Interventions to Reduce Spasticity and Improve Function in People With Chronic Incomplete Spinal Cord Injury: Distinctions Revealed by Different Analytical Methods.

Background. Spinal cord injury (SCI) results in impaired function, and ankle joint spasticity is a common secondary complication. Different interventions have been trialed with variable results. Objective. We investigated the effects of pharmacological and physical (locomotor training) interventions on function in people living with incomplete motor function loss caused by SCI and used different analytical techniques to understand whether functional levels affect recovery with different interventions. Methods. Participants with an incomplete SCI were assigned to 3 groups: no intervention, Lokomat, or tizanidine. Outcome measures were the 10-m walk test, 6-minute walk test, and the Timed Up and Go. Participants were classified in 2 ways: (1) based on achieving an improvement above the minimally important difference (MID) and (2) using growth mixture modeling (GMM). Functional levels of participants who achieved the MID were compared and random coefficient regression (RCR) was used to assess recovery in GMM classes. Results. Overall, walking speed and endurance improved, with no difference between interventions. Only a small number of participants achieved the MID. Both MID and GMM-RCR analyses revealed that tizanidine improved endurance in high-functioning participants. GMM-RCR classification also showed that speed and mobility improved after locomotor training. Conclusions. Improvements in function were achieved in a limited number of people with SCI. Using the MID and GMM techniques, differences in responses to interventions between high-and low-functioning participants could be identified. These techniques may, therefore, have potential to be used for characterizing therapeutic effects resulting from different interventions

Murine myoblast migration: influence of replicative ageing and nutrition

Cell migration is central to skeletal muscle repair following damage. Leucine and β-Hydroxy β-methylbutyric acid (HMB) are supplements consumed for recovery from muscle damaging exercise in humans, however, their impact on muscle cell migration with age is not yet understood. We hypothesised that replicatively aged (“aged”; P46–P48) myoblasts would be less efficient at basal and supplemented repair versus parental controls (“control”; P12–P16). Aged and control myoblasts were scratch-damaged and migration velocity, directionality and distance assessed over 48 h in the absence and presence of leucine (10 mM) or HMB (10 mM) ± PI3K/Akt (LY294002 10 μM), ERK (PD98059 5 μM) or mTOR (rapamycin 0.5 μM) inhibition. Opposing our hypothesis, aged cells displayed increased velocities, directionality and distance migrated (P < 0.001) versus control. Leucine and HMB significantly increased (P < 0.001) the same parameters in control cells. The supplements were with smaller, albeit significant impact on aged cell velocity (P < 0.001) and in the presence of HMB only, distance (P = 0.041). Inhibitor studies revealed that, PI3K and ERK activation were essential for velocity, directionality and migration distance of aged cells in basal conditions, whereas mTOR was important for directionality only. While PI3K activation was critical for all parameters in control cells (P < 0.001), inhibition of ERK or mTOR improved, rather than reduced, control cell migration distance. Enhanced basal velocity, directionality and distance in aged cells required ERK and PI3K activation. By contrast, in control cells, basal migration was underpinned by PI3K activation, and facilitated by leucine or HMB supplementation, to migration levels seen in aged cells. These data suggest that replicatively aged myoblasts are not anabolically resistant per se, but are capable of efficient repair, underpinned by altered signaling pathways, compared with unaged control myoblasts

Molecular footprints of the Holocene retreat of dwarf birch in Britain

© 2014 The Authors. Molecular Ecology Published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited

A validated severity score for haemorrhoids as an essential prerequisite for future haemorrhoid trials.

BACKGROUND: There is a lack of standardised outcomes for haemorrhoidal disease making comparison between trials difficult. A need for a very well validated severity score is essential to facilitate meta-analysis of comparative studies, enabling evidence-based clinical practice. METHODS: The Hubble trial provides a large cohort of patients with haemorrhoidal disease randomised to rubber band ligation (RBL) or haemorrhoidal artery ligation. The haemorrhoid severity score (HSS) was collected on each patient at baseline, 6 weeks and 1 year after intervention. This allows for the responsiveness of the HSS instrument to be examined and compared with a more specific instrument, the Vaizey incontinence score (also collected). Responsiveness was tested using four methods (effect size, standardised response means (SRM), significance of change, and responsiveness statistic). RESULTS: The four tests of responsiveness demonstrated that the HSS was more responsive to changes in the patient's health status following both of the interventions compared to the Vaizey questionnaire. For example, between baseline and 6 weeks, the RBL intervention effect size scores and SRM calculations indicated a non-significant small amount of change (0.20 and 0.16 respectively). However, using the HSS, the effect size and SRM demonstrated a large magnitude of change (1.12 and 1.01, respectively) which was significant. Similar results were observed at 1 year. Significance of change scores and the index of responsiveness were also higher for the HSS questionnaire than the Vaizey across both treatment modalities. CONCLUSIONS: The HSS is a highly responsive tool for the detection of changes in haemorrhoid symptoms. It should form an essential patient-reported outcome tool for future studies on haemorrhoidal disease

YouTube as a source of information for patients considering surgery for ulcerative colitis

© 2017 Elsevier Inc. Background With the range of health information online, assessing the resources that patients access may improve the content of preoperative information. Our aim was to assess the content of the most viewed videos on YouTube related to surgery for ulcerative colitis (UC). Methods YouTube was searched for videos containing information on surgery for UC. The 50 most viewed videos were identified and user interaction analyzed. Upload source was classified as patient, individual health care professional (HCP), or hospital/professional association. Video content was categorized using an inductive thematic analysis on a purposive sample list of videos. The overarching theme of each video was classified once data saturation was achieved. Results Thirty videos were uploaded by patients, 15 by hospitals and 5 by HCPs. Seventeen videos (34%) discussed life after surgery. Sixteen of these were uploaded by patients who had previously undergone surgery for UC. No videos of this theme were uploaded by HCPs. Ten videos (20%) described a number of different operations. Other themes identified were alternative health therapies (12%), colonoscopy (12%), life with UC (8%), miscellaneous (8%), and education for HCPs (6%). Patient uploaded videos had significantly more comments (P = 0.0079), with 28% of comments on patient videos being users requesting further information. Conclusions Understanding the sequelae of surgery is most important to preoperative patients. There are a lack of professional videos addressing this topic on YouTube. HCPs must participate in the production of videos and adapt preoperative consultations to address common preoperative concerns

Facilitatory effects of anti-spastic medication on robotic locomotor training in people with chronic incomplete spinal cord injury

Background: The objective of this study was to investigate whether an anti-spasticity medication can facilitate the effects of robotic locomotor treadmill training (LTT) to improve gait function in people with incomplete spinal cord injury (SCI). / Methods: Individuals with chronic incomplete SCI were recruited and carried out a 4 week intervention of either locomotor treadmill training (LTT) alone (n = 26) or LTT combined with Tizanidine (TizLTT), an anti-spasticity medication (n = 22). Gait function was evaluated using clinical outcome measures of gait, speed and endurance. To better understand the underlying mechanisms of the therapeutic effects, maximal strength, active range of motion (AROM) and peak velocity (Vp) of ankle dorsi- and planter-flexor muscles were also measured. Differences were assessed using two-way mixed design analysis of variance. The number of subjects that achieved the minimal important difference (MID) for clinical scores was also measured for each group, and the results of those that did attain the MID were compared with those that did not. / Results: Both LTT and TizLTT resulted in significant improvements in walking speed and dorsiflexion maximum strength, with no significant differences between them, using group-averaging analysis. However, using the MID analysis, a higher proportion of subjects in the TizLTT group achieved the MID for walking speed (40%) compared with LTT alone (13%). Those that achieved the MID for walking speed were significantly higher functioning at baseline than those that did not in the TizLTT group, and the change in walking speed was associated with the change in dorsiflexion peak velocity (R2 = 0.40; P < 0.05). / Conclusion: Tizanidine appears to facilitate the effects of LTT on gait function in individuals with chronic SCI that are higher functioning at baseline. We speculate that this may be due to restoration of inhibitory mechanisms by Tizanidine, resulting in greater stretch in the planterflexor muscles during the LTT

Scavenger 0.1: A Theorem Prover Based on Conflict Resolution

This paper introduces Scavenger, the first theorem prover for pure first-order logic without equality based on the new conflict resolution calculus. Conflict resolution has a restricted resolution inference rule that resembles (a first-order generalization of) unit propagation as well as a rule for assuming decision literals and a rule for deriving new clauses by (a first-order generalization of) conflict-driven clause learning.Comment: Published at CADE 201

Gut thinking: the gut microbiome and mental health beyond the head

Background: In recent decades, dominant models of mental illness have become increasingly focused on the head, with mental disorders being figured as brain disorders. However, research into the active role that the microbiome-gut-brain axis plays in affecting mood and behaviour may lead to the conclusion that mental health is more than an internalised problem of individual brains. Objective: This article explores the implications of shifting understandings about mental health that have come about through research into links between the gut microbiome and mental health problems such as depression and anxiety. It aims to analyse the different ways that the lines between mind and body and mental and physical health are re-shaped by this research, which is starting to inform clinical and public understanding. Design: As mental health has become a pressing issue of political and public concern it has become increasingly constructed in socio-cultural and personal terms beyond clinical spaces, requiring a conceptual response that exceeds biomedical inquiry. This article argues that an interdisciplinary critical medical humanities approach is well positioned to analyse the impact of microbiome-gut-brain research on conceptions of mind. Results: The entanglement of mind and matter evinced by microbiome-gut-brain axis research potentially provides a different way to conceptualise the physical and social concomitants of mental distress. Conclusion: Mental health is not narrowly located in the head but is assimilated by the physical body and intermingled with the natural world, requiring different methods of research to unfold the meanings and implications of gut thinking for conceptions of human selfhood

Spina bifida-predisposing heterozygous mutations in Planar Cell Polarity genes and Zic2 reduce bone mass in young mice

Fractures are a common comorbidity in children with the neural tube defect (NTD) spina bifida. Mutations in the Wnt/planar cell polarity (PCP) pathway contribute to NTDs in humans and mice, but whether this pathway independently determines bone mass is poorly understood. Here, we first confirmed that core Wnt/PCP components are expressed in osteoblasts and osteoclasts in vitro. In vivo, we performed detailed µCT comparisons of bone structure in tibiae from young male mice heterozygous for NTD-associated mutations versus WT littermates. PCP signalling disruption caused by Vangl2 (Vangl2Lp/+) or Celsr1 (Celsr1Crsh/+) mutations significantly reduced trabecular bone mass and distal tibial cortical thickness. NTD-associated mutations in non-PCP transcription factors were also investigated. Pax3 mutation (Pax3Sp2H/+) had minimal effects on bone mass. Zic2 mutation (Zic2Ku/+) significantly altered the position of the tibia/fibula junction and diminished cortical bone in the proximal tibia. Beyond these genes, we bioinformatically documented the known extent of shared genetic networks between NTDs and bone properties. 46 genes involved in neural tube closure are annotated with bone-related ontologies. These findings document shared genetic networks between spina bifida risk and bone structure, including PCP components and Zic2. Genetic variants which predispose to spina bifida may therefore independently diminish bone mass

Development and evaluation of a patient decision aid for patients considering ongoing medical or surgical treatment options for ulcerative colitis using a mixed-methods approach : protocol for DISCUSS study

Introduction: Approximately 20%–30% of patients with ulcerative colitis (UC) require surgery, the majority of these being elective due to chronic symptoms refractory to medical treatment. The decision for surgery is difficult and dependent on patient preferences. Current resources for patients considering surgery have been found not to meet minimum international standards. The overall aim of the ‘DISCUSS’ study is to develop and evaluate a new patient decision aid (PtDA) for patients considering surgery for UC created in line with international minimum standards. Methods and analysis: This is a prospective mixed-methods study of adults (18+ years) who are considering surgical intervention for UC across two regional centres in Yorkshire, UK. This study is in three stages. In stage 1 we will develop the PtDA and its content via systematic reviews and a patient questionnaire. In stage 2 we will assess the face validity of the PtDA using mixed-methods on key stakeholders using both semistructured interviews and questionnaires, following which the PtDA will be refined. In stage 3 we will assess the acceptability of using the PtDA in clinical practice. This will use a mixed-methods approach on clinicians and patients who are considering undergoing elective surgery. Questionnaires including the Preparation for Decision-Making Scale, a measure of anxiety and decisional conflict will be analysed at two timepoints using paired sample t-tests and CIs. Interviews with patients and clinicians will be analysed using thematic analysis. Ethics and dissemination: Research ethics approval from North East–Tyne & Wear South Research Ethics Committee (Ref: 19/NE/0073) and Health Research Authority approval (Ref: 257044) have been granted. Results will be published in open access peer-reviewed journals, presented in conferences and distributed through the Crohn’s and Colitis UK charity. External endorsement will be sought from the International Patient Decision Aid Standards Collaboration inventory of PtDAs