AKR1D1 knockout mice have impaired intestinal health with evidence of gut dybiosis and increased gut permeability and have increased incidence of colon cancer in females

AKR1D1 knockout mice have impaired intestinal health with evidence of gut dybiosis and increased gut permeability and have increased incidence of colon cancer in female

Trapping and Wiggling: Elastohydrodynamics of Driven Microfilaments

We present a general theoretical analysis of semiflexible filaments subject to viscous drag or point forcing. These are the relevant forces in dynamic experiments designed to measure biopolymer bending moduli. By analogy with the ``Stokes problems" in hydrodynamics (fluid motion induced by that of a wall bounding a viscous fluid), we consider the motion of a polymer one end of which is moved in an impulsive or oscillatory way. Analytical solutions for the time-dependent shapes of such moving polymers are obtained within an analysis applicable to small-amplitude deformations. In the case of oscillatory driving, particular attention is paid to a characteristic length determined by the frequency of oscillation, the polymer persistence length, and the viscous drag coefficient. Experiments on actin filaments manipulated with optical traps confirm the scaling law predicted by the analysis and provide a new technique for measuring the elastic bending modulus. A re-analysis of several published experiments on microtubules is also presented.Comment: RevTex, 24 pages, 15 eps figs, uses cite.sty, Biophysical

Qualitative Parental Perceptions of a Paediatric Multidisciplinary Team Clinic for Prader-Willi Syndrome

Objective:This preliminary review was conducted to inform the design of a new service to support families with children with Prader-Willi syndrome (PWS). Families were invited to attend a pilot clinic at a hospital outpatient department, comprising appointments with a multi-disciplinary team (MDT).Methods:Following the clinic, families (n=6) were invited to take part in semi-structured qualitative interviews that were audio-recorded, transcribed and analysed using thematic analysis.Results:Families reported that the clinic offered enhanced support in the following categories: integrated care; professional input; signposting to social support (respite and financial); connection with the wider PWS community; and behavioural support.Conclusion:This is the first paper that documents the parental perspective of an MDT clinic for children with PWS. The families felt an MDT clinic was superior to current care, offering more convenient access to an enhanced service, which would provide integrated and consistent care for their children’s diverse, challenging and changing needs

High-intensity interval training is safe, feasible and efficacious in nonalcoholic steatohepatitis : a randomized controlled trial

Background: High-Intensity Interval Training (HIIT) involves bursts of high-intensity exercise interspersed with lower-intensity exercise recovery. HIIT may benefit cardiometabolic health in people with nonalcoholic steatohepatitis (NASH). Aims: We aimed to examine the safety, feasibility, and efficacy of 12-weeks of supervised HIIT compared with a sham-exercise control (CON) for improving aerobic fitness and peripheral insulin sensitivity in biopsy-proven NASH. Methods: Participants based in the community [(n = 14, 56 ± 10 years, BMI 39.2 ± 6.7 kg/m2, 64% male), NAFLD Activity Score 5 (range 3–7)] were randomized to 12-weeks of supervised HIIT (n = 8, 4 × 4 min at 85–95% maximal heart rate, interspersed with 3 min active recovery; 3 days/week) or CON (n = 6, stretching; 3 days/week). Safety (adverse events) and feasibility determined a

The feasibility of online video calling to engage patients with cystic fibrosis in exercise training.

Introduction Physical activity, including structured exercise, is an essential component in the management of cystic fibrosis. The use of telehealth such as video-calling may be a useful method for the delivery of exercise and physical activity interventions, though the feasibility of this remains unknown. Methods Nine patients with cystic fibrosis (three female, six male, 30.9 ± 8.7 years) volunteered to participate. Participants completed an eight-week exercise training intervention conducted via Skype, using personalised exercises, with all sessions supervised by an exercise therapist. Feasibility was assessed by demand, implementation, practicality and acceptability. Changes in anthropometric, pulmonary, physical activity and quality of life variables were also assessed. Results Two male participants withdrew from the study, citing lack of available time. The remaining participants found use of Skype useful, with a mean satisfaction rating of 9/10, and three participants requesting to continue the sessions beyond the duration of the study. Mean compliance with sessions was 68%, with mean duration of sessions being 20 min. A total of 25% of calls suffered from technical issues such as video or audio lags. Anthropometric, pulmonary, physical activity and quality of life variables remained unchanged over the course of the study period. Discussion The use of Skype to deliver an exercise intervention to patients withcystic fibrosis was found to be technologically feasible, and acceptable among participants. Findings have implications for clinical practice and could allow care teams to engage patients remotely in exercise. Further research is required to assess the efficacy of this modality on increasing physical activity and associated health outcomes

The epidemiology of pre-hospital potential spinal cord injuries in Victoria, Australia: a six year retrospective cohort study

© 2016, The Author(s). Background: Traumatic Spinal Cord Injury (TSCI) is relatively uncommon, yet a devastating and costly condition. Despite the human and social impacts, studies describing patients with potential TSCI in the pre-hospital setting are scarce. This paper aims to describe the epidemiology of patients potentially at risk of or suspected to have a TSCI by paramedics, with a view to providing a better understanding of factors associated with potential TSCI. Methods: This is a retrospective cohort study of all adult patients managed and transported by Ambulance Victoria (AV) between 01 January 2007 and 31 December 2012 who, based on meeting pre-hospital triage protocols and criteria for spinal clearance, paramedic suspicion or spinal immobilisation, were classified to be at risk of or suspected to have a TSCI. Data was extracted from the AV data warehouse, including demographic details, trauma aetiology, paramedic assessment, management and other event characteristics. Results: A total of 106,059cases were included in the study, representing 2.3 % of all emergency transports by AV. Subjects had a median age of 51 years (interquartile range; 29–78) and 52.4 % were males (95 % CI 52–52.7). Males were significantly younger than females (M: 43 years [26–65] vs. F: 64 years [36–84], p =0.001). Falls and traffic accidents were the leading causes of injuries, comprising 46.9 and 39.4 % of cases, respectively. Other causes included accidents due to sport, animals, industrial work and diving, as well as violence and hanging. 29.9 % of patients were transported to a Major Trauma Service (MTS). A proportion of 48.8 % of the study population met the Pre-hospital Major Trauma criteria. Conclusion: This is the first study to describe the epidemiology of potential TSCI in Australia and is based on a large, state-wide sample. It provides background knowledge and a baseline for future research, as well as a reference point for future in policy. Falling and traffic related injuries were the leading causes of potential SCI. Future research is required to identify the proportion of confirmed TSCI among the potentials and factors associated with TSCI in prehospital settings

Geographically widespread C-13-depletion of grazing caddis larvae:a third way of fuelling stream food webs?

Stream ecosystems are supported by both green (i.e. based on grazing) and brown (i.e. detritus) food webs, whereas methane-derived carbon is not considered generally to be important; here, we add circumstantial evidence for this potential third way. Grazing cased-caddis (Trichoptera) larvae in the family Glossosomatidae can be very abundant in springs and headwaters and frequently have much lower stable carbon isotope ratios (i.e. they are depleted in the heavier C-13 stable isotope) than the biofilm (epilithon) on the upper surfaces of the stones on which they live, and which is their presumed diet. Evidence for similar isotopic depletion in other lotic invertebrates is currently limited, however; even for glossosomatids it has been observed so far only in some streams draining the southern English cretaceous chalk and in a few headwaters in northern California. If this phenomenon proves to be more widespread, among streams or taxa, it could imply a more general underpinning of stream food webs by isotopically light carbon derived from methane and accessed via consumers feeding on methanotrophic bacteria. Here, we sampled 58 stream sites to examine whether caddis larvae are also C-13-depleted in streams draining other geologies. We focused mainly on carboniferous limestone and sandstone, as well as on further chalk streams representative of most of the British chalk aquifer: together, these new sites covered an area of almost 90,000 km(2), around three times greater than that surveyed previously. At all 58 sites methane gas was supersaturated relative to the atmospheric equilibrium, and at 49 of them larvae were conspicuously C-13-depleted (from -17.5 parts per thousand to -3.6 parts per thousand) relative to the bulk epilithon (components of which we know can oxidise methane). Although still most pronounced on chalk, this phenomenon was geographically and geologically much more widespread than shown previously and suggests methane-derived carbon could indeed play a prominent role in stream food webs (i.e. the third way)

Voltage- and cold-dependent gating of single TRPM8 ion channels

Transient receptor potential (TRP) channels play critical roles in cell signaling by coupling various environmental factors to changes in membrane potential that modulate calcium influx. TRP channels are typically activated in a polymodal manner, thus integrating multiple stimuli. Although much progress has been made, the underlying mechanisms of TRP channel activation are largely unknown. The TRPM8 cation channel has been extensively investigated as a major neuronal cold sensor but is also activated by voltage, calcium store depletion, and some lipids as well as by compounds that produce cooling sensations, such as menthol or icilin. Several models of TRPM8 activation have been proposed to explain the interaction between these diverse stimuli. However, a kinetic scheme is not yet available that can describe the detailed single-channel kinetics to gain further insight into the underlying gating mechanism. To work toward this goal, we investigated voltage-dependent single-channel gating in cell-attached patches at two different temperatures (20 and 30°C) using HEK293 cells stably expressing TRPM8. Both membrane depolarization and cooling increased channel open probability (Po) mainly by decreasing the duration of closed intervals, with a smaller increase in the duration of open intervals. Maximum likelihood analysis of dwell times at both temperatures indicated gating in a minimum of five closed and two open states, and global fitting over a wide range of voltages identified a seven-state model that described the voltage dependence of Po, the single-channel kinetics, and the response of whole-cell currents to voltage ramps and steps. The major action of depolarization and cooling was to accelerate forward transitions between the same two sets of adjacent closed states. The seven-state model provides a general mechanism to account for TRPM8 activation by membrane depolarization at two temperatures and can serve as a starting point for further investigations of multimodal TRP activation

Ablative therapy for people with localised prostate cancer : a systematic review and economic evaluation

The research reported in this issue of the journal was funded by the HTA programme as project number 10/136/01. The contractual start date was in April 2012. The draft report began editorial review in October 2013 and was accepted for publication in April 2014. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to thank the reviewers for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report. Acknowledgements We thank l the people recruited from the local UCAN for providing valuable consumer insight and advice through their participation as members of the project focus group: - Mark Emberton (Professor of Interventional Oncology), Damian Greene (consultant urologist), Axel Heidenreich (Professor and Director of Department of Urology), Christoph von Klot (specialist in brachytherapy), Roger Kockelbergh (BAUS chairman and Clinical Director of Urology) and Axel Merserburger (Deputy Clinical Director of Urology and Urologic Oncology) for providing their clinical expertise as members of the project advisory group - Edgar Paez (consultant urologist) and Gill Lawrence (Head of Radiotherapy Physics) for providing a list of staff time by grade and specialty involved in EBRT - Debbie Bennett (Radiotherapy Service Manager) for providing estimates for the expected number of uses for EBRT - Ian Pedley (clinical director/clinical oncologist) and Gill Lawrence for providing a list of all resource inputs relevant to brachytherapy - Steve Locks (Consultant Clinical Scientist in Radiotherapy) for providing a list of reusable equipment and consumables used during brachytherapy, along with their unit costs - Sue Asterling (urology research nurse) and Mark Kelly (Acting Divisional General Manager – Theatres) for providing a list of all resource inputs relevant to cryotherapy - Lara Kemp for providing secretarial support. The Health Services Research Unit is core funded by the Chief Scientist Office of the Scottish Government Health Directorates.Peer reviewedPublisher PD