Integration of vanHAX downstream of a ribosomal RNA operon restores vancomycin resistance in a susceptible Enterococcus faecium strain.

During the genomic characterisation of Enterococcus faecium strains (n = 39) collected in a haematology ward, we identified an isolate (OI25), which contained vanA-type vancomycin resistance genes but was phenotypically susceptible to vancomycin. OI25 could revert to resistance when cultured in the presence of vancomycin and was thus considered to be vancomycin-variable. Long-read sequencing was used to identify structural variations within the vancomycin resistance region of OI25 and to uncover its resistance reversion mechanism.

Non-antibiotic pharmaceuticals are toxic against Escherichia coli with no evolution of cross-resistance to antibiotics.

Antimicrobial resistance can arise in the natural environment via prolonged exposure to the effluent released by manufacturing facilities. In addition to antibiotics, pharmaceutical plants also produce non-antibiotic pharmaceuticals, both the active ingredients and other components of the formulations. The effect of these on the surrounding microbial communities is less clear.

Longitudinal genomic surveillance of a UK intensive care unit shows a lack of patient colonisation by multi-drug-resistant Gram-negative bacterial pathogens.

Vulnerable patients in an intensive care unit (ICU) setting are at high risk of infection from bacteria including gut-colonising and species. Complex ICU procedures often depend on successful antimicrobial treatment, underscoring the importance of understanding the extent of patient colonisation by multi-drug-resistant organisms (MDROs) in large UK ICUs. Previous work on ICUs globally uncovered high rates of colonisation by transmission of MDROs, but the situation in UK ICUs is less understood.

Multidrug resistance plasmids commonly reprogram the expression of metabolic genes in .

Unlabelled: Multidrug-resistant is a leading cause of global mortality. Transfer of plasmids carrying genes encoding beta-lactamases, carbapenamases, and colistin resistance between lineages is driving the rising rates of hard-to-treat nosocomial and community infections. Multidrug resistance (MDR) plasmid acquisition commonly causes transcriptional disruption, and while a number of studies have shown strain-specific fitness and transcriptional effects of an MDR plasmid across diverse bacterial lineages, fewer studies have compared the impacts of different MDR plasmids in a common bacterial host.

Parallel loss of type VI secretion systems in two multi-drug-resistant lineages.

The repeated emergence of multi-drug-resistant (MDR) clones is a threat to public health globally. In recent work, drug-resistant were shown to be capable of displacing commensal in the human gut. Given the rapid colonization observed in travel studies, it is possible that the presence of a type VI secretion system (T6SS) may be responsible for the rapid competitive advantage of drug-resistant clones.

The highly diverse plasmid population found in colonizing travellers to Laos and its role in antimicrobial resistance gene carriage.

Increased colonization by antimicrobial-resistant organisms is closely associated with international travel. This study investigated the diversity of mobile genetic elements involved with antimicrobial resistance (AMR) gene carriage in extended-spectrum beta-lactamase (ESBL)-producing that colonized travellers to Laos. Long-read sequencing was used to reconstruct complete plasmid sequences from 48 isolates obtained from the daily stool samples of 23 travellers over a 3 week period.

The role of potentiating mutations in the evolution of pandemic Escherichia coli clones.

The Escherichia coli species exhibits a vast array of variable lifestyles, including environmental, commensal, and pathogenic organisms. Many of these E. coli contribute significantly to the global threat of antimicrobial resistance (AMR).

Dynamics of intestinal multidrug-resistant bacteria colonisation contracted by visitors to a high-endemic setting: a prospective, daily, real-time sampling study.

Background: Antimicrobial resistance is highly prevalent in low-income and middle-income countries. International travel contributes substantially to the global spread of intestinal multidrug-resistant Gram-negative bacteria. Hundreds of millions of annual visitors to low-income and middle-income countries are all exposed to intestinal multidrug-resistant Gram-negative bacteria resulting in 30-70% of them being colonised at their return.

Transcriptomic and Functional Screens Reveal MicroRNAs That Modulate Prostate Cancer Metastasis.

Identifying new mechanisms that underlie the complex process of metastasis is vital to combat this fatal step in prostate cancer (PCa) progression. Small non-coding RNAs are emerging as important regulators of tumor cell biology. Here we take an integrative approach to elucidate the contribution of microRNAs to metastatic progression, combining transcriptomic analysis with functional screens for migration and morphology.

Tumour-derived alkaline phosphatase regulates tumour growth, epithelial plasticity and disease-free survival in metastatic prostate cancer.

Background: Recent evidence suggests that bone-related parameters are the main prognostic factors for overall survival in advanced prostate cancer (PCa), with elevated circulating levels of alkaline phosphatase (ALP) thought to reflect the dysregulated bone formation accompanying distant metastases. We have identified that PCa cells express ALPL, the gene that encodes for tissue nonspecific ALP, and hypothesised that tumour-derived ALPL may contribute to disease progression.

Methods: Functional effects of ALPL inhibition were investigated in metastatic PCa cell lines.

Dystonia.

Introduction: Dystonia is usually a lifelong condition with persistent pain and disability. Focal dystonia affects a single part of the body; generalised dystonia can affect most or all of the body. It is more common in women, and some types of dystonia are more common in people of Ashkenazi descent.

Nursing the tropics: nurses as agents of imperial hygiene.

Background: Mrs Francis Piggott proposed the Colonial Nursing Association in 1895 as a means of supplying Britain's colonies and dominions with trained professional nurses, who would support the health of white colonists abroad. Over 8400 nurses were placed between 1896 and the Association's end in 1966. Despite the burgeoning of scholarship on gender and empire over the last few decades, there is still more research to be done examining nurses as professional, working women, who present a fascinating variation on the figure of the woman traveler.

Changing trends in surgery for Graves' disease: a cohort comparison of those having surgery intended to preserve thyroid function with those having ablative surgery.

Background: Surgery for Graves' disease may be performed with the intent of preserving thyroid function (subtotal thyroidectomy) or ablating thyroid function (total thyroidectomy). This study examines the evolving practice in a specialist endocrine surgical unit.

Method: Longitudinal cohort study of patients undergoing surgery for Graves' disease between 1986 and 2008.

Non-pharmacological interventions to reduce the risk of diabetes in people with impaired glucose regulation: a systematic review and economic evaluation.

Background: The prevalence of type 2 diabetes mellitus (T2DM) is increasing in the UK and worldwide. Before the onset of T2DM, there are two conditions characterised by blood glucose levels that are above normal but below the threshold for diabetes. If screening for T2DM in introduced, many people with impaired glucose tolerance (IGT) will be found and it is necessary to consider how they should be treated.

Glucagon-like peptide analogues for type 2 diabetes mellitus.

Background: Glucagon-like peptide analogues are a new class of drugs used in the treatment of type 2 diabetes that mimic the endogenous hormone glucagon-like peptide 1 (GLP-1). GLP-1 is an incretin, a gastrointestinal hormone that is released into the circulation in response to ingested nutrients. GLP-1 regulates glucose levels by stimulating glucose-dependent insulin secretion and biosynthesis, and by suppressing glucagon secretion, delayed gastric emptying and promoting satiety.

Dystonia.

Introduction: Dystonia is usually a lifelong condition with persistent pain and disability. Focal dystonia affects a single part of the body; generalised dystonia can affect most or all of the body. It is more common in women, and some types of dystonia are more common in people of European Ashkenazi Jewish descent.

Systematic review of outcome of downstaging hepatocellular cancer before liver transplantation in patients outside the Milan criteria.

Background: The aim of this systematic review was to assess the evidence on tumour downstaging before liver transplantation in patients with hepatocellular carcinoma (HCC) initially staged beyond the Milan criteria.

Methods: MEDLINE (from 1952), Embase (from 1980) and the Cochrane Library were searched. The review included cohort studies that reported the outcomes of patients with HCC outside the Milan criteria who underwent downstaging before transplantation.

(Author)ity abroad: the life writing of colonial nurses.

Objectives: This paper asserts the significance of nurses' writing within the developing field of life writing studies. It closely examines selected letters written by nurses in the Colonial Nursing Association (CNA) and models pertinent methods of literary analysis, in order to illuminate nurses' experiences and their skills of self-authorship. The figure of the CNA nurse is an especially rich subject for study: while these women travelled across political and geographical boundaries, they also demonstrated especially flexible and multifaceted 'travelling' identities.

Clinical effectiveness and cost-effectiveness of continuous subcutaneous insulin infusion for diabetes: systematic review and economic evaluation.

Background: The National Institute for Health and Clinical Excellence (NICE) was reviewing its previous guidance on continuous subcutaneous insulin infusion (CSII). The review provided an assessment of evidence which had been published since the previous NICE appraisal (TA 151) in 2007.

Objectives: To examine the clinical effectiveness and cost-effectiveness of using CSII to treat diabetes.

Helicobacter pylori: host genetics and disease outcomes.

Helicobacter pylori infection is the most common chronic bacterial infection worldwide and is associated with divergent clinical outcomes that range from simple asymptomatic gastritis to more serious conditions, such as peptic ulcer disease and gastric cancer. The key determinants of these outcomes are the severity and distribution of H. pylori-induced gastritis.

The potential for interaction between warfarin and coprescribed medication: a retrospective study in primary care.

Background And Objective: Warfarin is commonly involved in drug-related hospital admissions. The drug is most commonly prescribed to elderly patients in whom polypharmacy is common and, when administered in combination with other drugs such as NSAIDs, aspirin (acetylsalicylic acid) or macrolide antibacterials, is associated with increased bleeding risk. The aim of this study was to investigate the prevalence of prescriptions that might give rise to clinically relevant drug-drug interactions in a warfarinized population.

Dystonia.

Introduction: Dystonia is usually a lifelong condition with persistent pain and disability. Focal dystonia affects a single part of the body; generalised dystonia can affect most or all of the body. It is more common in women, and some types of dystonia are more common in people of European Ashkenazi Jewish descent.

The effectiveness and cost-effectiveness of cinacalcet for secondary hyperparathyroidism in end-stage renal disease patients on dialysis: a systematic review and economic evaluation.

Objectives: To establish the effectiveness and cost-effectiveness of cinacalcet for the treatment of secondary hyperparathyroidism (SHPT) for people on dialysis due to end-stage renal disease (ESRD).

Data Sources: Electronic databases were searched up to February 2006.

Review Methods: Included randomised controlled trials (RCTs) on the clinical effectiveness of cinacalcet for SHPT in ESRD were critically appraised, had relevant data extracted and were summarised narratively.

Attitudes and experiences of community pharmacists towards paediatric off-label prescribing: a prospective survey.

Aim: To identify community pharmacist experiences of, and attitudes towards paediatric off-label prescribing.

Methods: A prospective questionnaire-based study, with a 21-item questionnaire issued to 1500 randomly selected community pharmacies throughout the UK during 2005 on three separate occasions.

Results: Four hundred and eighty-two (32.