Effects of Intra-Articular Lipopolysaccharide Injection on Systemic Cytokine Gene Expression and Leukocyte Population in Young Horses

Nineteen yearling Quarter Horses were utilized in a randomized, complete block design to evaluate systemic cytokine gene expression and circulating leukocyte population in young horses following an intra-articular lipopolysaccharide (LPS) challenge. Horses were administered an injection of 0.25 ng (n = 7) or 0.50 ng (n = 6) of LPS or lactated Ringer?s solution (n = 6; control). Blood was collected via jugular catheter at pre-injection h 0 and at 2, 6, 12, and 24 h following aseptic injection of the left radiocarpal joint. Aseptic arthrocentesis was performed at the same times to sample synovial fluid for a companion study. Total RNA was isolated from leukocytes using a commercially available kit and real-time PCR was used to determine relative gene expression of the cytokines; interleukin (IL)-1beta (beta), IL-6, IL-8, IL-10, and tumor necrosis factor-alpha (TNF-alpha). Determination of total leukocyte subpopulations and differentials was performed by Texas Veterinary Medical Diagnostic Laboratory. Data were analyzed using the PROC MIX procedure of SAS. Gene expression of all cytokines analyzed was unaffected by treatment. However, changes over time were observed in some cytokines. Interleukin-1? was increased above baseline at 6, 12, and 24 h (P = 0.04), IL-6 was decreased slightly at 6 and 12 h and then increased at 24 h (P = 0.002), and TNF-alpha was increased at 6 and 12 h (P = 0.01). Only IL-8 exceeded a 2-fold change in expression (P = 0.01), peaking at 12 h and indicating greater responsiveness to arthrocentesis than was observed in the other cytokines. No treatment effects on the leukocyte population were observed; however, total circulating leukocytes increased over time (P = 0.04), peaking at 6 h post-injection. Similarly, an increase over time was observed in monocytes (P = 0.002) and in platelets (P = 0.01) at 24 h post-injection. The results indicate that regardless of treatment, a mild immune response was elicited, likely due to repeated arthrocentesis. Future experiments should consider the effects of arthrocentesis and potential systemic inflammatory response, even in control animals, when administering intra-articular LPS to young horses

Genetic Differences in Chicken Splenic Immune Gene Expression in Response to Dietary Immune Modulation

Chickens from broiler, Leghorn, and Fayoumi lines were fed diets with ingredients to affect immune function: β-glucans, ascorbic acid, or corticosterone. Spleens were tested for expression of genes involved in immune response: interleukin-4 (IL-4), IL-6, IL-18, and macrophage inflammatory protein-1β (MIP-1β). Birds from the broiler line did not show any change in splenic gene expression associated with the dietary immunomodulators, perhaps due to the stringent selection of these birds for growth. The corticosterone diet was associated with increased expression of IL-4, indicative of an immune response relying primarily on humoral defenses. The Leghorn and Fayoumi lines showed opposing changes in expression of IL-4, IL-6, and IL-18 in response to the ascorbic acid and β-glucans enhanced diets, suggesting that processing of these immunomodulators and/or immune signaling in these lines are different. Our findings emphasize the need to further evaluate the effects of dietary immunomodulators before applying them in commercial settings

A phage-targeting strategy for the design of spatiotemporal drug delivery from grafted matrices

Abstract Background The natural response to injury is dynamic and normally consists of complex temporal and spatial cellular changes in gene expression, which, when acting in synchrony, result in patent tissue repair and, in some instances, regeneration. However, current therapeutic regiments are static and most rely on matrices, gels and engineered skin tissue. Accordingly, there is a need to design next-generation grafting materials to enable biotherapeutic spatiotemporal targeting from clinically approved matrices. To this end, rather then focus on developing completely new grafting materials, we investigated whether phage display could be deployed onto clinically approved synthetic grafts to identify peptide motifs capable of linking pharmaceutical drugs with differential affinities and eventually, control drug delivery from matrices over both space and time. Methods To test this hypothesis, we biopanned combinatorial peptide libraries onto different formulations of a wound-healing matrix (Integra®) and eluted the bound peptides with 1) high salt, 2) collagen and glycosaminoglycan or 3) low pH. After three to six rounds of biopanning, phage recovery and phage amplification of the bound particles, any phage that had acquired a capacity to bind the matrix was sequenced. Results In this first report, we identify distinct classes of matrix-binding peptides which elute differently from the screened matrix and demonstrate that they can be applied in a spatially relevant manner. Conclusions We suggest that further applications of these combinatorial techniques to wound-healing matrices may offer a new way to improve the performance of clinically approved matrices so as to introduce temporal and spatial control over drug delivery

The Vehicle, Spring 2007

Table of Contents She Might Just Take You for GrantedRebecca M. Griffithpage 1 ShwagDarius Juttipage 2 In LoveAmanda Vealepage 9 SubmissiveSarah Ellerpage 10 Wedding SongRebecca M. Griffithpage 11 Why No Ladies and Gentlemen, My Shit Never StinksJacob Fosterpage 13 Death of an English MajorLindsey Durbinpage 14 Summer\u27s PerfumeRebecca M. Griffithpage 15 Gigavolt and ChrisEric Schumacherpage 16 UntitledKris Jonespage 22 Ode to the MuseGreg Harrellpage 23 TenderAmanda Vealepage 24 When the Muses HeaveElizabeth Hoodpage 25 Depression LiftingAmanda Vealepage 26 Red SwordAndrew Deckerpage 27 Warring IdeologyMargaret B. Hamperpage 29 ConfessionGreg Harrellpage 34 A Glass PuzzleBrittany Morganpage 35 Hey MaJacob Fosterpage 36 As July Faded AwayRebecca M. Griffithpage 37 About the LeftoversGina LoBiancopage 38 Me, Myself & ILindsey Durbinpage 39 Iced Parking LotRebecca M. Griffithpage 41 About the Authors Art Submissions Mike\u27s Revelation and MikeSean Walkercovers UntitledChad Navelpage 9 Morning in Tintern AbbeyCarrie Muellerpage 12 WestminsterCarrie Muellerpage 21 A Fighting ChanceOsha Rudduckpage 22 Rooftop SunsetJennifer O\u27Neilpage 25 EIU IVCarrie Muellerpage 28 MandolinOsha Rudduckpage 38 EIU IIICarrie Muellerpage 42https://thekeep.eiu.edu/vehicle/1087/thumbnail.jp

Caribbean Corals in Crisis: Record Thermal Stress, Bleaching, and Mortality in 2005

BACKGROUND The rising temperature of the world's oceans has become a major threat to coral reefs globally as the severity and frequency of mass coral bleaching and mortality events increase. In 2005, high ocean temperatures in the tropical Atlantic and Caribbean resulted in the most severe bleaching event ever recorded in the basin. METHODOLOGY/PRINCIPAL FINDINGS Satellite-based tools provided warnings for coral reef managers and scientists, guiding both the timing and location of researchers' field observations as anomalously warm conditions developed and spread across the greater Caribbean region from June to October 2005. Field surveys of bleaching and mortality exceeded prior efforts in detail and extent, and provided a new standard for documenting the effects of bleaching and for testing nowcast and forecast products. Collaborators from 22 countries undertook the most comprehensive documentation of basin-scale bleaching to date and found that over 80% of corals bleached and over 40% died at many sites. The most severe bleaching coincided with waters nearest a western Atlantic warm pool that was centered off the northern end of the Lesser Antilles. CONCLUSIONS/SIGNIFICANCE Thermal stress during the 2005 event exceeded any observed from the Caribbean in the prior 20 years, and regionally-averaged temperatures were the warmest in over 150 years. Comparison of satellite data against field surveys demonstrated a significant predictive relationship between accumulated heat stress (measured using NOAA Coral Reef Watch's Degree Heating Weeks) and bleaching intensity. This severe, widespread bleaching and mortality will undoubtedly have long-term consequences for reef ecosystems and suggests a troubled future for tropical marine ecosystems under a warming climate.This work was partially supported by salaries from the NOAA Coral Reef Conservation Program to the NOAA Coral Reef Conservation Program authors. NOAA provided funding to Caribbean ReefCheck investigators to undertake surveys of bleaching and mortality. Otherwise, no funding from outside authors' institutions was necessary for the undertaking of this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Water quality monitoring records for estimating tap water arsenic and nitrate: a validation study

<p>Abstract</p> <p>Background</p> <p>Tap water may be an important source of exposure to arsenic and nitrate. Obtaining and analyzing samples in the context of large studies of health effects can be expensive. As an alternative, studies might estimate contaminant levels in individual homes by using publicly available water quality monitoring records, either alone or in combination with geographic information systems (GIS).</p> <p>Methods</p> <p>We examined the validity of records-based methods in Washington State, where arsenic and nitrate contamination is prevalent but generally observed at modest levels. Laboratory analysis of samples from 107 homes (median 0.6 μg/L arsenic, median 0.4 mg/L nitrate as nitrogen) served as our "gold standard." Using Spearman's rho we compared these measures to estimates obtained using only the homes' street addresses and recent and/or historical measures from publicly monitored water sources within specified distances (radii) ranging from one half mile to 10 miles.</p> <p>Results</p> <p>Agreement improved as distance decreased, but the proportion of homes for which we could estimate summary measures also decreased. When including all homes, agreement was 0.05-0.24 for arsenic (8 miles), and 0.31-0.33 for nitrate (6 miles). Focusing on the closest source yielded little improvement. Agreement was greatest among homes with private wells. For homes on a water system, agreement improved considerably if we included only sources serving the relevant system (ρ = 0.29 for arsenic, ρ = 0.60 for nitrate).</p> <p>Conclusions</p> <p>Historical water quality databases show some promise for categorizing epidemiologic study participants in terms of relative tap water nitrate levels. Nonetheless, such records-based methods must be used with caution, and their use for arsenic may be limited.</p

Cost-effectiveness of non-invasive methods for assessment and monitoring of liver fibrosis and cirrhosis in patients with chronic liver disease: systematic review and economic evaluation

BACKGROUND: Liver biopsy is the reference standard for diagnosing the extent of fibrosis in chronic liver disease; however, it is invasive, with the potential for serious complications. Alternatives to biopsy include non-invasive liver tests (NILTs); however, the cost-effectiveness of these needs to be established. OBJECTIVE: To assess the diagnostic accuracy and cost-effectiveness of NILTs in patients with chronic liver disease. DATA SOURCES: We searched various databases from 1998 to April 2012, recent conference proceedings and reference lists. METHODS: We included studies that assessed the diagnostic accuracy of NILTs using liver biopsy as the reference standard. Diagnostic studies were assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Meta-analysis was conducted using the bivariate random-effects model with correlation between sensitivity and specificity (whenever possible). Decision models were used to evaluate the cost-effectiveness of the NILTs. Expected costs were estimated using a NHS perspective and health outcomes were measured as quality-adjusted life-years (QALYs). Markov models were developed to estimate long-term costs and QALYs following testing, and antiviral treatment where indicated, for chronic hepatitis B (HBV) and chronic hepatitis C (HCV). NILTs were compared with each other, sequential testing strategies, biopsy and strategies including no testing. For alcoholic liver disease (ALD), we assessed the cost-effectiveness of NILTs in the context of potentially increasing abstinence from alcohol. Owing to a lack of data and treatments specifically for fibrosis in patients with non-alcoholic fatty liver disease (NAFLD), the analysis was limited to an incremental cost per correct diagnosis. An analysis of NILTs to identify patients with cirrhosis for increased monitoring was also conducted. RESULTS: Given a cost-effectiveness threshold of £20,000 per QALY, treating everyone with HCV without prior testing was cost-effective with an incremental cost-effectiveness ratio (ICER) of £9204. This was robust in most sensitivity analyses but sensitive to the extent of treatment benefit for patients with mild fibrosis. For HBV [hepatitis B e antigen (HBeAg)-negative)] this strategy had an ICER of £28,137, which was cost-effective only if the upper bound of the standard UK cost-effectiveness threshold range (£30,000) is acceptable. For HBeAg-positive disease, two NILTs applied sequentially (hyaluronic acid and magnetic resonance elastography) were cost-effective at a £20,000 threshold (ICER: £19,612); however, the results were highly uncertain, with several test strategies having similar expected outcomes and costs. For patients with ALD, liver biopsy was the cost-effective strategy, with an ICER of £822. LIMITATIONS: A substantial number of tests had only one study from which diagnostic accuracy was derived; therefore, there is a high risk of bias. Most NILTs did not have validated cut-offs for diagnosis of specific fibrosis stages. The findings of the ALD model were dependent on assuptions about abstinence rates assumptions and the modelling approach for NAFLD was hindered by the lack of evidence on clinically effective treatments. CONCLUSIONS: Treating everyone without NILTs is cost-effective for patients with HCV, but only for HBeAg-negative if the higher cost-effectiveness threshold is appropriate. For HBeAg-positive, two NILTs applied sequentially were cost-effective but highly uncertain. Further evidence for treatment effectiveness is required for ALD and NAFLD. STUDY REGISTRATION: This study is registered as PROSPERO CRD42011001561. FUNDING: The National Institute for Health Research Health Technology Assessment programme

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors