The Effect of nutritional supplementation on subjective and objective measures of visual and retinal function:a random controlled trial

In industrialised countries age-related macular disease (ARMD) is the leading cause of visual loss in older people. Because oxidative stress is purported to be associated with an increased risk of disease development the role of antioxidant supplementation is of interest. Lutein is a carotenoid antioxidant that accumulates within the retina and is thought to filter blue light. Increased levels of lutein have been associated with reduced risk of developing ARMD and improvements in visual and retinal function in eyes with ARMD. The aim of this randomised controlled trial (RCT) was to investigate the effect of a lutein-based nutritional supplement on subjective and objective measures of visual function in healthy eyes and in eyes with age-related maculopathy (ARM) – an early form of ARMD. Supplement withdrawal effects were also investigated. A sample size of 66 healthy older (HO), healthy younger (HY), and ARM eyes were randomly allocated to receive a lutein-based supplement or no treatment for 40 weeks. The supplemented group then stopped supplementation to look at the effects of withdrawal over a further 20 weeks. The primary outcome measure was multifocal electroretinogram (mfERG) N1P1 amplitude. Secondary outcome measures were mfERG N1, P1 and N2 latency, contrast sensitivity (CS), Visual acuity (VA) and macular pigment optical density (MPOD). Sample sizes were sufficient for the RCT to have an 80% power to detect a significant clinical effect at the 5% significance level for all outcome measures when the healthy eye groups were combined, and CS, VA and mfERG in the ARM group. This RCT demonstrates significant improvements in MPOD in HY and HO supplemented eyes. When HY and HO supplemented groups were combined, MPOD improvements were maintained, and mfERG ring 2 P1 latency became shorter. On withdrawal of the supplement mfERG ring 1 N1P1 amplitude reduced in HO eyes. When HO and HY groups were combined, mfERG ring 1 and ring 2 N1P1 amplitudes were reduced. In ARM eyes, ring 3 N2 latency and ring 4 P1 latency became longer. These statistically significant changes may not be clinically significant. The finding that a lutein-based supplement increases MPOD in healthy eyes, but does not increase mfERG amplitudes contrasts with the CARMIS study and contributes to the debate on the use of nutritional supplementation in ARM.

Characterization of heparin-binding site of tissue transglutaminase:its importance in cell surface targeting, matrix deposition, and cell signaling

Tissue transglutaminase (TG2) is a multifunctional Ca2+ activated protein crosslinking enzyme secreted into the extracellular matrix (ECM), where it is involved in wound healing and scarring, tissue fibrosis, celiac disease and metastatic cancer. Extracellular TG2 can also facilitate cell adhesion important in wound healing through a non-transamidating mechanism via its association with fibronectin (FN), heparan sulphates (HS) and integrins. Regulating the mechanism how TG2 is translocated into the ECM therefore provides a strategy for modulating these physiological and pathological functions of the enzyme. Here, through molecular modelling and mutagenesis we have identified the HS binding site of TG2 202KFLKNAGRDCSRRSSPVYVGR222. We demonstrate the requirement of this binding site for translocation of TG2 into the ECM through a mechanism involving cell surface shedding of HS. By synthesizing a peptide NPKFLKNAGRDCSRRSS corresponding to the HS binding site within TG2, we also demonstrate how this mimicking peptide can in isolation compensate the RGD-induced loss of cell adhesion on FN via binding to syndecan-4, leading to activation of PKCa, pFAK-397 and ERK1/2 and the subsequent formation of focal adhesions and actin cytoskeleton organization. A novel regulatory mechanism for TG2 translocation into the extracellular compartment that depends upon TG2 conformation and the binding of HS is proposed.

Regulation of IL-1β-induced NFκB by hydroxylases links key hypoxic and inflammatory signaling pathways

Hypoxia is a prominent feature of chronically inflamed tissues. Oxygen-sensing hydroxylases control transcriptional adaptation to hypoxia through the regulation of hypoxia-inducible factor (HIF) and nuclear factor ?B (NF-?B), both of which can regulate the inflammatory response. Furthermore, pharmacologic hydroxylase inhibitors reduce inflammation in multiple animal models. However, the underlying mechanism(s) linking hydroxylase activity to inflammatory signaling remains unclear. IL-1ß, a major proinflammatory cytokine that regulates NF-?B, is associated with multiple inflammatory pathologies. We demonstrate that a combination of prolyl hydroxylase 1 and factor inhibiting HIF hydroxylase isoforms regulates IL-1ß-induced NF-?B at the level of (or downstream of) the tumor necrosis factor receptor-associated factor 6 complex. Multiple proteins of the distal IL-1ß-signaling pathway are subject to hydroxylation and form complexes with either prolyl hydroxylase 1 or factor inhibiting HIF. Thus, we hypothesize that hydroxylases regulate IL-1ß signaling and subsequent inflammatory gene expression. Furthermore, hydroxylase inhibition represents a unique approach to the inhibition of IL-1ß-dependent inflammatory signaling.

Conditional osmotic stress in yeast:a system to study transport through aquaglyceroporins and osmostress signaling

The accumulation and transport of solutes are hallmarks of osmoadaptation. In this study we have employed the inability of the Saccharomyces cerevisiae gpd1Δ gpd2Δ mutant both to produce glycerol and to adapt to high osmolarity to study solute transport through aquaglyceroporins and the control of osmostress-induced signaling. High levels of different polyols, including glycerol, inhibited growth of the gpd1Δ gpd2Δ mutant. This growth inhibition was suppressed by expression of the hyperactive allele Fps1-AΔ of the osmogated yeast aquaglyceroporin, Fps1. The degree of suppression correlated with the relative rate of transport of the different polyols tested. Transport studies in secretory vesicles confirmed that Fps1-Δ1 transports polyols at increased rates compared with wild type Fps1. Importantly, wild type Fps1 and Fps1-Δ1 showed similarly low permeability for water. The growth defect on polyols in the gpd1Δ gpd2Δ mutant was also suppressed by expression of a heterologous aquaglyceroporin, rat AQP9. We surmised that this suppression was due to polyol influx, causing the cells to passively adapt to the stress. Indeed, when aquaglyceroporin-expressing gpd1Δ gpd2Δ mutants were treated with glycerol, xylitol, or sorbitol, the osmosensing HOG pathway was activated, and the period of activation correlated with the apparent rate of polyol uptake. This observation supports the notion that deactivation of the HOG pathway is closely coupled to osmotic adaptation. Taken together, our "conditional" osmotic stress system facilitates studies on aquaglyceroporin function and reveals features of the osmosensing and signaling system. © 2005 by The American Society for Biochemistry and Molecular Biology, Inc.

Clinical techniques to assess the visual and optical performance of intraocular lenses:a review

A number of clinical techniques are available to assess the visual and optical performance of the eye. This report aims to review the advantages and limitations of techniques used in previous studies of patients implanted with intraocular lenses (IOLs), whose designs are ever increasing in optical complexity. Although useful, in-vitro measurements of IOL optical quality cannot account for the wide range of biological variation in ocular anatomy and corneal optics, which will impact on the visual outcome achieved. This further highlights the need for a standardised series of visual performance tests that can be applied to a wide range of IOL designs. The conclusions of this report intend to assistresearchers in developing a comprehensive series of investigations to evaluate IOL performance. Repeatable and reproducible in-vivo assessments of visual and optical performance are desirable to further develop IOL concepts and designs, in the hope of improving current postoperative visual satisfaction. © 2013 Nova Science Publishers, Inc.

Visual and quality outcomes following bilateral implantation of a trifocal intraocular lens

Purpose: To examine visual outcomes following bilateral implantation of the FineVision trifocal intraocular lens (IOL; PhysIOL, Liège, Belgium). Methods: 26 patients undergoing routine cataract surgery were implanted bilaterally with the FineVision Trifocal IOL and followed up post-operatively for 3 months. The FineVision optic features a combination of 2 diffractive structures, resulting in distance, intermediate (+1.75 D add) and near vision (+3.50 D add) zones. Apodization of the optic surface increases far vision dominance with pupil aperture. Data collected at the 3 month visit included uncorrected and corrected distance (CDVA) and near vision; subjective refraction; defocus curve testing (photopic and mesopic); contrast sensitivity (CSV-1000); halometry glare testing and a questionnaire (NAVQ) to gauge near vision function and patient satisfaction. Results: The cohort comprised 15 males and 11 females, aged 52.5–82.4 years (mean 70.6 ± 8.2 years). Mean post-operative UDVA was 0.22 ± 0.14 logMAR, with a mean spherical equivalent refraction of +0.02 ± 0.35 D. Mean CDVA was 0.13 ± 0.10 logMAR monocularly, and 0.09 ± 0.07 logMAR binocularly. Defocus curve testing showed an extensive range of clear vision in both photopic and mesopic conditions. Patients showed high levels of satisfaction with their near vision (mean ± 0.9 ± 0.6, where 0 = completely satisfied, and 4 = completely unsatisfied) and demonstrated good spectacle independence. Conclusion: The FineVision IOL can be considered in patients seeking spectacle dependence following cataract surgery, and provide good patient satisfaction with uncorrected vision.

Interval timing in children:effects of auditory and visual pacing stimuli and relationships with reading and attention variables

Motor timing tasks have been employed in studies of neurodevelopmental disorders such as developmental dyslexia and ADHD, where they provide an index of temporal processing ability. Investigations of these disorders have used different stimulus parameters within the motor timing tasks which are likely to affect performance measures. Here we assessed the effect of auditory and visual pacing stimuli on synchronised motor timing performance and its relationship with cognitive and behavioural predictors that are commonly used in the diagnosis of these highly prevalent developmental disorders. Twenty- one children (mean age 9.6 years) completed a finger tapping task in two stimulus conditions, together with additional psychometric measures. As anticipated, synchronisation to the beat (ISI 329 ms) was less accurate in the visually paced condition. Decomposition of timing variance indicated that this effect resulted from differences in the way that visual and auditory paced tasks are processed by central timekeeping and associated peripheral implementation systems. The ability to utilise an efficient processing strategy on the visual task correlated with both reading and sustained attention skills. Dissociations between these patterns of relationship across task modality suggest that not all timing tasks are equivalent.

NADPH oxidase signaling and cardiac myocyte function

The NADPH oxidase family of enzymes has emerged as a major source of reactive oxygen species (ROS) that is important in diverse cellular functions including anti-microbial defence, inflammation and redox signaling. Of the five known NADPH oxidase isoforms, several are expressed in cardiovascular cells where they are involved in physiological and pathological processes such as the regulation of vascular tone, cell growth, migration, proliferation, hypertrophy, apoptosis and matrix deposition. This article reviews current knowledge regarding the role of NADPH oxidases in cardiomyocyte function in health and disease. © 2009 Elsevier Inc. All rights reserved.

Refractive outcomes of laser-assisted subepithelial keratectomy for myopia, hyperopia, and astigmatism using a 213 nm wavelength solid-state laser

To study the visual and refractive outcomes after laser-assisted subepithelial keratectomy (LASEK) performed with a 213 nm solid-state laser for a broad range of refractive errors.

Attentional processes link perception and action

Behavioural studies on normal and brain-damaged individuals provide convincing evidence that the perception of objects results in the generation of both visual and motor signals in the brain, irrespective of whether or not there is an intention to act upon the object. In this paper we sought to determine the basis of the motor signals generated by visual objects. By examining how the properties of an object affect an observer's reaction time for judging its orientation, we provide evidence to indicate that directed visual attention is responsible for the automatic generation of motor signals associated with the spatial characteristics of perceived objects.

Lexical learning and dysgraphia in a group of adults with developmental dyslexia

We investigated the ability to learn new words in a group of 22 adults with developmental dyslexia/dysgraphia and the relationship between their learning and spelling problems. We identified a deficit that affected the ability to learn both spoken and written new words (lexical learning deficit). There were no comparable problems in learning other kinds of representations (lexical/semantic and visual) and the deficit could not be explained in terms of more traditional phonological deficits associated with dyslexia (phonological awareness, phonological STM). Written new word learning accounted for further variance in the severity of the dysgraphia after phonological abilities had been partialled out. We suggest that lexical learning may be an independent ability needed to create lexical/formal representations from a series of independent units. Theoretical and clinical implications are discussed. © 2005 Psychology Press Ltd.

Aberrant reactive oxygen and nitrogen species generation in rheumatoid arthritis (RA):causes and consequences for immune function, cell survival, and therapeutic intervention

The infiltration and persistence of hematopoietic immune cells within the rheumatoid arthritis (RA) joint results in elevated levels of pro-inflammatory cytokines, increased reactive oxygen (ROS) and -nitrogen (RNS) species generation, that feeds a continuous self-perpetuating cycle of inflammation and destruction. Meanwhile, the controlled production of ROS is required for signaling within the normal physiological reaction to perceived "foreign matter" and for effective apoptosis. This review focuses on the signaling pathways responsible for the induction of the normal immune response and the contribution of ROS to this process. Evidence for defects in the ability of immune cells in RA to regulate the generation of ROS and the consequence for their immune function and for RA progression is considered. As the hypercellularity of the rheumatoid joint and the associated persistence of hematopoietic cells within the rheumatoid joint are symptomatic of unresponsiveness to apoptotic stimuli, the role of apoptotic signaling proteins (specifically Bcl-2 family members and the tumor suppressor p53) as regulators of ROS generation and apoptosis are considered, evaluating evidence for their aberrant expression and function in RA. We postulate that ROS generation is required for effective therapeutic intervention.

Exploitation of fibre characteristics in temperature sensing and radio-over-fibre applications

The development of sensing devices is one of the instrumentation fields that has grown rapidly in the last decade. Corresponding to the swift advance in the development of microelectronic sensors, optical fibre sensors are widely investigated because of their advantageous properties over the electronics sensors such as their wavelength multiplexing capability and high sensitivity to temperature, pressure, strain, vibration and acoustic emission. Moreover, optical fibre sensors are more attractive than the electronics sensors as they can perform distributed sensing, in terms of covering a reasonably large area using a single piece of fibre. Apart from being a responsive element in the sensing field, optical fibre possesses good assets in generating, distributing, processing and transmitting signals in the future broadband information network. These assets include wide bandwidth, high capacity and low loss that grant mobility and flexibility for wireless access systems. Among these core technologies, the fibre optic signal processing and transmission of optical and radio frequency signals have been the subjects of study in this thesis. Based on the intrinsic properties of single-mode optical fibre, this thesis aims to exploit the fibre characteristics such as thermal sensitivity, birefringence, dispersion and nonlinearity, in the applications of temperature sensing and radio-over-fibre systems. By exploiting the fibre thermal sensitivity, a fully distributed temperature sensing system consisting of an apodised chirped fibre Bragg grating has been implemented. The proposed system has proven to be efficient in characterising grating and providing the information of temperature variation, location and width of the heat source applied in the area under test.To exploit the fibre birefringence, a fibre delay line filter using a single high-birefringence optical fibre structure has been presented. The proposed filter can be reconfigured and programmed by adjusting the input azimuth of launched light, as well as the strength and direction of the applied coupling, to meet the requirements of signal processing for different purposes in microwave photonic and optical filtering applications. To exploit the fibre dispersion and nonlinearity, experimental investigations have been carried out to study their joint effect in high power double-sideband and single-sideband modulated links with the presence of fibre loss. The experimental results have been theoretically verified based on the in-house implementation of the split-step Fourier method applied to the generalised nonlinear Schrödinger equation. Further simulation study on the inter-modulation distortion in two-tone signal transmission has also been presented so as to show the effect of nonlinearity of one channel on the other. In addition to the experimental work, numerical simulations have also been carried out in all the proposed systems, to ensure that all the aspects concerned are comprehensively investigated.

The influence of learning styles, enrolment status and gender on academic performance of optometry undergraduates

Purpose: This cross-sectional study was designed to determine whether the academic performance of optometry undergraduates is influenced by enrolment status, learning style or gender. Methods: Three hundred and sixty undergraduates in all 3 years of the optometry degree course at Aston University during 2008–2009 were asked for their informed consent to participate in this study. Enrolment status was known from admissions records. An Index of Learning Styles (http://www4.nscu.edu/unity/lockers/users/f/felder/public/Learning-Styles.html) determined learning style preference with respect to four different learning style axes; active-reflective, sensing-intuitive, visual-verbal and sequential-global. The influence of these factors on academic performance was investigated. Results: Two hundred and seventy students agreed to take part (75% of the cohort). 63% of the sample was female. There were 213 home non-graduates (entrants from the UK or European Union without a bachelor’s degree or higher), 14 home graduates (entrants from the UK or European Union with a bachelor’s degree or higher), 28 international non-graduates (entrants from outside the UK or European Union without a bachelor’s degree or higher) and 15 international graduates (entrants from outside the UK or European Union with a bachelor’s degree or higher). The majority of students were balanced learners (between 48% and 64% across four learning style axes). Any preferences were towards active, sensing, visual and sequential learning styles. Of the factors investigated in this study, learning styles were influenced by gender; females expressed a disproportionate preference for the reflective and visual learning styles. Academic performance was influenced by enrolment status; international graduates (95% confidence limits: 64–72%) outperformed all other student groups (home non graduates, 60–62%; international non graduates, 55–63%) apart from home graduates (57–69%). Conclusion: Our research has shown that the majority of optometry students have balanced learning styles and, from the factors studied, academic performance is only influenced by enrolment status. Although learning style questionnaires offer suggestions on how to improve learning efficacy, our findings indicate that current teaching methods do not need to be altered to suit varying learning style preferences as balanced learning styles can easily adapt to any teaching style (Learning Styles and Pedagogy in Post-16 Learning: A Systematic and Critical Review. London, UK: Learning and Skills Research Centre, 2004).