Purpose: To examine the role of systemic activation of the complement system (assessed by levels of circulating C3a, Ba, and sC5b-9) in patients (n = 122) with advanced age-related macular degeneration, geographic atrophy, and neovascular age-related macular degeneration, compared with cataract controls (n = 27). Methods: Plasma complement factors were measured using enzyme-linked immunosorbent assays. Statistical analysis included univariate and multivariate logistic regression (p < 0.05). Results: Adjusted for age, the odds ratios of C3a and sC5b-9 for any advanced age-related macular degeneration were 1.78 (95% confidence interval = 1.16–2.73, p < 0.01) and 1.20 (95% confidence interval = 1.04–1.39, p = 0.01), respectively. We found a significantly elevated adjusted odds ratio of C3a (adjusted odds ratio = 1.71, 95% confidence interval = 1.12–2.60, p = 0.01) and sC5b-9 (adjusted odds ratio = 1.22, 95% confidence interval = 1.04–1.43, p = 0.01) for neovascular age-related macular degeneration. Adjusted for age, neither C3a, sC5b-9, nor Ba were associated with geographic atrophy. Conclusion: We suggest a role for elevated plasma levels of C3a and sC5b-9 in patients with neovascular age-related macular degeneration. The study’s results reinforce the need for more investigation to assess the impact of therapeutic interventions targeted at the complement signaling pathways in age-related macular degeneration.
PurposeTo explore top-ranked plasma proteins related to neovascular age-related macular degeneration (AMD) and geographic atrophy (GA), and explore pathways related to neovascular AMD and GA.MethodsWe conducted a pilot study of patients with neovascular AMD (n = 10), GA (n = 10), and age-matched cataract controls (n = 10) who were recruited into an AMD registry. We measured 4001 proteins in ethylenediaminetetraacetic acid plasma samples using an aptamer-based proteomic technology. Relative concentrations of each of 4001 proteins were log (base 2) transformed and compared between cases of neovascular AMD and GA versus controls using linear regression. Pathway analysis was conducted using pathways downloaded from Reactome.ResultsIn this pilot study, higher levels of vinculin and lower levels of CD177 were found in patients with neovascular AMD compared with controls. Neuregulin-4 was higher and soluble intercellular adhesion molecule-1 was lower in patients with GA compared with controls. For neovascular AMD, cargo trafficking to the periciliary membrane, fibroblast growth factor receptor 3b ligand binding and activation, and vascular endothelial growth factor–related pathways were in the top ranked pathways. The top-ranked pathways for GA included several related to ErbB4 signaling.ConclusionsWe found different proteins and different pathways associated with neovascular AMD and GA. Vinculin and some of the top-ranked pathways have been previously associated with AMD, whereas others have not been described.Translational RelevanceBiomarkers identified in plasma likely reflect systemic alterations in protein expression and may improve our understanding of the mechanisms leading to AMD.
Females had home ranges of 28.3 ± 6.8 ha and males 96.6 ± 18.2 ha, which leads to an 43 estimated sustainable population or carrying capacity of 413-502 at Scotia. Captive bred 44 animals from Perth Zoo had a high mortality rate upon reintroduction at Scotia due to raptor 45 predation and starvation. The habitat preferences for mallee with a shrub understory appear 46 to be driven by termite availability, and other reintroduced ecosystem engineers appear to
Although most respondents followed the EVS guidelines, a minority deviated, and the majority generalized their strategy to other forms of endophthalmitis. There is significant variation in retreatment strategies, and while cultures are frequently obtained to help guide these treatments, they are utilized infrequently.
Making referrals to other hospital specialties is one of the key duties of the foundation doctor, which can be difficult and time consuming. In Ninewells hospital, Scotland, in our experience the effectiveness of referrals is limited by contact details not being readily accessible and foundation doctors not knowing what information is relevant to each specialty.We surveyed foundation doctors on their experience of the existing referral process to identify where we needed to focus to improve the process. The doctors reported significant delays in obtaining contact details from the operator, and found they did not know the specific information needed in each referral.To increase the information available to foundation doctors, we set up a page on the staff intranet called 'Referral Finder'. This page includes contact details, guidelines for referral, and links to relevant protocols for each specialty. By making this information readily accessible our objective was to increase the speed and quality of referrals.When surveyed two months after the web page was established, foundation doctors reported a reduction in calls to operator from baseline and reported achieving more effective referrals. When asked to comment, many doctors asked if the page could include details for other hospitals in our health board and provide more specialty specific information.This feedback prompted us to extend the scope of the page to include the district general hospital in our region, and update many of the existing details. Doctors were then surveyed after the updates, 100% agreed that the website saved time and there was a 49.3% reduction in doctors who reported not knowing the specific information needed for a referral.Having adequate information improved referrals and resulted in time saved. This would allow more time for patient care. The quality improvement project was praised among doctors as a useful, innovative and replicable project. ProblemIn Ninewells hospital, Dundee, Scotland, foundation doctors spent considerable time accessing referral contact details via the operator. This resulted in significant delays which impacted on other ward jobs and patient care. After obtaining the contact details from the operator, more time was spent accumulating patient information by the doctor to make the referral. Despite this, referrals were often lacking specific information resulting in inadequate referrals.Ninewells is a large teaching hospital with 26 specialties where the referral process, and the specific information required for referral, varies between each specialty. Existing paper records of referral contact details in the wards were incomplete and were not kept updated. In addition, there was no guidance on what to include in the referral for any specialty. As two foundation doctors, we had encountered frustration at wasted time, incomplete referrals, and patient safety issues caused by the lack of available referral information. We felt a simple online page where referral information was kept would mean the informat...
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