5,072 research outputs found

    Apolipoprotein E delivery by peritoneal implantation of encapsulated recombinant cells improves the hyperlipidaemic profile in apoE-deficient mice

    Get PDF
    Plasma apolipoprotein E (apoE) is a 34-kDa polymorphic protein which has atheroprotective actions by clearing remnant lipoproteins and sequestering excess cellular cholesterol. Low or dysfunctional apoE is a risk factor for hyperlipidaemia and atherosclerosis, and for restenosis after angioplasty. Here, in short-term studies designed to establish proof-of-principle, we investigate whether encapsulated recombinant Chinese hamster ovary (CHO) cells can secrete wild-type apoE3 protein in vitro and then determine whether peritoneal implantation of the microcapsules into apoE-deficient (apoE(-/-)) mice reduces their hypercholesterolaemia.Recombinant CHO-E3 cells were encapsulated into either alginate poly-L-lysine or alginate polyethyleneimine/polybrene microspheres. After verifying stability and apoE3 secretion, the beads were then implanted into the peritoneal cavity of apoE(-/-) mice; levels of plasma apoE3, cholesterol and lipoproteins were monitored for up to 14 days post-implantation.Encapsulated CHO-E3 cells continued to secrete apoE3 protein throughout a 60-day study period in vitro, though levels declined after 14 days. This cell-derived apoE3 was biologically active. When conditioned medium from encapsulated CHO-E3 cells was incubated with cultured cells pre-labelled with [H-3]-cholesterol, efflux of cholesterol was two to four times greater than with normal medium (at 8 h, for example, 7.4+/-0.3% vs. 2.4+/-0.2% of cellular cholesterol; P<0.001). Moreover, when secreted apoE3 was injected intraperitoneally into apoE(-/-) mice, apoE3 was detected in plasma and the hyperlipidaemia improved. Similarly, when alginate polyethyleneimine/polybrene capsules were implanted into the peritoneum of apoE(-/-) mice, apoE3 was secreted into plasma and at 7 days total cholesterol was reduced, while atheroprotective high-density lipoprotein (HDL) increased. In a second study, apoE was detectable in plasma of five mice treated with alginate poly-L-lysine beads, 4 and 7 days post-implantation, though not at day 14. Furthermore, their hypercholesterolaemia was reduced, while HDL was clearly elevated in all mice at days 4 and 7 (from 18.4+/-6.2% of total lipoproteins to 31.1+/-6.8% at 7 days; P<0.001); however, these had rebounded by day 14, possibly due to the emergence of anti-apoE antibodies.We conclude that microencapsulated apoE-secreting cells have the potential to ameliorate the hyperlipidaemia of apoE deficiency, but that the technology must be improved to become a feasible therapeutic to treat atherosclerosis. (C) 2004 Elsevier B.V. All rights reserved

    Breakdown of Hydrodynamics in a Simple One-Dimensional Fluid

    Full text link
    We investigate the behavior of a one-dimensional diatomic fluid under a shock wave excitation. We find that the properties of the resulting shock wave are in striking contrast with those predicted by hydrodynamic and kinetic approaches, e.g., the hydrodynamic profiles relax algebraically toward their equilibrium values. Deviations from local thermodynamic equilibrium are persistent, decaying as a power law of the distance to the shock layer. Non-equipartition is observed infinitely far from the shock wave, and the velocity-distribution moments exhibit multiscaling. These results question the validity of simple hydrodynamic theories to understand collective behavior in 1d fluids.Comment: 4 pages, 5 figure

    The association between seeking financial compensation and injury recovery following motor vehicle related orthopaedic trauma

    Full text link
    © 2016 The Author(s). Background: Motor vehicle related moderate-severe orthopaedic trauma has a major impact on the burden of injury. In Australia, all states and territories provide access to financial compensation following injury in a motor vehicle crash. The aim of this study was to investigate the influence of seeking financial compensation (i.e., making a claim) on injury recovery following motor vehicle related moderate-severe orthopaedic trauma. Methods: Patients admitted with upper/lower extremity fractures after a motor vehicle crash were recruited from two trauma hospitals. Baseline data were collected in person by written questionnaire within two weeks of injury. Follow up data were collected by a mailed written questionnaire at six, 12 and 24 months. Additional (demographic/injury-related) information was collected from hospital databases, all other measures were self-reported. Outcomes were: Short Form-36 Version 2.0 (SF36v2), Physical/Mental Component Scores (PCS/MCS); Post Traumatic Stress Disorder (PTSD) Checklist Civilian Version (PCL-C); and Global Rating of Change (GRC) scale. Analysis involved descriptive statistics and linear mixed models to examine the effect of compensation status on injury recovery over time. Results: There were 452 study participants. Baseline characteristics showed: mean age 40 years (17.1 Standard Deviation [SD]); 75 % male; 74 % worked pre-injury; 67 % in excellent-very good pre-injury health; 56 % sustained serious injuries, Injury Severity Score (ISS) 9-15; 61 % had a low-middle range household income. Overall, after controlling for possible confounders, the compensable group had poorer recovery compared to the non-compensable group for PCS (-2.97 Mean Difference (MD), 95 % CI -4.73, -1.22); MCS (-3.44 MD, 95 % CI -5. 62, -1.26); PCL-C (3.42MD, 95 % CI 0.87, 5.99); and GRC (-0.66MD, 95 % CI -1.15, -0.17). Injury recovery over time for all participants showed: PCS improved from 6-12 and 12-24 months; MCS and GRC improved from 6-12 months; and PCL-C did not significantly improve from 6-12 and 12-24 months. Injury recovery over time continued for compensable and non-compensable groups but compensable participants had poorer scores at each time period, especially MCS and PCL-C. Conclusions: Making a claim was associated with poor injury recovery following motor vehicle related orthopaedic trauma, mainly for mental health. Irrespective of claim status, the majority had poor injury recovery, especially for mental health

    Predictors of return to work following motor vehicle related orthopaedic trauma

    Full text link
    © 2016 Murgatroyd et al. Background: Work disability following motor vehicle related orthopaedic trauma is a significant contributor to the burden of injury and disease. Early identification of predictors for return to work (RTW) is essential for developing effective interventions to prevent work disability. The study aim was to determine the predictors (including compensation related factors) of time to RTW following motor vehicle related orthopaedic trauma. Methods: Admitted patients were recruited prospectively from two trauma hospitals with upper and/or lower extremity fractures following a motor vehicle crash. Baseline and follow up data were collected by written questionnaire. For baseline, this occurred in person within 2 weeks of injury. For follow up, this occurred by mail at six, 12 and 24 months. Additional demographic and injury-related information was retrieved from hospital databases. Analysis involved: descriptive statistics; logrank test to detect survival distributions of categorical variables; and Cox proportional hazards regression models for risks of time to RTW using baseline characteristic and compensation related variables (at 6 months). Results: Of 452 study participants 334 (74 %) were working pre-injury: results are based on this subset. Baseline characteristics were mean age 36 years (13.9 Standard Deviation [SD]), 80 % male; 72 % self-assessed very good-excellent pre-injury health, 83 % household income > AU$40,000 (Australian Dollar). Follow up data was available for 233 (70 %), 210 (63 %), and 182 (54 %) participants at six, 12 and 24 months respectively. Significant risks of a longer time to RTW were greater injury severity, as measured by the New Injury Severity Score (NISS) (Hazards Rate Ratio [HRR] = 0.54, 95 % CI 0.35-0.82); and lower occupational skill levels (HRR = 0.53, 95 % CI 0.34-0.83). Significant risks of a shorter time to RTW were: recovery expectations for usual activities within 90 days (HRR = 2.10, 95 % CI 1.49-2.95); full-time pre-injury work hours (HRR = 1.99, 95 % CI 1.26-3.14); and very good self-assessed pre-injury health status (HRR = 1.41, 95 % CI 0.98-2.02). Legal representation (analysed at six months only) was not associated with time to RTW. At each time period, there were 146 (63 %), 149 (71 %), and 137 (76 %) working participants. Conclusions: A longer time to RTW was associated with greater injury severity and lower occupational skill levels; while a shorter time to RTW was associated with recovery expectations for usual activities within 90 days, full-time pre-injury work hours, and very good self-assessed pre-injury health status. Our findings reinforce existing research. There is an opportunity to trial interventions that address potentially modifiable factors. The issues surrounding legal representation are complex and require further research

    Minimal detectable change for mobility and patient-reported tools in people with osteoarthritis awaiting arthroplasty

    Get PDF
    Background: Thoughtful use of assessment tools to monitor disease requires an understanding of clinimetric properties. These properties are often under-reported and, thus, potentially overlooked in the clinic. This study aimed to determine the minimal detectable change (MDC) and coefficient of variation per cent (CV%) for tools commonly used to assess the symptomatic and functional severity of knee and hip osteoarthritis. Methods. We performed a test-retest study on 136 people awaiting knee or hip arthroplasty at one of two hospitals. The MDC95 (the range over which the difference [change] for 95% of patients is expected to lie) and the coefficient of variation per cent (CV%) for the visual analogue scale (VAS) for joint pain, the six-minute walk test (6MWT), the timed up-and-go (TUG) test, the Knee Injury and Osteoarthritis Outcome Score (KOOS) and the Hip Disability and Osteoarthritis Outcome Score (HOOS) subscales were calculated. Results: Knee cohort (n = 75) - The MDC 95 and CV% values were as follows: VAS 2.8 cm, 15%; 6MWT 79 m, 8%; TUG +/-36.7%, 13%; KOOS pain 20.2, 19%; KOOS symptoms 24.1, 22%; KOOS activities of daily living 20.8, 17%; KOOS quality of life 26.6, 44. Hip cohort (n = 61) - The MDC95 and CV% values were as follows: VAS 3.3 cm, 17%; 6MWT 81.5 m, 9%; TUG +/-44.6%, 16%; HOOS pain 21.6, 22%; HOOS symptoms 22.7, 19%; HOOS activities of daily living 17.7, 17%; HOOS quality of life 24.4, 43%. Conclusions: Distinguishing real change from error is difficult in people with severe osteoarthritis. The 6MWT demonstrates the smallest measurement error amongst a range of tools commonly used to assess disease severity, thus, has the capacity to detect the smallest real change above measurement error in everyday clinical practice. © 2014 Naylor et al.; licensee BioMed Central Ltd

    Barriers to participation in a placebo-surgical trial for lumbar spinal stenosis

    Get PDF
    © 2019 Background: Placebo-controlled trials are an important tool when assessing the efficacy of spinal surgical procedures. The most common spinal surgical procedure in older adults is decompression for lumbar spinal stenosis. Before conducting a placebo-surgical trial on decompression surgery, an investigation of patients’ willingness to participate in a placebo-controlled trial of decompression surgery and barriers to participation were explored. Materials: An online survey. Methods: Descriptive analyses of demographic and clinical data, and participants' willingness to participate in a placebo-surgical trial. Logistic regression was used to examine potential predictors of willingness to participate. Two independent researchers performed a coded framework analysis of patients’ barriers to participation. Results: 68 patients were invited and 63 participants completed the survey (91.3% response, mean (SD) age 69.5 (10.9) years, 52% females), 71% suffered from moderate to very severe pain. Ten participants (15.9%) were willing to participate in a placebo-controlled trial. Being married was associated with decreased odds of participating (OR: 0.2; 95% CI, 0.05 to 0.8; P = 0.03), while the main barriers were a lack of information about the procedure, reassurance of a positive outcome with participation, and concerns about the risks and benefits of placebo surgery. Conclusions: A minority of patients with lumbar spinal stenosis were willing to participate in a placebo-controlled trial of surgery. The identified barriers indicate that educating eligible patients about: the need for placebo-surgical trials, the personal risks and benefits of participation, and the importance and potential benefits of placebo trials to others, may be crucial to ensure adequate recruitment into the placebo-controlled surgical trial. Conclusions should be read cautiously however, given the small sample size present in this study

    Low-temperature muon spin rotation studies of the monopole charges and currents in Y doped Ho2Ti2O7

    Get PDF
    In the ground state of Ho2Ti2O7 spin ice, the disorder of the magnetic moments follows the same rules as the proton disorder in water ice. Excitations take the form of magnetic monopoles that interact via a magnetic Coulomb interaction. Muon spin rotation has been used to probe the low-temperature magnetic behaviour in single crystal Ho2−xYxTi2O7 (x = 0, 0.1, 1, 1.6 and 2). At very low temperatures, a linear field dependence for the relaxation rate of the muon precession λ(B), that in some previous experiments on Dy2Ti2O7 spin ice has been associated with monopole currents, is observed in samples with x = 0, and 0.1. A signal from the magnetic fields penetrating into the silver sample plate due to the magnetization of the crystals is observed for all the samples containing Ho allowing us to study the unusual magnetic dynamics of Y doped spin ice

    SUcceSS, SUrgery for Spinal Stenosis: Protocol of a randomised, placebo-controlled trial

    Get PDF
    © Author(s) (or their employer(s)) 2019. Introduction: Central lumbar spinal stenosis (LSS) is a common cause of pain, reduced function and quality of life in older adults. Current management of LSS includes surgery to decompress the spinal canal and alleviate symptoms. However, evidence supporting surgical decompression derives from unblinded randomised trials with high cross-over rates or cohort studies showing modest benefits. This protocol describes the design of the SUrgery for Spinal Stenosis (SUcceSS) trial-the first randomised placebo-controlled trial of decompressive surgery for symptomatic LSS. Methods and analysis: SUcceSS will be a prospectively registered, randomised placebo-controlled trial of decompressive spinal surgery. 160 eligible participants (80 participants/group) with symptomatic LSS will be randomised to either surgical spinal decompression or placebo surgical intervention. The placebo surgical intervention is identical to surgical decompression in all other ways with the exception of the removal of any bone or ligament. All participants and assessors will be blinded to treatment allocation. Outcomes will be assessed at baseline and at 3, 6, 12 and 24 months. The coprimary outcomes will be function measured with the Oswestry Disability Index and the proportion of participants who have meaningfully improved their walking capacity at 3 months postrandomisation. Secondary outcomes include back pain intensity, lower limb pain intensity, disability, quality of life, anxiety and depression, neurogenic claudication score, perceived recovery, treatment satisfaction, adverse events, reoperation rate and rehospitalisation rate. Those who decline to be randomised will be invited to participate in a parallel observational cohort. Data analysis will be blinded and by intention to treat. A trial-based cost-effectiveness analysis will determine the potential incremental cost per quality-adjusted life year gained. Ethics and dissemination: Ethics approval has been granted by the NSW Health (reference:17/247/POWH/601) and the Monash University (reference: 12371) Human Research Ethics Committees. Dissemination of results will be via journal articles and presentations at national and international conferences
    • …
    corecore