Retinal and choroidal thickness measurements using spectral domain optical coherence tomography in anterior and intermediate uveitis.

BACKGROUND: Macular edema is a common cause of visual loss at uveitic patients. The aim of our study was to investigate retinal and choroidal thickness at the macula in anterior (AU) and intermediate (IMU) uveitis and in healthy individuals using spectral domain optical coherence tomography (SD-OCT). METHODS: Case-control study of 21 patients with AU and 23 patients with IMU and 34 age-matched healthy controls was performed with Spectralis SD-OCT (Heidelberg Engineering, Germany). High resolution SD-OCT scans and macular mapping were applied for automated measurement of retinal thickness. Standardized, masked manual measurement of the choroidal thickness was performed in the center of the ETDRS fields on enhanced depth imaging (EDI) scans. Evaluation of central retinal subfield thickness, 3 mm and 6 mm perifoveal rings was performed in the corresponding ETDRS zones in patient groups. RESULTS: The mean central retinal subfield thickness was significantly higher in IMU (368.65 ± 115.88 µm, p = 0.0003), but not significantly different in AU (290.42 ± 26.37 µm p = 0.6617) compared to that of in controls (278.55 ± 18.31 µm). In both uveitis groups retina was significantly thicker in the 3 and 6 mm perifoveal rings than that of in controls (359 ± 15.24 µm in AU and 390.55 ± 70.90 µm in IMU vs 345,41 ± 15.28 µm in the control group, p = 0.0388 and p < 0.0001) in the 3 mm and (313.83 ± 16.63 µm in AU and 343.33 ± 57.29 µm in IMU vs 299 ± 13.82 µm in the control group, p = 0.0171 and p < 0.0001) in the 6 mm ring. Central choroidal thickness was 311.94 ± 60.48 µm in the control eyes, showed no significant difference in AU (312.61 ± 90.35 µm) and IMU (303.17 ± 93.66 µm) eyes, and was also similar at the perifoveal rings. CONCLUSION: Significant topographical changes could be detected in the macula of AU and IMU patients. Retinal thickness in the perifoveal rings was increased both in AU and IMU, but in the center only in IMU. Choroidal thickness seems to be unaffected by uveitis, even in the presence of macular edema, at least in the early stage of the inflammatory disease process.

Structure and dynamics of molecular networks: a novel paradigm of drug discovery: a comprehensive review.

Despite considerable progress in genome- and proteome-based high-throughput screening methods and in rational drug design, the increase in approved drugs in the past decade did not match the increase of drug development costs. Network description and analysis not only give a systems-level understanding of drug action and disease complexity, but can also help to improve the efficiency of drug design. We give a comprehensive assessment of the analytical tools of network topology and dynamics. The state-of-the-art use of chemical similarity, protein structure, protein-protein interaction, signaling, genetic interaction and metabolic networks in the discovery of drug targets is summarized. We propose that network targeting follows two basic strategies. The "central hit strategy" selectively targets central nodes/edges of the flexible networks of infectious agents or cancer cells to kill them. The "network influence strategy" works against other diseases, where an efficient reconfiguration of rigid networks needs to be achieved by targeting the neighbors of central nodes/edges. It is shown how network techniques can help in the identification of single-target, edgetic, multi-target and allo-network drug target candidates. We review the recent boom in network methods helping hit identification, lead selection optimizing drug efficacy, as well as minimizing side-effects and drug toxicity. Successful network-based drug development strategies are shown through the examples of infections, cancer, metabolic diseases, neurodegenerative diseases and aging. Summarizing >1200 references we suggest an optimized protocol of network-aided drug development, and provide a list of systems-level hallmarks of drug quality. Finally, we highlight network-related drug development trends helping to achieve these hallmarks by a cohesive, global approach.

Disordered proteins and network disorder in network descriptions of protein structure, dynamics and function: hypotheses and a comprehensive review.

During the last decade, network approaches became a powerful tool to describe protein structure and dynamics. Here we review the links between disordered proteins and the associated networks, and describe the consequences of local, mesoscopic and global network disorder on changes in protein structure and dynamics. We introduce a new classification of protein networks into 'cumulus-type', i.e., those similar to puffy (white) clouds, and 'stratus-type', i.e., those similar to flat, dense (dark) low-lying clouds, and relate these network types to protein disorder dynamics and to differences in energy transmission processes. In the first class, there is limited overlap between the modules, which implies higher rigidity of the individual units; there the conformational changes can be described by an 'energy transfer' mechanism. In the second class, the topology presents a compact structure with significant overlap between the modules; there the conformational changes can be described by 'multi-trajectories'; that is, multiple highly populated pathways. We further propose that disordered protein regions evolved to help other protein segments reach 'rarely visited' but functionally-related states. We also show the role of disorder in 'spatial games' of amino acids; highlight the effects of intrinsically disordered proteins (IDPs) on cellular networks and list some possible studies linking protein disorder and protein structure networks.

Contrast independence of dynamic random dot correlogram evoked VEP amplitude.

Dynamic random dot correlograms (DRDCs) are binocular stimuli that evoke a percept and a visual evoked potential (VEP) only in case of a mature and functional binocular system. DRDC-VEP is a method extensively used to study cortical binocularity in human infants and nonverbal children. Although the DRDC-VEP was invented 3 decades ago, neither the fundamental parameters, including contrast, of the stimulation nor the cerebral processing mechanisms have been clarified. The objective of the present study was to investigate the variability and detectability of adults' VEPs to DRDC under different stimulus contrast conditions. DRDCs were presented on the red and green channels of a computer monitor and were viewed with red-green goggles. The steady state DRDC-VEPs were recorded in healthy adult volunteers, and response reliability was assessed by the T(circ)(2) statistic. DRDC-VEP amplitude was independent of contrast, while VEP phases showed a weak correlation with contrast. Contrast invariance of DRDC-VEP amplitude suggests a very high contrast gain and dominant magnocellular input to the binocular correlation processing system.

Ageing as a price of cooperation and complexity: self-organization of complex systems causes the gradual deterioration of constituent networks.

The network concept is increasingly used for the description of complex systems. Here, we summarize key aspects of the evolvability and robustness of the hierarchical network set of macromolecules, cells, organisms and ecosystems. Listing the costs and benefits of cooperation as a necessary behaviour to build this network hierarchy, we outline the major hypothesis of the paper: the emergence of hierarchical complexity needs cooperation leading to the ageing (i.e. gradual deterioration) of the constituent networks. A stable environment develops cooperation leading to over-optimization, and forming an 'always-old' network, which accumulates damage, and dies in an apoptosis-like process. A rapidly changing environment develops competition forming a 'forever-young' network, which may suffer an occasional over-perturbation exhausting system resources, and causing death in a necrosis-like process. Giving a number of examples we demonstrate how cooperation evokes the gradual accumulation of damage typical to ageing. Finally, we show how various forms of cooperation and consequent ageing emerge as key elements in all major steps of evolution from the formation of protocells to the establishment of the globalized, modern human society.