Anodal transcranial direct current stimulation over S1 differentially modulates proprioceptive accuracy in young and old adults

Background: Proprioception is a prerequisite for successful motor control but declines throughout the lifespan. Brain stimulation techniques such as anodal transcranial direct current stimulation (a-tDCS) are capable of enhancing sensorimotor performance across different tasks and age groups. Despite such growing evidence for a restorative potential of tDCS, its impact on proprioceptive accuracy has not been studied in detail yet. Objective: This study investigated online effects of a-tDCS over S1 on proprioceptive accuracy in young (YA) and old healthy adults (OA). Methods: The effect of 15 min of a-tDCS vs. sham on proprioceptive accuracy was assessed in a cross-over, double blind experiment in both age groups. Performance changes were tested using an arm position matching task in a robotic environment. Electrical field (EF) strengths in the target area S1 and control areas were assessed based on individualized simulations. Results: a-tDCS elicited differential changes in proprioceptive accuracy and EF strengths in the two groups: while YA showed a slight improvement, OA exhibited a decrease in performance during a-tDCS. Stronger EF were induced in target S1 and control areas in the YA group. However, no relationship between EF strength and performance change was found. Conclusion: a-tDCS over S1 elicits opposing effects on proprioceptive accuracy as a function of age, a result that is important for future studies investigating the restorative potential of a-tDCS in healthy aging and in the rehabilitation of neurological diseases that occur at advanced age. Modeling approaches could help elucidate the relationship between tDCS protocols, brain structure and performance modulation

Circulating markers of arterial thrombosis and late-stage age-related macular degeneration: a case-control study.

PURPOSE: The aim of this study was to examine the relation of late-stage age-related macular degeneration (AMD) with markers of systemic atherothrombosis. METHODS: A hospital-based case-control study of AMD was undertaken in London, UK. Cases of AMD (n=81) and controls (n=77) were group matched for age and sex. Standard protocols were used for colour fundus photography and to classify AMD; physical examination included height, weight, history of or treatment for vascular-related diseases and smoking status. Blood samples were taken for measurement of fibrinogen, factor VIIc (FVIIc), factor VIIIc, prothrombin fragment F1.2 (F1.2), tissue plasminogen activator, and von Willebrand factor. Odds ratios from logistic regression analyses of each atherothrombotic marker with AMD were adjusted for age, sex, and established cardiovascular disease risk factors, including smoking, blood pressure, body mass index, and total cholesterol. RESULTS: After adjustment FVIIc and possibly F1.2 were inversely associated with the risk of AMD; per 1 standard deviation increase in these markers the odds ratio were, respectively, 0.62 (95% confidence interval 0.40, 0.95) and 0.71 (0.46, 1.09). None of the other atherothrombotic risk factors appeared to be related to AMD status. There was weak evidence that aspirin is associated with a lower risk of AMD. CONCLUSIONS: This study does not provide strong evidence of associations between AMD and systematic markers of arterial thrombosis, but the potential effects of FVIIc, and F1.2 are worthy of further investigation

Clinical disorders affecting mesopic vision

Vision in the mesopic range is affected by a number of inherited and acquired clinical disorders. We review these conditions and summarize the historical background, describing the clinical characteristics alongside the genetic basis and molecular biological mechanisms giving rise to rod and cone dysfunction relevant to twilight vision. The current diagnostic gold standards for each disease are discussed and curative and symptomatic treatment strategies are summarized

Isotonic Glycerol and Sodium Hyaluronate Containing Artificial Tear Decreases Conjunctivochalasis after One and Three Months: A Self-Controlled, Unmasked Study.

Dry eye complaints are ranked as the most frequent symptoms of patients visiting ophthalmologists. Conjunctivochalasis is a common dry eye disorder, which can cause an unstable tear film and ocular discomfort. The severe conjunctivochalasis characterized by high LId-Parallel COnjunctival Folds (LIPCOF) degree usually requires surgical intervention, where a conservative therapy would be highly desirable. Here we examined the efficacy of a preservative-free, inorganic salt-free unit-dose artificial tear, called Conheal containing isotonic glycerol and 0.015% sodium hyaluronate in a prospective, unmasked, self-controlled study involving 20 patients. The regular use of the glycerol/hyaluronate artificial tear in three months caused a significant improvement in the recorded parameters. Conjunctivochalasis decreased from a mean LIPCOF degree of 2.9 ± 0.4 on both eyes to 1.4 ± 0.6 on the right (median decrease of -2 points, 95% CI from -2.0 to -1.0), and to 1.4 ± 0.7 on the left eye (median decrease of -1 points, 95% CI from -2.0 to -1.0) (p<0.001 for both sides). The tear film breakup time (TFBUT) lengthened from 4.8 ± 1.9 seconds on both eyes to 5.9 ± 2.3 seconds (mean increase of 1.1 seconds, 95% CI from 0.2 to 2.0) and 5.7 ± 1.8 seconds (mean increase of 0.9 seconds, 95% CI from 0.3 to 1.5) on the right and left eyes, respectively (p(right eyes) = 0.020, p(left eyes) = 0.004). The corneal lissamine staining (Oxford Scheme grade) was reduced from 1.3 ± 0.6 on the right and 1.4 ± 0.6 on the left eye significantly (p<0.001) to 0.3 ± 0.4 and 0.2 ± 0.4 on the right and the left eyes. The Ocular Surface Disease Index (OSDI) questionnaire score indicating the subjective complaints of the patients also decreased from a mean value of 36.2 ± 25.3 to 15.6 ± 16.7 (p<0.001). In this study, the artificial tear, Conheal decreased the grade of the conjunctivochalasis significantly after one month of regular use already, from the LIPCOF degree 3, considered as indication of conjunctival surgery, to a LIPCOF degree 2 or lower requiring a conservative therapy. Our results raise the possibility that vision-related quality of life can be significantly improved by conservative therapies even in severe conjunctivochalasis

Myths and Methodologies: Reducing scientific design ambiguity in studies comparing sexes and/or menstrual cycle phases

In recent years, the increase in scientific literature exploring sex differences has been beneficial to both clinicians and allied health science professionals, although female athletes are still significantly under‐represented in sport and exercise science research. Women have faced exclusion throughout history though the complexities of sociocultural marginalization and biomedical disinterest in women's health. These complexities have contributed to challenges of studying women and examining sex differences. One underlying complexity to methodological design may be hormonal perturbations of the menstrual cycle. The biphasic responses of oestrogen and progesterone across the menstrual cycle significantly influence physiological responses, which contribute to exercise capacity and adaptation in women. Moreover, oral contraceptives add complexity through the introduction of varying concentrations of circulating exogenous oestrogen and progesterone, which may moderate physiological adaptations to exercise in a different manner to endogenous ovarian hormones. Thus, applied sport and exercise science research focusing on women remains limited, in part, by poor methodological design that does not define reproductive status. By highlighting specific differences between phases with regard to hormone perturbations and the systems that are affected, methodological inconsistencies can be reduced, thereby improving scientific design that will enable focused research on female athletes in sports science and evaluation of sex differences in responses to exercise. The aims of this review are to highlight the differences between endogenous and exogenous hormone profiles across a standard 28–32 day menstrual cycle, with the goal to improve methodological design for studies exploring sex differences, menstrual cycle phase differences and/or endogenous versus exogenous female sex hormones

Analysis of copy number variation at DMBT1 and age-related macular degeneration

BACKGROUND: DMBT1 is a gene that shows extensive copy number variation (CNV) that alters the number of bacteria-binding domains in the protein and has been shown to activate the complement pathway. It lies next to the ARMS2/HTRA1 genes in a region of chromosome 10q26, where single nucleotide variants have been strongly associated with age-related macular degeneration (AMD), the commonest cause of blindness in Western populations. Complement activation is thought to be a key factor in the pathogenesis of this condition. We sought to investigate whether DMBT1 CNV plays any role in the susceptibility to AMD. METHODS: We analysed long-range linkage disequilibrium of DMBT1 CNV1 and CNV2 with flanking single nucleotide polymorphisms (SNPs) using our previously published CNV and HapMap Phase 3 SNP data in the CEPH Europeans from Utah (CEU). We then typed a large cohort of 860 AMD patients and 419 examined age-matched controls for copy number at DMBT1 CNV1 and CNV2 and combined these data with copy numbers from a further 480 unexamined controls. RESULTS: We found weak linkage disequilibrium between DMBT1 CNV1 and CNV2 with the SNPs rs1474526 and rs714816 in the HTRA1/ARMS2 region. By directly analysing copy number variation, we found no evidence of association of CNV1 or CNV2 with AMD. CONCLUSIONS: We have shown that copy number variation at DMBT1 does not affect risk of developing age-related macular degeneration and can therefore be ruled out from future studies investigating the association of structural variation at 10q26 with AMD

C2 and CFB Genes in Age-Related Maculopathy and Joint Action with CFH and LOC387715 Genes

Background: Age-related maculopathy (ARM) is a common cause of visual impairment in the elderly populations of industrialized countries and significantly affects the quality of life of those suffering from the disease. Variants within two genes, the complement factor H (CFH) and the poorly characterized LOC387715 (ARMS2), are widely recognized as ARM risk factors. CFH is important in regulation of the alternative complement pathway suggesting this pathway is involved in ARM pathogenesis. Two other complement pathway genes, the closely linked complement component receptor (C2) and complement factor B (CFB), were recently shown to harbor variants associated with ARM. Methods/Principal Findings: We investigated two SNPs in C2 and two in CFB in independent case-control and family cohorts of white subjects and found rs547154, an intronic SNP in C2, to be significantly associated with ARM in both our case-control (P-value 0.00007) and family data (P-value 0.00001). Logistic regression analysis suggested that accounting for the effect at this locus significantly (P-value 0.002) improves the fit of a genetic risk model of CFH and LOC387715 effects only. Modeling with the generalized multifactor dimensionality reduction method showed that adding C2 to the two-factor model of CFH and LOC387715 increases the sensitivity (from 63% to 73%). However, the balanced accuracy increases only from 71% to 72%, and the specificity decreases from 80% to 72%. Conclusions/Significance: C2/CFB significantly influences AMD susceptibility and although accounting for effects at this locus does not dramatically increase the overall accuracy of the genetic risk model, the improvement over the CFH-LOC387715 model is statistically significant. © 2008 Jakobsdottir et al

The positive impact of red palm oil in school meals on vitamin A status: study in Burkina Faso

BACKGROUND: Vitamin A (VA) deficiency is widespread in sub-Saharan Africa and school-age children are a vulnerable group. In Burkina Faso, the production and consumption of red palm oil (RPO) is being promoted as a food supplement for VA. The objective of the study was to assess the impact on serum retinol of adding RPO to school lunch in two test zones of Burkina Faso. METHODS: Over one school year, 15 ml RPO was added to individual meals 3 times a week in selected primary schools in two sites. Serum retinol was measured with HPLC at baseline and exactly 12 months later to take account of seasonality. A simple pre-post test design was used in the Kaya area (north-central Burkina), where 239 pupils from 15 intervention schools were randomly selected for the evaluation. In Bogandé (eastern Burkina), 24 schools were randomised for the controlled intervention trial: 8 negative controls (G1) with only the regular school lunch; 8 positive controls (G2) where the pupils received a single VA capsule (60 mg) at the end of the school year; and 8 schools with RPO through the school year (G3). A random sample of 128 pupils in each school group took part in the evaluation. RESULTS: In Kaya, serum retinol went from 0.77 ± 0.37 μmol/L at baseline to 1.07 ± 0.40 μmol/L one year later (p < 0.001). The rate of low serum retinol (<0.7 μmol/L) declined from 47.2% to 13.1%. In Bogandé, serum retinol increased significantly (p < 0.001) only in the capsule and RPO groups, going from 0.77 ± 0.28 to 0.98 ± 0.33 μmol/L in the former, and from 0.82 ± 0.3 to 0.98 ± 0.33 μmol/L in the latter. The rate of low serum retinol went from 46.1 to 17.1% in the VA capsule group and from 40.4% to 14.9% in the RPO group. VA-deficient children benefited the most from the capsule or RPO. Female sex, age and height-for-age were positively associated with the response to VA capsules or RPO. CONCLUSION: RPO given regularly in small amounts appears highly effective in the reduction of VA deficiency. RPO deserves more attention as a food supplement for VA and as a potential source of rural income in Sahelian countries

Sulforaphane promotes ER stress, autophagy and cell death: implications for cataract surgery

Posterior capsule opacification (PCO) commonly develops following cataract surgery and is a wound-healing response that can ultimately lead to secondary visual loss. Improved management of this problem is required. The isothiocyanate, sulforaphane (SFN) is reported to exert cytoprotective and cytotoxic actions and the latter may be exploited to treat/prevent PCO. SFN concentrations of 10µM and above significantly impaired wound-healing in a human lens capsular bag model. A similar pattern of response was also seen with a human lens cell line, FHL124. SFN treatment promoted increased expression of ER stress genes, which also corresponded with protein expression. Evidence of autophagy was observed in response to SFN as determined by increased LC3-II levels and detection of autophagic vesicles. This response was disrupted by established autophagy inhibitors chloroquine and 3-MA. SFN was found to promote MAPK signaling and inhibition of ERK activation using U0126 prevented SFN induced LC3-II elevation and vesicle formation. SFN also significantly increased levels of reactive oxygen species. Taken together, our findings suggest that SFN is capable of reducing lens cell growth and viability and thus could serve as a putative therapeutic agent for PCO