Analysis of gait kinematics to determine the effect of manipulating the appearance of stairs to improve safety: a linked series of laboratory-based, repeated measures studies

Background: Falls on stairs are a common and dangerous problem for older people. This series of studies evaluated whether or not selected changes to the appearance of stairs could make them safer for older people to negotiate. Objectives: To determine the effect of (1) a step edge highlighter and its position and (2) an optimised horizontal–vertical (H–V) visual illusion placed on a step riser on gait safety during stair descent and ascent. Design: A series of studies using a repeated measures, laboratory-based design, investigating gait control and safety in independently mobile older people. Setting: The University of Bradford Vision and Mobility Laboratory. Participants: Fit and healthy older people aged 60 years of age or more, independently mobile, reasonably active and with normal healthy eyes and corrected vision. Interventions: A step edge highlighter in a variety of offsets from the stair edge and an optimised H–V visual illusion placed on the stair riser. The H–V illusion was provided on a staircase by horizontal step edge highlighters on the tread edges and vertical stripes on the step risers. Main outcome measures: Gait parameters that are important for safe stepping in ascent and descent, measured using three-dimensional lower limb segmental kinematic data

Hypersensitivity of BRCA1 heterozygote lymphoblastoid cells to gamma radiation and PARP inhibitors

This article is made available through the Brunel Open Access Publishing Fund. Copyright @ 2013 Bourton EC, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.PARP inhibitors can be used to induce synthetic lethality in cells with bi-allelic BRCA1 and BRCA2 mutations. However the effect of PARP inhibitors in combination with radiation on cells with mono-allelic mutations of BRCA1 and BRCA2 is unknown. We have examined the cell survival response of lymphoblastoid cells derived from normal individuals and those derived from carriers of BRCA1 and BRCA2 mutations, following exposure to ionising radiation and the PARP inhibitor Olaparib. Two lymphoblastoid cell lines from normal individuals and three with mono-allelic mutations in BRCA1 and BRCA2 were exposed to increasing doses of gamma radiation either alone or in combination with 5 μM Olaparib. Cell survival was measured using the MTT assay. Exposure to increasing doses of gamma radiation caused a reduction in cell survival of all cell types. The combined exposure to gamma radiation and 5 μM Olaparib did not enhance cell kill in normal or BRCA2 heterozygote lymphoblastoid cells but significantly enhanced cell kill in cells derived from BRCA1 carriers (P = 0.02). The treatment of cancer patients carrying mutations in the BRCA1 gene with radiotherapy and the PARP inhibitor Olaparib may significantly enhance radiation induced normal tissue toxicity in these patients.Vidal Sassoon Foundation of America and “The Balls to Cancer” Charity, Coventry, U

What you see is what you step: the horizontal-vertical illusion increases toe clearance in older adults during stair ascent

PURPOSE Falls on stairs are a significant cause of morbidity and mortality in elderly people. A simple safety strategy to avoid tripping on stairs is increasing foot clearance. We determined whether a horizontal–vertical illusion superimposed onto stairs to create an illusory perceived increase in stair-riser height would increase stair ascent foot clearance in older participants

Differential expression of mTOR signalling components in drug resistance in ovarian cancer

This article has been made available through the Brunel Open Access Publishing Fund and is available from the specified link - Copyright @ 2010 The International Institute of Anticancer Research.Background/Aim: A limitation to successful cancer chemotherapy treatments is the acquisition of drug resistance. In advanced-stage ovarian cancer, the mammalian target of rapamycin (mTOR) pathway is upregulated, and inhibition of this pathway increases chemosensitivity in ovarian carcinoma cell lines. In this study, the expression of DEPTOR, mTOR, RICTOR, RAPTOR and S6 kinases were investigated in SKOV-3 and PEO1 parental and the paclitaxel-resistant (TaxR) SKOV-3TaxR and PEO1TaxR cell lines. Materials and Methods: RT-PCR, immunofluorescent analysis and Western blotting were carried out. Results: Quantitative RT-PCR revealed significant up-regulation of DEPTOR in both paclitaxel-resistant cell lines. SKOV-3TaxR exhibited down-regulation of RICTOR, RAPTOR and mTOR, whereas PEO1-TaxR showed down-regulation of RAPTOR and up-regulation of RICTOR and mTOR. Semi-quantitative RT-PCR analysis revealed marked changes in the expression of p70S6K splice variants mRNA in PEO1TaxR. Moreover, the phosphorylation status of p70S6K at Ser371 appears to be cell-type specific. Conclusion: We hypothesize that mTOR signalling may play a role in mediating paclitaxel resistance in ovarian cancer

Expression of mTOR and downstream signalling components in the JEG-3 and BeWo human placental choriocarcinoma cell lines

This article has been made available through the Brunel Open Access Publishing Fund.Emerging data suggest that nutritional status and body weight are related to reproductive function, and nutrient imbalances during pregnancy lead to changes in the expression of fetal genes. Recent studies show that the mTOR acts as a placental growth signalling sensor and its expression is down-regulated in intrauterine growth restriction. To date, very little is known about the expression of this signalling pathway in choriocarcinoma, one of the most lethal germ cell cancers. In this study, cultures of fusigenic (BeWo) and non-fusigenic (JEG-3) human choriocarcinoma cell lines were used to investigate the expression of mTOR and its downstream signalling components. The effects of an inducer of syncytialisation (forskolin) on mTOR, eIF4E binding proteins (4EBPs) and ribosomal protein S6 kinases (S6Ks) in BeWo cells were also assessed. RT-PCR studies revealed that mTOR, 4EBP and S6Ks are expressed at mRNA level in both JEG-3 and BeWo cells. Semi-quantitative RT-PCR analysis revealed that in early stages of syncytialisation (50 µM forskolin for 48 h), the expression of mTOR and 4EBP was down-regulated when compared to unstimulated cells. In fully syncytialised cells (50 µM forskolin for 72 h) the expression of both genes was similar to basal levels. Interestingly, the phosphorylation (Ser371, Thr389) status of p70S6K remained unaltered upon forskolin treatment. These data validate BeWo cells as an experimental model to study the effects of forskolin-induced syncytialisation on mTOR signalling.This article is available through the Brunel Open Access Publishing Fun

Intermediate addition multifocals provide safe stair ambulation with adequate ‘short-term’ reading

Purpose: A recent randomised controlled trial indicated that providing long-term multifocal wearers with a pair of distance single-vision spectacles for use outside the home reduced falls risk in active older people. However, it also found that participants disliked continually switching between using two pairs of glasses and adherence to the intervention was poor. In this study we determined whether intermediate addition multifocals (which could be worn most of the time inside and outside the home and thus avoid continual switching) could provide similar gait safety on stairs to distance single vision spectacles whilst also providing adequate 'short-term' reading and near vision. Methods: Fourteen healthy long-term multifocal wearers completed stair ascent and descent trials over a 3-step staircase wearing intermediate and full addition bifocals and progression-addition lenses (PALs) and single-vision distance spectacles. Gait safety/caution was assessed using foot clearance measurements (toe on ascent, heel on descent) over the step edges and ascent and descent duration. Binocular near visual acuity, critical print size and reading speed were measured using Bailey-Lovie near charts and MNRead charts at 40 cm. Results: Gait safety/caution measures were worse with full addition bifocals and PALs compared to intermediate bifocals and PALs. The intermediate PALs provided similar gait ascent/descent measures to those with distance single-vision spectacles. The intermediate addition PALs also provided good reading ability: Near word acuity and MNRead critical print size were better with the intermediate addition PALs than with the single-vision lenses (p < 0.0001), with a mean near visual acuity of 0.24 ± 0.13 logMAR (~N5.5) which is satisfactory for most near vision tasks when performed for a short period of time. Conclusions: The better ability to 'spot read' with the intermediate addition PALs compared to single-vision spectacles suggests that elderly individuals might better comply with the use of intermediate addition PALs outside the home. A lack of difference in gait parameters for the intermediate addition PALs compared to distance single-vision spectacles suggests they could be usefully used to help prevent falls in older well-adapted full addition PAL wearers. A randomised controlled trial to investigate the usefulness of intermediate multifocals in preventing falls seems warranted

Technology versus tradition: a non-inferiority trial comparing video to face-to-face consultations with a physiotherapist for people with knee osteoarthritis. Protocol for the PEAK randomised controlled trial.

BACKGROUND: Knee osteoarthritis (OA) is a global problem that causes significant pain and physical dysfunction, substantially impacting on quality of life and imposing enormous cost to the healthcare system. Exercise is pivotal to OA management, yet uptake by people with knee OA is inadequate. Limited access to appropriately skilled health professionals, such as physiotherapists, for prescription of an exercise program and support with exercise is a major barrier to optimal care. Internet-enabled video consultations permit widespread reach. However, services offering video consultations with physiotherapists for musculoskeletal conditions are scant in Australia where there is typically no Government or private health insurer funding for such services. The paucity of robust evidence demonstrating video consultations with physiotherapists are clinically effective, safe and cost-effective for knee OA is hampering implementation of, and willingness of healthcare policymakers to pay for, these services. METHODS: This is an assessor- and participant-blinded, two-arm, pragmatic, comparative effectiveness non-inferiority randomised controlled trial (RCT) conducted in Australia. We are recruiting 394 people from the community with chronic knee pain consistent with a clinical diagnosis of knee OA. Participants are randomly allocated to receive physiotherapy care via i) video-conferencing or; ii) face-to-face consultations. Participants are provided five consultations (30-45 min each) with a physiotherapist over 3 months for prescription of a home-based strengthening exercise program (to be conducted independently at home) and physical activity plan, as well as OA education. Participants in both groups are provided with educational booklets and simple exercise equipment via post. The co-primary outcomes are change in self-reported i) knee pain on walking; and ii) physical function, with a primary end-point of 3 months and a secondary end-point of 9 months. Secondary outcomes include changes in other clinical outcomes (health-related quality of life; therapeutic relationship; global ratings of change; satisfaction with care; self-efficacy; physical activity levels), time and financial costs of attending consultations, healthcare usage and convenience. Non-inferiority will be assessed using the per-protocol dataset. DISCUSSION: Findings will determine if video consultations with physiotherapists are non-inferior to traditional face-to-face consultations for management of people with knee OA. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12619001240134. http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377672&isReview=true

Intelligence and ambition are distributed equally around the globe

The impact of freely accessible knowledge distribution platforms is briefly discussed