Transplantation of novel human GDF5-expressing CHO cells is neuroprotective in models of Parkinson's disease

Growth/differentiation factor 5 (GDF5) is a neurotrophic factor that promotes the survival of midbrain dopaminergic neurons in vitro and in vivo and as such is potentially useful in the treatment of Parkinson's disease (PD). This study shows that a continuous supply of GDF5, produced by transplanted GDF5-overexpressing CHO cells in vivo, has neuroprotective and neurorestorative effects on midbrain dopaminergic neurons following 6-hydroxydopamine (6-OHDA)-induced lesions of the adult rat nigrostriatal pathway. It also increases the survival and improves the function of transplanted embryonic dopaminergic neurons in the 6-OHDA-lesioned rat model of PD. This study provides the first proof-of-principle that sustained delivery of GDF5 in vivo may be useful in the treatment of PD

Incentives as connectors : insights into a breastfeeding incentive intervention in a disadvantaged area of North-West England

PMID: 22458841 [PubMed - indexed for MEDLINE] PMCID: PMC3414740 Free PMC ArticlePeer reviewedPublisher PD

Evaluating rehabilitation following lumbar fusion surgery (REFS): study protocol for a randomised controlled trial

BACKGROUND: The rate of lumbar fusion surgery (LFS) is increasing. Clinical recovery often lags technical outcome. Approximately 40% of patients undergoing LFS rate themselves as symptomatically unchanged or worse following surgery. There is little research describing rehabilitation following LFS with no clear consensus as to what constitutes the optimum strategy. It is important to develop appropriate rehabilitation strategies to help patients manage pain and recover lost function following LFS. METHODS/DESIGN: The study design is a randomised controlled feasibility trial exploring the feasibility of providing a complex multi-method rehabilitation intervention 3 months following LFS. The rehabilitation protocol that we have developed involves small participant groups of therapist led structured education utilising principles of cognitive behavioral therapy (CBT), progressive, individualised exercise and peer support. Participants will be randomly allocated to either usual care (UC) or the rehabilitation group (RG). We will recruit 50 subjects, planning to undergo LFS, over 30 months. Following LFS all participants will experience normal care for the first 3 months. Subsequent to a satisfactory 3 month surgical review they will commence their allocated post-operative treatment (RG or UC). Data collection will occur at baseline (pre-operatively), 3, 6 and 12 months post-operatively. Primary outcomes will include an assessment of feasibility factors (including recruitment and compliance). Secondary outcomes will evaluate the acceptability and characteristics of a limited cluster of quantitative measures including the Oswestry Disability Index (ODI) and an aggregated assessment of physical function (walking 50 yards, ascend/descend a flight of stairs). A nested qualitative study will evaluate participants' experiences. DISCUSSION: This study will evaluate the feasibility of providing complex, structured rehabilitation in small groups 3 months following technically successful LFS. We will identify strengths and weakness of the proposed protocol and the usefulness and characteristics of the planned outcome measures. This will help shape the development of rehabilitation strategies and inform future work aimed at evaluating clinical efficacy. TRIAL REGISTRATION: ISRCTN60891364, 10/07/2014

Hyperfine resolved spectrum of the molecular dication DCl

We have obtained hyperfine-resolved infrared spectra of a PQ23(N) branch line in the v = 2-1 band of the X 3Σ- state of the molecular dication D35Cl2+. Analysis of the hyperfine structure allows us to estimate the magnitude of the Fermi contact interaction for the chlorine nucleus; bF(Cl) = 167 (25) MHz

Physical activity engagement in early rheumatoid arthritis: a qualitative study to inform intervention development

© 2015 Chartered Society of Physiotherapy Background Physical activity (PA) in patients with rheumatoid arthritis (RA) is lower than in the general population. PA can improve physical function in RA, decrease chronic inflammation and reduce pain, without adversely affecting disease activity. Objectives To explore patient's views on approaches to delivering PA programmes and inform a programme to maximise functional ability through long-term engagement with PA. Methods Qualitative data were collected via three focus groups which explored the views of people with RA of their PA support needs following diagnosis; experiences relating to PA; motivators and facilitators to support PA engagement and the suitability for people with RA of evidence based PA programmes designed for other long-term conditions. Results Study participants (15 female, 4 male; 59.9 (standard deviation (SD) 10.3) years) had a mean time (SD) since diagnosis of 44 (34) months. Data analysis yielded 4 key themes relating to PA programmes: (1) why people join and why they drop out; (2) venue and timing; (3) what people want to do and hear; and (4) who should deliver programmes and how. Conclusion Patients with RA are interested in PA programmes 6 to 12 months after diagnosis, which support safe exercise and provide expert physiotherapist input. Recommendation by trusted health professionals and promotion of the benefits for ‘people like me’ would positively impact recruitment and retention. Key elements of the programme include proficient, safety-oriented exercise guidance, RA education, peer support, relaxation, coping strategies and self-set goals. Findings indicate that a group-based programme with a social aspect would support adherence

Consensus definition and diagnostic criteria for neonatal encephalopathy-study protocol for a real-time modified delphi study

BACKGROUND: 'Neonatal encephalopathy' (NE) describes a group of conditions in term infants presenting in the earliest days after birth with disturbed neurological function of cerebral origin. NE is aetiologically heterogenous; one cause is peripartum hypoxic ischaemia. Lack of uniformity in the terminology used to describe NE and its diagnostic criteria creates difficulty in the design and interpretation of research and complicates communication with families. The DEFINE study aims to use a modified Delphi approach to form a consensus definition for NE, and diagnostic criteria.METHODS: Directed by an international steering group, we will conduct a systematic review of the literature to assess the terminology used in trials of NE, and with their guidance perform an online Real-time Delphi survey to develop a consensus diagnosis and criteria for NE. A consensus meeting will be held to agree on the final terminology and criteria, and the outcome disseminated widely.DISCUSSION: A clear and consistent consensus-based definition of NE and criteria for its diagnosis, achieved by use of a modified Delphi technique, will enable more comparability of research results and improved communication among professionals and with families.IMPACT: The terms Neonatal Encephalopathy and Hypoxic Ischaemic Encephalopathy tend to be used interchangeably in the literature to describe a term newborn with signs of encephalopathy at birth. This creates difficulty in communication with families and carers, and between medical professionals and researchers, as well as creating difficulty with performance of research. The DEFINE project will use a Real-time Delphi approach to create a consensus definition for the term 'Neonatal Encephalopathy'. A definition formed by this consensus approach will be accepted and utilised by the neonatal community to improve research, outcomes, and parental experience.</p

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

A systematic review of grandparents’ influence on grandchildren’s cancer risk factors

Many lifestyle patterns are established when children are young. Research has focused on the potential role of parents as a risk factor for non communicable disease in children, but there is limited investigation of the role of other caregivers, such as grandparents. The aim of this review was to identify and synthesise evidence for any influence grandparents&rsquo; care practices may have on their grandchildren&rsquo;s long term cancer risk factors. A systematic review was carried out with searches across four databases (MEDLINE, Embase, Web of Science, PsycINFO) as well as searches of reference lists and citing articles, and Google Scholar. Search terms were based on six areas of risk that family care could potentially influence&ndash;weight, diet, physical activity, tobacco, alcohol and sun exposure. All study designs were included, as were studies that provided an indication of the interaction of grandparents with their grandchildren. Studies were excluded if grandparents were primary caregivers and if children had serious health conditions. Study quality was assessed using National Institute for Health and Care Excellence checklists. Grandparent impact was categorised as beneficial, adverse, mixed or as having no impact. Due to study heterogeneity a meta-analysis was not possible. Qualitative studies underwent a thematic synthesis of their results. Results from all included studies indicated that there was a sufficient evidence base for weight, diet, physical activity and tobacco studies to draw conclusions about grandparents&rsquo; influence. One study examined alcohol and no studies examined sun exposure. Evidence indicated that, overall, grandparents had an adverse impact on their grandchildren&rsquo;s cancer risk factors. The theoretical work in the included studies was limited. Theoretically underpinned interventions designed to reduce these risk factors must consider grandparents&rsquo; role, as well as parents&rsquo;, and be evaluated robustly to inform the evidence base further

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment