An Investigation Into the Risk Factors for Transfusion Need After Neck of Femur Fracture Surgery.

Background: A common surgical procedure in the elderly is the operation on neck of femur fractures, with a primary complication being the need for a postoperative blood transfusion. Consequently, current standard practice involves cross-matching two units of red blood cells for each patient preoperatively. This incurs significant costs and is associated with blood product complications for transfused patients who are at low risk.

Emotional memory bias in adolescents with chronic pain: examining the relationship with neural, stress, and psychological factors.

Memory biases for pain-related information may contribute to the development and maintenance of chronic pain; however, evidence for when (and for whom) these biases occur is mixed. Therefore, we examined neural, stress, and psychological factors that could influence memory bias, focusing on memories that motivate disabling behaviors: pain perception, conditioned responses to threat-and-safety cues, and responses to aversive nonnoxious stimuli. Two studies were conducted with adolescents with and without chronic pain.

Use of tRNA gene barriers improves stability of transgene expression in CHO cells.

Instability of transgene expression is a major challenge for the biopharmaceutical industry, which can impact yields and regulatory approval. Some tRNA genes (tDNAs) can resist epigenetic silencing, the principal mechanism of expression instability, and protect adjacent genes against the spread of repressive heterochromatin. We have taken two naturally occurring clusters of human tDNAs and tested their ability to reduce epigenetic silencing of transgenes integrated into the genome of Chinese hamster ovary (CHO) cells.

Probing white matter microstructure in youth with chronic pain and its relation to catastrophizing using neurite orientation dispersion and density imaging.

Chronic pain is common in young people and can have a major life impact. Despite the burden of chronic pain, mechanisms underlying chronic pain development and persistence are still poorly understood. Specifically, white matter (WM) connectivity has remained largely unexplored in pediatric chronic pain.

Signature for Pain Recovery IN Teens (SPRINT): protocol for a multisite prospective signature study in chronic musculoskeletal pain.

Introduction: Current treatments for chronic musculoskeletal (MSK) pain are suboptimal. Discovery of robust prognostic markers separating patients who recover from patients with persistent pain and disability is critical for developing patient-specific treatment strategies and conceiving novel approaches that benefit all patients. Given that chronic pain is a biopsychosocial process, this study aims to discover and validate a robust prognostic signature that measures across multiple dimensions in the same adolescent patient cohort with a computational analysis pipeline.

The Human and Mouse Islet Peptidome: Effects of Obesity and Type 2 Diabetes, and Assessment of Intraislet Production of Glucagon-like Peptide-1.

To characterize the impact of metabolic disease on the peptidome of human and mouse pancreatic islets, LC-MS was used to analyze extracts of human and mouse islets, purified mouse alpha, beta, and delta cells, supernatants from mouse islet incubations, and plasma from patients with type 2 diabetes. Islets were obtained from healthy and type 2 diabetic human donors, and mice on chow or high fat diet. All major islet hormones were detected in lysed islets as well as numerous peptides from vesicular proteins including granins and processing enzymes.

A cross-platform approach identifies genetic regulators of human metabolism and health.

In cross-platform analyses of 174 metabolites, we identify 499 associations (P < 4.9 × 10) characterized by pleiotropy, allelic heterogeneity, large and nonlinear effects and enrichment for nonsynonymous variation. We identify a signal at GLP2R (p.

The neural correlates of pain-related fear: A meta-analysis comparing fear conditioning studies using painful and non-painful stimuli.

Compared to the field of anxiety research, the use of fear conditioning paradigms for studying chronic pain is relatively novel. Developments in identifying the neural correlates of pain-related fear are important for understanding the mechanisms underlying chronic pain and warrant synthesis to establish the state-of-the-art. Using effect-size signed differential mapping, this meta-analysis combined nine MRI studies and compared the overlap in these correlates of pain-related fear to those of other non-pain-related conditioned fears (55 studies).

The acquisition and generalization of fear of touch.

Objectives Contemporary fear-avoidance models of chronic pain posit that fear of pain, and overgeneralization of fear to non-threatening stimuli is a potential pathway to chronic pain. While increasing experimental evidence supports this hypothesis, a comprehensive investigation requires testing in multiple modalities due to the diversity of symptomatology among individuals with chronic pain. In the present study we used an established tactile fear conditioning paradigm as an experimental model of allodynia and spontaneous pain fluctuations, to investigate whether stimulus generalization occurs resulting in fear of touch spreading to new locations.

Glucose-Dependent Insulinotropic Polypeptide Receptor-Expressing Cells in the Hypothalamus Regulate Food Intake.

Ambiguity regarding the role of glucose-dependent insulinotropic polypeptide (GIP) in obesity arises from conflicting reports asserting that both GIP receptor (GIPR) agonism and antagonism are effective strategies for inhibiting weight gain. To enable identification and manipulation of Gipr-expressing (Gipr) cells, we created Gipr-Cre knockin mice. As GIPR-agonists have recently been reported to suppress food intake, we aimed to identify central mediators of this effect.

Important Role of the GLP-1 Axis for Glucose Homeostasis after Bariatric Surgery.

Bariatric surgery is widely used to treat obesity and improves type 2 diabetes beyond expectations from the degree of weight loss. Elevated post-prandial concentrations of glucagon-like peptide 1 (GLP-1), peptide YY (PYY), and insulin are widely reported, but the importance of GLP-1 in post-bariatric physiology remains debated. Here, we show that GLP-1 is a major driver of insulin secretion after bariatric surgery, as demonstrated by blocking GLP-1 receptors (GLP1Rs) post-gastrectomy in lean humans using Exendin-9 or in mice using an anti-GLP1R antibody.

Itraconazole targets cell cycle heterogeneity in colorectal cancer.

Cellular dormancy and heterogeneity in cell cycle length provide important explanations for treatment failure after adjuvant therapy with S-phase cytotoxics in colorectal cancer (CRC), yet the molecular control of the dormant versus cycling state remains unknown. We sought to understand the molecular features of dormant CRC cells to facilitate rationale identification of compounds to target both dormant and cycling tumor cells. Unexpectedly, we demonstrate that dormant CRC cells are differentiated, yet retain clonogenic capacity.

Development and characterisation of a novel glucagon like peptide-1 receptor antibody.

Aims/hypothesis: Glucagon like peptide-1 (GLP-1) enhances glucose-dependent insulin secretion by binding to GLP-1 receptors (GLP1Rs) on pancreatic beta cells. GLP-1 mimetics are used in the clinic for the treatment of type 2 diabetes, but despite their therapeutic success, several clinical effects of GLP-1 remain unexplained at a mechanistic level, particularly in extrapancreatic tissues. The aim of this study was to generate and characterise a monoclonal antagonistic antibody for the GLP1R for use in vivo.

The Acquisition and Extinction of Fear of Painful Touch: A Novel Tactile Fear Conditioning Paradigm.

Unlabelled: Fear of touch, due to allodynia and spontaneous pain, is not well understood. Experimental methods to advance this topic are lacking, and therefore we propose a novel tactile conditioning paradigm. Seventy-six pain-free participants underwent acquisition in a predictable as well as an unpredictable pain context.

Scaling it down: new in vitro tools to get the balance right.

Treatments for diabetes and obesity based on enteroendocrine hormones are a focus of research interest, partly due to the successes of glucagon-like peptide-1 (GLP-1) mimetic peptides in the treatment of diabetes and the correlation of altered enteroendocrine profiles with the positive metabolic outcomes of gastric bypass surgery. It is thought that simultaneous stimulation of more than one receptor might mimic the superior efficacy of the latter and dual or triple-agonist peptides are under investigation. An important step in developing multiple agonists is to establish the relative pharmacological potency and efficacy of new molecules at its different target receptors, and to optimise the balance of activities to achieve the desired treatment outcome.