Advice about diet and smoking for people with or at risk of age-related macular degeneration: a cross-sectional survey of eye care professionals in the UK.

BACKGROUND: In the absence of a cure, there has been considerable interest in attempts to prevent or reduce the progression of age-related macular degeneration (AMD) by targeting particular modifiable risk factors. The aim of this study was to conduct a cross-sectional survey of the current practice of UK eye care professionals in relation to advice given on diet and other lifestyle modifications for patients with or at risk of AMD. METHODS: Optometrists and ophthalmologists on the membership databases of professional organisations for the two professions were invited to participate in an online survey. The survey was open for 12 weeks between July and September 2012. RESULTS: A total of 1,468 responses were received (96.3% from optometrists and 3.7% from ophthalmologists). The response rate of those receiving the invitation was 16.2% (1,414/8735) for optometrists and 6% (54/1460) for ophthalmologists. A majority of respondents reported that they frequently provide dietary advice to patients with established AMD (67.9%) and those at risk of AMD (53.6%). Typical advice consisted of a recommendation to eat plenty of leafy green vegetables and eat more oily fish. The decision to recommend nutritional supplements was based on the risk of progression to advanced AMD, with approximately 93% of respondents recommending supplementation in a patient with advanced AMD in one eye. However for the majority, the type of supplement recommended did not comply with current best research evidence, based on the findings of the Age-related Eye Disease Study (AREDS). Only one in three optometrists regularly assessed smoking status and advised on smoking cessation. CONCLUSIONS: Within a large sample of eye care professionals, consisting predominantly of optometrists, who responded to a cross-sectional survey, there was active engagement in providing nutritional advice to patients with or at risk of AMD. However, the results demonstrate a need to raise awareness of the evidence underpinning the use of nutritional supplements together with an increased involvement in targeted smoking cessation

Reversal of the ΔdegP Phenotypes by a Novel rpoE Allele of Escherichia coli

RseA sequesters RpoE (σE) to the inner membrane of Escherichia coli when envelope stress is low. Elevated envelope stress triggers RseA cleavage by the sequential action of two membrane proteases, DegS and RseP, releasing σE to activate an envelope stress reducing pathway. Revertants of a ΔdegP ΔbamB strain, which fails to grow at 37°C due to high envelope stress, harbored mutations in the rseA and rpoE genes. Null and missense rseA mutations constitutively hyper-activated the σE regulon and significantly reduced the major outer membrane protein (OMP) levels. In contrast, a novel rpoE allele, rpoE3, resulting from the partial duplication of the rpoE gene, increased σE levels greater than that seen in the rseA mutant background but did not reduce OMP levels. A σE-dependent RybB::LacZ construct showed only a weak activation of the σE pathway by rpoE3. Despite this, rpoE3 fully reversed the growth and envelope vesiculation phenotypes of ΔdegP. Interestingly, rpoE3 also brought down the modestly activated Cpx envelope stress pathway in the ΔdegP strain to the wild type level, showing the complementary nature of the σE and Cpx pathways. Through employing a labile mutant periplasmic protein, AcrAL222Q, it was determined that the rpoE3 mutation overcomes the ΔdegP phenotypes, in part, by activating a σE-dependent proteolytic pathway. Our data suggest that a reduction in the OMP levels is not intrinsic to the σE-mediated mechanism of lowering envelope stress. They also suggest that under extreme envelope stress, a tight homeostasis loop between RseA and σE may partly be responsible for cell death, and this loop can be broken by mutations that either lower RseA activity or increase σE levels

Outer membrane protein folding from an energy landscape perspective

The cell envelope is essential for the survival of Gram-negative bacteria. This specialised membrane is densely packed with outer membrane proteins (OMPs), which perform a variety of functions. How OMPs fold into this crowded environment remains an open question. Here, we review current knowledge about OFMP folding mechanisms in vitro and discuss how the need to fold to a stable native state has shaped their folding energy landscapes. We also highlight the role of chaperones and the β-barrel assembly machinery (BAM) in assisting OMP folding in vivo and discuss proposed mechanisms by which this fascinating machinery may catalyse OMP folding

Primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is an immune-mediated chronic cholestatic liver disease with a slowly progressive course. Without treatment, most patients eventually develop fibrosis and cirrhosis of the liver and may need liver transplantation in the late stage of disease. PBC primarily affects women (female preponderance 9–10:1) with a prevalence of up to 1 in 1,000 women over 40 years of age. Common symptoms of the disease are fatigue and pruritus, but most patients are asymptomatic at first presentation. The diagnosis is based on sustained elevation of serum markers of cholestasis, i.e., alkaline phosphatase and gamma-glutamyl transferase, and the presence of serum antimitochondrial antibodies directed against the E2 subunit of the pyruvate dehydrogenase complex. Histologically, PBC is characterized by florid bile duct lesions with damage to biliary epithelial cells, an often dense portal inflammatory infiltrate and progressive loss of small intrahepatic bile ducts. Although the insight into pathogenetic aspects of PBC has grown enormously during the recent decade and numerous genetic, environmental, and infectious factors have been disclosed which may contribute to the development of PBC, the precise pathogenesis remains enigmatic. Ursodeoxycholic acid (UDCA) is currently the only FDA-approved medical treatment for PBC. When administered at adequate doses of 13–15 mg/kg/day, up to two out of three patients with PBC may have a normal life expectancy without additional therapeutic measures. The mode of action of UDCA is still under discussion, but stimulation of impaired hepatocellular and cholangiocellular secretion, detoxification of bile, and antiapoptotic effects may represent key mechanisms. One out of three patients does not adequately respond to UDCA therapy and may need additional medical therapy and/or liver transplantation. This review summarizes current knowledge on the clinical, diagnostic, pathogenetic, and therapeutic aspects of PBC

Holocene development and anthropogenic disturbance of a shallow lake system in Central Ireland recorded by diatoms

Three cores from two connected lakes in Central Ireland (Lough Kinale and Derragh Lough) were investigated using diatom analysis to establish the Holocene development of the lacustrine system, any local variations within the lakes and any anthropogenic influences. The study area was situated in a lowland location and the lakes were shallow, unstratified and interconnected. Litho-and bio-stratigraphical analyses of the lake cores and deposits beneath a mire separating the two lakes showed the changing spatial configuration of the lake system in the early Holocene and the separation of the initial lake into three basins (cf. lacustrine cells) and finally into two interlinked lakes. The evolution of the lake system is conceptualised as the development of distinct lacustrine cells, and its sediments have recorded changes in the physical (geography, depth and sedimentation) and chemical (water chemistry) properties of the lakes inferred through diatom analyses. The longest sequence, from the early Holocene, records fluctuating lake levels and these are correlated with geomorphological mapping and surveying of palaeoshorelines. The diatom assemblages of the upper 2 m of the three cores, covering approximately the last 2000–3000 radiocarbon years show considerable difference in trophic status and life-form categories. This is related to the location of the cores in the lake and also the distance from human settlement with particular reference to proximity to crannog (artificial island) construction and use. The most central core from the deepest part of Lough Kinale has the least representation of the human settlement and agricultural activity in the catchment and on the fringes of the lake, whereas the core taken from the edge of a crannog is able to identify when construction and use of the crannog occurred. The local nature of the palaeoecological response to human activity due to incomplete water mixing has the advantage of allowing the lake sediment cores to be used to determine spatially discrete settlement patterns

The palaeolimnological record from lake Cullulleraine, lower Murray River (south-east Australia): implications for understanding riverine histories

Australia’s largest river system, the Murray-Darling Basin, is the focus of scientific and political attention, due mainly to the competing issues of economic productivity versus environmental flows. Central to this dialogue is the need to know about the Basin’s natural condition and the degree to which the system has deviated from this pre-disturbance, baseline status. This study examines the patterns of ecological change in Lake Cullulleraine, a permanently connected artificial wetland adjacent to Lock Nine on the Murray River, south-east Australia. A 43-cm sediment core was collected in January 1998 and diatoms were analysed at 1-cm intervals for use as aquatic ecological indicators. The sediment core was dated using ²¹⁰Pb. Changes in the diatom community have occurred since the time of lake formation in 1926, particularly shifts between Aulacoseira subborealis, Staurosira construens var. venter, Aulacoseira granulata, Staurosirella pinnata and Pseudostaurosira brevistriata. An electrical conductivity (EC) transfer function was applied to the fossil diatom assemblages and inferred EC values were compared to long-term, historical EC data from the River. Despite the presence of good analogues between fossil and modern diatom assemblages, inferred EC did not reflect measured EC accurately. In recent decades, patterns in the two data sets were reversed. Despite clear changes in the fossil record, quantitative palaeo-environmental interpretation was limited because the dominant taxa occupy broad ecological niches. Despite these limitations, changes in the Lake Cullulleraine record, particularly in the planktonic taxa, can be interpreted in terms of landscape change. Furthermore, because of the good chronology from the site, the record may be useful for dating changes observed in sites with poor chronological control.Jennie Fluin, John Tibby and Peter Gel

Multi-proxy studies in palaeolimnology

Multi-proxy studies are becoming increasingly common in palaeolimnology. Eight basic requirements and challenges for a multi-proxy study are outlined in this essay – definition of research questions, leadership, site selection and coring, data storage, chronology, presentation of results, numerical tools, and data interpretation. The nature of proxy data is discussed in terms of physical proxies and biotic proxies. Loss-on-ignition changes and the use of transfer functions are reviewed as examples of problems in the interpretation of data from multi-proxy studies. The importance of pollen analysis and plant macrofossil analysis in multi-proxy studies is emphasised as lake history cannot be interpreted without knowledge of catchment history. Future directions are outlined about how multi-proxy studies can contribute to understanding biotic responses to environmental change