Transcranial attenuation in bone conduction stimulation.

In bone conduction (BC) stimulation, the sound travels from the site of stimulation to the ipsilateral and contralateral cochlea. A frequency dependent reduction in BC hearing sensitivity occurs when sound travels to the contralateral cochlea as compared to the ipsilateral cochlea. This effect is called transcranial attenuation (TA) that is affected by several factors. Experimental and clinical studies describe TA and the factors that have an effect on it. These factors include stimulus location, coupling of a bone conduction hearing aid to the underlying tissue, and the properties of the head (such as geometry of the head, thickness of the skin and/or skull, changes due to aging, iatrogenic changes such as bone removal in mastoidectomy, and occlusion of the external auditory canal). While TA has an effect of the patient's benefit of BCHAs, there seems to be a discrepancy between experimental measurements and clinical relevance. The effects are small and the interindividual variability, in comparison, is rather large. However, a better understanding of these factors may help to determine the site of attachment, the coupling mode, and possibly the fitting of a BCHA, depending on its indication.

Identification of salicylic acid-independent responses in an Arabidopsis phosphatidylinositol 4-kinase beta double mutant.

BACKGROUND AND AIMS: We have recently shown that an Arabidopsis thaliana double mutant of type III phosphatidylinositol-4-kinases (PI4Ks), pi4kß1ß2, constitutively accumulated a high level of salicylic acid (SA). By crossing this pi4kß1ß2 double mutant with mutants impaired in SA synthesis (such as sid2 impaired in isochorismate synthase) or transduction, we demonstrated that the high SA level was responsible for the dwarfism phenotype of the double mutant. Here we aimed to distinguish between the SA-dependent and SA-independent effects triggered by the deficiency in PI4Kß1 and PI4Kß2. METHODS: To achieve this we used the sid2pi4kß1ß2 triple mutant. High-throughput analyses of phytohormones were performed on this mutant together with pi4kß1ß2 and sid2 mutants and wild-type plants. Responses to pathogens, namely Hyaloperonospora arabidopsidis, Pseudomonas syringae and Botrytis cinerea, and also to the non-host fungus Blumeria graminis, were also determined. Callose accumulation was monitored in response to flagellin. KEY RESULTS: We show here the prominent role of high SA levels in influencing the concentration of many other tested phytohormones, including abscisic acid and its derivatives, the aspartate-conjugated form of indole-3-acetic acid and some cytokinins such as cis-zeatin. We show that the increased resistance of pi4kß1ß2 plants to the host pathogens H. arabidopsidis, P. syringae pv. tomato DC3000 and Bothrytis cinerea is dependent on accumulation of high SA levels. In contrast, accumulation of callose in pi4kß1ß2 after flagellin treatment was independent of SA. Concerning the response to Blumeria graminis, both callose accumulation and fungal penetration were enhanced in the pi4kß1ß2 double mutant compared to wild-type plants. Both of these processes occurred in an SA-independent manner. CONCLUSIONS: Our data extensively illustrate the influence of SA on other phytohormone levels. The sid2pi4kß1ß2 triple mutant revealed the role of PI4Kß1/ß2 per se, thus showing the importance of these enzymes in plant defence responses.

Influence of angular positioning of the prosthesis in stapes surgeries with a NiTiBond prosthesis: Investigation in cadaveric temporal bones.

In incus stapedotomy surgeries, the longitudinal direction of the piston prosthesis should ideally be perpendicular to the stapes footplate. However, in reality, some amounts of angular deviation of the prosthesis from the ideal angular position is unavoidable due to anatomical constraints and surgical conditions. This study aims to evaluate the influence of angular positioning of the prosthesis on surgical outcomes in incus stapedotomy and to provide surgical guidelines related to practical tolerance of the angular positioning. In this study, this influence was assessed with a Kurz NiTiBond prosthesis (0.4-mm diameter) and fenestra sizes of 0.5- and 0.6-mm diameter in cadaveric temporal bones (n = 7 including 2 preliminary tests). Angular position of the prosthesis relative to the footplate was modulated by rotating the stapes about the long and short axes of the footplate. At each angular position, the tympanic membrane was acoustically stimulated in the frequency range of 0.2-10 kHz, and motion of the prosthesis was measured using a Laser Doppler vibrometer (LDV). Furthermore, micro-computed tomography (micro-CT) data of the middle-ear ossicles were used for anatomical analysis of angular positioning of the prosthesis. The results showed that changes of angular position of the prosthesis relative to the stapes footplate do not cause significant changes of prosthesis motion until a certain angular position threshold, and sharply attenuate prosthesis motion when the angular position reaches the threshold. The threshold of the angular position, as the tilting angle of the prosthesis from the direction normal to the stapes footplate, was 26.9 ±â€¯2.5° with the fenestration hole of 0.5-mm diameter and 30.6 ±â€¯3.0° with the fenestration hole of 0.6-mm diameter (n = 5, p < 0.01 for difference between the two fenestra sizes). Analysis of the middle-ear anatomy in this study revealed that the tolerances of the angular positions of the prosthesis does not always cover possible positions of prosthesis crimping. This study suggests that if an anterior offset of the stapes head and/or the thickened footplate is suspected, efforts to locate prosthesis crimping closer to the tip of the incus and/or to make a sufficiently large fenestration hole are favorable.

Interaction between osseous and non-osseous vibratory stimulation of the human cadaveric head.

Bone conduction (BC) stimulation can be applied by vibration to the bony or skin covered skull (osseous BC), or on soft tissue such as the neck (non-osseous BC). The interaction between osseous and non-osseous bone conduction pathways is assessed in this study. The relation between bone vibrations measured at the cochlear promontory and the intracranial sound pressure for stimulation directly on the dura and for stimulation at the mastoid between 0.2 and 10 kHz was compared. First, for stimulation on the dura, varying the static coupling force of the BC transducer on the dura had only a small effect on promontory vibration. Second, the presence or absence of intracranial fluid did not affect promontory vibration for stimulation on the dura. Third, stimulation on the mastoid elicited both promontory vibration and intracranial sound pressure. Stimulation on the dura caused intracranial sound pressure to a similar extent above 0.5 kHz compared to stimulation on the mastoid, while promontory vibration was less by 20-40 dB. From these findings, we conclude that intracranial sound pressure (non-osseous BC) only marginally affects bone vibrations measured on the promontory (osseous BC), whereas skull vibrations affect intracranial sound pressure.

Biomechanics of the incudo-malleolar-joint - Experimental investigations for quasi-static loads.

Under large quasi-static loads, the incudo-malleolar joint (IMJ), connecting the malleus and the incus, is highly mobile. It can be classified as a mechanical filter decoupling large quasi-static motions while transferring small dynamic excitations. This is presumed to be due to the complex geometry of the joint inducing a spatial decoupling between the malleus and incus under large quasi-static loads. Spatial Laser Doppler Vibrometer (LDV) displacement measurements on isolated malleus-incus-complexes (MICs) were performed. With the malleus firmly attached to a probe holder, the incus was excited by applying quasi-static forces at different points. For each force application point the resulting displacement was measured subsequently at different points on the incus. The location of the force application point and the LDV measurement points were calculated in a post-processing step combining the position of the LDV points with geometric data of the MIC. The rigid body motion of the incus was then calculated from the multiple displacement measurements for each force application point. The contact regions of the articular surfaces for different load configurations were calculated by applying the reconstructed motion to the geometry model of the MIC and calculate the minimal distance of the articular surfaces. The reconstructed motion has a complex spatial characteristic and varies for different force application points. The motion changed with increasing load caused by the kinematic guidance of the articular surfaces of the joint. The IMJ permits a relative large rotation around the anterior-posterior axis through the joint when a force is applied at the lenticularis in lateral direction before impeding the motion. This is part of the decoupling of the malleus motion from the incus motion in case of large quasi-static loads.

Optimization of a lensless digital holographic otoscope system for transient measurements of the human tympanic membrane.

In this paper, we propose a multi-pulsed double exposure (MPDE) acquisition method to quantify in full-field-of-view the transient (i.e., >10 kHz) acoustically induced nanometer scale displacements of the human tympanic membrane (TM or eardrum). The method takes advantage of the geometrical linearity and repeatability of the TM displacements to enable high-speed measurements with a conventional camera (i.e., <20 fps). The MPDE is implemented on a previously developed digital holographic system (DHS) to enhance its measurement capabilities, at a minimum cost, while avoiding constraints imposed by the spatial resolutions and dimensions of high-speed (i.e., >50 kfps) cameras. To our knowledge, there is currently no existing system to provide such capabilities for the study of the human TM. The combination of high temporal (i.e., >50 kHz) and spatial (i.e., >500k data points) resolutions enables measurements of the temporal and frequency response of all points across the surface of the TM simultaneously. The repeatability and accuracy of the MPDE method are verified against a Laser Doppler Vibrometer (LDV) on both artificial membranes and ex-vivo human TMs that are acoustically excited with a sharp (i.e., <100 µs duration) click. The measuring capabilities of the DHS, enhanced by the MPDE acquisition method, allow for quantification of spatially dependent motion parameters of the TM, such as modal frequencies, time constants, as well as inferring local material properties.

Assessing interaction thresholds for trichloroethylene in combination with tetrachloroethylene and 1,1,1-trichloroethane using gas uptake studies and PBPK modeling.

The volatile organic solvents trichloroethylene (TCE), tetrachloroethylene (perchloroethylene, PERC), and 1,1,1-trichloroethane (methylchloroform, MC) are widely distributed environmental pollutants and common contaminants of many chemical waste sites. To investigate the mode of pharmacokinetic interactions among TCE, PERC, and MC and to calculate defined "interaction thresholds", gas-uptake experiments were performed using a closed-chamber exposure system. In each experiment, two rats (Fischer 344, male, 8-9 weeks old) were exposed to different initial concentrations of TCE, PERC, and MC, applied singly or as a mixture, and their concentration in the gas phase of the chamber was monitored over a period of 6 h. A physiologically based pharmacokinetic (PBPK) model was developed to test multiple mechanisms of inhibitory interactions, i.e., competitive, non-competitive, or uncompetitive. All mixture exposure data were accurately described by a system of equations in which a PBPK model was provided for each chemical and each was regarded as an inhibitor of the others' metabolism. Sensitivity-analysis techniques were used to investigate the impact of key parameters on model output and optimize experimental design. Model simulations indicated that, among these three chemicals, the inhibition was competitive. The PBPK model was extended to assess occupationally relevant exposures at or below the current threshold-limit values (TLVs). Based on 10% elevation in TCE blood levels as a criterion for significant interaction and assuming TCE exposure is set at TLV of 50 ppm, the calculated interaction thresholds for PERC and MC were 25 and 135 ppm, respectively. TLV exposures to binary TCE/PERC mixture were below the 10% significance level. The interaction threshold for TCE and MC co-exposure would be reached at 50 and 175 ppm, respectively. Such interactive PBPK models should be of value in risk assessment of occupational and environmental exposure to solvent mixtures.

Physiological modeling reveals novel pharmacokinetic behavior for inhaled octamethylcyclotetrasiloxane in rats.

Octamethylcyclotetrasiloxane (D4) is an ingredient in selected consumer and precision cleaning products. Workplace inhalation exposures may occur in some D4 production operations. In this study, we analyzed tissue, plasma, and excreta time-course data following D4 inhalation in Fischer 344 rats (K. Plotzke et al., 2000, Drug Metab. Dispos. 28, 192-204) to assess the degree to which the disposition of D4 is similar to or different from that of volatile hydrocarbons that lack silicone substitution. We first applied a basic physiologically based pharmacokinetic (PBPK) model (J. C. Ramsey and M. E. Andersen, 1984, Toxicol. Appl. Pharmacol. 73, 159-175) to characterize the biological determinants of D4 kinetics. Parameter estimation techniques indicated an unusual set of characteristics, i.e., a low blood:air (P(b:a) congruent with 0.9) and a high fat:blood partition coefficient (P(f:b) congruent with 550). These parameters were then determined experimentally by equilibrating tissue or liquid samples with saturated atmospheres of D4. Consistent with the estimates from the time-course data, blood:air partition coefficients were small, ranging from 1.9 to 6.9 in six samples. Perirenal fat:air partition coefficients were large, from 1400 to 2500. The average P(f:b) was determined to be 485. This combination of partitioning characteristics leads to rapid exhalation of free D4 at the cessation of the inhalation exposure followed by a much slower redistribution of D4 from fat and tissue storage compartments. The basic PK model failed to describe D4 tissue kinetics in the postexposure period and had to be expanded by adding deep-tissue compartments in liver and lung, a mobile chylomicron-like lipid transport pool in blood, and a second fat compartment. Model parameters for the refined model were optimized using single-exposure data in male and female rats exposed at three concentrations: 7, 70, and 700 ppm. With inclusion of induction of D4 metabolism at 700 ppm (3-fold in males, 1-fold in females), the parameter set from the single exposures successfully predicted PK results from 14-day multiple exposures at 7 and 700 ppm. A common parameter set worked for both genders. Despite its very high lipophilicity, D4 does not show prolonged retention because of high hepatic and exhalation clearance. The high lipid solubility, low blood:air partition coefficient, and plasma lipid storage with D4 led to novel distributional characteristics not previously noted for inhaled organic hydrocarbons. These novel characteristics were only made apparent by analysis of the time-course data with PBPK modeling techniques.

Complement fixing antibodies to respiratory viruses in children in Jos, Nigeria.

One-hundred serum samples obtained from children in Jos were tested for the presence of complement fixing antibodies against several respiratory viruses. Sixty-two per cent of the samples were positive for adenoviruses, 53 per cent for para-influenza viruses, 47 and 41 per cent for influenza A and B, respectively, 31 per cent for respiratory syncytial virus, 29 per cent for coronaviruses, and 19 per cent for reoviruses.

Structural studies on periodate-oxidized chicken ovomucoid. Spectral behaviour of the tyrosine residues.

About 50% of the carbohydrate moiety of ovomucoid was destroyed by periodate oxidation. The oxidation was carried out for 6 h or 24 h. The data obtained showed that in the carbohydrate chain 2-5 glucosamines and 1-2 neutral sugar residues were decomposed with the consumption of 16 mol and 29 mol of periodate respectively. Periodic oxidation slightly changed the inhibitory activity of the ovomucoid, but altered its spectral properties. An increase of the absorption maximum at 278 nm was noted, as well as a tendency for normalization of phenolic ionization and an increase of the relative fluorescence. The reactivity of tyrosine residues towards tetranitromethane is also changed. It was suggested that even in native ovomucoid the tyrosines could be regarded as 'dissolved' in the 'carbohydrate solvent'. This contact could be achieved by the hydrogen bonds in the formation of which the NHCOCH3 groups of the glucosamine residues play an essential role. Peroxidate oxidation seems to lead to an alteration of the nature of the 'sugar solvent' and disturbs the conformation of the sugar chain.