6,213 research outputs found

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

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    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

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    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

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

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    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

    Associations between birth size and later height from infancy through adulthood : an individual based pooled analysis of 28 twin cohorts participating in the CODATwins project

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    Background: There is evidence that birth size is positively associated with height in later life, but it remains unclear whether this is explained by genetic factors or the intrauterine environment. Aim: To analyze the associations of birth weight, length and ponderal index with height from infancy through adulthood within mono- and dizygotic twin pairs, which provides insights into the role of genetic and environmental individual-specific factors. Methods: This study is based on the data from 28 twin cohorts in 17 countries. The pooled data included 41,852 complete twin pairs (55% monozygotic and 45% same-sex dizygotic) with information on birth weight and a total of 112,409 paired height measurements at ages ranging from 1 to 69 years. Birth length was available for 19,881 complete twin pairs, with a total of 72,692 paired height measurements. The association between birth size and later height was analyzed at both the individual and within-pair level by linear regression analyses. Results: Within twin pairs, regression coefficients showed that a 1-kg increase in birth weight and a 1-cm increase in birth length were associated with 1.14-4.25 cm and 0.18-0.90 cm taller height, respectively. The magnitude of the associations was generally greater within dizygotic than within monozygotic twin pairs, and this difference between zygosities was more pronounced for birth length. Conclusion: Both genetic and individual-specific environmental factors play a role in the association between birth size and later height from infancy to adulthood, with a larger role for genetics in the association with birth length than with birth weight

    Topology by Design in Magnetic nano-Materials: Artificial Spin Ice

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    Artificial Spin Ices are two dimensional arrays of magnetic, interacting nano-structures whose geometry can be chosen at will, and whose elementary degrees of freedom can be characterized directly. They were introduced at first to study frustration in a controllable setting, to mimic the behavior of spin ice rare earth pyrochlores, but at more useful temperature and field ranges and with direct characterization, and to provide practical implementation to celebrated, exactly solvable models of statistical mechanics previously devised to gain an understanding of degenerate ensembles with residual entropy. With the evolution of nano--fabrication and of experimental protocols it is now possible to characterize the material in real-time, real-space, and to realize virtually any geometry, for direct control over the collective dynamics. This has recently opened a path toward the deliberate design of novel, exotic states, not found in natural materials, and often characterized by topological properties. Without any pretense of exhaustiveness, we will provide an introduction to the material, the early works, and then, by reporting on more recent results, we will proceed to describe the new direction, which includes the design of desired topological states and their implications to kinetics.Comment: 29 pages, 13 figures, 116 references, Book Chapte

    Predictors of return to work following motor vehicle related orthopaedic trauma

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    © 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

    Discharge to inpatient rehabilitation following arthroplasty is a strong predictor of persistent opioid use 90 days after surgery: a prospective, observational study

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    Background: Total knee and hip arthroplasty are considered a clinically and cost-effective intervention, however, persistent pain post-surgery can occur, and some continue to take opioid medications long-term. One factor which has infrequently been included in prediction modelling is rehabilitation pathway, in particular, one which includes inpatient rehabilitation. As discharge to inpatient rehabilitation post-arthroplasty is common practice, we aimed to identify whether rehabilitation pathway (discharge to in-patient rehabilitation or not) predicts continued use of opioids at 3 months (90 days) post- total knee arthroplasty (TKA) and total hip arthroplasty (THA) whilst controlling for other covariates. Methods: The study was nested within a prospective observational study capturing pre-operative, acute care and longer-term data from 1900 osteoarthritis (OA) patients who underwent primary TKA or THA. The larger study involved a part-random, part-convenience sample of 19 high-volume hospitals across Australia. Records with complete pre-and post-operative analgesic (35 days and 90 days) use were identified [1771 records (93% of sample)] and included in logistic regression analyses. Results: Three hundred and thirteen people (17.8%) reported ongoing opioid use at 90 days post-operatively. In the adjusted model, admission to inpatient rehabilitation after surgery was identified as an independent and significant predictor of opioid use at 90-days. Inpatient rehabilitation was associated with almost twice the odds of persistent opioid use at 90-days compared to discharge directly home (OR = 1.9 (1.4, 2.5), p <.001). Conclusion: The inpatient rehabilitation pathway is a strong predictor of longer-term opioid use (90 days) post-arthroplasty, accounting for many known and possible confounders of use including sex, age, insurance status, major complications, smoking status and baseline body pain levels. Trial registration: The study was nested within a prospective cohort observational study capturing pre-operative, acute-care and longer-term data from patients undergoing primary TKA or THA for osteoarthritis (ClinicalTrials.gov NCT01899443)

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

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    © 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

    The impact of cement fixation on early mortality in arthroplasty for hip fracture

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    Aims Cementing in arthroplasty for hip fracture is associated with improved postoperative function, but may have an increased risk of early mortality compared to uncemented fixation. Quantifying this mortality risk is important in providing safe patient care. This study investigated the association between cement use in arthroplasty and mortality at 30 days and one year in patients aged 50 years and over with hip fracture. Methods This retrospective cohort study used linked data from the Australian Hip Fracture Registry and the National Death Index. Descriptive analysis and Kaplan-Meier survival curves tested the unadjusted association of mortality between cemented and uncemented procedures. Multilevel logistic regression, adjusted for covariates, tested the association between cement use and 30-day mortality following arthroplasty. Given the known institutional variation in preference for cemented fixation, an instrumental variable analysis was also performed to minimize the effect of unknown confounders. Adjusted Cox modelling analyzed the association between cement use and mortality at 30 days and one year following surgery. Results The 30-day mortality was 6.9% for cemented and 4.9% for uncemented groups (p = 0.003). Cement use was significantly associated with 30-day mortality in the Kaplan-Meier survival curve (p = 0.003). After adjusting for covariates, no significant association between cement use and 30-day mortality was shown in the adjusted multilevel logistic regression (odd rati0 (OR) 1.1, 95% confidence interval (CI) 0.9 to 1.5; p = 0.366), or in the instrumental variable analysis (OR 1.0, 95% CI 0.9 to 1.0, p=0.524). There was no significant between-group difference in mortality within 30days (hazard ratio (HR) 0.9, 95% CI 0.7to 1.1; p = 0.355) or one year (HR 0.9 95% CI 0.8 to 1.1; p = 0.328) in the Cox modelling. Conclusion No statistically significant difference in patient mortality with cement use in arthroplasty was demonstrated in this population, once adjusted for covariates. This study concludes that cementing in arthroplasty for hip fracture is a safe means of surgical fixation
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