Epstein-Barr virus (EBV) - specific antibodies in multiple sclerosis patients, including targeted investigation of a candidate EBV nuclear antigen-1 (EBNA-1) B cell epitope

Multiple Sclerosis (MS) is a very complex disease, with different genetic and environmental factors contributing to its risk. In particular, infection with Epstein-Barr Virus (EBV) has been shown to increase MS risk. This risk is moderately associated with anti-viral capsid antigen (VCA) antibodies, but very strongly associated for anti-EBV nuclear antigen-1 (EBNA-1) antibodies. Focus on EBNA-1 has uncovered that antibody reactivity against a C-terminal part the of the protein (amino acid (aa) positions 385-420) is a stronger risk marker than antibodies against the whole EBNA-1 protein. Recently, in a small study in twins (n=12), a putative B cell epitope within this region (aa 401-411) has been identified as a target for antibodies that are specifically enriched in MS patients compared with healthy controls

Estimating Crime in Rural America: The Contribution of the First Phase of The West Virginia Community Quality of Life Survey

The study of crime, law, and social control is now much less urban-biased than it was at the start of this millennium, and there is an ongoing significant increase in international qualitative and quantitative rural criminological research. Nonetheless, a conspicuous absence of reliable estimates of crime victimization in rural parts of the United States continues to exist. This article helps fill a major research gap by presenting the results of the first phase of the West Virginia Community Quality of Life Survey

Checks and cheques : implementing a population health and recall system to improve coverage of patients with diabetes in a rural general practice

Identification of all diabetic patients in the population is essential if diabetic care is to be effective in achieving the targets of the St Vincent Declaration.1 The challenge therefore is to establish population based monitoring and control systems by means of state of the art technology in order to achieve quality assurance in the provision of care for patients with diabetes. 2,3 Disease management receives extensive international support as the most appropriate approach to organising and delivering healthcare for chronic conditions like diabetes.4 This approach is achieved through a combination of guidelines for practice, patient education, consultations and follow up using a planned team approach and a strong focus on continuous quality improvement using information technology. 5,6 The current software (Medical Director) could not easily meet these requirements which led us to adopt a trial of Ferret. In designing this project we used change management7 and the plan, do, study, act cycle8 illustrated in Diagram 1.<br /

Genetic diversity among five T4-like bacteriophages

BACKGROUND: Bacteriophages are an important repository of genetic diversity. As one of the major constituents of terrestrial biomass, they exert profound effects on the earth's ecology and microbial evolution by mediating horizontal gene transfer between bacteria and controlling their growth. Only limited genomic sequence data are currently available for phages but even this reveals an overwhelming diversity in their gene sequences and genomes. The contribution of the T4-like phages to this overall phage diversity is difficult to assess, since only a few examples of complete genome sequence exist for these phages. Our analysis of five T4-like genomes represents half of the known T4-like genomes in GenBank. RESULTS: Here, we have examined in detail the genetic diversity of the genomes of five relatives of bacteriophage T4: the Escherichia coli phages RB43, RB49 and RB69, the Aeromonas salmonicida phage 44RR2.8t (or 44RR) and the Aeromonas hydrophila phage Aeh1. Our data define a core set of conserved genes common to these genomes as well as hundreds of additional open reading frames (ORFs) that are nonconserved. Although some of these ORFs resemble known genes from bacterial hosts or other phages, most show no significant similarity to any known sequence in the databases. The five genomes analyzed here all have similarities in gene regulation to T4. Sequence motifs resembling T4 early and late consensus promoters were observed in all five genomes. In contrast, only two of these genomes, RB69 and 44RR, showed similarities to T4 middle-mode promoter sequences and to the T4 motA gene product required for their recognition. In addition, we observed that each phage differed in the number and assortment of putative genes encoding host-like metabolic enzymes, tRNA species, and homing endonucleases. CONCLUSION: Our observations suggest that evolution of the T4-like phages has drawn on a highly diverged pool of genes in the microbial world. The T4-like phages harbour a wealth of genetic material that has not been identified previously. The mechanisms by which these genes may have arisen may differ from those previously proposed for the evolution of other bacteriophage genomes

Macular Pigment and its Contribution to Visual Performance and Experience [El pigmento macular y su contribución al rendimiento y experiencia visuals]

There is now a consensus, based on histological, biochemical and spectral absorption data, that the yellow colour observed at the macula lutea is a consequence of the selective accumulation of dietary xanthophylls in the central retina of the living eye. Scientific research continues to explore the function(s) of MP in the human retina, with two main hypotheses premised on its putative capacity to (1) protect the retina from (photo)-oxidative damage by means of its optical filtration and/or antioxidant properties, the so-called protective hypothesis and (2) influence the quality of visual performance by means of selective short wavelength light absorption prior to photoreceptor light capture, thereby attenuating the effects of chromatic aberration and light scatter, the so-called acuity and visibility hypotheses. The current epidemic of age-related macular degeneration has directed researchers to investigate the protective hypothesis of MP, while there has been a conspicuous lack of work designed to investigate the role of MP in visual performance. The aim of this review is to present and critically appraise the current literature germane to the contribution of MP, if any, to visual performance and experience

Genomes of the T4-related bacteriophages as windows on microbial genome evolution

The T4-related bacteriophages are a group of bacterial viruses that share morphological similarities and genetic homologies with the well-studied Escherichia coli phage T4, but that diverge from T4 and each other by a number of genetically determined characteristics including the bacterial hosts they infect, the sizes of their linear double-stranded (ds) DNA genomes and the predicted compositions of their proteomes. The genomes of about 40 of these phages have been sequenced and annotated over the last several years and are compared here in the context of the factors that have determined their diversity and the diversity of other microbial genomes in evolution. The genomes of the T4 relatives analyzed so far range in size between ~160,000 and ~250,000 base pairs (bp) and are mosaics of one another, consisting of clusters of homology between them that are interspersed with segments that vary considerably in genetic composition between the different phage lineages. Based on the known biological and biochemical properties of phage T4 and the proteins encoded by the T4 genome, the T4 relatives reviewed here are predicted to share a genetic core, or "Core Genome" that determines the structural design of their dsDNA chromosomes, their distinctive morphology and the process of their assembly into infectious agents (phage morphogenesis). The Core Genome appears to be the most ancient genetic component of this phage group and constitutes a mere 12-15% of the total protein encoding potential of the typical T4-related phage genome. The high degree of genetic heterogeneity that exists outside of this shared core suggests that horizontal DNA transfer involving many genetic sources has played a major role in diversification of the T4-related phages and their spread to a wide spectrum of bacterial species domains in evolution. We discuss some of the factors and pathways that might have shaped the evolution of these phages and point out several parallels between their diversity and the diversity generally observed within all groups of interrelated dsDNA microbial genomes in nature

Visual Performance in Patients with Neovascular Age Related Macular Degeneration Undergoing Treatment With Intravitreal Ranibizumab

Purpose. To assess visual function and its response to serial intravitreal ranibizumab (Lucentis, Genentech) in patients with neovascular age-related macular degeneration (nv-AMD). Methods. Forty-seven eyes of 47 patients with nv-AMD, and corrected distance visual acuity (CDVA) logMAR 0.7 or better, undergoing intravitreal injections of ranibizumab, were enrolled into this prospective study. Visual function was assessed using a range of psychophysical tests, while mean foveal thickness (MFT) was determined by optical coherence tomography (OCT). Results. Groupmean (±sd)MFT reduced significantly frombaseline (233±59)) to exit (205±40)) (p = 0.001). CDVA exhibited no change between baseline and exit visits (p = 0.48 and p = 0.31 resp.). Measures of visual function that did exhibit statistically significant improvements (p \u3c 0.05 for all) included reading acuity, reading speed, mesopic and photopic contrast sensitivity (CS), mesopic and photopic glare disability (GD), and retinotopic ocular sensitivity (ROS) at all eccentricities. Conclusion. Eyes with nv-AMD undergoing intravitreal ranibizumab injections exhibit improvements in many parameters of visual function. Outcome measures other than CDVA, such as CS, GD, and ROS, should not only be considered in the design of studies investigating nv-AMD, but also in treatment and retreatment strategies for patients with the condition

Augmentation of Macular Pigment following Implantation of Blue Light–Filtering Intraocular Lenses at the Time of Cataract Surgery

PURPOSE. (Photo)-oxidative stress is believed to play a role in the pathogenesis of age-related macular degeneration (AMD), with the threshold for retinal damage being lowest for shortwavelength (blue) light. Macular pigment (MP), consisting of the carotenoids lutein (L), zeaxanthin (Z) and meso-Z, has a maximum absorption at 460 nm and protects the retina from (photo)-oxidative injury. This study was designed to investigate whether the blue light–filtering properties of the Alcon Acry- Sof Natural intraocular lens (ANIOL) implanted during cataract surgery affects MP optical density (MPOD). METHODS. Forty-two patients scheduled for cataract surgery were recruited for the study. These patients all had a preoperative best corrected visual acuity rating (BCVAR) of at least 0.5 (logMAR) in the study eye. The patients were randomized to have either the standard Alcon AcrySof three-piece acrylic intraocular lens (AIOL) (controls) or the ANIOL implanted at the time of cataract surgery. The spatial profile of MPOD (i.e., at 0.25°, 0.5°, 1.0°, and 1.75° eccentricity) was measured with customized heterochromatic flicker photometry (cHFP) 1 week before and 1 week after surgery, and at 3, 6, and 12 months after surgery. Serum concentrations of L and Z were also measured at each study visit. RESULTS. There was a highly significant and positive correlation between all MPODs (e.g., at 0.25°) recorded 1 week before and after surgery in eyes with an AIOL implant (r � 0.915, P � 0.01; paired samples t-test, P � 0.631) and in those ANIOL implants (r � 0.868, P � 0.01; paired samples t-test, P � 0.719). Average MPOD across the retina increased significantly with time (after 3 months) in the ANIOL group (repeatedmeasures, general linear model, P � 0.05), but remained stable in the AIOL group (repeated-measures, general linear model, P � 0.05). There were no significant time or lens effects observed for serum L over the study period (P � 0.05). There was a significant time effect for serum Z over the study perio