Genetic variation in lipid desaturases and its impact on the development of human disease

Perturbations in lipid metabolism characterize many of the chronic diseases currently plaguing our society, such as obesity, diabetes, and cardiovascular disease. Thus interventions that target plasma lipid levels remain a primary goal to manage these diseases. The determinants of plasma lipid levels are multi-factorial, consisting of both genetic and lifestyle components. Recent evidence indicates that fatty acid desaturases have an important role in defining plasma and tissue lipid profiles. This review will highlight the current state-of-knowledge regarding three desaturases (Scd-1, Fads1 and Fads2) and their potential roles in disease onset and development. Although research in rodent models has provided invaluable insight into the regulation and functions of these desaturases, the extent to which murine research can be translated to humans remains unclear. Evidence emerging from human-based research demonstrates that genetic variation in human desaturase genes affects enzyme activity and, consequently, disease risk factors. Moreover, this genetic variation may have a trans-generational effect via breastfeeding. Therefore inter-individual variation in desaturase function is attributed to both genetic and lifestyle components. As such, population-based research regarding the role of desaturases on disease risk is challenged by this complex gene-lifestyle paradigm. Unravelling the contribution of each component is paramount for understanding the inter-individual variation that exists in plasma lipid profiles, and will provide crucial information to develop personalized strategies to improve health management

Removal of nucleus pulposus from the intervertebral disc – the use of chymopapain enhances mechanical removal with rongeurs: a laboratory study

<p>Abstract</p> <p>Background</p> <p>A laboratory study was conducted, on cadaveric sheep spines to develop an effective procedure for removing as much nucleus as possible from an intervertebral disc with minimal disruption to the annulus. The results of many studies involving removal of nucleus, including chemonucleolysis, using chymopapain, have been published but we are not aware of any previous quantitative studies on procedures for removing as much nucleus as possible from the disc.</p> <p>Methods</p> <p>All procedures were performed via a 3 mm trocar. Four procedures were compared: (I) unilateral approach using rongeurs alone, (II) bilateral approach using rongeurs alone, (III) unilateral approach using rongeurs followed by chymopapain and (IV) bilateral approach using rongeurs followed by chymopapain.</p> <p>Results</p> <p>The percentages of nucleus removed were: (I) 34%, (II) 41%, (III) 52% and (IV) 75%; there were significant differences between the four sets of results according to ANOVA.</p> <p>Conclusion</p> <p>Significantly more nucleus is removed using a bilateral than a unilateral approach; significantly more nucleus is removed if chymopapain is used in addition to rongeurs. A brush is useful in removing strands of nucleus loosened by chymopapain.</p

Recommending anchor points in structure-preserving hypertext document retrieval

Traditional WWW search engines index and recommend individual Web pages to assist users in locating relevant documents. Users are often overwhelmed by the large answer set recommended by the search engines. The logical starting point of the hyper-document is thus hidden among the large basket of matching pages. Users need to spend a lot of effort browsing through the pages to locate the starting point, a very time consuming process. This paper studies the anchor point indexing problem. The anchor points of a given user query is a small set of key pages from which the larger set of documents that are relevant to the query can be easily reached. The use of anchor points help solve the problems of huge answer set and low precision suffered by most search engines by considering the hyper-link structures of the relevant documents, and by providing a summary view of the result set.published_or_final_versio

Cryptosporidium, Enterocytozoon, and Cyclospora Infections in Pediatric and Adult Patients with Diarrhea in Tanzania.

Cryptosporidiosis, microsporidiosis, and cyclosporiasis were studied in four groups of Tanzanian inpatients: adults with AIDS-associated diarrhea, children with chronic diarrhea (of whom 23 of 59 were positive [+] for human immunodeficiency virus [HIV]), children with acute diarrhea (of whom 15 of 55 were HIV+), and HIV control children without diarrhea. Cryptosporidium was identified in specimens from 6/86 adults, 5/59 children with chronic diarrhea (3/5, HIV+), 7/55 children with acute diarrhea (0/7, HIV+), and 0/20 control children. Among children with acute diarrhea, 7/7 with cryptosporidiosis were malnourished, compared with 10/48 without cryptosporidiosis (P < .01). Enterocytozoon was identified in specimens from 3/86 adults, 2/59 children with chronic diarrhea (1 HIV+), 0/55 children with acute diarrhea, and 4/20 control children. All four controls were underweight (P < .01). Cyclospora was identified in specimens from one adult and one child with acute diarrhea (HIV-). Thus, Cryptosporidium was the most frequent and Cyclospora the least frequent pathogen identified. Cryptosporidium and Enterocytozoon were associated with malnutrition. Asymptomatic fecal shedding of Enterocytozoon in otherwise healthy, HIV children has not been described previously

Supporting energy regulation by monitoring land motion on a regional and national scale: a case study of Scotland

The advent of new satellite and data processing techniques have meant that routine, operational and reliable surveys of land motion on a regional and national scale are now possible. In this paper, we apply a novel satellite remote sensing technique, the Intermittent Small Baseline Subset method, to data from a new satellite mission, Sentinel-1, and demonstrate that a wide area map of ground deformation can be generated that supports the regulation of a range of energy related activities. The area for the demonstration is mainland Scotland (75,000 km2) and the land motion map required the processing of some 627 images acquired from March 2015 to April 2017. The results show that land motion is encountered almost everywhere across Scotland, dominated by subsidence over peatland areas. However, many other phenomena are also encountered including landslides and deformation associated with mining and civil engineering activities. Considering specifically Petroleum Exploration and Development Licence areas offered under the 14th Onshore Licensing Round in the UK, examples of the types of land motion are shown, including an example related to soil restoration by a wind farm. It is demonstrated that, in Scotland at least, almost all licence areas contain deformation of one form or another and, furthermore, the causes of that subsidence are dynamic and likely to be changing from year-to-year. Therefore, maps like this are likely to be of enormous use in a regulatory framework to scope out pre-existing problems in a licence area and to ensure that the correct monitoring framework is put in place once activities begin. They can also provide evidence of good practice and give assurance against litigation by third parties

Viscoelastic properties of bovine knee joint articular cartilage : dependency on thickness and loading frequency

BackgroundThe knee is an incongruent joint predisposed to developing osteoarthritis, with certain regions being more at risk of cartilage degeneration even in non-osteoarthrosed joints.At present it is unknown if knee regions prone to cartilage degeneration have similar storage and/or loss stiffness, and frequency-dependent trends, to other knee joint cartilage. The aim of this study was to determine the range of frequency-dependent, viscoelastic stiffness of articular cartilage across the bovine knee joint. Such changes were determined at frequencies associated with normal and rapid heel-strike rise times.MethodsCartilage on bone, obtained from bovine knee joints, was tested using dynamic mechanical analysis (DMA). DMA was performed at a range of frequencies between 1 and 88 Hz (i.e. relevant to normal and rapid heel-strike rise times). Viscoelastic stiffness of cartilage from the tibial plateau, femoral condyles and patellar groove were compared.ResultsFor all samples the storage stiffness increased, but the loss stiffness remained constant, with frequency. They were also dependent on cartilage thickness. Both the loss stiffness and the storage stiffness decreased with cartilage thickness. Femoral condyles had the thinnest cartilage but had the highest storage and loss stiffness. Tibial plateau cartilage not covered by the meniscus had the thickest cartilage and lowest storage and loss stiffness.ConclusionDifferences in regional thickness of knee joint cartilage correspond to altered frequency-dependent, viscoelastic stiffness

Pulsed low-intensity ultrasound increases proliferation and extracelluar matrix production by human dermal fibroblasts in three-dimensional culture

This study evaluated the effect of pulsed low-intensity ultrasound on cell proliferation, collagen production and glycosaminoglycan deposition by human dermal fibroblasts encapsulated in alginate. Hoechst 33258 assay for cell number, hydroxyproline assay for collagen content, dimethylmethylene blue assay for glycosaminoglycan content and scanning electron microscopy were performed on the encapsulated cells treated with pulsed low-intensity ultrasound and a control group that remained untreated. Pulsed low-intensity ultrasound showed a significant effect on cell proliferation and collagen deposition but no consistent pattern for glycosaminoglycan content. Alcian blue staining showed that glycosaminoglycans were deposited around the cells in both treated and control groups. These results suggest that pulsed low-intensity ultrasound alone shows a positive effect on cell proliferation and collagen deposition even without growth factor supplements

Wear of the Charité® lumbar intervertebral disc replacement investigated using an electro-mechanical spine simulator

The Charité(®) lumbar intervertebral disc replacement was subjected to wear testing in an electro-mechanical spine simulator. Sinusoidally varying compression (0.6–2 kN, frequency 2 Hz), rotation (±2°, frequency 1 Hz), flexion–extension (6° to −3°, frequency 1 Hz) and lateral bending (±2°, frequency 1 Hz) were applied out of phase to specimens immersed in diluted calf serum at 37 °C. The mass of the ultra-high-molecular weight polyethylene component of the device was measured at intervals of 0.5, 1, 2, 3, 4 and 5 million cycles; its volume was also measured by micro-computed tomography. Total mass and volume losses were 60.3 ± 4.6 mg (mean ± standard deviation) and 64.6 ± 6.0 mm(3). Corresponding wear rates were 12.0 ± 1.4 mg per million cycles and 12.8 ± 1.2 mm(3) per million cycles; the rate of loss of volume corresponds to a mass loss of 11.9 ± 1.1 mg per million cycles, that is, the two sets of measurements of wear agree closely. Wear rates also agree closely with measurements made in another laboratory using the same protocol but using a conventional mechanical spine simulator

Effect of lubricants on friction in laboratory tests of a total disc replacement device

Some designs of total disc replacement devices have articulating bearing surfaces, and these devices are tested in vitro with a lubricant of diluted calf serum. It is believed that the lubricant found in total disc replacement devices in vivo is interstitial fluid that may have properties between that in Ringer’s solution and diluted calf serum. To investigate the effect of lubricants, a set of friction tests were performed on a generic model of a metal against metal ball-and-socket total disc replacement device. Two devices were tested: one with a ball radius of 10 mm and other with a ball radius of 16 mm; each device had a radial clearance of 0.015 mm. A spine simulator was used to measure frictional torque for each device in axial rotation, flexion–extension and lateral bending at frequencies of 0.25–2 Hz, under 1200 N axial load. Each device was tested with two different lubricants: a solution of new born calf serum diluted with deionised water and Ringer’s solution. The results showed that the frictional torque generated between the bearing surfaces was significantly higher in Ringer’s solution than in diluted calf serum. The use of Ringer’s solution as a lubricant provides a stringent test condition to detect possible problems. Diluted calf serum is more likely to provide an environment closer to that in vivo. However, the precise properties of the fluid lubricating a total disc replacement device are not known; hence, tests using diluted calf serum may not necessarily give the same results as those obtained in vivo. </jats:p