The Knee Osteoarthritis Grading System for Arthroplasty

Background: The aim of this study is to validate the Knee Osteoarthritis Grading System (KOGS) of progressive osteoarthritic degeneration for the tri-compartmental knee. This system defines the site and severity of osteoarthritis to determine a specific knee arthroplasty. Methods: The radiographic sequence for KOGS includes standing coronal (anteroposterior), lateral, 30° skyline patella, 15° and 45° Rosenberg and stress views in 20° of flexion. Cohen's kappa and related agreement statistical methods were used to assess the level of concordance of the 7 evaluators between A and B cohorts for each evaluator and also against the actual arthroplasty used. Sensitivity and specificity was also assessed for the KOGS in identifying true partial knee arthroplasties (PKAs) and total knee arthroplasties (TKAs) as decided from the cohort A evaluations. Results: From a cohort of 330 patients who were included in the study, 71 (22.5%) underwent a TKA procedure, 258 (78.2%) a PKA, and 1 (0.3%) was neither a TKA nor PKA. KOGS was able to identify true PKAs (sensitivity) in the range of 92.2%-98.5% across all the different evaluators. The KOGS method was able to identify a PKA or a TKA with an accuracy ranging from 92% to 98.8% across all different evaluators. The surgical results after 20 months are at least comparable with the expected average in the academic literature. Conclusion: The KOGS classification provides a reliable and accurate tool to assess suitability of an individual patient for undergoing PKA or TKA

Long range transport of soil dust and smoke pollution in the South Asian Region.

Transboundary transport of air pollution in the South Asian region has been an issue of increasing importance over the past several decades. Long–range transport of anthropogenic pollution is contrasted with that of pollution produced by natural processes such as dust storms or natural forest fires. Airborne particulate matter datasets covering the period from 2002 to 2007 from the neighboring countries like Bangladesh, India, Pakistan and Sri Lanka were used to find the source areas that are primarily responsible for long range transported pollutants. All four countries collected samples with the same type of sampler and follow the same technique for mass and BC measurements. It was found that high fine soil contributions were from dust storms. On the other hand, smoke in this region mainly comes from northern India where agricultural waste is often burned. © Elsevier B.V

Features of mammalian microRNA promoters emerge from polymerase II chromatin immunoprecipitation data

Background: MicroRNAs (miRNAs) are short, non-coding RNA regulators of protein coding genes. miRNAs play a very important role in diverse biological processes and various diseases. Many algorithms are able to predict miRNA genes and their targets, but their transcription regulation is still under investigation. It is generally believed that intragenic miRNAs (located in introns or exons of protein coding genes) are co-transcribed with their host genes and most intergenic miRNAs transcribed from their own RNA polymerase II (Pol II) promoter. However, the length of the primary transcripts and promoter organization is currently unknown. Methodology: We performed Pol II chromatin immunoprecipitation (ChIP)-chip using a custom array surrounding regions of known miRNA genes. To identify the true core transcription start sites of the miRNA genes we developed a new tool (CPPP). We showed that miRNA genes can be transcribed from promoters located several kilobases away and that their promoters share the same general features as those of protein coding genes. Finally, we found evidence that as many as 26% of the intragenic miRNAs may be transcribed from their own unique promoters. Conclusion: miRNA promoters have similar features to those of protein coding genes, but miRNA transcript organization is more complex. © 2009 Corcoran et al

Effects of the total replacement of fish-based diet with plant-based diet on the hepatic transcriptome of two European sea bass (Dicentrarchus labrax) half-sibfamilies showing different growth rates with the plant-based diet

Background: Efforts towards utilisation of diets without fish meal (FM) or fish oil (FO) in finfish aquaculture have been being made for more than two decades. Metabolic responses to substitution of fishery products have been shown to impact growth performance and immune system of fish as well as their subsequent nutritional value, particularly in marine fish species, which exhibit low capacity for biosynthesis of long-chain poly-unsaturated fatty acids (LC-PUFA). The main objective of the present study was to analyse the effects of a plant-based diet on the hepatic transcriptome of European sea bass (Dicentrarchus labrax). Results: We report the first results obtained using a transcriptomic approach on the liver of two half-sibfamilies of the European sea bass that exhibit similar growth rates when fed a fish-based diet (FD), but significantly different growth rates when fed an all-plant diet (VD). Overall gene expression was analysed using oligo DNA microarrays (GPL9663). Statistical analysis identified 582 unique annotated genes differentially expressed between groups of fish fed the two diets, 199 genes regulated by genetic factors, and 72 genes that exhibited diet-family interactions. The expression of several genes involved in the LC-PUFA and cholesterol biosynthetic pathways was found to be up-regulated in fish fed VD, suggesting a stimulation of the lipogenic pathways. No significant diet-family interaction for the regulation of LC-PUFA biosynthesis pathways could be detected by microarray analysis. This result was in agreement with LC-PUFA profiles, which were found to be similar in the flesh of the two half-sibfamilies. In addition, the combination of our transcriptomic data with an analysis of plasmatic immune parameters revealed a stimulation of complement activity associated with an immunodeficiency in the fish fed VD, and different inflammatory status between the two half-sibfamilies. Biological processes related to protein catabolism, amino acid transaminations, RNA splicing and blood coagulation were also found to be regulated by diet, while the expression of genes involved in protein and ATP synthesis differed between the half-sibfamilies. Conclusions: Overall, the combined gene expression, compositional and biochemical studies demonstrated a large panel of metabolic and physiological effects induced by total substitution of both FM and FO in the diets of European sea bass and revealed physiological characteristics associated with the two half-sibfamilies

Perioperative events influence cancer recurrence risk after surgery.

Surgery is a mainstay treatment for patients with solid tumours. However, despite surgical resection with a curative intent and numerous advances in the effectiveness of (neo)adjuvant therapies, metastatic disease remains common and carries a high risk of mortality. The biological perturbations that accompany the surgical stress response and the pharmacological effects of anaesthetic drugs, paradoxically, might also promote disease recurrence or the progression of metastatic disease. When cancer cells persist after surgery, either locally or at undiagnosed distant sites, neuroendocrine, immune, and metabolic pathways activated in response to surgery and/or anaesthesia might promote their survival and proliferation. A consequence of this effect is that minimal residual disease might then escape equilibrium and progress to metastatic disease. Herein, we discuss the most promising proposals for the refinement of perioperative care that might address these challenges. We outline the rationale and early evidence for the adaptation of anaesthetic techniques and the strategic use of anti-adrenergic, anti-inflammatory, and/or antithrombotic therapies. Many of these strategies are currently under evaluation in large-cohort trials and hold promise as affordable, readily available interventions that will improve the postoperative recurrence-free survival of patients with cancer

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.

BACKGROUND: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. RESULTS: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. CONCLUSIONS: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk

Statistical Analysis for Prediction of Distribution Coefficient of Soil-Contaminant System

The soil-contaminant interaction is significantly influenced by various attributes of soil and contaminant, and it can be quantified by employing a term known as distribution coefficient (k(d)). However, because of the involvement of many parameters related to soil and contaminant, determination of k(d) becomes a tedious and time-consuming exercise that requires extensive experimental investigations. In this context, application of the Taguchi method for minimizing the number of experiments and establishing the most critical parameters which influence k(d) (obtained from the linear isotherm) has been shown to be quite useful by the researchers in the recent past. Keeping this point in view, application of L25 orthogonal array (OA) used in the Taguchi method has been employed to design experiments which would facilitate establishment of the influence of various parameters concomitantly on k(d) and its prediction as well. The k(d) has been predicted by employing two methods viz, the Taguchi method and the statistical regression model (SRM). With this in view, four parameters (viz, cation exchange capacity of the soil, ionic species, temperature, and interaction time of the soil-contaminant system) were selected for developing the L25OA, and it has been clearly demonstrated that these methodologies help in easily (1) identifying the most significant parameter on which k(d) is dependent and (2) predicting the precise k(d) by inputting the four parameters. Moreover, based on this study, the sorption mechanism that yields a maximum k(d) for a given soil-contaminant system (SCS) by employing the most optimized parameters has also been proposed. (C) 2015 American Society of Civil Engineers