Molecular characterization of a multidrug resistance IncF plasmid from the globally disseminated Escherichia coli ST131 clone.

Escherichia coli sequence type 131 (E. coli ST131) is a recently emerged and globally disseminated multidrug resistant clone associated with urinary tract and bloodstream infections. Plasmids represent a major vehicle for the carriage of antibiotic resistance genes in E. coli ST131. In this study, we determined the complete sequence and performed a comprehensive annotation of pEC958, an IncF plasmid from the E. coli ST131 reference strain EC958. Plasmid pEC958 is 135.6 kb in size, harbours two replicons (RepFIA and RepFII) and contains 12 antibiotic resistance genes (including the blaCTX-M-15 gene). We also carried out hyper-saturated transposon mutagenesis and multiplexed transposon directed insertion-site sequencing (TraDIS) to investigate the biology of pEC958. TraDIS data showed that while only the RepFII replicon was required for pEC958 replication, the RepFIA replicon contains genes essential for its partitioning. Thus, our data provides direct evidence that the RepFIA and RepFII replicons in pEC958 cooperate to ensure their stable inheritance. The gene encoding the antitoxin component (ccdA) of the post-segregational killing system CcdAB was also protected from mutagenesis, demonstrating this system is active. Sequence comparison with a global collection of ST131 strains suggest that IncF represents the most common type of plasmid in this clone, and underscores the need to understand its evolution and contribution to the spread of antibiotic resistance genes in E. coli ST131

Pain education for adolescents and young adults living beyond cancer: An interdisciplinary meeting report

© Copyright 2019, Mary Ann Liebert, Inc., publishers 2019. Pain is an understudied and undertreated consequence of cancer survival. Pain education is now a recommended treatment approach for persistent non-cancer pain, yet it has not been well applied to the context of adolescent and young adult (AYA) cancer survival. In March 2018, an interdisciplinary meeting was held in Adelaide, South Australia to set a research agenda for pain education in AYA cancer survivors. We identified that AYAs with persistent pain and those with heightened pain-related fear have the potential to benefit from pain education. We identified a number of unique challenges of engaging AYA survivors in pain education, and point towards future research directions

A randomised controlled trial of a theory-based intervention to improve sun protective behaviour in adolescents ('you can still be HOT in the shade'): study protocol

Background: Most skin cancers are preventable by encouraging consistent use of sun protective behaviour. In Australia, adolescents have high levels of knowledge and awareness of the risks of skin cancer but exhibit significantly lower sun protection behaviours than adults. There is limited research aimed at understanding why people do or do not engage in sun protective behaviour, and an associated absence of theory-based interventions to improve sun safe behaviour. This paper presents the study protocol for a school-based intervention which aims to improve the sun safe behaviour of adolescents. Methods/design: Approximately 400 adolescents (aged 12-17 years) will be recruited through Queensland, Australia public and private schools and randomized to the intervention (n = 200) or 'wait-list' control group (n = 200). The intervention focuses on encouraging supportive sun protective attitudes and beliefs, fostering perceptions of normative support for sun protection behaviour, and increasing perceptions of control/self-efficacy over using sun protection. It will be delivered during three × one hour sessions over a three week period from a trained facilitator during class time. Data will be collected one week pre-intervention (Time 1), and at one week (Time 2) and four weeks (Time 3) post-intervention. Primary outcomes are intentions to sun protect and sun protection behaviour. Secondary outcomes include attitudes toward performing sun protective behaviours (i.e., attitudes), perceptions of normative support to sun protect (i.e., subjective norms, group norms, and image norms), and perceived control over performing sun protective behaviours (i.e., perceived behavioural control). Discussion: The study will provide valuable information about the effectiveness of the intervention in improving the sun protective behaviour of adolescents

Lineage-Specific Methyltransferases Define the Methylome of the Globally Disseminated Escherichia coli ST131 Clone.

UNLABELLED: Escherichia coli sequence type 131 (ST131) is a clone of uropathogenic E. coli that has emerged rapidly and disseminated globally in both clinical and community settings. Members of the ST131 lineage from across the globe have been comprehensively characterized in terms of antibiotic resistance, virulence potential, and pathogenicity, but to date nothing is known about the methylome of these important human pathogens. Here we used single-molecule real-time (SMRT) PacBio sequencing to determine the methylome of E. coli EC958, the most-well-characterized completely sequenced ST131 strain. Our analysis of 52,081 methylated adenines in the genome of EC958 discovered three (m6)A methylation motifs that have not been described previously. Subsequent SMRT sequencing of isogenic knockout mutants identified the two type I methyltransferases (MTases) and one type IIG MTase responsible for (m6)A methylation of novel recognition sites. Although both type I sites were rare, the type IIG sites accounted for more than 12% of all methylated adenines in EC958. Analysis of the distribution of MTase genes across 95 ST131 genomes revealed their prevalence is highly conserved within the ST131 lineage, with most variation due to the presence or absence of mobile genetic elements on which individual MTase genes are located. IMPORTANCE: DNA modification plays a crucial role in bacterial regulation. Despite several examples demonstrating the role of methyltransferase (MTase) enzymes in bacterial virulence, investigation of this phenomenon on a whole-genome scale has remained elusive until now. Here we used single-molecule real-time (SMRT) sequencing to determine the first complete methylome of a strain from the multidrug-resistant E. coli sequence type 131 (ST131) lineage. By interrogating the methylome computationally and with further SMRT sequencing of isogenic mutants representing previously uncharacterized MTase genes, we defined the target sequences of three novel ST131-specific MTases and determined the genomic distribution of all MTase target sequences. Using a large collection of 95 previously sequenced ST131 genomes, we identified mobile genetic elements as a major factor driving diversity in DNA methylation patterns. Overall, our analysis highlights the potential for DNA methylation to dramatically influence gene regulation at the transcriptional level within a well-defined E. coli clone

Long-term myocardial recovery after mitral valve replacement in noncompaction cardiomyopathy

Isolated noncompaction of the left ventricle is a congenital cardiomyopathy, which has been described recently, with literature limited to case reports and case series. Even though various complications have been reported with noncompaction cardiomyopathy, among them severe mitral regurgitation has been reported recently in a few cases. There is no great evidence in the literature about its management, apart from some cases of mitral valve repair and replacement in young patients. We are reporting a case of an elderly lady with isolated left ventricular noncompaction cardiomyopathy associated with severe mitral regurgitation treated with mitral valve replacement with one and half year of follow up demonstrating significant myocardial recovery

Static stretching of the hamstring muscle for injury prevention in football codes: a systematic review

Purpose: Hamstring injuries are common among football players. There is still disagreement regarding prevention. The aim of this review is to determine whether static stretching reduces hamstring injuries in football codes. Methods: A systematic literature search was conducted on the online databases PubMed, PEDro, Cochrane, Web of Science, Bisp and Clinical Trial register. Study results were presented descriptively and the quality of the studies assessed were based on Cochrane’s ‘risk of bias’ tool. Results: The review identified 35 studies, including four analysis studies. These studies show deficiencies in the quality of study designs. Conclusion: The study protocols are varied in terms of the length of intervention and follow-up. No RCT studies are available, however, RCT studies should be conducted in the near future

How can latent trajectories of back pain be translated into defined subgroups?

Background: Similar types of trajectory patterns have been identified by Latent Class Analyses (LCA) across multiple low back pain (LBP) cohorts, but these patterns are impractical to apply to new cohorts or individual patients. It would be useful to be able to identify trajectory subgroups from descriptive definitions, as a way to apply the same definitions of mutually exclusive subgroups across populations. In this study, we investigated if the course trajectories of two LBP cohorts fitted with previously suggested trajectory subgroup definitions, how distinctly different these subgroups were, and if the subgroup definitions matched with LCA-derived patterns. Methods: Weekly measures of LBP intensity and frequency during 1 year were available from two clinical cohorts. We applied definitions of 16 possible trajectory subgroups to these observations and calculated the prevalence of the subgroups. The probability of belonging to each of eight LCA-derived patterns was determined within each subgroup. LBP intensity and frequency were described within subgroups and the subgroups of 'fluctuating' and 'episodic' LBP were compared on clinical characteristics. Results: All of 1077 observed trajectories fitted with the defined subgroups. 'Severe episodic LBP' was the most frequent pattern in both cohorts and 'ongoing LBP' was almost non-existing. There was a clear relationship between the defined trajectory subgroups and LCA-derived trajectory patterns, as in most subgroups, all patients had high probabilities of belonging to only one or two of the LCA patterns. The characteristics of the six defined subgroups with minor LBP were very similar. 'Fluctuating LBP' subgroups were significantly more distressed, had more intense leg pain, higher levels of activity limitation, and more negative expectations about future LBP than 'episodic LBP' subgroups. Conclusion: Previously suggested definitions of LBP trajectory subgroups could be readily applied to patients' observed data resulting in subgroups that matched well with LCA-derived trajectory patterns. We suggest that the number of trajectory subgroups can be reduced by merging some subgroups with minor LBP. Stable levels of LBP were almost not observed and we suggest that minor fluctuations in pain intensity might be conceptualised as 'ongoing LBP'. Lastly, we found clear support for distinguishing between fluctuating and episodic LBP