Moving from non-emergency bleeps and long-range pagers to a hospital-wide, EHR-integrated secure messaging system: an implementer report.

Introduction: Obsolete bleep/long-range pager equipment remains firmly embedded in the National Health Service (NHS).

Objective: To introduce a secure, chart-integrated messaging system (Epic Secure Chat) in a large NHS tertiary referral centre to replace non-emergency bleeps/long-range pagers.

Methods: The system was socialised in the months before go-live.

Multicentre randomised controlled trial comparing standard and high resolution optical technologies in colorectal cancer screening.

Background And Objectives: The UK bowel cancer screening programme (BCSP) has been established for the early detection of colorectal cancer offering colonoscopy to patients screened positive by faecal occult blood tests. In this multisite, prospective, randomised controlled trial, we aimed to compare the performance of Standard Definition Olympus Lucera (SD-OL) with Scope Guide and the High Definition Pentax HiLine (HD-PHL).

Patients And Methods: Subjects undergoing a colonoscopy as part of the UK National BCSP at four UK sites were randomised to an endoscopy list run using either SD-OL or HD-PHL.

Dynamic control of endogenous metabolism with combinatorial logic circuits.

Controlling gene expression during a bioprocess enables real-time metabolic control, coordinated cellular responses, and staging order-of-operations. Achieving this with small molecule inducers is impractical at scale and dynamic circuits are difficult to design. Here, we show that the same set of sensors can be integrated by different combinatorial logic circuits to vary when genes are turned on and off during growth.

Probiotic strains detect and suppress cholera in mice.

Microbiota-modulating interventions are an emerging strategy to promote gastrointestinal homeostasis. Yet, their use in the detection, prevention, and treatment of acute infections remains underexplored. We report the basis of a probiotic-based strategy to promote colonization resistance and point-of-need diagnosis of cholera, an acute diarrheal disease caused by the pathogen Oral administration of , a common dietary fermentative bacterium, reduced intestinal burden and improved survival in infected infant mice through the production of lactic acid.

The Association of Geriatric Syndromes with Hospital Outcomes.

Background: Frailty, history of dementia (HoD), and acute confusional states (ACS) are common in older patients admitted to hospital.

Objective: To study the association of frailty (≥6 points in the Clinical Frailty Scale [CFS]), HoD, and ACS with hospital outcomes, controlling for age, gender, acute illness severity (measured by a Modified Early Warning Score in the emergency department), comorbidity (Charlson Comorbidity Index), and discharging specialty (general medicine, geriatric medicine, surgery).

Design: Retrospective observational study.

Creating Single-Copy Genetic Circuits.

Synthetic biology is increasingly used to develop sophisticated living devices for basic and applied research. Many of these genetic devices are engineered using multi-copy plasmids, but as the field progresses from proof-of-principle demonstrations to practical applications, it is important to develop single-copy synthetic modules that minimize consumption of cellular resources and can be stably maintained as genomic integrants. Here we use empirical design, mathematical modeling, and iterative construction and testing to build single-copy, bistable toggle switches with improved performance and reduced metabolic load that can be stably integrated into the host genome.

The McKittrick-Wheelock syndrome: a rare cause of curable diabetes.

Unlabelled: McKittrick-Wheelock syndrome (MWS) is a rare consequence of severe dehydration and electrolyte depletion due to mucinous diarrhoea secondary to a rectosigmoid villous adenoma. Reported cases of MWS commonly describe hypersecretion of mucinous diarrhoea in association with dehydration, hypokalaemia, hyponatraemia, hypochloraemia and pre-renal azotemia. Hyperglycaemia and diabetes are rarely reported manifestations of MWS.

'Deadman' and 'Passcode' microbial kill switches for bacterial containment.

Biocontainment systems that couple environmental sensing with circuit-based control of cell viability could be used to prevent escape of genetically modified microbes into the environment. Here we present two engineered safeguard systems known as the 'Deadman' and 'Passcode' kill switches. The Deadman kill switch uses unbalanced reciprocal transcriptional repression to couple a specific input signal with cell survival.

Boosting Wnt activity during colorectal cancer progression through selective hypermethylation of Wnt signaling antagonists.

Background: There is emerging evidence that Wnt pathway activity may increase during the progression from colorectal adenoma to carcinoma and that this increase is potentially an important step towards the invasive stage. Here, we investigated whether epigenetic silencing of Wnt antagonists is the biological driver for this increased Wnt activity in human tissues and how these methylation changes correlate with MSI (Microsatelite Instability) and CIMP (CpG Island Methylator Phenotype) statuses as well as known mutations in genes driving colorectal neoplasia.

Methods: We conducted a systematic analysis by pyrosequencing, to determine the promoter methylation of CpG islands associated with 17 Wnt signaling component genes.

Paper-based synthetic gene networks.

Synthetic gene networks have wide-ranging uses in reprogramming and rewiring organisms. To date, there has not been a way to harness the vast potential of these networks beyond the constraints of a laboratory or in vivo environment. Here, we present an in vitro paper-based platform that provides an alternate, versatile venue for synthetic biologists to operate and a much-needed medium for the safe deployment of engineered gene circuits beyond the lab.

Tunable protein degradation in bacteria.

Tunable control of protein degradation in bacteria would provide a powerful research tool. Here we use components of the Mesoplasma florum transfer-messenger RNA system to create a synthetic degradation system that provides both independent control of steady-state protein level and inducible degradation of targeted proteins in Escherichia coli. We demonstrate application of this system in synthetic circuit development and control of core bacterial processes and antibacterial targets, and we transfer the system to Lactococcus lactis to establish its broad functionality in bacteria.

Oral gel choline salicylate induced refractory gastric ulceration.

Common over the counter oral ulcer soothing gel can be an unexpected source of salicylate and cause refractory gastrointestinal ulcers if not identified.

A comparison of outcomes for adults and children undergoing resection for inflammatory bowel disease: is there a difference?

Background. The incidence of inflammatory bowel disease (IBD) is increasing in the paediatric population. Since 2007, a single surgeon whose main practice is in the treatment of adults has performed surgery for IBD in adults and children within two dedicated multidisciplinary teams.

A brief history of synthetic biology.

The ability to rationally engineer microorganisms has been a long-envisioned goal dating back more than a half-century. With the genomics revolution and rise of systems biology in the 1990s came the development of a rigorous engineering discipline to create, control and programme cellular behaviour. The resulting field, known as synthetic biology, has undergone dramatic growth throughout the past decade and is poised to transform biotechnology and medicine.

Safety of the colonoscope magnetic imaging device (ScopeGuide) in patients with implantable cardiac devices.

Background And Study Aims: Use of the colonoscope magnetic imaging device (ScopeGuide, Olympus Medical Systems, Tokyo, Japan) is currently contraindicated by the manufacturer for patients with implantable cardiac devices, a group of patients that is increasing annually along with the number of colonoscopies performed in the era of colorectal cancer screening. This is the first study to examine the safety of ScopeGuide in patients with permanent pacemakers, implantable cardioverter defibrillators, and cardiac resynchronization therapy.

Patients And Methods: Nonimplanted cardiac devices were exposed to the electromagnetic field of ScopeGuide ex vivo and assessed for evidence of interference or change in device settings.

Sir James Young Simpson and religion: myths and controversies.

This paper analyses two key aspects of the life and work of Sir James Young Simpson: his evangelical Christianity and his reaction to criticism following his use of anaesthesia in obstetrics. Simpson's personal religious struggle is placed in the context of the devastating events surrounding the Disruption of the established Church of Scotland in 1843. Whatever his involvement in the events of that year, the development of his faith demonstrates his simple evangelical conviction in the atonement of Christ, very much in keeping with that of many believers in Victorian Britain.

Comparison of Pentax HiLine and Olympus Lucera systems at screening colonoscopy.

Aim: To compare the performance characteristics of Pentax HiLine (PHL) (with i-scan) and Olympus Lucera (OL) systems in a screening population.

Methods: Screening colonoscopies in asymptomatic guaiac faecal occult blood test-positive patients with PHL (n = 58) and OL (n = 425) colonoscopes were analysed. All procedures were performed by a single colonoscopist.

A multidomain hub anchors the chromosome segregation and chemotactic machinery to the bacterial pole.

The cell poles constitute key subcellular domains that are often critical for motility, chemotaxis, and chromosome segregation in rod-shaped bacteria. However, in nearly all rods, the processes that underlie the formation, recognition, and perpetuation of the polar domains are largely unknown. Here, in Vibrio cholerae, we identified HubP (hub of the pole), a polar transmembrane protein conserved in all vibrios, that anchors three ParA-like ATPases to the cell poles and, through them, controls polar localization of the chromosome origin, the chemotactic machinery, and the flagellum.

Quorum sensing and a global regulator TsrA control expression of type VI secretion and virulence in Vibrio cholerae.

Vibrio cholerae is a human pathogen that causes the life-threatening diarrheal disease cholera. A type VI secretion system (T6SS) was recently shown to be required for full virulence in the O37 serogroup strain V52, which causes only sporadic human disease, but T6SS is not expressed in seventh pandemic O1 El Tor strains under standard laboratory conditions. In this study, we show that in the O1 El Tor strain C6706, T6SS is repressed by both quorum sensing and the uncharacterized protein VC0070 (TsrA).

A defined transposon mutant library and its use in identifying motility genes in Vibrio cholerae.

Defined mutant libraries allow for efficient genome-scale screening and provide a convenient collection of mutations in almost any nonessential gene of interest. Here, we present a near-saturating transposon insertion library in Vibrio cholerae strain C6706, a clinical isolate belonging to the O1 El Tor biotype responsible for the current cholera pandemic. Automated sequencing analysis of 23,312 mutants allowed us to build a 3,156-member subset library containing a representative insertion in every disrupted ORF.