stenotrophomonas maltophilia is a nosocomial opportunistic pathogen of the Xanthomonadaceae. The organism has been isolated from both clinical and soil environments in addition to the sputum of cystic fibrosis patients and the immunocompromised. Whilst relatively distant phylogenetically, the closest sequenced relatives of S. maltophilia are the plant pathogenic xanthomonads.
Results
The genome of the bacteremia-associated isolate S. maltophilia K279a is 4,851,126 bp and of high G+C content. The sequence reveals an organism with a remarkable capacity for drug and heavy metal resistance. In addition to a number of genes conferring resistance to antimicrobial drugs of different classes via alternative mechanisms, nine resistance-nodulation-division (RND)-type putative antimicrobial efflux systems are present. Functional genomic analysis confirms a role in drug resistance for several of the novel RND efflux pumps. S. maltophilia possesses potentially mobile regions of DNA and encodes a number of pili and fimbriae likely to be involved in adhesion and biofilm formation that may also contribute to increased antimicrobial drug resistance.
Conclusion
The panoply of antimicrobial drug resistance genes and mobile genetic elements found suggests that the organism can act as a reservoir of antimicrobial drug resistance determinants in a clinical environment, which is an issue of considerable concern.
doi:10.1186/gb-2008-9-4-r74
PMCID: PMC2643945  PMID: 18419807
5.  nalD Encodes a Second Repressor of the mexAB-oprM Multidrug Efflux Operon of Pseudomonas aeruginosa▿  
Journal of Bacteriology  2006;188(24):8649-8654.
The Pseudomonas aeruginosa nalD gene encodes a TetR family repressor with homology to the SmeT and TtgR repressors of the smeDEF and ttgABC multidrug efflux systems of Stenotrophomonas maltophilia and Pseudomonas putida, respectively. A sequence upstream of mexAB-oprM and overlapping a second promoter for this efflux system was very similar to the SmeT and TtgR operator sequences, and NalD binding to this region was, in fact, demonstrated. Moreover, increased expression from this promoter was seen in a nalD mutant, consistent with NalD directly controlling mexAB-oprM expression from a second promoter.
doi:10.1128/JB.01342-06
PMCID: PMC1698243  PMID: 17028276

Results 1-5 (5)