Generation of a large volume of clinically relevant nanometre-sized ultra-high-molecular-weight polyethylene wear particles for cell culture studies.

It has recently been shown that the wear of ultra-high-molecular-weight polyethylene in hip and knee prostheses leads to the generation of nanometre-sized particles, in addition to micron-sized particles. The biological activity of nanometre-sized ultra-high-molecular-weight polyethylene wear particles has not, however, previously been studied due to difficulties in generating sufficient volumes of nanometre-sized ultra-high-molecular-weight polyethylene wear particles suitable for cell culture studies. In this study, wear simulation methods were investigated to generate a large volume of endotoxin-free clinically relevant nanometre-sized ultra-high-molecular-weight polyethylene wear particles. Both single-station and six-station multidirectional pin-on-plate wear simulators were used to generate ultra-high-molecular-weight polyethylene wear particles under sterile and non-sterile conditions. Microbial contamination and endotoxin levels in the lubricants were determined. The results indicated that microbial contamination was absent and endotoxin levels were low and within acceptable limits for the pharmaceutical industry, when a six-station pin-on-plate wear simulator was used to generate ultra-high-molecular-weight polyethylene wear particles in a non-sterile environment. Different pore-sized polycarbonate filters were investigated to isolate nanometre-sized ultra-high-molecular-weight polyethylene wear particles from the wear test lubricants. The use of the filter sequence of 10, 1, 0.1, 0.1 and 0.015 µm pore sizes allowed successful isolation of ultra-high-molecular-weight polyethylene wear particles with a size range of < 100 nm, which was suitable for cell culture studies

Abnormalities in autonomic function in obese boys at-risk for insulin resistance and obstructive sleep apnea.

Study objectivesCurrent evidence in adults suggests that, independent of obesity, obstructive sleep apnea (OSA) can lead to autonomic dysfunction and impaired glucose metabolism, but these relationships are less clear in children. The purpose of this study was to investigate the associations among OSA, glucose metabolism, and daytime autonomic function in obese pediatric subjects.MethodsTwenty-three obese boys participated in: overnight polysomnography; a frequently sampled intravenous glucose tolerance test; and recordings of spontaneous cardiorespiratory data in both the supine (baseline) and standing (sympathetic stimulus) postures.ResultsBaseline systolic blood pressure and reactivity of low-frequency heart rate variability to postural stress correlated with insulin resistance, increased fasting glucose, and reduced beta-cell function, but not OSA severity. Baroreflex sensitivity reactivity was reduced with sleep fragmentation, but only for subjects with low insulin sensitivity and/or low first-phase insulin response to glucose.ConclusionsThese findings suggest that vascular sympathetic activity impairment is more strongly affected by metabolic dysfunction than by OSA severity, while blunted vagal autonomic function associated with sleep fragmentation in OSA is enhanced when metabolic dysfunction is also present

Racial difference in Acylation Stimulating Protein (ASP) correlates to triglyceride in non-obese and obese African American and Caucasian women

© 2009 Scantlebury-Manning et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium

The Dementia with Lewy Bodies (DLB) Consortium has refined its recommendations about the clinical and pathologic diagnosis of DLB, updating the previous report, which has been in widespread use for the last decade. The revised DLB consensus criteria now distinguish clearly between clinical features and diagnostic biomarkers, and give guidance about optimal methods to establish and interpret these. Substantial new information has been incorporated about previously reported aspects of DLB, with increased diagnostic weighting given to REM sleep behavior disorder and $^{123}$iodine-metaiodobenzylguanidine (MIBG) myocardial scintigraphy. The diagnostic role of other neuroimaging, electrophysiologic, and laboratory investigations is also described. Minor modifications to pathologic methods and criteria are recommended to take account of Alzheimer disease neuropathologic change, to add previously omitted Lewy-related pathology categories, and to include assessments for substantia nigra neuronal loss. Recommendations about clinical management are largely based upon expert opinion since randomized controlled trials in DLB are few. Substantial progress has been made since the previous report in the detection and recognition of DLB as a common and important clinical disorder. During that period it has been incorporated into DSM-5, as major neurocognitive disorder with Lewy bodies. There remains a pressing need to understand the underlying neurobiology and pathophysiology of DLB, to develop and deliver clinical trials with both symptomatic and disease-modifying agents, and to help patients and carers worldwide to inform themselves about the disease, its prognosis, best available treatments, ongoing research, and how to get adequate support.The DLB Consortium meeting was organized by the Mayo School of Continuous Professional Development (MSCPD) and supported by Acadia Pharmaceuticals, Alzheimer’s Association, Axovant Sciences, Banner Health, GE Healthcare, the Lewy Body Dementia Association, the Lewy Body Society, Lundbeck, the National Institute on Aging, the National Institute on Neurologic Disease and Stroke, and an NIH grant (R13 NS095618). Kathy Fuqua, Julie Reed, and colleagues at the MSCPD provided administrative support to the consortium meeting in Fort Lauderdale. I.G.M., D.B., J.-P.T., J.A., and A.T. receive support from the UK NIHR Biomedical Research Centre awarded to the Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University. Travel grant support was provided by the Alzheimer’s Research UK ARUK NE Network Centre. B.F.B., D.W.D., K.K., and T.J.F. are supported by the NIH (P50-AG016574) and the Mangurian Foundation for Lewy Body Research. G.H. is a senior principal research fellowship holder from the National Health and Medical Research Council of Australia (1079679). D.A. is a Royal Society Wolfson Research Merit Award Holder and thanks the Wolfson Foundation and the Royal Society for their support. C.G.B. thanks the Maudsley BRC for Mental Health and BRU dementia for supporting his involvement in the work. A.C.-P. receives research support from the NIH (RO1 NS082265, UO1 NS082134, P50 NS053488), the Burroughs Wellcome Fund, the Alzheimer’s Association/Michael J. Fox Foundation/Weston Biomarkers Across Neurodegenerative Disease initiative, and the Pechenik Montague Award Fund. D.f. acknowledges support from NIHR Programme Grants for Applied Research (RP-PG-0610-10100 SHAPED). O.E.-A. acknowledges support for OE laboratory from the Michael J. Fox Foundation for Parkinson’s Research (New York). S.N.G. receives support from R21 NS 090243 and the National Parkinson’s Foundation. O.A.R. is supported through the Mayo Clinic: A Morris K. Udall Parkinson’s Disease Research Center of Excellence (NINDS P50 NS072187), NINDS R01 NS078086, the Michael J. Fox Foundation for Parkinson’s Research, the Mayo Clinic AD and Related Dementias Genetics Program, and The Little Family Foundation. A.S.’s work is supported by the Intramural Research Program of the National Institute on Aging, Department of Health and Human Services. D.T. acknowledges the work of Cyrus Zabetian, MD, and Ignacio Mata, PhD, from VA Puget Sound Health Care System. J.Q.T. and V.M.Y.L.’s contributions were supported in part by a P50 NS053488 Morris K. Udall Parkinson’s Disease Research Center of Excellence grant from NINDS. P.T. acknowledges support from the Italian Ministry of Health “Ricerca Corrente.” M.Y. acknowledges support from the Japan Foundation for Neuroscience and Mental Health