Novel TULP1 mutation causing leber congenital amaurosis or early onset retinal degeneration

PURPOSE: To report a large, consanguineous Algerian family affected with Leber congenital amaurosis (LCA) or early-onset retinal degeneration (EORD). METHODS: All accessible family members underwent a complete ophthalmic examination, and blood was obtained for DNA extraction. Homozygosity mapping was performed with markers flanking 12 loci associated with LCA. The 15 exons of TULP1 were sequenced. RESULTS: Seven of 30 examined family members were affected, including five with EORD and two with LCA. All patients had nystagmus, hemeralopia, mild myopia, and low visual acuity without photophobia. Fundus features were variable among EORD patients: typical spicular retinitis pigmentosa or clumped pigmented retinopathy with age-dependent macular involvement. A salt-and-pepper retinopathy with midperipheral retinal pigment epithelium (RPE) atrophy was present in the older patients with LCA, whereas the retina appeared virtually normal in the younger ones. Both scotopic and photopic electroretinograms were nondetectable. Fundus imaging revealed a perifoveal ring of increased fundus autofluorescence (FAF) in the proband, and optical coherence tomography disclosed a thinned retina, mainly due to photoreceptor loss. Linkage analysis identified a region of homozygosity on chromosome 6, region p21.3, and mutation screening revealed a novel 6-base in-frame duplication, in the TULP1 gene. CONCLUSIONS: Mutation in the TULP1 gene is a rare cause of LCA/EORD, with only 14 mutations reported so far. The observed intrafamilial phenotypic variability could be attributed to disease progression or possibly modifier alleles. This study provides the first description of FAF and quantitative reflectivity profiles in TULP1-related retinopathy.

Ethnic differences in macular pigment density and distribution

PURPOSE: Many epidemiologic studies suggest a number of risk factors that may be associated with progression of age-related maculopathy (ARM). In this study, the authors investigate ethnic differences in macular pigment density (MPD) and macular pigment (MP) distribution. METHODS: Inclusion criteria were healthy subjects, aged 35 to 49 years, visual acuity >or=20/20, race ethnicity white non-Hispanic (WNH) or African. All subjects underwent the following examinations: best-corrected ETDRS visual acuity (VA), measurements of MPD, and spatial distribution of MP with a modified confocal scanning laser ophthalmoscope according to a standard protocol. MPD maps were calculated from autofluorescence images recorded at 488 nm and 514 nm. Central macular pigment density (MPDc) was quantified from MPD maps within 0.5 degrees around the center of the fovea. RESULTS: In total, 118 healthy subjects (61 women, 57 men) aged 35 to 49 years (mean, 42.5 +/- 3.6 years) were recruited for the study. Sixty-seven healthy subjects were WNH and 51 were African. Visual acuity ranged from 20/20 to 20/16 in the study eye. Significant differences were found among MPDc between the group of WNH (MPDc, 0.36 +/- 0.13 density units [DU]; P < 0.0001) and African subjects (MPDc, 0.59 +/- 0.14 DU). A parafoveal ring was significantly more frequent in African subjects than in WNH subjects (86% [African] vs. 68% [WNH]; P < 0.0001). CONCLUSIONS: This study demonstrates that ethnicity plays a role in MPD values and in MP distribution. The association of different distribution patterns and their relevance as possible prognostic factors for diseases leading to oxidative retinal damage requires further studies.

EFFECT OF AGING ON MACULAR FEATURES OF X-LINKED RETINOSCHISIS ASSESSED WITH OPTICAL COHERENCE TOMOGRAPHY

X-linked retinoschisis (XLRS) is one of the most common causes of macular degeneration in young men. The purpose of this study was to use optical coherence tomography combined with ophthalmoscopy to study the effects of aging on the morphologic changes associated with XLRS.

Macular edema: Miscellaneous

Abstract. This article provides the reader with practical information to be applied to the various remaining causes of macular edema. Some macular edemas linked to ocular diseases like radiotherapy after ocular melanomas remained of poor functional prognosis due to the primary disease. On the contrary, macular edemas occurring after retinal detachment or after some systemic or local treatment use are often temporary. Macular edema associated with epiretinal membranes or vitreomacular traction is the main cause of poor functional recovery. However, the delay to observe a significant improvement of vision after surgery should be long, as usually observed in tractional myopic vitreoschisis. Finally, some circumstances of macular edemas such as hemangiomas or macroaneurysms should be treated, if symptomatic, with the treatments currently used in diabetic macular edema or exudative macular degeneration.

Macular edema. Miscellaneous

This chapter provides the reader with practical information to be applied to the various remaining causes of macular edema. Some clinical cases of macular edema linked to ocular diseases like postradiotherapy for ocular melanomas remained of poor functional prognosis due to the primary disease. On the contrary, macular edema occurring after retinal detachment or after diverse systemic or local treatment use is often temporary. Macular edema associated with epiretinal membranes or vitreomacular traction is the main cause of poor functional recovery. In other cases, as in tractional myopic vitreoschisis, the delay to observe a significant improvement of the vision after surgery should be long. Finally, macular edema associated with hemangiomas or macroaneurysms should be treated, if symptomatic, using the same current treatment as in diabetic macular edema or exudative macular degeneration.

Impaired endothelial progenitor cell function predicts age-dependent carotid intimal thickening

OBJECTIVES: We investigated whether qualitative or quantitative alterations of the endothelial progenitor cell (EPC) pool predict age-related structural vessel wall changes. BACKGROUND: We have previously shown that age-related endothelial dysfunction is accompanied by qualitative rather than quantitative changes of EPCs. Animal studies suggest that impaired EPC functions lead to accelerated arterial intimal thickening. METHODS: Intima-media thickness (IMT) was measured in the common carotid artery in our previously published groups of younger (25 +/- 1 years, n = 20) and older (61 +/- 2 years, n = 20) healthy non-smoking volunteers without arterial hypertension, hypercholesterolemia, and diabetes mellitus. Endothelial progenitor cells (EPCs, KDR(+)/CD34(+) and KDR(+)/CD133(+)) were counted in peripheral blood using flow cytometry. In ex vivo expanded EPCs, the function was determined as chemotaxis to VEGF, proliferation, and survival. RESULTS: We observed thicker IMT in older as compared to younger subjects (0.68 +/- 0.03 mm Vs. 0.48 +/- 0.02 mm, P < 0.001). Importantly, there were significant inverse univariate correlations between IMT, EPC chemotaxis, and survival (r = -0.466 P < 0.05; r = -0.463, P < 0.01). No correlation was observed with numbers of circulating EPCs. Multivariate regression analysis revealed that age, mean arterial pressure and migration of EPCs were independent predictors of IMT (R (2 )= 0.58). CONCLUSION: Impaired EPC function may lead to accelerated vascular remodeling due to chronic impairment of endothelial maintenance.

Age-dependent decrease in 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) activity in hypertensive patients

BACKGROUND: The prevalence of arterial hypertension lacking a defined underlying cause increases with age. Age-related arterial hypertension is insufficiently understood, yet known characteristics suggest an aldosterone-independent activation of the mineralocorticoid receptor. Therefore, we hypothesized that 11beta-HSD2 activity is age-dependently impaired, resulting in a compromised intracellular inactivation of cortisol (F) with F-mediated mineralocorticoid hypertension. METHODS: Steroid hormone metabolites in 24-h urine samples of 165 consecutive hypertensive patients were analyzed for F and cortisone (E), and their TH-metabolites tetrahydro-F (THF), 5alphaTHF, TH-deoxycortisol (THS), and THE by gas chromatography-mass spectroscopy. Apparent 11beta-HSD2 and 11beta-hydroxylase activity and excretion of F metabolites were assessed. RESULTS: In 72 female and 93 male patients aged 18-84 years, age correlated positively with the ratios of (THF + 5alphaTHF)/THE (P = 0.065) and F/E (P < 0.002) suggesting an age-dependent reduction in the apparent 11beta-HSD2 activity, which persisted (F/E; P = 0.020) after excluding impaired renal function. Excretion of F metabolites remained age-independent most likely as a consequence of an age-dependent diminished apparent 11beta-hydroxylase activity (P = 0.038). CONCLUSION: Reduced 11beta-HSD2 activity emerges as a previously unrecognized risk factor contributing to the rising prevalence of arterial hypertension in elderly. This opens new perspectives for targeted treatment of age-related hypertension.

Does Age Matter? Semantic Memory in Healthy Young and Elderly Adults

Background: Semantic memory processes have been well described in literature. However, the available findings are mostly based on relatively young subjects and concrete word material (e.g. tree). Comparatively little information exists about semantic memory for abstract words (e.g. mind) and possible age related changes in semantic retrieval. In this respect, we developed a paradigm that is useful to investigate the implicit (i.e. attentionindependent) access to concrete and abstract semantic memory. These processes were then compared between young and elderly healthy subjects. Methods: A well established tool for investigating semantic memory processes is the semantic priming paradigm, which consists both of semantically unrelated and related word pairs. In our behavioral task these noun-noun word pairs were further divided into concrete, abstract and matched pronounceable non-word conditions. With this premise, the young and elderly participants performed a lexical decision task: they were asked to press a choice of two buttons as an indication for whether the word pair contained a non-word or not. In order to minimize controlled (i.e. attention-dependent) retrieval strategies, a short stimulus onset asynchrony (SOA) of 150ms was set. Reaction time (RT) changes and accuracy to related and unrelated words (priming effect) in the abstract vs. concrete condition (concreteness effect) were the dependent variables of interest. Results and Discussion: Statistical analysis confirmed both a significant priming effect (i.e. shorter RTs in semantically related compared to unrelated words) and a concreteness effect (i.e. RT decrease for concrete compared to abstract words) in the young and elderly subjects. There was no age difference in accuracy. The only age effect was a commonly known general slowing in RT over all conditions. In conclusion, age is not a critical factor in the implicit access to abstract and concrete semantic memory.

Image-based biomechanical assessment of vertebral body and intervertebral disc in the human lumbar spine

Life expectancy continuously increases but our society faces age-related conditions. Among musculoskeletal diseases, osteoporosis associated with risk of vertebral fracture and degenerative intervertebral disc (IVD) are painful pathologies responsible for tremendous healthcare costs. Hence, reliable diagnostic tools are necessary to plan a treatment or follow up its efficacy. Yet, radiographic and MRI techniques, respectively clinical standards for evaluation of bone strength and IVD degeneration, are unspecific and not objective. Increasingly used in biomedical engineering, CT-based finite element (FE) models constitute the state-of-art for vertebral strength prediction. However, as non-invasive biomechanical evaluation and personalised FE models of the IVD are not available, rigid boundary conditions (BCs) are applied on the FE models to avoid uncertainties of disc degeneration that might bias the predictions. Moreover, considering the impact of low back pain, the biomechanical status of the IVD is needed as a criterion for early disc degeneration. Thus, the first FE study focuses on two rigid BCs applied on the vertebral bodies during compression test of cadaver vertebral bodies, vertebral sections and PMMA embedding. The second FE study highlights the large influence of the intervertebral disc’s compliance on the vertebral strength, damage distribution and its initiation. The third study introduces a new protocol for normalisation of the IVD stiffness in compression, torsion and bending using MRI-based data to account for its morphology. In the last study, a new criterion (Otsu threshold) for disc degeneration based on quantitative MRI data (axial T2 map) is proposed. The results show that vertebral strength and damage distribution computed with rigid BCs are identical. Yet, large discrepancies in strength and damage localisation were observed when the vertebral bodies were loaded via IVDs. The normalisation protocol attenuated the effect of geometry on the IVD stiffnesses without complete suppression. Finally, the Otsu threshold computed in the posterior part of annulus fibrosus was related to the disc biomechanics and meet objectivity and simplicity required for a clinical application. In conclusion, the stiffness normalisation protocol necessary for consistent IVD comparisons and the relation found between degeneration, mechanical response of the IVD and Otsu threshold lead the way for non-invasive evaluation biomechanical status of the IVD. As the FE prediction of vertebral strength is largely influenced by the IVD conditions, this data could also improve the future FE models of osteoporotic vertebra.

The effect of age and time perspective on implicit motives

People differ in how open-ended or limited they perceive their future. We argue that individual differences in future time perspective affect the activation of implicit motives. Perceiving the time remaining for the satisfaction of one’s motives as limited should be associated with a higher activation of these motives than perceiving one’s future as more open-ended. Given that future time perspective decreases across adulthood, older adults should score higher on implicit motives than younger adults. This hypothesis was supported in a study with young (n = 53, age M = 25.60 years) and older adults (n = 55, age M = 68.05 years). Additionally, an experimental manipulation of future time perspective showed that age-related differences in implicit motives are influenced by future time perspective. These findings demonstrate that future time perspective is an important factor to explain the strength of motives.

Wanting to Get More or Protecting One's Assets: Age-Differential Effects of Gain Versus Loss Perceptions on the Willingness to Engage in Collective Action

OBJECTIVES: The present research examined motivational differences across adulthood that might contribute to age-related differences in the willingness to engage in collective action. Two experiments addressed the role of gain and loss orientation for age-related differences in the willingness to engage in collective action across adulthood. METHOD: In Experiment 1, N = 169 adults (20-85 years) were confronted with a hypothetical scenario that involved either an impending increase or decrease of health insurance costs for their respective age group. In Experiment 2, N = 231 adults (18-83 years) were asked to list an advantage or disadvantage they perceived in being a member of their age group. Subsequently, participants indicated their willingness to engage in collective action on behalf of their age group. RESULTS: Both experiments suggest that, with increasing age, people are more willing to engage in collective action when they are confronted with the prospect of loss or a disadvantage. DISCUSSION: The findings highlight the role of motivational processes for involvement in collective action across adulthood. With increasing age, (anticipated) loss or perceived disadvantages become more important for the willingness to participate in collective action.

Changes of olfactory abilities in relation to age: odor identification in more than 1400 people aged 4 to 80 years

The currently presented large dataset (n = 1,422) consists of results that have been assembled over the last 8 years at science fairs using the 16-item odor identification part of the "Sniffin' Sticks". In this context, the focus was on olfactory function in children; in addition before testing, we asked participants to rate their olfactory abilities and the patency of the nasal airways. We reinvestigated some simple questions, e.g., differences in olfactory odor identification abilities in relation to age, sex, self-ratings of olfactory function and nasal patency. Three major results evolved: first, consistent with previously published reports, we found that identification scores of the youngest and the oldest participants were lower than the scores obtained by people aged 20-60. Second, we observed an age-related increase in the olfactory abilities of children. Moreover, the self-assessed olfactory abilities were related to actual performance in the smell test, but only in adults, and self-assessed nasal patency was not related to the "Sniffin' Sticks" identification score.