Early motion and directed exercise (EMADE) versus usual care post ankle fracture fixation: study protocol for a pragmatic randomised controlled trial

Background: Following surgical fixation of ankle fractures, the traditional management has included immobilisation for 6 weeks in a below-knee cast. However, this can lead to disuse atrophy of the affected leg and joint stiffness. While early rehabilitation from 2 weeks post surgery is viewed as safe, controversy remains regarding its benefits. We will compare the effectiveness of early motion and directed exercise (EMADE) ankle rehabilitation, against usual care, i.e. 6 weeks’ immobilisation in a below-knee cast. Method/design: We have designed a pragmatic randomised controlled trial (p-RCT) to compare the EMADE intervention against usual care. We will recruit 144 independently living adult participants, absent of tissue-healing comorbidities, who have undergone surgical stabilisation of isolated Weber B ankle fractures. The EMADE intervention consists of a non-weight-bearing progressive home exercise programme, complemented with manual therapy and education. Usual care consists of immobilisation in a non-weight-bearing below-knee cast. The intervention period is between week 2 and week 6 post surgery. The primary outcome is the Olerud and Molander Ankle Score (OMAS) patient-reported outcome measure (PROM) at 12 weeks post surgery. Secondary PROMs include the EQ-5D-5 L questionnaire, return to work and return to driving, with objective outcomes including ankle range of motion. Analysis will be on an intention-to-treat basis. An economic evaluation will be included. Discussion: The EMADE intervention is a package of care designed to address the detrimental effects of disuse atrophy and joint stiffness. An advantage of the OMAS is the potential of meta-analysis with other designs. Within the economic evaluation, the cost-utility analysis, may be used by commissioners, while the use of patient-relevant outcomes, such as return to work and driving, will ensure that the study remains pertinent to patients and their families. As it is being conducted in the clinical environment, this p-RCT has high external validity. Accordingly, if significant clinical benefits and cost-effectiveness are demonstrated, EMADE should become a worthwhile treatment option. A larger-scale, multicentre trial may be required to influence national guidelines. Trial registration: ISRCTN, ID: ISRCTN11212729. Registered retrospectively on 20 March 2017

TTF-1 Action on the Transcriptional Regulation of Cyclooxygenase-2 Gene in the Rat Brain

We have recently found that thyroid transcription factor-1 (TTF-1), a homeodomain-containing transcription factor, is postnatally expressed in discrete areas of the hypothalamus and closely involved in neuroendocrine functions. We now report that transcription of cyclooxygenase-2 (COX-2), the rate limiting enzyme in prostaglandin biosynthesis, was inhibited by TTF-1. Double immunohistochemistry demonstrated that TTF-1 was expressed in the astrocytes and endothelial cells of blood vessel in the hypothalamus. Promoter assays and electrophoretic mobility shift assays showed that TTF-1 inhibited COX-2 transcription by binding to specific binding domains in the COX-2 promoter. Furthermore, blocking TTF-1 synthesis by intracerebroventricular injection of an antisense oligomer induced an increase of COX-2 synthesis in non-neuronal cells of the rat hypothalamus, and resulted in animals' hyperthermia. These results suggest that TTF-1 is physiologically involved in the control of thermogenesis by regulating COX-2 transcription in the brain

Aquadynamics and the Athletocracy: Jennie Fletcher and the British Women's 4 x 100 metre Freestyle Relay Team at the 1912 Stockholm Olympic Games

This article considers the part played by aquadynamics, or a concern for the technical properties of swimming costumes, in the career of Jennie Fletcher (1890–1968) who won Britain’s first individual Olympic female swimming medal (bronze) at the Stockholm Olympic Games in 1912 and contributed to the first women’s team gold in the 4 × 100 metre Freestyle Relay. Her light silk one-piece racing swimsuit represented a new kind of modernity: the revealed sporting body enabled competitive principles, rather than modesty, to define the appearance of the female swimmer. The article also examines the place of the working-class competitor in our understanding of the early Games, an ‘athletocracy’ where performance, not background, enabled individuals to compete. The work therefore also explores the relevance of Fletcher’s birthplace, Leicester, in the development of amateur and professional swimming and in the production of swmming costumes for both sport and leisure.This research has been developed with the support of a De Montfort University Research Investment Fund grant for 2011–12 to look at the relationship between sport and fashion, particularly in the county of Leicestershire.

Interactions of the histamine and hypocretin systems in CNS disorders

International audienceHistamine and hypocretin neurons are localized to the hypothalamus, a brain area critical to autonomic function and sleep. Narcolepsy type 1, also known as narcolepsy with cataplexy, is a neurological disorder characterized by excessive daytime sleepiness, impaired night-time sleep, cataplexy, sleep paralysis and short latency to rapid eye movement (REM) sleep after sleep onset. In narcolepsy, 90% of hypocretin neurons are lost; in addition, two groups reported in 2014 that the number of histamine neurons is increased by 64% or more in human patients with narcolepsy, suggesting involvement of histamine in the aetiology of this disorder. Here, we review the role of the histamine and hypocretin systems in sleep-wake modulation. Furthermore, we summarize the neuropathological changes to these two systems in narcolepsy and discuss the possibility that narcolepsy-associated histamine abnormalities could mediate or result from the same processes that cause the hypocretin cell loss. We also review the changes in the hypocretin and histamine systems, and the associated sleep disruptions, in Parkinson disease, Alzheimer disease, Huntington disease and Tourette syndrome. Finally, we discuss novel therapeutic approaches for manipulation of the histamine system

Neural Control of Energy Expenditure

The continuous rise in obesity is a major concern for future healthcare management. Many strategies to control body weight focus on a permanent modification of food intake with limited success in the long term. Metabolism or energy expenditure is the other side of the coin for the regulation of body weight, and strategies to enhance energy expenditure are a current focus for obesity treatment, especially since the (re)-discovery of the energy depleting brown adipose tissue in adult humans. Conversely, several human illnesses like neurodegenerative diseases, cancer, or autoimmune deficiency syndrome suffer from increased energy expenditure and severe weight loss. Thus, strategies to modulate energy expenditure to target weight gain or loss would improve life expectancies and quality of life in many human patients. The aim of this book chapter is to give an overview of our current understanding and recent progress in energy expenditure control with specific emphasis on central control mechanisms