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Weisenheim am Sand, Germany

Grueb M.,Villa im Lindengarten | Grueb M.,University of Tuebingen | Rohrbach J.M.,Villa im Lindengarten
European Journal of Ophthalmology

Purpose: Timolol is an effective and safe medication that is widely used in glaucoma treatment. Although it is known that it is quickly taken up by the cornea following topical administration and that the cornea exhibits β-adrenergic receptors, there are few studies available on the clinical impact of timolol on central corneal thickness (CCT). Methods: Twenty healthy subjects were tested in a double-blind, prospective, and randomized study. Intraocular pressure (IOP) and CCT were measured before and during administration of timolol 0.5% eyedrops over 28 days. Results: Administration of timolol 0.5% resulted in a reduction of IOP from an initial value of 16 ± 2 mm Hg to 13 ± 0 mm Hg (p<0.001, R2 = 0.7033) as well as an increase in CCT from 555 ± 11 μm from the time of the baseline examination to 567 ± 9 μm (p = 0.005, R2 = 0.8754), an increase of epithelial thickness from 53 ± 2 μm to 59 ± 3 μm (p<0.001, R2 = 0.5063), and an increase of stromal thickness from 494 ± 4 μm to 498 ± 9 μm (p = 0.045, R2 = 0.4352) after 9 days each. From day 10 on, a decrease in CCT (R2 = 0.6164), epithelial thickness (R2 = 0.2216), and stromal thickness (R2 = 0.2092) was observed. At the end, the values had returned toward the initial values measured (CCT 553 ± 8 μm, p = 0.391; epithelial thickness, 50 ± 2 μm, p = 0.214; and stromal thickness, 493 ± 8 μm, p = 0.483). In contrast, endothelial thickness did not vary following administration of timolol 0.5% (p = 0.727, R2 = 0.009). Conclusions: Topical administration of timolol 0.5% results in a reversible increase in CCT. These modest changes are unlikely to influence tonometry or clinical decision-making. © 2013 Wichtig Editore. Source

Reilmann R.,George Huntington Institute | Reilmann R.,University of Tuebingen | Leavitt B.R.,University of British Columbia | Ross C.A.,Johns Hopkins University
Movement Disorders

Huntington's disease (HD) is currently diagnosed based on the presence of motor signs indicating 99% "diagnostic confidence" for HD. Recent advances in the understanding of HD natural history and neurobiology indicate that disease-related brain changes begin at least 12 to 15 years before the formal diagnosis based on motor onset. Furthermore, subtle motor dysfunction, cognitive changes, and behavioral alterations are often seen before diagnosis made according to the current criteria. As disease-modifying treatments are developed, likely beginning therapy early will be desirable. We therefore suggest that expanded diagnostic criteria for HD should be adapted to better reflect the natural history of the disease, to enable the conduct of clinical trials in premanifest subjects targeting prevention of neurodegeneration, and to facilitate earlier symptomatic treatment. We propose a new set of criteria for HD diagnostic categories in the International Classification of Diseases that reflect our current understanding of HD natural history and pathogenesis. Based on defined criteria, for example, the Diagnostic Confidence Level and the Total Functional Capacity scales of the Unified Huntington's Disease Rating Scale, HD should be divided in the categories "genetically confirmed" with the subcategories "presymptomatic," "prodromal," and "manifest" and "not genetically confirmed" subdivided into "clinically at risk," "clinically prodromal," and "clinically manifest." 2014 International Parkinson and Movement Disorder Society . Source

Kilias A.,Aristotle University of Thessaloniki | Frisch W.,University of Tuebingen | Avgerinas A.,Aristotle University of Thessaloniki | Dunkl I.,University of Goettingen | And 2 more authors.
Austrian Journal of Earth Sciences

Geological mapping and detailed structural investigations combined with geochronological and stratigraphic data, as well as fissiontrack age dating carried out on the northern part of the Pelagonian basement and the adjacent Vardar/Axios sedimentary and metamorphic sequences in the Hellenic Alps (northwestern Greece and Former Yugoslavian Republic of Macedonia) allow us to reconstruct the geometry, kinematics and deformation history of the Pelagonian nappe pile during the Alpine orogeny. We distinguish seven deformational events (D Hp and D 1 to D 6). Deformation started in Middle to Late Jurassic time and was associated with inneroceanic P thrusting, ophiolite obduction, and NW to WNW-directed nappe stacking of the Lower and Upper Pelagonian unit (D 1). The lower unit was metamorphosed under greenschist to amphibolite facies conditions with relatively high pressures (T=450-620°C, P=8-12,5 kb). Blueschist-facies metamorphic assemblages (D HP, T=450-500°C, P>12,5 kb) are restricted to the boundary zone between both Pelagonian units. Transgressive Late Jurassic to Early Cretaceous shallow-water limestones and clastic sediments on top of the obducted ophiolites are probably related to extension and basin formation simultaneously with nappe stacking and metamorphism in the Pelagonian nappes beneath. Contractional tectonics with the same kinematics as during D 1 continued in Aptian-Albian time and was asso-1 ciated with intense retrogression (D 2, T=280-380°C, P=4-5 kb). Low-angle mylonitic extensional shear zones of low-grade metamorphism with top-to-NE sense of movement (D 3) developed simultaneously with basin formation and sedimentation of shallow-water limestones and flysch-like sediments in Late Cretaceous to Paleocene times. Intense imbrication under semi-ductile to brittle conditions of all tectonic units occurred during Paleocene to Eocene time with SW-directed movement towards the foreland (D 4). A large Pelagonian antiformal structure formed during D 4 shortening. In Oligocene to recent time, D 5 and D 6 created brittle low and highangle normal faults, respectively. Source

Floriddia E.,University of Tuebingen
Journal of visualized experiments : JoVE

Axons in the central nervous system (CNS) do not regenerate while those in the peripheral nervous system (PNS) do regenerate to a limited extent after injury (Teng et al., 2006). It is recognized that transcriptional programs essential for neurite and axonal outgrowth are reactivated upon injury in the PNS (Makwana et al., 2005). However the tools available to analyze neuronal gene regulation in vivo are limited and often challenging. The dorsal root ganglia (DRG) offer an excellent injury model system because both the CNS and PNS are innervated by a bifurcated axon originating from the same soma. The ganglia represent a discrete collection of cell bodies where all transcriptional events occur, and thus provide a clearly defined region of transcriptional activity that can be easily and reproducibly removed from the animal. Injury of nerve fibers in the PNS (e.g. sciatic nerve), where axonal regeneration does occur, should reveal a set of transcriptional programs that are distinct from those responding to a similar injury in the CNS, where regeneration does not take place (e.g. spinal cord). Sites for transcription factor binding, histone and DNA modification resulting from injury to either PNS or CNS can be characterized using chromatin immunoprecipitation (ChIP). Here, we describe a ChIP protocol using fixed mouse DRG tissue following axonal injury. This powerful combination provides a means for characterizing the pro-regeneration chromatin environment necessary for promoting axonal regeneration. Source

Insel N.,University of Tuebingen | Insel N.,University of Chicago | Poulsen C.J.,University of Tuebingen | Sturm C.,University of Stockholm | Ehlers T.A.,University of Tubingen
Journal of Geophysical Research: Atmospheres

The stable oxygen isotopic composition of precipitation (δ18Op) is used as a proxy for modern and past atmospheric, biologic, and surface processes. Although the physical processes that fractionate 18O in vapor are known, regional controls of δ18Op are not well understood. Here we present results from a limited-domain general circulation model (REMOiso) to quantify regional controls on modern (1976-1999) interannual and spatial variations of δ18Op across four Andean domains spanning 50° latitude. Results are compared to observed δ18Op from meteorological stations. Simulated annual amount-weighted mean δ18Op ranges between -4 and -7‰ (0-5°S), -8 and -20‰ (14°S-26°S), -4 and -8.5‰ (30°S-35°S), and -7 to -10‰ (45°S-50°S). Relationships between climate and δ18Op on interannual timescale vary along the Andes and are tied to changes in precipitation and large-scale dynamics. In the northern Andes, interannual variations in δ18Op are mainly associated with precipitation amounts driven by low-latitude sea surface temperature and Amazon Basin conditions. In the north central Andes, δ18Op correlates with precipitation amount and wind trajectory, which is related to the position of the Bolivian High. In the south central Andes, δ18Op variability is mainly influenced by precipitation amounts that are controlled by the position and strength of the westerlies. In the southern Andes, interannual δ18Op variability is linked to the intensification and weakening of the South Pacific High. The regional climate- δ18Op relationships are discussed in the context of pre-Quaternary sedimentary δ18O proxy records. Key Points Simulated annual amount-weighted mean d18O vary significantly along the AndesPrecipitation d18O is influenced by large-scale processes varying across regionsVapor trajectories are the dominant control on d18O in the central Andes ©2013. American Geophysical Union. All Rights Reserved. Source

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