Ocular manifestations in Gorlin-Goltz syndrome

Background: Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome, is a rare genetic disorder that is transmitted in an autosomal dominant manner with complete penetrance and variable expressivity. It is caused in 85% of the cases with a known etiology by pathogenic variants in the PTCH1 gene, and is characterized by a wide range of developmental abnormalities and a predisposition to multiple neoplasms. The manifestations are multiple and systemic and consist of basal cell carcinomas in various regions, odontogenic keratocistic tumors and skeletal anomalies, to name the most frequent. Despite the scarce medical literature on the topic, ocular involvement in this syndrome is frequent and at the level of various ocular structures. Our study focuses on the visual apparatus and its annexes in subjects with this syndrome, in order to better understand how this syndrome affects the ocular system, and to evaluate with greater accuracy and precision the nature of these manifestations in this group of patients. Results: Our study confirms the presence of the commonly cited ocular findings in the general literature regarding the syndrome [hypertelorism (45.5%), congenital cataract (18%), nystagmus (9%), colobomas (9%)] and highlights strabismus (63% of the patients), epiretinal membranes (36%) and myelinated optic nerve fiber layers (36%) as the most frequent ophthalmological findings in this group of patients. Conclusions: The presence of characteristic and frequent ocular signs in the Gorlin- Goltz syndrome could help with the diagnostic process in subjects suspected of having the syndrome who do not yet have a diagnosis. The ophthalmologist has a role as part of a multidisciplinary team in managing these patients. The ophthalmological follow-up that these patients require, can allow, if necessary, a timely therapy that could improve the visual prognosis of such patients

Vitamin D Attenuates Oxidative Damage and Inflammation in Retinal Pigment Epithelial Cells

Age-related macular degeneration (AMD), the most common visual disorder in elderly people, is characterized by the formation of deposits beneath the retinal pigment epithelium (RPE) and by dysfunction of RPE and photoreceptor cells. The biologically active form of vitamin D, 1,25-(OH)2D3 (VITD), is categorized as a multifunctional steroid hormone that modulates many transcriptional processes of different genes and is involved in a broad range of cellular functions. Epidemiological and genetic association studies demonstrate that VITD may have a protective role in AMD, while single nucleotide polymorphisms in the vitamin D metabolism gene (CYP24A1) increase the risk of AMD. However, the functional mechanisms of VITD in AMD are not fully understood. In the current study, we investigated the impact of VITD on H2O2-induced oxidative stress and inflammation in human RPE cells. We demonstrate that exposure to H2O2 caused significantly reduced cell viability, increased production of reactive oxygen species (ROS), lowered expression of antioxidant enzymes and enhanced inflammation. VITD exposure notably counteracted the above H2O2-induced effects. Our data suggest that VITD protects the RPE from oxidative damage and elucidate molecular mechanisms of VITD deficiency in the development of AMD

Clinical and biochemical response to neridronate treatment in a patient with osteoporosis-pseudoglioma syndrome (OPPG)

Osteoporosis-pseudoglioma syndrome (OPPG) is a rare autosomal recessive syndrome characterized by juvenile-onset osteoporosis and ocular abnormalities due to a low-density lipoprotein receptor-related protein 5 (LRP5) gene mutation. Treatment with bisphosphonates, particularly with pamidronate and risedronate, has been reported to be of some efficacy in this condition. We report on a patient with OPPG due to an LRP5 gene mutation, who showed an encouraging response after a 36-month period of neridronate therapy. We report a case of a patient treated with bisphosphonates. Bisphosphonates should be administered in OPPG patients as a first-line therapy during early childhood

A New Geometric Approach to Latent Topic Modeling and Discovery

A new geometrically-motivated algorithm for nonnegative matrix factorization is developed and applied to the discovery of latent "topics" for text and image "document" corpora. The algorithm is based on robustly finding and clustering extreme points of empirical cross-document word-frequencies that correspond to novel "words" unique to each topic. In contrast to related approaches that are based on solving non-convex optimization problems using suboptimal approximations, locally-optimal methods, or heuristics, the new algorithm is convex, has polynomial complexity, and has competitive qualitative and quantitative performance compared to the current state-of-the-art approaches on synthetic and real-world datasets.Comment: This paper was submitted to the IEEE International Conference on Acoustics, Speech and Signal Processing (ICASSP) 2013 on November 30, 201

Detection of amblyopia utilizing generated retinal reflexes

Investigation confirmed that GRR images can be consistently obtained and that these images contain information required to detect the optical inequality of one eye compared to the fellow eye. Digital analyses, electro-optical analyses, and trained observers were used to evaluate the GRR images. Two and three dimensional plots were made from the digital analyses results. These plotted data greatly enhanced the GRR image content, and it was possible for nontrained observers to correctly identify normal vs abnormal ocular status by viewing the plots. Based upon the criteria of detecting equality or inequality of ocular status of a person's eyes, the trained observer correctly identified the ocular status of 90% of the 232 persons who participated in this program

Theory of Reciprocating Contact for Viscoelastic Solids

A theory of reciprocating contacts for linear viscoelastic materials is presented. Results are discussed for the case of a rigid sphere sinusoidally driven in sliding contact with a viscoelastic half-space. Depending on the size of the contact, the frequency and amplitude of the reciprocating motion, and on the relaxation time of the viscoelastic body, we establish that the contact behavior may range from the steady-state viscoelastic solution, in which traction forces always oppose the direction of the sliding rigid punch, to a more elaborate trend, never observed before, which is due to the strong interaction between different regions of the path covered during the reciprocating motion. Practical implications span a number of applications, ranging from seismic engineering to biotechnology.Comment: 8 pages, 5 figures, accepted for publication on Physical Review E, March 22, 201

Perspectives on the revised Ghent criteria for the diagnosis of Marfan syndrome

Three international nosologies have been proposed for the diagnosis of Marfan syndrome (MFS): the Berlin nosology in 1988; the Ghent nosology in 1996 (Ghent-1); and the revised Ghent nosology in 2010 (Ghent-2). We reviewed the literature and discussed the challenges and concepts of diagnosing MFS in adults. Ghent-1 proposed more stringent clinical criteria, which led to the confirmation of MFS in only 32%-53% of patients formerly diagnosed with MFS according to the Berlin nosology. Conversely, both the Ghent-1 and Ghent-2 nosologies diagnosed MFS, and both yielded similar frequencies of MFS in persons with a causative FBN1 mutation (90% for Ghent-1 versus 92% for Ghent-2) and in persons not having a causative FBN1 mutation (15% versus 13%). Quality criteria for diagnostic methods include objectivity, reliability, and validity. However, the nosology-based diagnosis of MFS lacks a diagnostic reference standard and, hence, quality criteria such as sensitivity, specificity, or accuracy cannot be assessed. Medical utility of diagnosis implies congruency with the historical criteria of MFS, as well as with information about the etiology, pathogenesis, diagnostic triggers, prognostic triggers, and potential complications of MFS. In addition, social and psychological utilities of diagnostic criteria include acceptance by patients, patient organizations, clinicians and scientists, practicability, costs, and the reduction of anxiety. Since the utility of a diagnosis or exclusion of MFS is context-dependent, prioritization of utilities is a strategic decision in the process of nosology development. Screening tests for MFS should be used to identify persons with MFS. To confirm the diagnosis of MFS, Ghent-1 and Ghent-2 perform similarly, but Ghent-2 is easier to use. To maximize the utility of the diagnostic criteria of MFS, a fair and transparent process of nosology development is essential

Minimum Number of Probes for Brain Dynamics Observability

In this paper, we address the problem of placing sensor probes in the brain such that the system dynamics' are generically observable. The system dynamics whose states can encode for instance the fire-rating of the neurons or their ensemble following a neural-topological (structural) approach, and the sensors are assumed to be dedicated, i.e., can only measure a state at each time. Even though the mathematical description of brain dynamics is (yet) to be discovered, we build on its observed fractal characteristics and assume that the model of the brain activity satisfies fractional-order dynamics. Although the sensor placement explored in this paper is particularly considering the observability of brain dynamics, the proposed methodology applies to any fractional-order linear system. Thus, the main contribution of this paper is to show how to place the minimum number of dedicated sensors, i.e., sensors measuring only a state variable, to ensure generic observability in discrete-time fractional-order systems for a specified finite interval of time. Finally, an illustrative example of the main results is provided using electroencephalogram (EEG) data.Comment: arXiv admin note: text overlap with arXiv:1507.0720