Identification and molecular characterisation of a homozygous missense mutation in the ADAMTS10 gene in a patient with Weill-Marchesani syndrome

Weill-Marchesani syndrome is a rare disorder of the connective tissue. Functional variants in ADAMTS10 are associated with Weill-Marchesani syndrome-1. We identified a homozygous missense mutation, c.41T>A, of the ADAMTS10 gene in a 19-year-old female with typical symptoms of WMS1: proportionate short stature, brachydactyly, joint stiffness, and microspherophakia. The ADAMTS10 missense mutation was analysed in silico, with conflicting results as to its effects on protein function, but it was predicted to affect the leader sequence. Molecular characterisation in HEK293 Ebna cells revealed an intracellular mis-targeting of the ADAMTS10 protein with a reduced concentration of the polypeptide in the endoplasmic reticulum. A large reduction in glycosylation of the cytoplasmic fraction of the mutant ADAMTS10 protein versus the wild-type protein and a lack of secretion of the mutant protein are also evident in our results.In conclusion, we identified a novel missense mutation of the ADAMTS10 gene and confirmed the functional consequences suggested by the in silico analysis by conducting molecular studies

Weghaupt H. Contrast acuity in cataracts of different morphology and association to self-reported visual function. Invest Ophthalmol Vis Sci

PURPOSE. To evaluate the relationship between contrast acuity at declining contrast levels and the type and density of lens opacity in cataract. METHODS. Contrast acuity at declining contrast levels was determined with the Holladay Contrast Acuity Test, in relation to the type and density of age-related cataract in 180 patients with bilateral cataract and 20 control subjects with normal macular function. Cataracts were graded according to the Lens Opacities Classification System (LOCS) III of nuclear color (NC), nuclear opalescence (NO), cortical (C), and posterior subcapsular (P) cataract. Best-corrected visual acuity and near contrast acuity were determined in randomized order monocularly in both eyes. Visual difficulties in everyday life were evaluated, using the VF-14 questionnaire and the Cataract Symptom Score. RESULTS. The contrast-dependent effect of cataract on contrast acuity was statistically significant (P Ͻ 0.001; two-way ANOVA). In the comparison of early, intermediate, and advanced nuclear, nuclear-cortical, and posterior subcapsular cataracts (PSCs), significantly reduced contrast acuity scores were found for the PSC groups (P Ͻ 0.001). Comparison of nuclear and nuclear-cortical cataracts showed the contrast acuity scores to be comparable at all contrast levels (P Ͼ 0.05). High correlation coefficients were found between the LOCS III P score and the contrast acuity measurements (r ϭ 0.77-0.84; P Ͻ 0.001). In contrast, the correlation coefficients of the NO, NC, and C scores were considerably lower (r ϭ 0.45-0.66; P Ͻ 0.001). High correlation coefficients were also found between the contrast acuity measurements and self-reported functional vision. CONCLUSIONS. The statistically significant, contrast-dependent effect of cataract on contrast acuity supports the clinical relevance of recording visual acuity at low contrast levels in patients with age-related cataract. Particularly, the severity of PSC has a strong influence on the impairment of contrast acuity. Contrast acuity corresponded closely to the self-reported visual difficulties in everyday life. (Invest Ophthalmol Vis Sci. 2006; 47:5412-5422 As a standardized procedure, high-contrast VA measurements are based on the ability to discriminate standardized optotypes of logarithmically decreasing print size. 14 -16 Even though VA is the main outcome variable of many clinical studies, high-contrast black optotypes on white background cannot represent real-world vision. This may be one of the reasons why self-reported functional vision reflects patients' satisfaction with visual performance better than high-contrast VA alone. 12 Particularly, when considering day and night driving, contrast sensitivity is often used in clinical studies for evaluating visual function, because impairment in real-world visual performance is better predicted by a contrast-sensitivity test than by high-contrast VA measurements. Because cataract morphologies directly influence the optical quality of the retinal image, clinically relevant differences between nuclear, nuclear-cortical, and posterior subcapsular cataracts (PSCs) have been observed for the functional vision VF-14 score and reading performance in previous studies: both were significantly reduced in patients with PSCs. PATIENTS AND METHODS The present study was conducted at the Department of Ophthalmology, Medical University of Vienna, Austria, according to the tenets of the Declaration of Helsinki. One-hundred-eighty patients with bilateral cataract and 20 normalsighted control subjects (mean age Ϯ SD: 66.9 Ϯ 9.2 years; 400 eyes) were included in the study. Exclusion criteria were a history of ocular disease, intraocular surgery, laser treatment, glaucoma, diabetic retinopathy, amblyopia, and age-related macular degeneration. In the control group, only participants without ocular disease and full VA (logMAR 0.0 or better) were included

Impairment of visual acuity and reading performance and the relationship with cataract type and density. Invest Ophthalmol Vis Sci.

PURPOSE. To evaluate the association between the density of nuclear, cortical, and posterior subcapsular lens opacities and visual impairment in patients with cataract. METHODS. In 80 patients, visual acuity and reading performance were evaluated 1 day before and 4 weeks after cataract surgery. Cataracts were categorized and graded according to the Lens Opacities Classification System (LOCS) III of nuclear color (NC), nuclear opalescence (NO), cortical (C), and posterior subcapsular cataract (P). A multiple linear regression analysis and partial correlation coefficients were calculated. Data were also checked for significant pre-and postoperative differences in visual performance related to cataract grading. RESULTS. In the multiple linear regression analysis, significant associations were found between the improvement in visual acuity and reading performance after cataract surgery and the NC, NO, and P scores (P Ͻ 0.001); no significant association was found for the C score (P Ͼ 0.05). High partial correlation coefficients were found between the P score and the preoperative visual acuity (r ϭ 0.6; P Ͻ 0.001), reading acuity (r ϭ 0.74; P Ͻ 0.001), and maximum reading speed (MRS; r ϭ Ϫ0.77; P Ͻ 0.001). Significant but lower partial correlation coefficients were found for the NO score. No significant partial correlation coefficients were found for the NC and C score. Significant pre-and postoperative differences in MRS were found in patients with P scores Ն3 or NO and NC scores Ն5, representing functionally relevant impairment. CONCLUSIONS. A strong association was found between visual impairment in patients with cataract and the severity of posterior subcapsular cataract (PSC) and nuclear opacity. Particularly in patients with PSC, deficits in reading performance significantly increased. The functionally relevant deficits in patients with P scores Ն3 or NO and NC scores Ն5, should be carefully considered for planning cataract surgery or visual rehabilitation. (Invest Ophthalmol Vis Sci

MASMICRO micro-/nano-materials processing, analysis, inspection and materials knowledge management

A main goal of the 'Material Innovation and Testing' within MASMICRO is identification of the miniature/micro-materials which are formable, development of new materials for forming and machining, development of an integrated material-testing system, and study of material properties for design/analysis applications. Examples of collaborative work and results are presented regarding the processing of functional electrospun polymer micro-/nano-fibre structures and the characterization of their interface properties with tribological testing. By means of Optical Coherence Tomography, a non-destructive inspection approach for these micro-/nano-structured webs was developed and it is also documented in the paper. Further, an application example of Artifical Neural Networks (ANNs) is given, concerning the modelling of nanofibres material behaviour under tensile testing. It is shown how Artificial Intelligence approaches (Knowledge Based Systems - KBS and ANNs) can support, significantly, the representation and processing of materials' knowledge of both, symbolic type in the case of KBS and algorithmic type in the case of ANNs, for the cases dealt within the MASMICRO

Individuelle Folgen von Arbeitslosigkeit und Berufsnot - Entlastungen durch sportliche Aktivitaeten? Ergebnisse einer empirischen Untersuchung ; Projektabschlussbericht

SIGLEUuStB Koeln(38)-880106435 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman