A Feasibility Study in Measuring Soft Tissue Artifacts on the Upper Leg Using Inertial and Magnetic Sensors

Soft-tissue artifacts cause inaccurate estimates of body segment orientations. The inertial sensor (or optical marker) is orientating (or displacing) with respect to the bone it has to measure, due to muscle and skin movement [1]. In this pilot study 11 inertial and magnetic sensors (MTw, Xsens Technologies) were placed on the rectus femoris, vastus medialis and vastus lateralis (upper leg). One sensor was positioned on the tendon plate behind the quadriceps (iliotibial tract, as used in Xsens MVN [1]) and used as reference sensor. Walking, active and passive knee extensions and muscle contractions without flexion/extension were recorded using one subject. The orientation of each sensor with respect to the reference sensor was calculated. During walking, relative orientations of up to 28.6º were measured (22.4±3.6º). During muscle contractions without flexion/extension the largest relative orientations were measured on the rectus femoris (up to 11.1º) [2]. This pilot showed that the ambulatory measurement of deformation of the upper leg is feasible; however, improving the measurement technology is required. We therefore have designed a new inertial and magnetic sensor system containing smaller sensors, based on the design of an instrumented glove for the assessment of hand kinematics [3]. This new sensor system will then be used to investigate soft-tissue artifacts more accurately; in particular we will focus on in-use estimation and elimination of these artifacts

Apolipoprotein E4 and Insulin Resistance Interact to Impair Cognition and Alter the Epigenome and Metabolome

Apolipoprotein E4 (E4) and type 2 diabetes are major risk factors for cognitive decline and late onset Alzheimer’s disease (AD). E4-associated phenotypes and insulin resistance (IR) share several features and appear to interact in driving cognitive dysfunction. However, shared mechanisms that could explain their overlapping pathophysiology have yet to be found. We hypothesized that, compared to E3 mice, E4 mice would be more susceptible to the harmful cognitive effects of high fat diet (HFD)-induced IR due to apoE isoform-specific differences in brain metabolism. While both E3 and E4 mice fed HFD displayed impairments in peripheral metabolism and cognition, deficits in hippocampal-dependent spatial learning and memory were exaggerated in E4 mice. Combining genome-wide measures of DNA hydroxymethylation with comprehensive untargeted metabolomics, we identified novel alterations in purine metabolism, glutamate metabolism, and the pentose phosphate pathway. Finally, in E4 mice, the metabolic and cognitive deficiencies caused by HFD were rescued by switching to a low fat diet for one month, suggesting a functional role was associated with reversal of the same metabolic pathways described above. These results suggest a susceptibility of E4 carriers to metabolic impairments brought on by IR, and may guide development of novel therapies for cognitive decline and dementia

Phytochemical characterization of Tabernanthe iboga root bark and its effects on dysfunctional metabolism and cognitive performance in high-fat-fed C57BL/6J mice

Preparations of the root bark of Tabernanthe iboga have long been used in Central and West African traditional medicine to combat fatigue, as a neuro-stimulant in rituals, and for treatment of diabetes. The principal alkaloid of T. iboga, ibogaine, has attracted attention in many countries around the world for providing relief for opioid craving in drug addicts. Using a plant metabolomics approach, we detected five phenolic compounds, including 3- O-caffeoylquinic acid, and 30 alkaloids, seven of which were previously reported from T. iboga root bark. Following a report that iboga extracts contain insulinotropic agents, we aimed to determine the potential alleviating effects of the water extract of iboga root bark on high-fat diet (HFD)-induced hyperglycemia as well as its effects on cognitive function in male C57BL/6J mice. Feeding a HFD to mice for 10 weeks produced manifestations of metabolic syndrome such as increased body weight and increased plasma levels of glucose, triacylglycerols, total cholesterol, LDL-cholesterol, insulin, leptin, and pro-inflammatory mediators (IL-6, MCP-1, ICAM-1), as compared to mice fed a low-fat diet (LFD). Supplementation of HFD with iboga extract at ibogaine doses of 0.83 (low) and 2.07 (high) mg/kg/day did not improve these HFD-induced metabolic effects except for a reduction of plasma MCP-1 in the low dose group, indicative of an anti-inflammatory effect. When the HFD mice were tested in the water maze, the high-dose iboga extract caused hippocampus-dependent impairments in spatial learning and memory, as compared to mice receiving only a HFD.Peer reviewedFinal Published versio

Ocean processes at the Antarctic continental slope

The Antarctic continental shelves and slopes occupy relatively small areas, but, nevertheless, are important for global climate, biogeochemical cycling and ecosystem functioning. Processes of water mass transformation through sea ice formation/melting and ocean-atmosphere interaction are key to the formation of deep and bottom waters as well as determining the heat flux beneath ice shelves. Climate models, however, struggle to capture these physical processes and are unable to reproduce water mass properties of the region. Dynamics at the continental slope are key for correctly modelling climate, yet their small spatial scale presents challenges both for ocean modelling and for observational studies. Cross-slope exchange processes are also vital for the flux of nutrients such as iron from the continental shelf into the mixed layer of the Southern Ocean. An © 2014 The Authors

Systematic review and metaanalysis comparing the bias and accuracy of the modification of diet in renal disease and chronic kidney disease epidemiology collaboration equations in community-based population

BACKGROUND The majority of patients with chronic kidney disease are diagnosed and monitored in primary care. Glomerular filtration rate (GFR) is a key marker of renal function, but direct measurement is invasive; in routine practice, equations are used for estimated GFR (eGFR) from serum creatinine. We systematically assessed bias and accuracy of commonly used eGFR equations in populations relevant to primary care. CONTENT MEDLINE, EMBASE, and the Cochrane Library were searched for studies comparing measured GFR (mGFR) with eGFR in adult populations comparable to primary care and reporting both the Modification of Diet in Renal Disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations based on standardized creatinine measurements. We pooled data on mean bias (difference between eGFR and mGFR) and on mean accuracy (proportion of eGFR within 30% of mGFR) using a random-effects inverse-variance weighted metaanalysis. We included 48 studies of 26875 patients that reported data on bias and/or accuracy. Metaanalysis of within-study comparisons in which both formulae were tested on the same patient cohorts using isotope dilution-mass spectrometry-traceable creatinine showed a lower mean bias in eGFR using CKD-EPI of 2.2 mL/min/1.73 m2 (95% CI, 1.1–3.2; 30 studies; I2 = 74.4%) and a higher mean accuracy of CKD-EPI of 2.7% (1.6–3.8; 47 studies; I2 = 55.5%). Metaregression showed that in both equations bias and accuracy favored the CKD-EPI equation at higher mGFR values. SUMMARY Both equations underestimated mGFR, but CKD-EPI gave more accurate estimates of GFR

Activity of Meadowfoam (Limnanthes alba) Seed Meal Glucolimnanthin Degradation Products against Soilborne Pathogens

Meadowfoam (Limnanthes alba L.) is a herbaceous winter spring annual grown as a commercial oilseed crop. The meal remaining after oil extraction from the seed contains up to 4% of the glucosinolate glucolimnanthin. Degradation of glucolimnanthin yields toxic breakdown products, and therefore the meal may have potential in the management of soilborne pathogens. To maximize the pest-suppressive potential of meadowfoam seed meal, it would be beneficial to know the toxicity of individual glucolimnanthin degradation products against specific soilborne pathogens. Meloidogyne hapla second-stage juveniles (J2) and Pythium irregulare and Verticillium dahliae mycelia] cultures were exposed to glucolimnanthin as well as its degradation products. Glucolimnanthin and its degradation product, 2-(3-methoxyphenyl)acetamide, were not toxic to any of the soilborne pathogens at concentrations up to 1.0 mg/mL. Two other degradation products, 2-(3-methoxymethyl)ethanethioamide and 3-methoxyphenylacetonitrile, were toxic to M. hapla and P. irregulare but not V. dahliae. The predominant enzyme degradation product, 3-methoxybenzyl isothiocyanate, was the most toxic compound against all of the soilborne pathogens, with M. hapla being the most sensitive with EC(50) values (0.0025 +/- 0.0001 to 0.0027 +/- 0.0001 mg/mL) 20-40 times lower than estimated EC(50) mortality values generated for P. irregulare and V. dahliae (0.05 and 0.1 mg/mL, respectively). The potential exists to manipulate meadowfoam seed meal to promote the production of specific degradation products. The conversion of glucolimnanthin into its corresponding isothiocyanate should optimize the biopesticidal properties of meadowfoam seed meal against M. hapla, P. irregulare, and V. dahliae.Keywords: Seed meal, Nematicidal effect, Fungicidal effect, Lethal concentratio

¹⁸O-Tracer Metabolomics Reveals Protein Turnover and CDP-Choline Cycle Activity in Differentiating 3T3-L1 Pre-Adipocytes

The differentiation of precursor cells into mature adipocytes (adipogenesis) has been an area of increased focus, spurred by a rise in obesity rates. Though our understanding of adipogenesis and its regulation at the cellular level is growing, many questions remain, especially regarding the regulation of the metabolome. The 3T3-L1 cell line is the most well characterized cellular model of adipogenesis. Using a time course metabolomics approach, we show that the 3T3-L1 preadipocyte metabolome is greatly altered during the first 48 hours of differentiation, where cells go through about two rounds of cell division, a process known as mitotic clonal expansion. Short-chain peptides were among several small molecules that were increased during mitotic clonal expansion. Additional indicators of protein turnover were also increased, including bilirubin, a degradation product of heme-containing proteins, and 3-methylhistidine, a post-translationally modified amino acid that is not reutilized for protein synthesis. To study the origin of the peptides, we treated differentiating preadipocytes with ¹⁸O labeled water and found that ¹⁸O was incorporated into the short chain peptides, confirming them, at least in part, as products of hydrolysis. Inhibitors of the proteasome or matrix metalloproteinases affected the peptide levels during differentiation, but inhibitors of autophagy or peptidases did not. ¹⁸O was also incorporated into several choline metabolites including cytidine 5'-diphosphocholine (CDP-choline), glycerophosphocholine, and several phosphatidylcholine species, indicative of phosphatidylcholine synthesis/degradation and of flux through the CDP-choline cycle, a hallmark of proliferating cells. ¹⁸O-Tracer metabolomics further showed metabolic labeling of glutamate, suggestive of glutaminolysis, also characteristic of proliferating cells. Together, these results highlight the utility of ¹⁸O isotope labeling in combination with metabolomics to uncover changes in cellular metabolism that are not detectable by time-resolved metabolomics

Ticagrelor versus clopidogrel in patients with acute coronary syndromes intended for non-invasive management: substudy from prospective randomised PLATelet inhibition and patient Outcomes (PLATO) trial

Objective To evaluate efficacy and safety outcomes in patients in the PLATelet inhibition and patient Outcomes (PLATO) trial who at randomisation were planned for a non-invasive treatment strategy

High apex predator biomass on remote Pacific islands

Author Posting. © The Author(s), 2006. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Coral Reefs 26 (2007): 47-51, doi:10.1007/s00338-006-0158-x.On coral reefs in Palmyra—a central Pacific atoll with limited fishing pressure—total fish biomass is 428 and 299% greater than on reefs in nearby Christmas and Fanning Islands. Large apex predators –groupers, sharks, snappers, and jacks larger than 50 cm in length- account for 56% of total fish biomass in Palmyra on average, but only 7% and 3% on Christmas and Fanning. These biomass proportions are remarkably similar to those previously reported for the remote and uninhabited Northwest Hawaiian Islands (NWHI) and densely populated Main Hawaiian Islands (MHI), although Palmyra’s reefs are dominated in biomass by sharks (44% of the total), whereas the NWHI by jacks (39%). Herbivorous fish biomass was also greater on Palmyra than on Christmas and Fanning (343% and 207%, respectively). These results and previous findings indicate that remote, uninhabited islands support high levels of consumers, and highlight the importance of healthy coral reef ecosystems as reference points for assessment of human impacts and establishment of restoration goals