Adipokines and body fat composition in South Asians: results of the Metabolic Syndrome and Atherosclerosis in South Asians Living in America (MASALA) study.

ObjectiveTo investigate whether leptin and adiponectin are associated with body fat composition in a South Asian population independent of metabolic variables.DesignCross-sectional study.Subjects150 South Asian men and women, between the ages of 45-79 years, in the San Francisco Bay Area without pre-existing clinical cardiovascular disease.MeasurementsBlood samples were obtained to measure glucose metabolism variables, lipid profiles and adipokines. Total body fat was determined using dual-energy X-ray absorptiometry. Abdominal computed tomography was used to measure subcutaneous, visceral and hepatic fat.ResultsAverage body mass index (BMI) was overweight at 26.1±4.6 kg m(-2) and did not differ by sex. However, women had significantly more total body fat (P<0.001) and subcutaneous fat (P<0.001) than men, whereas men had significantly more visceral fat (P<0.001) and hepatic fat (P=0.04) than women. Women had significantly higher levels of adiponectin (P<0.01) and leptin (P<0.01). In sex-stratified analyses, leptin was strongly associated with all-body composition measures in women (P<0.05) as well as in men (P<0.05 except for hepatic fat), whereas there was an insignificant trend towards an inverse association between adiponectin and body composition in both women and men, which was significant in combined bivariate analyses. In multivariate analyses, leptin was strongly associated with all measures of adiposity, including BMI (P<0.001), total body fat (P<0.001), visceral fat (P<0.001) and hepatic fat (P=0.01). However, adiponectin's inverse association with adiposity was significantly attenuated by high-density lipoprotein (HDL), triglycerides and insulin resistance. The association between adipokines and diabetes was markedly attenuated after adjusting for body composition.ConclusionDespite only modestly elevated BMI, South Asians have elevated levels of total and regional adiposity. Leptin is strongly associated with adiposity, whereas adiponectin's association with adiposity is attenuated by metabolic variables in South Asians. Adipokines in association with adiposity have an important role in the development of diabetes

Why do we observe significant differences between measured and ‘back-calculated’ properties of natural fibres?

The drive towards sustainability, even in materials technologies, has fuelled an increasing interest in bio-based composites. Cellulosic fibres, such as flax and jute, are being considered as alternatives to technical synthetic fibres, such as glass, as reinforcements in fibre reinforced polymer composites for a wide range of applications. A critical bottleneck in the advancement of plant fibre composites (PFRPs) is our current inability to predict PFRP properties from data on fibre properties. This is highly desirable in the cost- and time-effective development and design of optimised PFRP materials with reliable behaviour. This study, alongside limited other studies in literature, have found that the experimentally determined (through single fibre tests) fibre properties are significantly different from the predicted (‘back-calculated’ using the popular rule-of-mixtures) fibre properties for plant fibres. In this note, we explore potential sources of the observed discrepancy and identify the more likely origins relating to both measurement and errors in predictions based on the rule-of-mixtures. The explored content in this discussion facilitates the design of a future investigation to (1) identify the sensitivity of the discrepancy between measured and predicted fibre properties to the various potential origins, (2) form a unified hypothesis on the observed phenomenon, and (3) determine whether the rule-of-mixtures model (in specific cases) can be improved and may be able to predict properties precisely.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s10570-016-0926-

Recommendations for the use of endoscopic lung volume reduction in South Africa: Role in the treatment of emphysema

Emphysema is a very common cause of morbidity and mortality in South Africa (SA). Therapeutic options in severe emphysema are limited. Endoscopic lung volume reduction (ELVR) is increasingly being used internationally for the treatment of advanced emphysema in a subset of patients with advanced disease, aiming to obtain the same functional advantages as surgical lung volume reduction while reducing risks and costs. In addition to endobronchial valves, ELVR using endobronchial coils is now available in SA. The high cost of these interventions underscores the need for careful patient selection to best identify those who may or may not benefit from ELVR-related procedures. The Assembly on Interventional Pulmonology of the South African Thoracic Society appointed a committee comprising both local and international experts to extensively review all relevant evidence and provide advice on the use of ELVR in SA based on published evidence, expert opinion and local access to the various devices

Impact of Meshed HVDC Grid Operation and Control on the Dynamics of AC/DC Systems

IEEE The efficacy of long-distance and bulk power transmission largely depends on the efficient control and reliable operation of a multiterminal high-voltage direct current (MT-HVdc) grid, more precisely, a meshed HVdc grid. The capability of enduring the dc grid fault eventually enhances the reliability and improves the dynamic performance of the grid. This article investigates the operation and control of an AC/multiterminal dc (MTDC) system with bipolar topology incorporating the dc grid protection schemes. Based on the scale of a circuit breaker's operating time, the performance of three different protection strategies is compared and analyzed using DIgSILENT PowerFactory. Simulation results explicitly reveal that the dynamic performance of the MTDC grid significantly deteriorates with the slow functioning of the protection schemes, followed by a dc grid fault. Besides, prolonged recovery time causes a substantial loss of power infeed and affects the ac/dc grid's stability. Finally, to assess the frailty of the MTDC grid, a transient energy stability index is proposed considering the voltage variation in the prestate and poststate fault clearing interval. Relevant case studies are performed on the MTDC grid using an analytical approach and nonlinear simulation studies to validate the effectiveness of the proposed index

C-Terminal Domain of the Human Zinc Transporter hZnT8 Is Structurally Indistinguishable from Its Disease Risk Variant (R325W)

The human zinc transporter 8 (hZnT8) plays important roles in the storage of insulin in the secretory vesicles of pancreatic β cells. hZnT8 consists of a transmembrane domain, with its N- and C-termini protruding into the cytoplasm. Interestingly, the exchange of arginine to tryptophan at position 325 in the C-terminal domain (CTD) increases the risk of developing type 2 diabetes mellitus (T2D). In the present study, the CTDs of hZnT8 (the wild-type (WT) and its disease risk variant (R325W)) were expressed, purified, and characterized in their native forms by biophysical techniques. The data reveal that the CTDs form tetramers which are stabilized by zinc binding, and exhibit negligible differences in their secondary structure content and zinc-binding affinities in solution. These findings provide the basis for conducting further structural studies aimed at unravelling the molecular mechanism underlying the increased susceptibility to develop T2D, which is modulated by the disease risk variant

Integrative analysis of subcellular quantitative proteomics studies reveals functional cytoskeleton membrane–lipid raft interactions in cancer

Lipid rafts are dynamic membrane microdomains that orchestrate molecular interactions and are implicated in cancer development. To understand the functions of lipid rafts in cancer, we performed an integrated analysis of quantitative lipid raft proteomics data sets modeling progression in breast cancer, melanoma, and renal cell carcinoma. This analysis revealed that cancer development is associated with increased membrane raft-cytoskeleton interactions, with ∼40% of elevated lipid raft proteins being cytoskeletal components. Previous studies suggest a potential functional role for the raft-cytoskeleton in the action of the putative tumor suppressors PTRF/Cavin-1 and Merlin. To extend the observation, we examined lipid raft proteome modulation by an unrelated tumor suppressor opioid binding protein cell-adhesion molecule (OPCML) in ovarian cancer SKOV3 cells. In agreement with the other model systems, quantitative proteomics revealed that 39% of OPCML-depleted lipid raft proteins are cytoskeletal components, with microfilaments and intermediate filaments specifically down-regulated. Furthermore, protein-protein interaction network and simulation analysis showed significantly higher interactions among cancer raft proteins compared with general human raft proteins. Collectively, these results suggest increased cytoskeleton-mediated stabilization of lipid raft domains with greater molecular interactions as a common, functional, and reversible feature of cancer cells

Can quantitative analysis of multi-parametric MRI independently predict failure of focal salvage HIFU therapy in men with radio-recurrent prostate cancer?

OBJECTIVES: Focal salvage HIFU is a feasible therapeutic option in some men who have recurrence after primary radiotherapy for prostate cancer. We aimed to determine if multi-parametric quantitative parameters, in addition to clinical factors, might have a role in independently predicting focal salvage HIFU outcomes. METHODS: A retrospective registry analysis included 150 consecutive men who underwent focal salvage HIFU (Sonablate500) (2006-2015); 89 had mpMRI available. Metastatic disease was excluded by nodal assessment on pelvic MRI, a radioisotope bone-scan and/or choline or FDG PET/CT scan. All men had mpMRI and either transperineal template prostate mapping biopsy or targeted and systematic TRUS-biopsy. mpMRI included T2-weighted, diffusion-weighted and dynamic contrast-enhancement. Pre-HIFU quantitative mpMRI data was obtained using Horos DICOM Viewer v3.3.5 for general MRI parameters and IB DCE v2.0 plug-in. Progression-free survival (PFS) was defined by biochemical failure and/or positive localized or distant imaging results and/or positive biopsy and/or systemic therapy and/or metastases/prostate cancer-specific death. Potential predictors of PFS were analyzed by univariable and multivariable Cox-regression. RESULTS: Median age at focal salvage HIFU was 71 years (interquartile range [IQR] 65-74.5) and median PSA pre-focal salvage treatment was 5.8ng/ml (3.8-8). Median follow-up was 35 months (23-47) and median time to failure was 15 months (7.8-24.3). D-Amico low, intermediate and high-risk disease was present in 1% (1/89), 40% (36/89) and 43% (38/89) prior to focal salvage HIFU (16% missing data). 56% (50/89) failed by the composite outcome. A total of 22 factors were evaluated on univariable and 8 factors on multivariable analysis. The following quantitative parameters were included: Ktrans, Kep, Ve, Vp, IS, rTTP and TTP. On univariable analysis, PSA, prostate volume at time of radiotherapy failure and Ve (median) value were predictors for failure. Ve represents extracellular fraction of the whole tissue volume. On multivariable analysis, only Ve (median) value remained as an independent predictor. CONCLUSIONS: One pharmacokinetic quantitative parameter based on DCE sequences seems to independently predict failure following focal salvage HIFU for radio-recurrent prostate cancer. This likely relates to the tumor microenvironment producing heat-sinks which counter the heating effect of HIFU. Further validation in larger datasets and evaluating mechanisms to reduce heat-sinks are required