The genetic predictors of severe outcome in patients with anterior uveitis

Uveitis is a generic term for a wide variety of different types of intraocular inflammation with different clinical phenotypes and visual outcomes. The explanation for why some patients develop chronic anterior disease whereas others do not is unknown. It seems likely that host factors such as the cytokine milieu of the aqueous humor may be an important factor in determining outcome. In turn, their secretion is genetically determined and cytokine gene polymorphisms have been associated with high or low level production whatever the stimulus. Purpose: The aim of this study was to identify key cytokine and chemokine polymorphisms associated with disease susceptibility, clinical phenotype, and development of visually significant complications in patients with anterior uveitis. Methods: PCR amplification was used to genotype a number of biallelic SNPs in several cytokine genes. This genetic data was then compared between patients and healthy controls, and within the patient group itself for association with clinical disease outcomes. Results: Our results show that a significant difference in the frequency of TNF-857T allele in patients with idiopathic anterior uveitis. We found a significant association between TNF-308 allele G and patients with anterior uveitis who were HLA-B27 positive. Patients with HLA-B27 associated anterior uveitis who developed visually threatening complications were more likely to carry the TNFRSF1A-201T or TNFRSF1A-1135T alleles. In addition, the frequency of IL- 1ra allele T was found to be significantly associated with chronicity of the disease. The frequency of MCP-1 (-2076T) allele was found to be significantly higher in healthy individuals when compared to patients with acute idiopathic anterior uveitis. Conclusions: These results suggest that genetic variations in proinflammatory mediators may influence the susceptibility and severity of the inflammatory response in eyes of patients with anterior uveitis. This knowledge may be useful in identifying prognosis and responsiveness to anti-TNF blockade in patients with anterior uveitis

The case for a scalable coherence protocol for complex on-chip cache hierarchies in many-core systems

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Interaction of NoC design and coherence protocol in 3D-Stacked CMPs

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Isolated sixth cranial nerve palsy as the presenting symptom of a rapidly expanding ACTH positive pituitary adenoma: a case report

<p>Abstract</p> <p>Background</p> <p>Pituitary adenoma may present with neuro-ophthalmic manifestations and, typically, rapid tumor expansion is the result of apoplexy. Herein, we present the first case of an isolated sixth cranial nerve palsy as initial feature of a rapidly expanding ACTH positive silent tumor without apoplexy.</p> <p>Case Presentation</p> <p>A 44 year old female with a history of sarcoidosis presented with an isolated sixth cranial nerve palsy as the initial clinical feature of a rapidly expanding ACTH positive silent pituitary adenoma. The patient underwent emergent transsphenoidal hypophysectomy for this rapidly progressive tumor and subsequently regained complete vision and ocular motility. Despite tumor extension into the cavernous sinus, the other cranial nerves were spared during the initial presentation.</p> <p>Conclusions</p> <p>This case illustrates the need to consider a rapidly growing pituitary tumor as a possibility when presented with a rapidly progressive ophthalmoplegia.</p

The effectiveness of pharmacological agents for the treatment of uveitic macular oedema (UMO): a systematic review protocol

PRISMA-P 2015 checklist: recommended items to include in a systematic review protocol. a (PDF 153 kb

Effects of Glyphosate and its Formulation, Roundup, on Reproduction in Zebrafish (Danio rerio)

This is an open access article that is freely available in ORE or from the publisher's web site. Please cite the published version.Copyright © 2014 American Chemical SocietyRoundup and its active ingredient glyphosate are among the most widely used herbicides worldwide and may contaminate surface waters. Research suggests both Roundup and glyphosate induce oxidative stress in fish and may also cause reproductive toxicity in mammalian systems. We aimed to investigate the reproductive effects of Roundup and glyphosate in fish and the potential associated mechanisms of toxicity. To do this, we conducted a 21-day exposure of breeding zebrafish (Danio rerio) to 0.01, 0.5, and 10 mg/L (glyphosate acid equivalent) Roundup and 10 mg/L glyphosate. 10 mg/L glyphosate reduced egg production but not fertilization rate in breeding colonies. Both 10 mg/L Roundup and glyphosate increased early stage embryo mortalities and premature hatching. However, exposure during embryogenesis alone did not increase embryo mortality, suggesting that this effect was caused primarily by exposure during gametogenesis. Transcript profiling of the gonads revealed 10 mg/L Roundup and glyphosate induced changes in the expression of cyp19a1 and esr1 in the ovary and hsd3b2, cat, and sod1 in the testis. Our results demonstrate that these chemicals cause reproductive toxicity in zebrafish, although only at high concentrations unlikely to occur in the environment, and likely mechanisms of toxicity include disruption of the steroidogenic biosynthesis pathway and oxidative stress.Natural Environment Research Counci