Importance of Micromilieu for Pathophysiologic Mineralocorticoid Receptor Activity-When the Mineralocorticoid Receptor Resides in the Wrong Neighborhood.

The mineralocorticoid receptor (MR) is a member of the steroid receptor family and acts as a ligand-dependent transcription factor. In addition to its classical effects on water and electrolyte balance, its involvement in the pathogenesis of cardiovascular and renal diseases has been the subject of research for several years. The molecular basis of the latter has not been fully elucidated, but an isolated increase in the concentration of the MR ligand aldosterone or MR expression does not suffice to explain long-term pathologic actions of the receptor. Several studies suggest that MR activity and signal transduction are modulated by the surrounding microenvironment, which therefore plays an important role in MR pathophysiological effects. Local changes in micromilieu, including hypoxia, ischemia/reperfusion, inflammation, radical stress, and aberrant salt or glucose concentrations affect MR activation and therefore may influence the probability of unphysiological MR actions. The surrounding micromilieu may modulate genomic MR activity either by causing changes in MR expression or MR activity; for example, by inducing posttranslational modifications of the MR or novel interaction with coregulators, DNA-binding sites, or non-classical pathways. This should be considered when developing treatment options and strategies for prevention of MR-associated diseases.

Cortical networks for auditory detection with and without informational masking: Task effects and implications for conscious perception.

Ambiguous and masked stimuli have been used to study conscious perception by comparing neural activity during different percepts of identical physical stimuli. One limitation of this approach is that it typically requires a reporting task that may engage neural processes beyond those required for conscious perception. Here, we explored potential fMRI correlates of auditory conscious perception with and without overt report. In experiment 1, regular tone patterns were presented as targets under informational masking, and participants reported their percepts on each trial. In experiment 2, regular tone patterns were presented without masking, while the uninformed participants (i) passively fixated, (ii) performed an orthogonal visual task, and (iii) reported trial-wise the presence of the auditory pattern as in experiment 1 (in fixed order). Under informational masking, target-pattern detection was associated with activity in auditory cortex, superior temporal sulcus, and a distributed fronto-parieto-insular network. Unmasked and task-irrelevant tone patterns elicited activity that overlapped with the network observed under informational masking in auditory cortex, the right superior temporal sulcus, and the ventral precentral sulcus in an ROI analysis. We therefore consider these structures candidate regions for a neural substrate of auditory conscious perception. In contrast, activity in the intraparietal sulcus, insula, and dorsal precentral sulcus were only observed for unmasked tone patterns when they were task relevant. These areas therefore appear more closely related to task performance or top-down attention rather than auditory conscious perception, per se.

Transient human auditory cortex activation during volitional attention shifting.

While strong activation of auditory cortex is generally found for exogenous orienting of attention, endogenous, intra-modal shifting of auditory attention has not yet been demonstrated to evoke transient activation of the auditory cortex. Here, we used fMRI to test if endogenous shifting of attention is also associated with transient activation of the auditory cortex. In contrast to previous studies, attention shifts were completely self-initiated and not cued by transient auditory or visual stimuli. Stimuli were two dichotic, continuous streams of tones, whose perceptual grouping was not ambiguous. Participants were instructed to continuously focus on one of the streams and switch between the two after a while, indicating the time and direction of each attentional shift by pressing one of two response buttons. The BOLD response around the time of the button presses revealed robust activation of the auditory cortex, along with activation of a distributed task network. To test if the transient auditory cortex activation was specifically related to auditory orienting, a self-paced motor task was added, where participants were instructed to ignore the auditory stimulation while they pressed the response buttons in alternation and at a similar pace. Results showed that attentional orienting produced stronger activity in auditory cortex, but auditory cortex activation was also observed for button presses without focused attention to the auditory stimulus. The response related to attention shifting was stronger contralateral to the side where attention was shifted to. Contralateral-dominant activation was also observed in dorsal parietal cortex areas, confirming previous observations for auditory attention shifting in studies that used auditory cues.

Functional magnetic resonance imaging confirms forward suppression for rapidly alternating sounds in human auditory cortex but not in the inferior colliculus.

Forward suppression at the level of the auditory cortex has been suggested to subserve auditory stream segregation. Recent results in non-streaming stimulation contexts have indicated that forward suppression can also be observed in the inferior colliculus; whether this holds for streaming-related contexts remains unclear. Here, we used cardiac-gated fMRI to examine forward suppression in the inferior colliculus (and the rest of the human auditory pathway) in response to canonical streaming stimuli (rapid tone sequences comprised of either one repetitive tone or two alternating tones). The first stimulus is typically perceived as a single stream, the second as two interleaved streams. In different experiments using either pure tones differing in frequency or bandpass-filtered noise differing in inter-aural time differences, we observed stronger auditory cortex activation in response to alternating vs. repetitive stimulation, consistent with the presence of forward suppression. In contrast, activity in the inferior colliculus and other subcortical nuclei did not significantly differ between alternating and monotonic stimuli. This finding could be explained by active amplification of forward suppression in auditory cortex, by a low rate (or absence) of cells showing forward suppression in inferior colliculus, or both.

Cortical representation of the combination of monaural and binaural unmasking.

The audibility of a target tone is improved by introducing either -amplitude modulations that are coherent across different frequency channels of the masker (comodulation masking release, CMR) or interaural phase differences that are -different for target and masker (binaural masking-level difference, BMLD). Although the two effects are likely to be based on different processing strategies, they both result in improved figure-background decomposition for a target-in-noise situation. In this study, we analyzed the combination of CMR and BMLD for a -target tone in a masker with six 48-Hz-wide noise bands, distributed over a wide frequency range from 216 Hz to 2.78 kHz. Psychoacoustical detection thresholds for the tones in noise were determined for two masker conditions (comodulated or unmodulated bands) and two interaural phase differences of the target tone (0 or 180°). The mean results indicate that the effects of unmasking add independently. The lowest thresholds are found for the dichotic signal embedded in a -modulated masker with an overall threshold difference of about 16 dB compared to the -unmodulated condition with no binaural cues. Based on the psychoacoustic results, a set of 12 signal-masker configurations was selected individually to explore the representation of the audibility of the test tone in brain activation maps by means of auditory functional MR imaging. The comparison of the results for the combination of CMR and BMLD with the results for the separate effects indicates a large overlap of the activated brain regions, where a largely extended area is activated, covering primary auditory cortex and adjacent regions. The result is in agreement with previous fMRI studies on auditory masking, identifying specific regions in the auditory cortex representing a change of the audibility of a target tone in a noise masker, irrespective of the overall sound pressure level of the stimulus.

Suprathel, a new skin substitute, in the management of partial-thickness burn wounds: results of a clinical study.

OBJECTIVE: A prospective, randomized, bicentric, nonblinded, clinical study was conducted to evaluate the impact on wound healing of Suprathel in partial-thickness burn injuries. Suprathel represents an absorbable, synthetic wound dressing with properties of natural epithelium. METHODS: Thirty patients suffering from second-degree burn injuries were included in the study, with a mean of age 40.4 years old. Burn injuries were randomly selected, partly treated with Omiderm and partly treated with Suprathel. The first gauze change was applied the fifth day postoperatively, followed by regular wound inspection until complete reepithelization. The study focused on patient pain score, healing time, analysis of wound bed, ease of care, and treatment costs. RESULTS: There was no significant difference between the 2 materials tested regarding healing time and reepithelization. There was a significant lower pain score for patients treated with Suprathel (P = 0.0072). Suprathel becomes transparent when applied, thus allowing close monitoring of wound healing. In contrast to Omiderm, Suprathel shows better attachment and adherence to wounds. During the course of healing, it detaches smoothly, without damaging the reepithelized wound surface. Moreover, it reduces the frequency of dressing changes required. Ease of care of Suprathel has been rated outstanding by patients and healthcare professionals. When interviewed, patients reported Suprathel as their treatment preference. As dressing material, Omiderm is more cost-effective than Suprathel. CONCLUSION: Suprathel represents a reliable epidermal skin substitute, with a good impact on wound healing and pain reduction in partial-thickness burn injuries. Although it is less cost-effective than Omiderm, the significant increase of patient comfort makes this material represent a reliable and solid treatment alternative when dealing with partial-thickness burn injuries. Further studies with this synthetic dressing on other types of wounds are warranted.