Hydroxymethylation profile of cell-free DNA is a biomarker for early colorectal cancer.

Early detection of cancer will improve survival rates. The blood biomarker 5-hydroxymethylcytosine has been shown to discriminate cancer. In a large covariate-controlled study of over two thousand individual blood samples, we created, tested and explored the properties of a 5-hydroxymethylcytosine-based classifier to detect colorectal cancer (CRC).

Trail Use, Motivations, and Environmental Attitudes of 3780 European Mountain Bikers: What Is Sustainable?

Background: The extent to which mountain biking impacts upon the environment is largely determined by rider behaviours. The purpose of this study was to gain a better understanding of how mountain bikers interact with the natural environment and explore their attitudes towards sustainability.

Methods: 3780 European mountain bikers completed an online cross-sectional survey.

Immune Response of Elite Enduro Racers to Laboratory and Racing Environments: The Influence of Training Impulse and Vibration.

Introduction: Understanding the sport-specific immune response elicited during both training and competition is imperative to maximise athlete health and performance. Despite a growing population of professional enduro mountain bike athletes, little is known about the recovery of the immune system following enduro racing events.

Methods: Nine international level elite enduro mountain bike athletes (age 24.

SCAI expert consensus update on best practices in the cardiac catheterization laboratory: This statement was endorsed by the American College of Cardiology (ACC), the American Heart Association (AHA), and the Heart Rhythm Society (HRS) in April 2021.

The current document commissioned by the Society for Cardiovascular Angiography and Interventions (SCAI) and endorsed by the American College of Cardiology, the American Heart Association, and Heart Rhythm Society represents a comprehensive update to the 2012 and 2016 consensus documents on patient-centered best practices in the cardiac catheterization laboratory. Comprising updates to staffing and credentialing, as well as evidence-based updates to the pre-, intra-, and post-procedural logistics, clinical standards and patient flow, the document also includes an expanded section on CCL governance, administration, and approach to quality metrics. This update also acknowledges the collaboration with various specialties, including discussion of the heart team approach to management, and working with electrophysiology colleagues in particular.

Organizational Support in Healthcare Redesign Education: A Mixed-Methods Exploratory Study of Expert Coach and Executive Sponsor Experiences.

Healthcare organizations must continue to improve services to meet the rising demand and patient expectations. For this to occur, the health workforce needs to have knowledge and skills to design, implement, and evaluate service improvement interventions. Studies have shown that effective training in health service improvement and redesign combines didactic education with experiential project-based learning and on-the-ground coaching.

Learning in Practice: Collaboration Is the Way to Improve Health System Outcomes.

Evidence suggests that it is challenging for universities to develop workplace-relevant content and curricula by themselves, and this can lead to suboptimal educational outcomes. This paper examines the development, implementation, and evaluation of Australia's first tertiary graduate course in healthcare redesign, a partnership initiative between industry and university. The course not only provides students with an understanding of person-centered sustainable healthcare but also the skills and confidence to design, implement, and evaluate interventions to improve health service delivery.

AKR1D1 regulates glucocorticoid availability and glucocorticoid receptor activation in human hepatoma cells.

Steroid hormones, including glucocorticoids and androgens, have potent actions to regulate many cellular processes within the liver. The steroid A-ring reductase, 5β-reductase (AKR1D1), is predominantly expressed in the liver, where it inactivates steroid hormones and, in addition, plays a crucial role in bile acid synthesis. However, the precise functional role of AKR1D1 to regulate steroid hormone action in vitro has not been demonstrated.

The impact of leadership coaching in an Australian healthcare setting.

Purpose There is limited empirical literature on the effectiveness of leadership coaching in healthcare settings. The purpose of this paper is to explore the efficacy of leadership coaching for individuals implementing strategic change in the Australian public health system. Design/methodology/approach Using a within-subjects (pre-post) design, participants ( n=31) undertook six one-hour coaching sessions.

A novel bidirectional positive-feedback loop between Wnt-β-catenin and EGFR-ERK plays a role in context-specific modulation of epithelial tissue regeneration.

By operating as both a subunit of the cadherin complex and a key component of Wnt signalling, β-catenin acts as the lynchpin between cell-cell contact and transcriptional regulation of proliferation, coordinating epithelial tissue homeostasis and regeneration. The integration of multiple growth-regulatory inputs with β-catenin signalling has been observed in cancer-derived cells, yet the existence of pathway crosstalk in normal cells is unknown. Using a highly regenerative normal human epithelial culture system that displays contact inhibition, we demonstrate that the receptor tyrosine kinase (RTK)-driven MAPK and Wnt-β-catenin signalling axes form a bidirectional positive-feedback loop to drive cellular proliferation.

Differential expression of Oct4 variants and pseudogenes in normal urothelium and urothelial cancer.

The transcription factor octamer-binding protein 4 (Oct4; encoded by POU5F1) has a key role in maintaining embryonic stem cell pluripotency during early embryonic development and it is required for generation of induced pluripotent stem cells. Controversy exists concerning Oct4 expression in somatic tissues, with reports that Oct4 is expressed in normal and in neoplastic urothelium carrying implications for a bladder cancer stem cell phenotype. Here, we show that the pluripotency-associated Oct4A transcript was absent from cultures of highly regenerative normal human urothelial cells and from low-grade to high-grade urothelial carcinoma cell lines, whereas alternatively spliced variants and transcribed pseudogenes were expressed in abundance.

Functional expression of purinergic P2 receptors and transient receptor potential channels by the human urothelium.

In addition to its role as a physical barrier, the urothelium is considered to play an active role in mechanosensation. A key mechanism is the release of transient mediators that activate purinergic P2 receptors and transient receptor potential (TRP) channels to effect changes in intracellular Ca²⁺. Despite the implied importance of these receptors and channels in urothelial tissue homeostasis and dysfunctional bladder disease, little is known about their functional expression by the human urothelium.

Differentiation-associated reprogramming of the transforming growth factor β receptor pathway establishes the circuitry for epithelial autocrine/paracrine repair.

Transforming growth factor (TGF) β has diverse and sometimes paradoxical effects on cell proliferation and differentiation, presumably reflecting a fundamental but incompletely-understood role in regulating tissue homeostasis. It is generally considered that downstream activity is modulated at the ligand:receptor axis, but microarray analysis of proliferative versus differentiating normal human bladder epithelial cell cultures identified unexpected transcriptional changes in key components of the canonical TGFβ R/activin signalling pathway associated with cytodifferentiation. Changes included upregulation of the transcriptional modulator SMAD3 and downregulation of inhibitory modulators SMURF2 and SMAD7.

Aquaporin expression contributes to human transurothelial permeability in vitro and is modulated by NaCl.

It is generally considered that the bladder is impervious and stores urine in unmodified form on account of the barrier imposed by the highly-specialised uro-epithelial lining. However, recent evidence, including demonstration of aquaporin (AQP) expression by human urothelium, suggests that urothelium may be able to modify urine content. Here we have we applied functional assays to an in vitro-differentiated normal human urothelial cell culture system and examined both whether AQP expression was responsive to changes in osmolality, and the effects of blocking AQP channels on water and urea transport.

Deregulation of Rab and Rab effector genes in bladder cancer.

Growing evidence indicates that Rab GTPases, key regulators of intracellular transport in eukaryotic cells, play an important role in cancer. We analysed the deregulation at the transcriptional level of the genes encoding Rab proteins and Rab-interacting proteins in bladder cancer pathogenesis, distinguishing between the two main progression pathways so far identified in bladder cancer: the Ta pathway characterized by a high frequency of FGFR3 mutation and the carcinoma in situ pathway where no or infrequent FGFR3 mutations have been identified. A systematic literature search identified 61 genes encoding Rab proteins and 223 genes encoding Rab-interacting proteins.

Immortalisation of normal human urothelial cells compromises differentiation capacity.

Background: The development of urothelial malignancy is not solely a consequence of loss of proliferation constraints but also involves loss of cellular differentiation, defined histopathologically as grade. Although tumour grade is an independent prognostic marker for urothelial carcinoma (UC), the molecular events underpinning the loss of urothelial differentiation are poorly understood.

Objective: To examine the effect of gene alterations implicated in UC development on the ability of human urothelial cells to undergo molecular differentiation and form a functional urothelial barrier.

Differential regulation of growth-promoting signalling pathways by E-cadherin.

Background: Despite the well-documented association between loss of E-cadherin and carcinogenesis, as well as the link between restoration of its expression and suppression of proliferation in carcinoma cells, the ability of E-cadherin to modulate growth-promoting cell signalling in normal epithelial cells is less well understood and frequently contradictory. The potential for E-cadherin to co-ordinate different proliferation-associated signalling pathways has yet to be fully explored.

Methodology/principal Findings: Using a normal human urothelial (NHU) cell culture system and following a calcium-switch approach, we demonstrate that the stability of NHU cell-cell contacts differentially regulates the Epidermal Growth Factor Receptor (EGFR)/Extracellular Signal-Regulated Kinase (ERK) and Phosphatidylinositol 3-Kinase (PI3-K)/AKT pathways.

Minimizing the complications associated with migrating catheters.

This article seeks to explore the clinical practice of urinary catheter fixation. Traditionally, this area of practice has been neglected and nurses are familiar with tension lesions and dermal problems associated with inappropriate or incorrect urinary catheter fixation. A novel solution to this problem is a catheter fixation device.

Risk of malnutrition in a sample of acute and long-stay NHS Fife in-patients: an audit.

Background: Hospital malnutrition (undernutrition) continues to attract concern. The implementation of standards for food and fluids in Scotland provided the stimulus for an audit of current practices in NHS Fife hospitals in order to provide baseline data with which to evaluate progress.

Methods: One hundred and fifty in-patients were recruited from wards likely to yield those with a high risk of malnutrition.

Effects of advice on dietary intake and/or physical activity on body composition, blood lipids and insulin resistance following a low-fat, sucrose-containing, high-carbohydrate, energy-restricted diet.

Aim: To determine the effect of dietary advice in conjunction with advice to increase physical activity on the body composition, blood lipid and insulin profiles in overweight women.

Design: A 12-week randomized controlled intervention study. subjects were assigned to one of four groups: (1) no advice, (2) low-fat, high-carbohydrate (including sucrose) energy-reduced diet, (3) 60 min/day brisk walking, and (4) diet and activity advice as previous.

Investigation into potential mechanisms promoting biocompatibility of polymeric biomaterials containing the phosphorylcholine moiety. A physicochemical and biological study.

Phosphorylcholine (PC) moieties were chemically attached to surfaces of polymer microparticles by addition of 2-methylacryloyloxyethyl phosphorylcholine monomer to the seeded, semi-continuous polymerisations of methyl methacrylate (MMA) and butyl acrylate (BA). The surface of the bio-functionalised polymer microparticles was principally characterised using X-ray photoelectron spectroscopy (XPS), dynamic nuclear magnetic resonance (NMR) spectroscopy, scanning electron microscopy (SEM), photon correlation spectroscopy (PCS), acoustophoresis and enzyme-linked immunosorbent assays (ELISA). It was found that the persulphate initiating species are concealed behind the phosphorylcholine containing monomer sequence located on the surface of the microparticles.

An artist's perspective on body image, the media, and contemporary society.

The purpose of The Body Image Project is to help in the fight to change the way we look at ourselves and at others. By using the human body as subject matter, I am trying to focus on aesthetic appreciation of the human form and to deal with self-worth by exploring the concept of beauty. Unfortunately, our culture has become obsessed with the image and keeping up appearances.

Wettable phosphorylcholine-containing polymers useful in blood filtration.

The use of phosphorylcholine (PC)-containing polymers has long been acknowledged as a method to improve the haemocompatibility of blood contacting devices. Such polymers were investigated for coating leukocyte filters, as a means of preserving precious platelet numbers and function. It was demonstrated that by use of such coated filters, the platelet recovery could be significantly increased by some 30%.

Local gene transfer of phVEGF-2 plasmid by gene-eluting stents: an alternative strategy for inhibition of restenosis.

Background: Drug-eluting stents represent a useful strategy for the prevention of restenosis using various antiproliferative drugs. These strategies share the liability of impairing endothelial recovery, thereby altering the natural biology of the vessel wall and increasing the associated risk of stent thrombosis. Accordingly, we tested the hypothesis that local delivery via gene-eluting stent of naked plasmid DNA encoding for human vascular endothelial growth factor (VEGF)-2 could achieve similar reductions in neointima formation while accelerating, rather than inhibiting, reendothelialization.

Biological evaluation and drug delivery application of cationically modified phospholipid polymers.

Phospholipid-like polymers based on 2-methacryloyloxyethyl phosphorylcholine containing varying amounts of the cationically charged monomer choline methacrylate (CMA) from 0 to 30 wt% have been prepared. Substrates coated with these materials were shown to bind significantly lower amounts of specific proteins compared to the uncoated control. ELISA assays demonstrated that fibrinogen did not bind appreciably to coatings containing 0-30% CMA, whereas albumin binding was seen to increase significantly as the CMA content of the coating increased.