Fabrication and Characterization of PDMS Waveguides for Flexible Optrodes.

With the growth of optogenetic research, the demand for optical probes tailored to specific applications is ever rising. Specifically, for applications like the coiled cochlea of the inner ear, where planar, stiff, and nonconformable probes can hardly be used, transitioning from commonly used stiff glass fibers to flexible probes is required, especially for long-term use. Following this demand, polydimethylsiloxane (PDMS) with its lower Young's modulus compared to glass fibers can serve as material of choice. Hence, the long-term usability of PDMS as a waveguide material with respect to variations in transmission and refractive index over time is investigated. Different manufacturing methods for PDMS-based flexible waveguides are established and compared with the aim to minimize optical losses and thus maximize optical output power. Finally, the waveguides with lowest optical losses (-4.8 dB cm-1 ± 1.3 dB cm-1 at 472 nm) are successfully inserted into the optogenetically modified cochlea of a Mongolian gerbil (Meriones unguiculatus), where optical stimuli delivered by the waveguides evoked robust neuronal responses in the auditory pathway.

Dynamic reconfiguration of cortical functional connectivity across brain states.

Throughout each day, the brain displays transient changes in state, as evidenced by shifts in behavior and vigilance. While the electrophysiological correlates of brain states have been studied for some time, it remains unclear how large-scale cortico-cortical functional connectivity systematically reconfigures across states. Here, we investigate state-dependent shifts in cortical functional connectivity by recording local field potentials (LFPs) during spontaneous behavioral transitions in the ferret using chronically implanted micro-electrocorticographic (µECoG) arrays positioned over occipital, parietal, and temporal cortical regions. To objectively classify brain state, we describe a data-driven approach that projects time-varying LFP spectral properties into brain state space. Distinct brain states displayed markedly different patterns of cross-frequency phase-amplitude coupling and inter-electrode phase synchronization across several LFP frequency bands. The largest across-state differences in functional connectivity were observed between periods of presumed slow-wave and rapid-eye-movement-sleep/active-state, which were characterized by the contrasting phenomena of cortical network fragmentation and global synchronization, respectively. Collectively, our data provide strong evidence that large-scale functional interactions in the brain dynamically reconfigure across behavioral states.

Intrinsic coupling modes reveal the functional architecture of cortico-tectal networks.

In the absence of sensory stimulation or motor output, the brain exhibits complex spatiotemporal patterns of intrinsically generated neural activity. Analysis of ongoing brain dynamics has identified the prevailing modes of cortico-cortical interaction; however, little is known about how such patterns of intrinsically generated activity are correlated between cortical and subcortical brain areas. We investigate the correlation structure of ongoing cortical and superior colliculus (SC) activity across multiple spatial and temporal scales. Ongoing cortico-tectal interaction was characterized by correlated fluctuations in the amplitude of delta, spindle, low gamma, and high-frequency oscillations (>100 Hz). Of these identified coupling modes, topographical patterns of high-frequency coupling were the most consistent with patterns of anatomical connectivity, reflecting synchronized spiking within cortico-tectal networks. Cortico-tectal coupling at high frequencies was temporally parcellated by the phase of slow cortical oscillations and was strongest for SC-cortex channel pairs that displayed overlapping visual spatial receptive fields. Despite displaying a high degree of spatial specificity, cortico-tectal coupling in lower-frequency bands did not match patterns of cortex-to-SC anatomical connectivity. Collectively, our findings demonstrate that neural activity is spontaneously coupled between cortex and SC, with high- and low-frequency modes of coupling reflecting direct and indirect cortico-tectal interactions, respectively.

Exogenous histamine aggravates eczema in a subgroup of patients with atopic dermatitis.

Food and beverages may contain high amounts of histamine and thus may cause symptoms after ingestion. The aim of this study was to investigate the role of ingested histamine in atopic dermatitis. Patients with atopic dermatitis had to maintain a histamine-free diet for one week. Consecutively, double-blind, placebo-controlled provocations were performed with histamine-hydrochloride and placebo. The clinical outcome was assessed by determination of the SCORAD. Before and 30 min after each provocation blood was collected for measurement of plasma histamine levels and diamine oxidase activity. Thirty-six patients with atopic dermatitis completed the diet. Twelve of 36 showed a significant improvement of the SCORAD after one week of the diet. After provocation tests 11 of 36 showed aggravation of eczema. Plasma histamine was significantly higher in patients with atopic dermatitis compared with controls (p><0.001), whereas diamine oxidase activity was similar in both groups. Our data indicate that ingestion of moderate or high amounts of histamine-hydrochloride may aggravate eczema in a subgroup of patients with atopic dermatitis. Plasma histamine and diamine oxidase activity were not associated with the clinical response to histamine.

Introducing genetic testing for adult-type hypolactasia.

BACKGROUND AND AIMS: To evaluate genotyping for two DNA variants (c.1993+327C>T and c.1438+117G>A), recently found to be associated with adult-type hypolactasia, in the diagnosis of lactose intolerance. METHODS: In total, 166 consecutive patients with gastrointestinal symptoms mimicking hypolactasia admitted to the clinic between March 2002 and December 2002 were included. Genotyping for the two DNA variants (c.1993+327C>T and c.1438+117G>A) and standard H2 breath test was performed. RESULTS: Among 116 patients with positive H2 breath test, the c.1993+327C variant was detectable in 106 (91.4%) patients. Among 50 patients with negative H2 breath test, the c.1993+327C variant was seen in 2 patients. Sensitivity, specificity, positive and negative predictive values for the c.1993+327C variant were 91.4, 96.0, 98.1 and 82.8%, respectively. Genotyping for the c.1438+117G variant did not bring any additional information. Among 4 of the 10 patients with positive H2 breath test but negative for the c.1993+327C and the c.1438+117G variant,further evaluation revealed other diseases known to cause secondary hypolactasia such as celiac disease and short bowel syndrome. CONCLUSION: In symptomatic patients, genotyping for the DNA variant c.1993+327C is a reliable test for adult-type hypolactasia with high sensitivity and specificity and thus provides a new tool in the diagnostic workup of hypolactasia.

Immunoglobulin E-reactivity of wheat-allergic subjects (baker's asthma, food allergy, wheat-dependent, exercise-induced anaphylaxis) to wheat protein fractions with different solubility and digestibility.

Baker's asthma, food allergy to wheat, and wheat-dependent, exercise-induced anaphylaxis (WDEIA) are different clinical forms of wheat allergy. We investigated the correlation of solubility and digestion stability of wheat allergens with the IgE-reactivity patterns of different patient groups. Three wheat protein fractions were extracted according to their solubility: salt-soluble albumins and globulins, ethanol-soluble gliadins, and glutenins soluble only after treatment with detergents and reducing reagents. Sera from subjects with history of each variant of wheat allergy were characterized by CAP FEIA and immunoblotting. There was a high degree of heterogeneity of recognized allergens between the different subject groups as well as within these groups. However, subjects with WDEIA showed similar immunoglobulin E (IgE)-reactivity patterns to gliadins and especially to a 65 kDa protein. Subjects with baker's asthma as well as the food-allergic subjects had the most intense IgE-reactivity to the albumin/globulin fraction. The latter group additionally showed IgE-reactivity to the other fractions. Divergent results of immunoblotting and CAP-FEIA demonstrated that the detection of wheat-specific IgE highly depends on the applied method, thus the diagnostic tool must be carefully chosen. Most wheat allergens were rapidly digested as analyzed by determination of IgE-reactivity on immunoblots to wheat extracts after simulation of gastric and duodenal digestion. However, ethanol-soluble gliadins were stable to gastric enzymes and exhibit low solubility in gastric and duodenal fluids. Therefore, they are likely to be important in food allergy to wheat.