The effects of a 12-week leisure centre-based, group exercise intervention for people moderately affected with multiple sclerosis: a randomized controlled pilot study

<b>Objective:</b> To establish the effects of a 12-week, community-based group exercise intervention for people moderately affected with multiple sclerosis. <b>Design:</b> Randomised controlled pilot trial. <b>Setting:</b> Two community leisure centres. <b>Participants:</b> Thirty-two participants with multiple sclerosis randomised into intervention or control groups. <b>Intervention:</b> The intervention group received 12 weeks of twice weekly, 60-minute group exercise sessions, including mobility, balance and resistance exercises. The control group received usual care. <b>Main outcome measures:</b> An assessor blinded to group allocation assessed participants at baseline, after eight weeks and after 12 weeks. The primary outcome measure was 25-foot (7.6 m) walk time, secondary outcomes assessed walking endurance, balance, physical function, leg strength, body mass index, activity levels, fatigue, anxiety and depression, quality of life and goal attainment. <b>Results:</b> The intervention made no statistically significant difference to the results of participants’ 25-foot walk time. However the intervention led to many improvements. In the intervention group levels of physical activity improved statistically between baseline and week 8 (P < 0.001) and baseline and week 12 (P = 0.005). Balance confidence results showed a significant difference between baseline and week 12 (P = 0.013). Good effect sizes were found for dynamic balance (d = 0.80), leg strength (d = 1.33), activity levels (d = 1.05) and perceived balance (d = 0.94). <b>Conclusion:</b> The results of the study suggest that community-based group exercise classes are a feasible option for people moderately affected with multiple sclerosis, and offer benefits such as improved physical activity levels, balance and leg strength

Development and evaluation of a novel interprofessional learning activity addressing the management of phenylketonuria.

This new initiative across the School of Pharmacy and Life Sciences at Robert Gordon University focuses around students from the Overseas Pharmacist's Assessment Programme (OSPAP), and third-year Nutrition and Dietetics students working in an interprofessional setting to manage the care of individuals with Phenylketonuria (PKU). A problem-based learning approach was employed, which involved small-group interprofessional working to solve a series of simulated case studies concerned with the management of phenylketonuria. The session was further enhanced by an expert patient narrative and the opportunity to test a series of commercially-available low protein/low phenylalanine food substitutes, which are used in the disease management. The substitutes were provided by SHS-Nutricia and Vitaflo. Group evaluation of the activity was generally positive, with all groups indicating that the learning objectives had been achieved in a setting that promoted collaborative interprofessional working, acquisition of knowledge pertaining to the management of PKU, and a format that enabled a breadth and depth of material to be covered in a relatively short time. The contributions of the expert patient and availability of test samples enhanced the interactivity of the session, and provided a meaningful insight into the lived experience of PKU patients. Limitations of the session included the rather narrow range of healthcare professional students involved in the activity and the need for better signposting of preparatory reading material. Planned future developments of this initiative aim to involve health visiting, biomedical science and social work students, in order to enable consideration of a more holistic approach to the health and social care issues of PKU. Additionally, future developments include the creation of an Articulate quiz activity for student self-evaluation, prior to the event. In conclusion, this initiative addressed the six learning objectives in an interactive manner, receiving positive learner feedback and having a clear strategy for future development

An exploration of the experiences and utility of functional electrical stimulation for foot drop in people with multiple sclerosis

Purpose: Functional electrical stimulation (FES) is effective in improving walking in people with multiple sclerosis (MS) with foot drop. There is limited research exploring people’s experiences of using this device. This study aims to explore the utility, efficacy, acceptability, and impact on daily life of the device in people with MS. Methods: An interpretative phenomenological approach was employed. Ten participants who had used FES for 12 months were interviewed. Transcripts were analysed, and emergent themes identified. Results: Nine participants continued to use the device. Three relevant super-ordinate themes were identified; impact of functional electrical stimulation, sticking with functional electrical stimulation, and autonomy and control. Participants reported challenges using the device; however, all reported positive physical and psychological benefits. Intrinsic and external influences such as; access to professional help, the influence of others, an individual’s ability to adapt, and experiences using the device, influenced their decisions to continue with the device. A thematic model of these factors was developed. Conclusions: This study has contributed to our understanding of people with MS experiences of using the device and will help inform prescribing decisions and support the continued, appropriate use of FES over the longer term

Craniometric Analysis of the Hindbrain and Craniocervical Junction of Chihuahua, Affenpinscher and Cavalier King Charles Spaniel Dogs With and Without Syringomyelia Secondary to Chiari-Like Malformation

Objectives To characterize and compare the phenotypic variables of the hindbrain and craniocervical junction associated with syringomyelia (SM) in the Chihuahua, Affenpinscher and Cavalier King Charles Spaniel (CKCS). Method Analysis of 273 T1-weighted mid-sagittal DICOM sequences of the hindbrain and craniocer-vical junction from 99 Chihuahuas, 42 Affenpinschers and 132 CKCSs. The study compared 22 morphometric features (11 lines, eight angles and three ratios) of dogs with and without SM using refined techniques based on previous studies of the Griffon Bruxellois (GB) using Discriminant Function Analysis and ANOVA with post-hoc corrections. Results The analysis identified 14/22 significant traits for SM in the three dog breeds, five of which were identical to those reported for the GB and suggest inclusion of a common aetiology. One ratio, caudal fossa height to the length of the skull base extended to an imaginary point of alignment between the atlas and supraoccipital bones, was common to all three breeds (p values 0.029 to <0.001). Associated with SM were a reduced occipital crest and two acute changes in angulation i) 'sphenoid flexure' at the spheno-occipital synchondrosis ii) 'cervical flexure' at the foramen magnum allied with medulla oblongata elevation. Comparing dogs with and without SM, each breed had a unique trait: Chihuahua had a smaller angle between the dens, atlas and basioccipital bone (p value <0.001); Affenpinschers had a smaller dis-tance from atlas to dens (p value 0.009); CKCS had a shorter distance between the spheno-occipital synchondrosis and atlas (p value 0.007). Conclusion The selected morphometries successfully characterised conformational changes in the brain and craniocervical junction that might form the basis of a diagnostic tool for all breeds. The severity of SM involved a spectrum of abnormalities, incurred by changes in both angulation and size that could alter neural parenchyma compliance and/or impede cerebrospinal fluid channels.Peer reviewe

Cytochrome P450 CYP1B1 activity in renal cell carcinoma

Renal cell carcinoma (RCC) is the most common malignancy of the kidney and has a poor prognosis due to its late presentation and resistance to current anticancer drugs. One mechanism of drug resistance, which is potentially amenable to therapeutic intervention, is based on studies in our laboratory. CYP1B1 is a cytochrome P450 enzyme overexpressed in a variety of malignant tumours. Our studies are now elucidating a functional role for CYP1B1 in drug resistance. Cytochrome P450 reductase (P450R) is required for optimal metabolic activity of CYP1B1. Both CYP1B1 and P450R can catalyse the biotransformation of anticancer drugs at the site of the tumour. In this investigation, we determined the expression of CYP1B1 and P450R in samples of normal kidney and RCC (11 paired normal and tumour and a further 15 tumour samples). The O-deethylation of ethoxyresorufin to resorufin was used to measure CYP1B1 activity in RCC. Cytochrome P450 reductase activity was determined by following the reduction of cytochrome c at 550 nm. The key finding of this study was the presence of active CYP1B1 in 70% of RCC. Coincubation with the CYP1B1 inhibitor alpha-naphthoflavone (10nM) inhibited this activity. No corresponding CYP1B1 activity was detected in any of the normal tissue examined (n = 11). Measurable levels of active P450R were determined in all normal (n = 11) and tumour samples (n = 26). The presence of detectable CYP1B1, which is capable of metabolising anticancer drugs in tumour cells, highlights a novel target for therapeutic intervention

The effectiveness and satisfaction of web-based physiotherapy in people with spinal cord injury: a pilot randomised controlled trial

Study Design: Pilot randomised controlled trial. Objectives: The aims of this study were to evaluate the effectiveness and participant satisfaction of web-based physiotherapy for people with Spinal Cord Injury (SCI). Setting: Community patients of a national spinal injury unit in a university teaching hospital, Scotland, UK. Methods: Twenty-four participants were recruited and randomised to receive eight weeks of web-based physiotherapy (intervention), twice per week, or usual care (control). Individual exercise programmes were prescribed based upon participant’s abilities. The intervention was delivered via a website (www.webbasedphysio.com) and monitored and progressed remotely by the physiotherapist. Results: Participants logged on to the website an average of 1.4±0.8 times per week. Between-group differences, although not significant were more pronounced for the 6 minute walk test. Participants were positive about using web-based physiotherapy and stated they would be happy to use it again and would recommend it to others. Overall it was rated as either good or excellent. Conclusions: Web-based physiotherapy was feasible and acceptable for people with SCI. Participants achieved good compliance with the intervention, rated the programme highly and beneficial for health and well-being at various states post injury. The results of this study warrant further work with a more homogenous sample

Pharmacokinetics, Safety, and Antiviral Effects of Multiple Doses of the Respiratory Syncytial Virus (RSV) Fusion Protein Inhibitor, JNJ-53718678, in Infants Hospitalized With RSV Infection: A Randomized Phase 1b Study

BACKGROUND: This phase 1b study evaluated the pharmacokinetics, safety, and antiviral effects of the respiratory syncytial virus (RSV)-specific fusion inhibitor JNJ-53718678 (JNJ-8678) in hospitalized RSV-infected patients aged > 1 to /=6 to /=3 to 1 to < 3 months) were randomized to oral JNJ-8678 or placebo once daily for 7 days. Dose increases followed data review committee recommendations (cohort 1: 2/6/8/9 mg/kg; cohort 2: 1.5/4.5/6 mg/kg; cohort 3: 1/3/5 mg/kg). Cohort 1 included a 9 mg/kg dose, as target exposures were not reached at lower doses. Sparse pharmacokinetic samples were assessed using population pharmacokinetics modeling. Safety was assessed by adverse events (AEs), laboratory tests, and electrocardiograms. To assess antiviral effects, RSV RNA viral load from nasal swabs was quantified over time using reverse-transcription quantitative polymerase chain reaction. RESULTS: Patients received JNJ-8678 (n = 37) or placebo (n = 7). Pharmacokinetic parameters were similar at the highest doses for cohorts 1-3 (area under the plasma concentration-time curve from time of administration up to 24 hours postdosing at day 7: 35 840, 34 980, and 39 627 ng x hour/mL, respectively). Two grade 3 AEs were reported (both bronchiolitis; 1 JNJ-8678, 1 placebo), reported as serious AEs; all other AEs were grade 1 or 2. Two additional serious AEs were reported (rhinitis [JNJ-8678]; pneumonia [placebo]). No deaths, grade 4 AEs, or AEs leading to discontinuation were reported. Median RSV viral load change from baseline in JNJ-8678 vs placebo by day 3 was -1.98 vs -0.32 log10 copies/mL. CONCLUSIONS: In RSV-infected infants, JNJ-8678 was well tolerated. Target exposures were reached and antiviral activity was observed. CLINICAL TRIALS REGISTRATION: NCT02593851

Howard walnut trees can be brought into bearing without annual pruning

In traditionally managed Howard walnut orchards, trees are pruned annually during the orchard development phase, an expensive operation in terms of labor and prunings disposal costs. Our observations and some prior research by others had suggested that pruning may not be necessary in walnut. In a trial of pruned and unpruned hedgerow trees over 8 years, beginning a year after planting, we documented canopy growth, tree height, yield and nut quality characteristics and also the effects of fruit removal. Pruning altered canopy shape but did not lead to increases in canopy development, yield or nut quality. Although fruit removal stimulated more vegetative growth in both the pruned and unpruned treatments, fruit removal did not result in an increase in midday canopy photosynthetically active radiation interception or cumulative yield when fruit removal was stopped after year 4. After 8 years, there were no significant differences in tree height, nut quality or cumulative yield among any of the treatments, which suggests that not pruning young Howard orchards could provide a net benefit to growers