Spinal release of tumour necrosis factor activates c-Jun N-terminal kinase and mediates inflammation-induced hypersensitivity.

BackgroundMounting evidence points to individual contributions of tumour necrosis factor-alpha (TNF) and the c-Jun N-terminal kinase (JNK) pathway to the induction and maintenance of various pain states. Here we explore the role of spinal TNF and JNK in carrageenan-induced hypersensitivity. As links between TNF and JNK have been demonstrated in vitro, we investigated if TNF regulates spinal JNK activity in vivo.MethodsTNF levels in lumbar cerebrospinal fluid (CSF) were measured by enzyme-linked immunosorbent assay, spinal TNF gene expression by real-time polymerase chain reaction and TNF protein expression, JNK and c-Jun phosphorylation by western blotting. The role of spinal TNF and JNK in inflammation-induced mechanical and thermal hypersensitivity was assessed by injecting the TNF inhibitor etanercept and the JNK inhibitors SP600125 and JIP-1 intrathecally (i.t.). TNF-mediated regulation of JNK activity was examined by assessing the effect of i.t. etanercept on inflammation-induced spinal JNK activity.ResultsTNF levels were increased in CSF and spinal cord following carrageenan-induced inflammation. While JNK phosphorylation followed the same temporal pattern as TNF, c-jun was only activated at later time points. Intrathecal injection of TNF and JNK inhibitors attenuated carrageenan-induced mechanical and thermal hypersensitivity. TNF stimulation induced JNK phosphorylation in cultured spinal astrocytes and blocking the spinal actions of TNF in vivo by i.t. injection of etanercept reduced inflammation-induced spinal JNK activity.ConclusionsHere we show that spinal JNK activity is dependent on TNF and that both TNF and the JNK signalling pathways modulate pain-like behaviour induced by peripheral inflammation

The Nebraska Natural Legacy Project: State Wildlife Action Plan 2nd edition

Nebraska’s rich biological diversity is composed of thousands of plant and animal species interacting with each other and the environment. The flora and fauna of the state, along with the natural habitats they occupy, form Nebraska’s natural heritage – a legacy that should be treasured just as much as our cultural heritage. Unfortunately, populations of many once common species have declined because of a variety of stresses, including habitat loss, habitat degradation, diseases, and competition and predation from invasive species. While conservation actions in the past have had notable successes, they have not been sufficient to stem the overall tide of species decline. There is a need for a comprehensive, systematic and proactive approach to conserving the full array of Nebraska’s biological diversity. The goals of the Nebraska Natural Legacy Project are to: 1. Reverse the decline of at-risk species (and avoid the need for state or federal listing as threatened or endangered) 2. Recover currently listed species and allow for their de-listing 3. Keep common species common 4. Conserve natural communities Almost all existing natural habitat in Nebraska, and the biological diversity it supports, resides on lands under private ownership. All Nebraskans can benefit from the strong conservation tradition and sound stewardship of private landowners. The Nebraska Natural Legacy Project seeks to continue this tradition, while at the same time creating new opportunities for collaboration between farmers, ranchers, communities, private and governmental organizations and others for conserving Nebraska’s biological diversity, our natural heritage. The Nebraska Natural Legacy Project is non-regulatory, voluntary, incentive-based conservation. As stewards for the next generation, it is everyone’s responsibility to ensure the treasures that were handed to us by nature and our predecessors are still here for future generations of Nebraskans to enjoy

Evaluation of neurotoxicity and long-term function and behavior following intrathecal 1 % 2-chloroprocaine in juvenile rats

Spinally-administered local anesthetics provide effective perioperative anesthesia and/or analgesia for children of all ages. New preparations and drugs require preclinical safety testing in developmental models. We evaluated age-dependent efficacy and safety following 1 % preservative-free 2-chloroprocaine (2-CP) in juvenile Sprague-Dawley rats. Percutaneous lumbar intrathecal 2-CP was administered at postnatal day (P)7, 14 or 21. Mechanical withdrawal threshold pre- and post-injection evaluated the degree and duration of sensory block, compared to intrathecal saline and naive controls. Tissue analyses one- or seven-days following injection included histopathology of spinal cord, cauda equina and brain sections, and quantification of neuronal apoptosis and glial reactivity in lumbar spinal cord. Following intrathecal 2-CP or saline at P7, outcomes assessed between P30 and P72 included: spinal reflex sensitivity (hindlimb thermal latency, mechanical threshold); social approach (novel rat versus object); locomotor activity and anxiety (open field with brightly-lit center); exploratory behavior (rearings, holepoking); sensorimotor gating (acoustic startle, prepulse inhibition); and learning (Morris Water Maze). Maximum tolerated doses of intrathecal 2-CP varied with age (1.0 μL/g at P7, 0.75 μL/g at P14, 0.5 μL/g at P21) and produced motor and sensory block for 10−15 min. Tissue analyses found no significant differences across intrathecal 2-CP, saline or naïve groups. Adult behavioral measures showed expected sex-dependent differences, that did not differ between 2-CP and saline groups. Single maximum tolerated in vivo doses of intrathecal 2-CP produced reversible spinal anesthesia in juvenile rodents without detectable evidence of developmental neurotoxicity. Current results cannot be extrapolated to repeated dosing or prolonged infusion

Phenotypic and genotypic monitoring of Schistosoma mansoni in Tanzanian schoolchildren five years into a preventative chemotherapy national control programme

We conducted combined in vitro PZQ efficacy testing with population genetic analyses of S. mansoni collected from children from two schools in 2010, five years after the introduction of a National Control Programme. Children at one school had received four annual PZQ treatments and the other school had received two mass treatments in total. We compared genetic differentiation, indices of genetic diversity, and estimated adult worm burden from parasites collected in 2010 with samples collected in 2005 (before the control programme began) and in 2006 (six months after the first PZQ treatment). Using 2010 larval samples, we also compared the genetic similarity of those with high and low in vitro sensitivity to PZQ

Evaluation of the London Measure of Unplanned Pregnancy in a United States population of women

Copyright @ 2012 Morof et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Objective: To evaluate the reliability and validity of the London Measure of Unplanned Pregnancy (a U.K.-developed measure of pregnancy intention), in English and Spanish translation, in a U.S. population of women. Methods: A psychometric evaluation study of the London Measure of Unplanned Pregnancy (LMUP), a six-item, self-completion paper measure was conducted with 346 women aged 15–45 who presented to San Francisco General Hospital for termination of pregnancy or antenatal care. Analyses of the two language versions were carried out separately. Reliability (internal consistency) was assessed using Cronbach’s alpha and item-total correlations. Test-retest reliability (stability) was assessed using weighted Kappa. Construct validity was assessed using principal components analysis and hypothesis testing. Results: Psychometric testing demonstrated that the LMUP was reliable and valid in both U.S. English (alpha = 0.78, all item-total correlations .0.20, weighted Kappa = 0.72, unidimensionality confirmed, hypotheses met) and Spanish translation (alpha = 0.84, all item-total correlations .0.20, weighted Kappa = 0.77, unidimensionality confirmed, hypotheses met). Conclusion: The LMUP was reliable and valid in U.S. English and Spanish translation and therefore may now be used with U.S. women.The study was funded by an anonymous donation

Introgressive Hybridization of Schistosoma haematobium Group Species in Senegal: Species Barrier Break Down between Ruminant and Human Schistosomes

The file attached is the Published/publisher’s pdf version of the article.Copyright: © 2013 Webster et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Equal pay by gender and by nationality: a comparative analysis of Switzerland's unequal equal pay policy regimes across time

What explains the adoption of two different policies on equal pay by gender (EPG) and by nationality (EPN) in Switzerland? And why is the liberal, litigation-based, equal pay policy regime set up by the Gender Equality Act of 1996 much less effective than the neocorporatist ‘accompanying measures' to the Bilateral European Union-Switzerland Agreement on Free Movement of Persons adopted in 1999 to ensure equal pay for workers of different national origins? The formation of two different policy regimes cannot be explained by different levels of political will. Equally, different ‘varieties of capitalism' cannot explain the setup of the two different equal pay policy regimes within the very same country. Instead, our qualitative comparative analysis across time suggests that the differences can be best explained by a particular constellation of attributes, namely the use of different policy frames—i.e. ‘anti-discrimination' in the EPG and ‘unfair competition' in the EPN case—and the different setting of interest politics epitomised by the opposite stances adopted by Switzerland's employer associations in the two case

Hybridization in parasites: consequences for adaptive evolution, pathogenesis and public health in a changing world

[No abstract available

Estimation of changes in the force of infection for intestinal and urogenital schistosomiasis in countries with Schistosomiasis Control Initiative-assisted programmes

The last decade has seen an expansion of national schistosomiasis control programmes in Africa based on large-scale preventative chemotherapy. In many areas this has resulted in considerable reductions in infection and morbidity levels in treated individuals. In this paper, we quantify changes in the force of infection (FOI), defined here as the per (human) host parasite establishment rate, to ascertain the impact on transmission of some of these programmes under the umbrella of the Schistosomiasis Control Initiative (SCI)

Apophallus microsoma N. SP. from Chicks Infected with Metacercariae from Coho Salmon (Oncorhynchus kisutch ) and Review of the Taxonomy and Pathology of the Genus Apophallus (Heterophyidae)

Metacercariae of an unidentified species of Apophallus Luhe, 1909 are associated with overwinter mortality in coho salmon, Oncorhynchus kisutch (Walbaum, 1792), in the West Fork Smith River, Oregon. We infected chicks with these metacercariae in order to identify the species. The average size of adult worms was 197 x 57 μm, which was 2 to 11 times smaller than other described Apophallus species. Eggs were also smaller, but larger in proportion to body size, than in other species of Apophallus. Based on these morphological differences, we describe Apophallus microsoma n. sp. In addition, sequences from the cytochrome c oxidase 1 gene from Apophallus sp. cercariae collected in the study area, which are likely conspecific with experimentally cultivated A. microsoma, differ by >12% from those we obtained from Apophallus donicus (Skrjabin and Lindtrop, 1919) and from Apophallus brevis Ransom, 1920. The taxonomy and pathology of Apophallus species is reviewed.Keywords: Mortality, St. Lawrence River, Life cycle, Parasite, Perch Perca flavescens, Trematoda, Yellow perch, Brevis, Oregon, Nanophyetus salmincol