OrChem - An open source chemistry search engine for Oracle®

<p>Abstract</p> <p>Background</p> <p>Registration, indexing and searching of chemical structures in relational databases is one of the core areas of cheminformatics. However, little detail has been published on the inner workings of search engines and their development has been mostly closed-source. We decided to develop an open source chemistry extension for Oracle, the de facto database platform in the commercial world.</p> <p>Results</p> <p>Here we present OrChem, an extension for the Oracle 11G database that adds registration and indexing of chemical structures to support fast substructure and similarity searching. The cheminformatics functionality is provided by the Chemistry Development Kit. OrChem provides similarity searching with response times in the order of seconds for databases with millions of compounds, depending on a given similarity cut-off. For substructure searching, it can make use of multiple processor cores on today's powerful database servers to provide fast response times in equally large data sets.</p> <p>Availability</p> <p>OrChem is free software and can be redistributed and/or modified under the terms of the GNU Lesser General Public License as published by the Free Software Foundation. All software is available via <url>http://orchem.sourceforge.net</url>.</p

Which Design and Biomaterial Factors Affect Clinical Wear Performance of Total Disc Replacements? A Systematic Review

Background Total disc replacement was clinically introduced to reduce pain and preserve segmental motion of the lumbar and cervical spine. Previous case studies have reported on the wear and adverse local tissue reactions around artificial prostheses, but it is unclear how design and biomaterials affect clinical outcomes. Questions/purposes Which design and material factors are associated with differences in clinical wear performance (implant wear and periprosthetic tissue response) of (1) lumbar and (2) cervical total disc replacements? Methods We performed a systematic review on the topics of implant wear and periprosthetic tissue response using an advanced search in MEDLINE and Scopus electronic databases. Of the 340 references identified, 33 were retrieved for full-text evaluation, from which 16 papers met the inclusion criteria (12 on lumbar disc replacement and five on cervical disc replacement; one of the included studies reported on both lumbar and cervical disc replacement), which involved semiquantitative analysis of wear and adverse local tissue reactions along with a description of the device used. An additional three papers were located by searching bibliographies of key articles. There were seven case reports, three case series, two case-control studies, and seven analytical studies. The Methodological Index for Non-randomized Studies (MINORS) Scale was used to score case series and case-control studies, which yielded mean scores of 10.3 of 16 and 17.5 of 24, respectively. In general, the case series (three) and case-control (two) studies were of good quality. Results In lumbar regions, metal-on-polymer devices with mobile-bearing designs consistently generated small and large polymeric wear debris, triggering periprosthetic tissue activation of macrophages and giant cells, respectively. In the cervical regions, metal-on-polymer devices with fixed-bearing designs had similar outcomes. All metal-on-metal constructs tended to generate small metallic wear debris, which typically triggered an adaptive immune response of predominantly activated lymphocytes. There were no retrieval studies on one-piece prostheses. Conclusions This review provides evidence that design and biomaterials affect the type of wear and inflammation. However, clinical study design, followup, and analytical techniques differ among investigations, preventing us from drawing firm conclusions about the relationship between implant design and wear performance for both cervical and lumbar total disc replacement

Chemical modification of extracellular matrix by cold atmospheric plasma-generated reactive species affects chondrogenesis and bone formation.

The goal of this study was to investigate whether cold plasma generated by dielectric barrier discharge (DBD) modifies extracellular matrices (ECM) to influence chondrogenesis and endochondral ossification. Replacement of cartilage by bone during endochondral ossification is essential in fetal skeletal development, bone growth and fracture healing. Regulation of this process by the ECM occurs through matrix remodelling, involving a variety of cell attachment molecules and growth factors, which influence cell morphology and protein expression. The commercially available ECM, Matrigel, was treated with microsecond or nanosecond pulsed (μsp or nsp, respectively) DBD frequencies conditions at the equivalent frequencies (1 kHz) or power (~1 W). Recombinant human bone morphogenetic protein-2 was added and the mixture subcutaneously injected into mice to simulate ectopic endochondral ossification. Two weeks later, the masses were extracted and analysed by microcomputed tomography. A significant increase in bone formation was observed in Matrigel treated with μsp DBD compared with control, while a significant decrease in bone formation was observed for both nsp treatments. Histological and immunohistochemical analysis showed Matrigel treated with μsp plasma increased the number of invading cells, the amount of vascular endothelial growth factor and chondrogenesis while the opposite was true for Matrigel treated with nsp plasma. In support of the in vivo Matrigel study, 10 T1/2 cells cultured in vitro on μsp DBD-treated type I collagen showed increased expression of adhesion proteins and activation of survival pathways, which decreased with nsp plasma treatments. These results indicate DBD modification of ECM can influence cellular behaviours to accelerate or inhibit chondrogenesis and endochondral ossification. Copyright © 2016 John Wiley & Sons, Ltd

Influence of internal bores on larval fish abundance and community composition

A persistent semidiurnal internal tidal bore feature occurs at the head of the Monterey Bay Submarine Canyon and drives regular intrusions of cold, subthermocline waters onto the adjacent shelf. In this study, we examine the influence of this internal tidal bore feature on the larval fish community using over a year of periodic larval fish samples collected coincidently with physical measurements. Larval samples were categorized into one of two water mass periods: a “warm period” representative of shallow coastal shelf waters and a “cold period” characteristics of colder waters present during internal bore forcing. Using multivariate statistical methods, we show warm and cold periods, along with seasonality, are the primary drivers of larval fish community composition. A significantly different community composition was observed between warm and cold water mass periods. This difference was primarily due to decreased abundance in most taxa during the cold periods, and did not indicate an obvious shift in the assemblage of the taxa. However, our data do indicate that some taxa may show higher abundance during cold periods compared to warm periods, but further studies are warranted. Along with seasonality, the presence/absence of subthermocline waters driven by internal bores appears to be a key control on nearshore larval fish community composition at this location

Expert Testimony on Proximate Cause

Expert testimony is common in tort litigation, especially on issues of standard of care and cause-in-fact. Rule 704 of the Federal Rules of Evidence and its state counterparts abolished the prohibition of testimony on ultimate issues, leading to the possibility of expert testimony on the often crucial issue of proximate cause. The situation is easy to imagine. After counsel has qualified an expert witness and elicited an opinion that the particular act or omission caused the injury in question, counsel might very well be tempted to inquire whether the witness has an opinion as to whether the act or omission was a proximate or legal cause of the accident. Or, counsel may merge the two lines of inquiry and ask whether the act or omission proximately resulted in the accident or injury to the plaintiff. The inquiry seems harmless. The term proximate is commonly understood to mean only near or close to. The question is not innocuous, however. The issue of expert testimony on the question of proximate cause implicates several restrictions on expert testimony that survive the broad permission of Rule 704, and touches upon the serious issue of the proper roles of expert and fact-finder in the application of law to facts. The few published cases that have considered the issue of expert testimony on proximate cause are split.\u27 The question arises far more often, however, than is indicated by the relative scarcity of reported decisions. This Article addresses the usefulness and propriety of expert testimony on the issue of proximate cause. After briefly defining the concept of proximate cause, this Article argues that expert testimony on proximate cause is inadmissible under Rule 704, despite the general admissibility of testimony on ultimate issues. In addition, opinion on proximate cause is inadmissible because it fails to clear the separate hurdles of Rules 702\u27 and 4036 of the Federal Rules of Evidence. A technical expert on standard of care or actual cause is not qualified to opine on the issue of proximate cause and thus fails the expertise test of Rule 702. Furthermore, even the testimony of a genuine expert on the issue of proximate cause should be excluded because such testimony fails the helpfulness test of Rule 702. Finally, expert testimony on the issue of proximate cause is inadmissible under Rule 403 because its probative value is substantially outweighed by the possibility that such testimony will confuse the issues and mislead the jury

Facebook as a recruitment tool for adolescent health research: A systematic review

BACKGROUND: Researchers are increasingly using social media to recruit participants to surveys and clinical studies. However, the evidence of the efficacy and validity of adolescent recruitment through Facebook is yet to be established. OBJECTIVE: To conduct a systematic review of the literature on the use of Facebook to recruit adolescents for health research. DATA SOURCES: Nine electronic databases and reference lists were searched for articles published between 2004 and 2013. STUDY ELIGIBILITY CRITERIA: Studies were included in the review if: 1) participants were aged 10 to 18 years, 2) studies addressed a physical or mental health issue, 3) Facebook was identified as a recruitment tool, 4) recruitment details using Facebook were outlined in the methods section and considered in the discussion, or information was obtained by contacting the authors, 5) results revealed how many participants were recruited using Facebook, and 6) studies addressed how adolescent consent and/or parental consent was obtained. STUDY APPRAISALS AND SYNTHESIS METHODS: Titles, abstracts, and keywords were scanned and duplicates removed by 2 reviewers. Full text was evaluated for inclusion criteria, and 2 reviewers independently extracted data. RESULTS: The search resulted in 587 publications, of which 25 full-text papers were analyzed. Six studies met all the criteria for inclusion in the review. Three recruitment methods using Facebook was identified: 1) paid Facebook advertising, 2) use of the Facebook search tool, and 3) creation and use of a Facebook Page. CONCLUSIONS: Eligible studies described the use of paid Facebook advertising and Facebook as a search tool as methods to successfully recruit adolescent participants. Online and verbal consent was obtained from participants recruited from Facebook

Mast cells and hypoxia drive tissue metaplasia and heterotopic ossification in idiopathic arthrofibrosis after total knee arthroplasty

ABSTRACT: BACKGROUND: Idiopathic arthrofibrosis occurs in 3-4% of patients who undergo total knee arthroplasty (TKA). However, little is known about the cellular or molecular changes involved in the onset or progression of this condition. To classify the histomorphologic changes and evaluate potential contributing factors, periarticular tissues from the knees of patients with arthrofibrosis were analyzed for fibroblast and mast cell proliferation, heterotopic ossification, cellular apoptosis, hypoxia and oxidative stress. RESULTS: The arthrofibrotic tissue was composed of dense fibroblastic regions, with limited vascularity along the outer edges. Within the fibrotic regions, elevated numbers of chymase/fibroblast growth factor (FGF)-expressing mast cells were observed. In addition, this region contained fibrocartilage and associated heterotopic ossification, which quantitatively correlated with decreased range of motion (stiffness). Fibrotic, fibrocartilage and ossified regions contained few terminal dUTP nick end labeling (TUNEL)-positive or apoptotic cells, despite positive immunostaining for lactate dehydrogenase (LDH)5, a marker of hypoxia, and nitrotyrosine, a marker for protein nitrosylation. LDH5 and nitrotyrosine were found in the same tissue areas, indicating that hypoxic areas within the tissue were associated with increased production of reactive oxygen and nitrogen species. CONCLUSIONS: Taken together, we suggest that hypoxia-associated oxidative stress initiates mast cell proliferation and FGF secretion, spurring fibroblast proliferation and tissue fibrosis. Fibroblasts within this hypoxic environment undergo metaplastic transformation to fibrocartilage, followed by heterotopic ossification, resulting in increased joint stiffness. Thus, hypoxia and associated oxidative stress are potential therapeutic targets for fibrosis and metaplastic progression of idiopathic arthrofibrosis after TKA

Reactive oxygen and nitrogen species induce protein and DNA modifications driving arthrofibrosis following total knee arthroplasty

BACKGROUND: Arthrofibrosis, occurring in 3%-4% of patients following total knee arthroplasty (TKA), is a challenging condition for which there is no defined cause. The hypothesis for this study was that disregulated production of reactive oxygen species (ROS) and nitrogen species (RNS) mediates matrix protein and DNA modifications, which result in excessive fibroblastic proliferation. RESULTS: We found increased numbers of macrophages and lymphocytes, along with elevated amounts of myeloperoxidase (MPO) in arthrofibrotic tissues when compared to control tissues. MPO expression, an enzyme that generates ROS/RNS, is usually limited to neutrophils and some macrophages, but was found by immunohistochemistry to be expressed in both macrophages and fibroblasts in arthrofibrotic tissue. As direct measurement of ROS/RNS is not feasible, products including DNA hydroxylation (8-OHdG), and protein nitrosylation (nitrotyrosine) were measured by immunohistochemistry. Quantification of the staining showed that 8-OHdg was significantly increased in arthrofibrotic tissue. There was also a direct correlation between the intensity of inflammation and ROS/RNS to the amount of heterotopic ossification (HO). In order to investigate the aberrant expression of MPO, a real-time oxidative stress polymerase chain reaction array was performed on fibroblasts isolated from arthrofibrotic and control tissues. The results of this array confirmed the upregulation of MPO expression in arthrofibrotic fibroblasts and highlighted the downregulated expression of the antioxidants, superoxide dismutase1 and microsomal glutathione S-transferase 3, as well as the significant increase in thioredoxin reductase, a known promoter of cell proliferation, and polynucleotide kinase 3\u27-phosphatase, a key enzyme in the base excision repair pathway for oxidative DNA damage. CONCLUSION: Based on our current findings, we suggest that ROS/RNS initiate and sustain the arthrofibrotic response driving aggressive fibroblast proliferation and subsequent HO

A Metadata description of the data in "A metabolomic comparison of urinary changes in type 2 diabetes in mouse, rat, and human.".

BACKGROUND: Metabolomics is a rapidly developing functional genomic tool that has a wide range of applications in diverse fields in biology and medicine. However, unlike transcriptomics and proteomics there is currently no central repository for the depositing of data despite efforts by the Metabolomics Standard Initiative (MSI) to develop a standardised description of a metabolomic experiment. FINDINGS: In this manuscript we describe how the MSI description has been applied to a published dataset involving the identification of cross-species metabolic biomarkers associated with type II diabetes. The study describes sample collection of urine from mice, rats and human volunteers, and the subsequent acquisition of data by high resolution 1H NMR spectroscopy. The metadata is described to demonstrate how the MSI descriptions could be applied in a manuscript and the spectra have also been made available for the mouse and rat studies to allow others to process the data. CONCLUSIONS: The intention of this manuscript is to stimulate discussion as to whether the MSI description is sufficient to describe the metadata associated with metabolomic experiments and encourage others to make their data available to other researchers