Role for DPP4 inhibitor therapy in cystic fibrosis related diabetes: A single centre experience.

Introduction: Insulin remains the only recommended medical treatment for cystic fibrosis related diabetes (CFRD) Whilst there is an established role for orally bioavailable incretin mimetic agents such as the dipeptidyl peptidase-4 inhibitors (DPP4-I) in Type 2 diabetes mellitus, there exists little data on their utility in CFRD.

Aim: To examine the use of DPP4-I therapy in patients with CFRD at a single large adult cystic fibrosis center.

Method: People with CFRD prescribed a DPP4-I were identified from our specialist CFRD clinic and records were retrospectively examined for indication for therapy, tolerability and effectiveness.

Exploiting breakdown in nonhost effector-target interactions to boost host disease resistance.

Plants are resistant to most microbial species due to nonhost resistance (NHR), providing broad-spectrum and durable immunity. However, the molecular components contributing to NHR are poorly characterised. We address the question of whether failure of pathogen effectors to manipulate nonhost plants plays a critical role in NHR.

Time-series transcriptomics reveals a BBX32-directed control of acclimation to high light in mature Arabidopsis leaves.

The photosynthetic capacity of mature leaves increases after several days' exposure to constant or intermittent episodes of high light (HL) and is manifested primarily as changes in chloroplast physiology. How this chloroplast-level acclimation to HL is initiated and controlled is unknown. From expanded Arabidopsis leaves, we determined HL-dependent changes in transcript abundance of 3844 genes in a 0-6 h time-series transcriptomics experiment.

Widespread premature transcription termination of NLR genes by the spen protein FPA.

Genes involved in disease resistance are some of the fastest evolving and most diverse components of genomes. Large numbers of nucleotide-binding, leucine-rich repeat (NLR) genes are found in plant genomes and are required for disease resistance. However, NLRs can trigger autoimmunity, disrupt beneficial microbiota or reduce fitness.

The Effect of a Quality Improvement Intervention on Sleep and Delirium in Critically Ill Patients in a Surgical ICU.

Background: Delirium is a deleterious condition affecting up to 60% of patients in the surgical ICU (SICU). Few SICU-focused delirium interventions have been implemented, including those addressing sleep-wake disruption, a modifiable delirium risk factor common in critically ill patients.

Research Question: What is the effect on delirium and sleep quality of a multicomponent nonpharmacologic intervention aimed at improving sleep-wake disruption in patients in the SICU setting?

Study Design And Methods: Using a staggered pre-post design, we implemented a quality improvement intervention in two SICUs (general surgery or trauma and cardiovascular) in an academic medical center.

Outcomes Following Immediate Vertical Rectus Abdominis Myocutaneous (VRAM) Flap-Based Perineal Reconstruction Following Resectional Surgery For Pelvic Malignancies.

Background: Increasingly radical surgery combined with neo-adjuvant radiotherapy present a challenge for the reconstructive surgeon. The study objective was to review outcomes of Vertical Rectus Abdominis Myocutaneous (VRAM) flap-based perineal reconstruction following resectional surgery for pelvic malignancies.

Methods: Single-centre retrospective analysis of patients undergoing immediate VRAM flap reconstruction of a perineal/pelvic defect for pelvic malignancy between July 2009 and November 2017.

ARMADILLO REPEAT ONLY proteins confine Rho GTPase signalling to polar growth sites.

Polar growth requires the precise tuning of Rho GTPase signalling at distinct plasma membrane domains. The activity of Rho of plant (ROP) GTPases is regulated by the opposing action of guanine nucleotide-exchange factors (GEFs) and GTPase-activating proteins (GAPs). Whereas plant-specific ROPGEFs have been shown to be embedded in higher-level regulatory mechanisms involving membrane-bound receptor-like kinases, the regulation of GAPs has remained enigmatic.

Downy Mildew effector HaRxL21 interacts with the transcriptional repressor TOPLESS to promote pathogen susceptibility.

Hyaloperonospora arabidopsidis (Hpa) is an oomycete pathogen causing Arabidopsis downy mildew. Effector proteins secreted from the pathogen into the plant play key roles in promoting infection by suppressing plant immunity and manipulating the host to the pathogen's advantage. One class of oomycete effectors share a conserved 'RxLR' motif critical for their translocation into the host cell.

Statement of the Independent Forensic Expert Group on Conversion Therapy.

Conversion therapy is a set of practices that aim to change or alter an individual's sexual orientation or gender identity. It is premised on a belief that an individual's sexual orientation or gender identity can be changed and that doing so is a desirable outcome for the individual, family, or community. Other terms used to describe this practice include sexual orientation change effort (SOCE), reparative therapy, reintegrative therapy, reorientation therapy, ex-gay therapy, and gay cure.

Impact of social deprivation, demographics and centre on HbA outcomes with continuous subcutaneous insulin infusion.

Aims: To assess the impact of social deprivation, demographics and centre on HbA outcomes with continuous subcutaneous insulin infusion (CSII) in adults with Type 1 diabetes.

Methods: Demographic data, postcode-derived English Index of Multiple Deprivation data and 12-month average HbA (mmol/mol) pre- and post-CSII were collated from three diabetes centres in the north west of England, University Hospital of South Manchester (UHSM), Salford Royal Foundation Hospital (SRFT) and Manchester Royal Infirmary (MRI). Univariable and multivariable regression models explored relationships between demographics, Index of Multiple Deprivation, centre and HbA outcomes.

Thrombocytosis as a Marker for Postoperative Complications in Colorectal Surgery.

Background: Blood platelet measurement is a widely available and inexpensive test that is performed routinely. Platelets are thought to act by inducing inflammation and play a role in clotting and antimicrobial defence. A postoperative rise in the platelet count (thrombocytosis) is often dismissed as an incidental finding, but there is growing evidence to suggest that it may act as an indicator to underlying pathology.

Meta-analysis of the prognostic value of CpG island methylator phenotype in rectal cancer.

Purpose: The pathological and prognostic importance of CpG island methylator phenotype (CIMP) in rectal cancer, as a sub-population of colorectal cancer, is unknown. A meta-analysis was preformed to estimate the prognostic significance of CIMP in rectal cancer.

Methods: A systematic search was performed of PubMed, Embase, MEDLINE, PubMed Central, and Cochrane electronic databases for articles pertaining to CIMP and rectal cancer.

Inflammatory cell ratios predict major septic complications following rectal cancer surgery.

Introduction: The inflammatory response is known to have an important role in tumourigenesis and the response to treatment. Previous studies have demonstrated that inflammatory cell ratios such as the neutrophil-to-lymphocyte ratio (NLR) can predict survival and recurrence following surgery for various cancers. The objective of this study was to demonstrate if pre-operative NLR has a role in predicting post-operative septic complications in patients undergoing rectal cancer surgery.

DNA hypermethylation as a predictor of extramural vascular invasion (EMVI) in rectal cancer.

Purpose: DNA hypermethylation in gene promoter regions (CpG islands) is emerging as an important pathway in colorectal cancer tumourigenesis. Whilst genetic mutations have been associated with extramural vascular invasion (EMVI) in rectal cancer, no such association has yet been made with epigenetic factors.

Methods: 100 consecutive neoadjuvant-naïve patients undergoing curative surgery for rectal were classified according to the presence or absence of EMVI on histopathological examination.

The Next Generation of Training for Arabidopsis Researchers: Bioinformatics and Quantitative Biology.

Training for experimental plant biologists needs to combine bioinformatics, quantitative approaches, computational biology, and training in the art of collaboration, best achieved through fully integrated curriculum development.

Extramural vascular invasion and response to neoadjuvant chemoradiotherapy in rectal cancer: Influence of the CpG island methylator phenotype.

Aim: To identify whether CpG island methylator phenotype (CIMP) is predictive of response to neoadjuvant chemoradiotherapy (NACRT) and outcomes in rectal cancer.

Methods: Patients undergoing NACRT and surgical resection for rectal cancer in a tertiary referral centre between 2002-2011 were identified. Pre-treatment tumour biopsies were analysed for CIMP status (high, intermediate or low) using methylation specific PCR.

Genetic and Epigenetic Intra-tumour Heterogeneity in Colorectal Cancer.

Introduction: Colorectal cancer (CRC) is a highly heterogeneous disease, with pathologically similar cancers having completely different responses to treatment and patient survival. Intra-tumour heterogeneity (defined as distinct morphological and phenotypic differences) has recently been demonstrated to be an important factor in the development and behaviour of cancer cells and can be used to determine response to anticancer therapy.

Method: Patients with resected CRC had DNA extracted from eight defined tumour areas which were analysed for two genetic mutations (BRAF and KRAS) and one epigenetic trait (CpG island methylator phenotype/CIMP).

The Transcription Factor ATHB5 Affects GA-Mediated Plasticity in Hypocotyl Cell Growth during Seed Germination.

Gibberellic acid (GA)-mediated cell expansion initiates the seed-to-seedling transition in plants and is repressed by DELLA proteins. Using digital single-cell analysis, we identified a cellular subdomain within the midhypocotyl, whose expansion drives the final step of this developmental transition under optimal conditions. Using network inference, the transcription factor ATHB5 was identified as a genetic factor whose localized expression promotes GA-mediated expansion specifically within these cells.

Protocol for a multicentre randomised feasibility trial evaluating early Surgery Alone In LOw Rectal cancer (SAILOR).

Introduction: There are 11 500 rectal cancers diagnosed annually in the UK. Although surgery remains the primary treatment, there is evidence that preoperative radiotherapy (RT) improves local recurrence rates. High-quality surgery in rectal cancer is equally important in minimising local recurrence.

Opportunities and Challenges in Developing a Cohort of Patients with Type 2 Diabetes Mellitus Using Electronic Primary Care Data.

Purpose: To develop a cohort of patients with T2DM treated with insulin using CPRD to obtain an accurate diagnosis date. This was used to analyse time from T2DM diagnosis to first ever insulin prescription between 01/01/2000 and 30/06/2012, for patients in England and Wales.

Methods: Patients aged 18 years and over at diagnosis, were included if prescribed an anti-diabetic drug and were excluded if first diagnosis-specific code was inconsistent with a T2DM diagnosis.

Locally advanced rectal cancer: management challenges.

Between 5% and 10% of patients with rectal cancer present with locally advanced rectal cancer (LARC), and 10% of rectal cancers recur after surgery, of which half are limited to locoregional disease only (locally recurrent rectal cancer). Exenterative surgery offers the best long-term outcomes for patients with LARC and locally recurrent rectal cancer so long as a complete (R0) resection is achieved. Accurate preoperative multimodal staging is crucial in assessing the potential operability of advanced rectal tumors, and resectability may be enhanced with neoadjuvant therapies.

Patterns of anti-diabetic medication use in patients with type 2 diabetes mellitus in England and Wales.

Purpose: The purpose of this study is to characterise how Type 2 Diabetes Mellitus (T2DM) is treated in England and Wales and whether this adheres to 2009 National Institute for Health and Care Excellence (NICE) guidance on management of T2DM.

Methods: Data for T2DM patients aged 18+ years prescribed at least one anti-diabetic drug between 01/01/2000-30/06/2012 were extracted from the Clinical Practice Research Datalink. We examined the sequences in which anti-diabetic drugs were prescribed and, for patients on the most common anti-diabetic drug pathways, evaluated average HbA1c values at treatment initiation and at progression to a second or third-line anti-diabetic drug class, including insulin.