Morbus Darier und Depression - besteht eine genetische Verbindung?: Übersicht und klinischer Fall

Zusammenfassung: Der Morbus Darier ist eine seltene Hauterkrankung, die autosomal-dominant vererbt wird und durch eine Mutation im SERCA (sarco/endoplasmatic reticulum calcium transporter)-2-Gen verursacht wird. In einigen Stammbäumen ist das Auftreten des Morbus Darier eng mit dem Vorkommen affektiver Erkrankungen verknüpft. Die wahrscheinlichste Ursache ist ein Suszeptibilitätsgen für affektive Erkrankungen in der Nähe des SERCA-2-Gens. Als Suszeptibilitätslokus konnte eine 6,5-Mb-Region identifiziert werden. Auch Studien mit affektiv erkrankten Stichproben, die nicht an Morbus Darier leiden, weisen ein Signal in der gleichen Region auf. Das zugrunde liegende Gen ist jedoch noch nicht identifizier

Feel it in my bones: Composing multimodal experience through tissue conduction

We outline here the feasibility of coherently utilising tissue conduction for spatial audio and tactile input. Tissue conduction display-specific compositional concerns are discussed; it is hypothesised that the qualia available through this medium substantively differ from those for conventional artificial means of appealing to auditory spatial perception. The implications include that spatial music experienced in this manner constitutes a new kind of experience, and that the ground rules of composition are yet to be established. We refer to results from listening experiences with one hundred listeners in an unstructured attribute elicitation exercise, where prominent themes such as “strange”, “weird”, “positive”, “spatial” and “vibrations” emerged. We speculate on future directions aimed at taking maximal advantage of the principle of multimodal perception to broaden the informational bandwidth of the display system. Some implications for composition for hearing-impaired are elucidated.n/

Effects of pretreatment hypothermia during resuscitated porcine hemorrhagic shock

OBJECTIVES: Accidental hypothermia increases mortality and morbidity after hemorrhage, but controversial data are available on the effects of therapeutic hypothermia. Therefore, we tested the hypothesis whether moderate pretreatment hypothermia would beneficially influence organ dysfunction during long-term, porcine hemorrhage and resuscitation. DESIGN: Prospective, controlled, randomized study. SETTING: University animal research laboratory. SUBJECTS: Twenty domestic pigs of either gender. INTERVENTIONS: Using an extracorporeal heat exchanger, anesthetized and instrumented animals were maintained at 38 degrees C, 35 degrees C, or 32 degrees C core temperature and underwent 4 hours of hemorrhage (removal of 40% of the blood volume and subsequent blood removal/retransfusion to maintain mean arterial pressure at 30 mm Hg). Resuscitation comprised of hydroxyethyl starch and norepinephrine infusion titrated to maintain mean arterial pressure at preshock values. MEASUREMENTS AND MAIN RESULTS: Before, immediately at the end of, and 12 and 22 hours after hemorrhage, we measured systemic and regional hemodynamics (portal vein, hepatic and right kidney artery ultrasound flow probes) and oxygen transport, and nitric oxide and cytokine production. Hemostasis was assessed by rotation thromboelastometry. Postmortem biopsies were analyzed for histomorphology (hematoxylin and eosin staining) and markers of apoptosis (kidney Bcl-xL and caspase-3 expression). Hypothermia at 32 degrees C attenuated the shock-related lactic acidosis but caused metabolic acidosis, most likely resulting from reduced carbohydrate oxidation. Although hypothermia did not further aggravate shock-related coagulopathy, it caused a transitory attenuation of kidney and liver dysfunction, which was ultimately associated with reduced histological damage and more pronounced apoptosis. CONCLUSIONS: During long-term porcine hemorrhage and resuscitation, moderate pretreatment hypothermia was associated with a transitory attenuation of organ dysfunction and less severe histological tissue damage despite more pronounced metabolic acidosis. This effect is possibly due to a switch from necrotic to apoptotic cell death, ultimately resulting from reduced tissue energy deprivation during the shock phase

Effects of the PPAR-β/δ agonist GW0742 during resuscitated porcine septic shock.

BACKGROUND: In un-resuscitated rodent models of septic shock, the peroxisome proliferator-activated receptor-β/δ (PPAR-β/δ) agonist GW0742 improved visceral organ function. Therefore, we tested the hypothesis whether GW0742 would attenuate kidney injury during long-term, resuscitated, porcine polymicrobial septic shock. METHODS: Six, 12, and 18 h after the induction of fecal peritonitis by inoculation of autologous feces, anesthetized, mechanically ventilated, and instrumented male pigs with pre-existing atherosclerosis resulting from familial hypercholesteremia and atherogenic diet randomly received either vehicle (dimethyl sulfoxide, n = 12) or GW0742 (n = 10). Resuscitation comprised hydroxyethyl starch and norepinephrine infusion titrated to maintain mean arterial pressure at baseline values. RESULTS: Despite aggressive fluid resuscitation, fecal peritonitis was associated with arterial hypotension requiring norepinephrine infusion, ultimately resulting in progressive lactic acidosis and acute kidney injury. GW0742 did not beneficially affect any parameter of systemic and regional hemodynamics, gas exchange, metabolism, or organ function. The parameters of inflammation, oxidative and nitrosative stress, and organ injury (post-mortem analysis for histomorphology and markers of apoptosis) were not influenced either. Immunohistochemistry of pre-shock kidney biopsies from a previous study in this swine strain showed markedly lower PPAR-β/δ receptor expression than in healthy animals. CONCLUSIONS: In swine with pre-existing atherosclerosis, the PPAR-β/δ agonist GW0742 failed to attenuate septic shock-induced circulatory failure and kidney dysfunction, most likely due to reduced receptor expression coinciding with cardiovascular and metabolic co-morbidity

Solar System Processes Underlying Planetary Formation, Geodynamics, and the Georeactor

Only three processes, operant during the formation of the Solar System, are responsible for the diversity of matter in the Solar System and are directly responsible for planetary internal-structures, including planetocentric nuclear fission reactors, and for dynamical processes, including and especially, geodynamics. These processes are: (i) Low-pressure, low-temperature condensation from solar matter in the remote reaches of the Solar System or in the interstellar medium; (ii) High-pressure, high-temperature condensation from solar matter associated with planetary-formation by raining out from the interiors of giant-gaseous protoplanets, and; (iii) Stripping of the primordial volatile components from the inner portion of the Solar System by super-intense solar wind associated with T-Tauri phase mass-ejections, presumably during the thermonuclear ignition of the Sun. As described herein, these processes lead logically, in a causally related manner, to a coherent vision of planetary formation with profound implications including, but not limited to, (a) Earth formation as a giant gaseous Jupiter-like planet with vast amounts of stored energy of protoplanetary compression in its rock-plus-alloy kernel; (b) Removal of approximately 300 Earth-masses of primordial gases from the Earth, which began Earth's decompression process, making available the stored energy of protoplanetary compression for driving geodynamic processes, which I have described by the new whole-Earth decompression dynamics and which is responsible for emplacing heat at the mantle-crust-interface at the base of the crust through the process I have described, called mantle decompression thermal-tsunami; and, (c)Uranium accumulations at the planetary centers capable of self-sustained nuclear fission chain reactions.Comment: Invited paper for the Special Issue of Earth, Moon and Planets entitled Neutrino Geophysics Added final corrections for publicatio

Self-regulation of the dopaminergic reward circuit in cocaine users with mental imagery and neurofeedback

BACKGROUND: Enhanced drug-related reward sensitivity accompanied by impaired sensitivity to non-drug related rewards in the mesolimbic dopamine system are thought to underlie the broad motivational deficits and dysfunctional decision-making frequently observed in cocaine use disorder (CUD). Effective approaches to modify this imbalance and reinstate non-drug reward responsiveness are urgently needed. Here, we examined whether cocaine users (CU) can use mental imagery of non-drug rewards to self-regulate the ventral tegmental area and substantia nigra (VTA/SN). We expected that obsessive and compulsive thoughts about cocaine consumption would hamper the ability to self-regulate the VTA/SN activity and tested if real-time fMRI (rtfMRI) neurofeedback (NFB) can improve self-regulation of the VTA/SN. METHODS: Twenty-two CU and 28 healthy controls (HC) were asked to voluntarily up-regulate VTA/SN activity with non-drug reward imagery alone, or combined with rtfMRI NFB. RESULTS: On a group level, HC and CU were able to activate the dopaminergic midbrain and other reward regions with reward imagery. In CU, the individual ability to self-regulate the VTA/SN was reduced in those with more severe obsessive-compulsive drug use. NFB enhanced the effect of reward imagery but did not result in transfer effects at the end of the session. CONCLUSION: CU can voluntary activate their reward system with non-drug reward imagery and improve this ability with rtfMRI NFB. Combining mental imagery and rtFMRI NFB has great potential for modifying the maladapted reward sensitivity and reinstating non-drug reward responsiveness. This motivates further work to examine the use of rtfMRI NFB in the treatment of CUD

Sensory and cognitive mechanisms of change detection in the context of speech

The aim of this study was to dissociate the contributions of memory-based (cognitive) and adaptation-based (sensory) mechanisms underlying deviance detection in the context of natural speech. Twenty healthy right-handed native speakers of English participated in an event-related design scan in which natural speech stimuli, /de:/ (“deh”) and /deI/ (“day”); (/te:/ (“teh”) and /teI/ (“tay”) served as standards and deviants within functional magnetic resonance imaging event-related “oddball” paradigm designed to elicit the mismatch negativity component. Thus, “oddball” blocks could involve either a word deviant (“day”) resulting in a “word advantage” effect, or a non-word deviant (“deh” or “tay”). We utilized an experimental protocol controlling for refractoriness similar to that used previously when deviance detection was studied in the context of tones. Results showed that the cognitive and sensory mechanisms of deviance detection were located in the anterior and posterior auditory cortices, respectively, as was previously found in the context of tones. The cognitive effect, that was most robust for the word deviant, diminished in the “oddball” condition. In addition, the results indicated that the lexical status of the speech stimulus interacts with acoustic factors exerting a top-down modulation of the extent to which novel sounds gain access to the subject’s awareness through memory-based processes. Thus, the more salient the deviant stimulus is the more likely it is to be released from the effects of adaptation exerted by the posterior auditory cortex

Compression of Auditory Space during Forward Self-Motion

<div><h3>Background</h3><p>Spatial inputs from the auditory periphery can be changed with movements of the head or whole body relative to the sound source. Nevertheless, humans can perceive a stable auditory environment and appropriately react to a sound source. This suggests that the inputs are reinterpreted in the brain, while being integrated with information on the movements. Little is known, however, about how these movements modulate auditory perceptual processing. Here, we investigate the effect of the linear acceleration on auditory space representation.</p> <h3>Methodology/Principal Findings</h3><p>Participants were passively transported forward/backward at constant accelerations using a robotic wheelchair. An array of loudspeakers was aligned parallel to the motion direction along a wall to the right of the listener. A short noise burst was presented during the self-motion from one of the loudspeakers when the listener’s physical coronal plane reached the location of one of the speakers (null point). In Experiments 1 and 2, the participants indicated which direction the sound was presented, forward or backward relative to their subjective coronal plane. The results showed that the sound position aligned with the subjective coronal plane was displaced ahead of the null point only during forward self-motion and that the magnitude of the displacement increased with increasing the acceleration. Experiment 3 investigated the structure of the auditory space in the traveling direction during forward self-motion. The sounds were presented at various distances from the null point. The participants indicated the perceived sound location by pointing a rod. All the sounds that were actually located in the traveling direction were perceived as being biased towards the null point.</p> <h3>Conclusions/Significance</h3><p>These results suggest a distortion of the auditory space in the direction of movement during forward self-motion. The underlying mechanism might involve anticipatory spatial shifts in the auditory receptive field locations driven by afferent signals from vestibular system.</p> </div