Outcome of laryngeal and velopharyngeal biofeedback treatment in children and young adults: A pilot study

A relatively new management strategy for the treatment of voice disorders is the use of laryngeal (LB) and velopharyngeal biofeedback (VB). The main purpose of the present pilot study is to document the outcome of vocal and velopharyngeal performances after a well-defined LB and VB treatment. Four subjects were studied pretreatment (1 week before LB or VB treatment) and posttreatment (1 week after the LB or VB treatment). To measure and compare the effect of LB and VB, objective and subjective assessment techniques were used. Perceptual voice assessment included a perceptual rating of the voice using the GRBAS scale. Furthermore, the vocal quality in this population is modeled by means of the Dysphonia Severity Index. For the objective assessment of nasal resonance, the Nasometer and the Glatzel test were used. A perceptual evaluation of speech, the Gutzmann test, and the tests from Bzoch were used as subjective assessment techniques. Both patients selected for LB and VB treatment showed improvement of their performances. The resulting improvement, as measured by means of an objective approach, is in agreement with the perceived (auditory) improvement of voice and resonance. The use of LB and VB treatment in patients, especially in some subjects who are not responding to traditional voice or velopharyngeal therapy, must be encouraged.     

Investigation of techniques to quantify in vivo lesion volume based on comparison of water apparent diffusion coefficient (ADC) maps with histology in focal cerebral ischemia of rats

Stroke lesion-volume estimates derived from calculated water apparent diffusion coefficient (ADC) maps provide a quantitative surrogate end-point for investigating the efficacy of drug treatment or studying the temporal evolution of cerebral ischemia. Methodology is described for estimating ischemic lesion volumes in a rat model of permanent middle cerebral artery occlusion (MCAO) based on absolute and percent-reduction threshold values of the water ADC at 3 h post-MCAO. Volume estimates derived from average ADC (ADC(av)) maps were compared with those derived from post-mortem histological sections. Optimum ADC thresholds were established as those that provided the best correlation and one-to-one correspondence between ADC- and histologically derived lesion-volume estimates. At 3 h post-MCAO, an absolute-ADC(av) threshold of 47 x 10(-5) mm(2)/s (corresponding to a 33% reduction in ADC(av) based on a contralateral hemisphere comparison) provided the most accurate estimate of percent hemispheric lesion volume (%HLV). Experimental and data analysis issues for improving and validating the usefulness of DWI as a surrogate endpoint for the quantification of ischemic lesion volume are discussed.     

Structure of the Cryptosporidium parvum microneme: a metabolically and osmotically labile apicomplexan organelle

From an EM study of thin sections, the rod-like microneme organelles within conventionally glutaraldehyde fixed Cryptosporidium parvum sporozoites have been shown to undergo a shape change to a more spherical structure when the sporozoites age in vitro for a period of approximately 12 to 24 h. This correlates with the shape change of intact sporozoites, from motile hence viable thin banana-shaped cells to swollen pear-shaped cells, shown by differential interference contrast light microscopy of unstained unfixed and glutaraldehyde-fixed samples, as well as by thin section EM of fixed sporozoites. From negatively stained EM specimens of unfixed and fixed sporozoites the cellular shape change has been confirmed as has the rod to sphere micronemal shape change. Intact micronemes released directly from sporozoites exclude negative stain and appear as smooth-surfaced electron transparent particles. Biochemically purified rod-shaped C. parvum micronemes are shown to be fragile organelles that inevitably undergo variable damage during isolation, storage and subsequent specimen preparation for EM study. In the absence of glutaraldehyde fixation, damaged micronemes allow the negative stain to enter and loose their contents and during storage undergo a rod-to-sphere shape transformation. Glutaraldehyde-fixed micronemes maintain the rod shape; intact fixed micronemes still exclude negative stain but damaged micronemes reveal a complex quasi-helical arrangement of internal protein within the rod-like micronemes. Loss of this internal organized structure appears to be responsible for the micronemal shape change. This interpretation has been advanced from mutually supportive data obtained from cryoelectron microscopy of unstained vitrified samples, conventional air-dry negative staining and cryo-negative staining. Attempts to biochemically solubilize the micronemal content by lysis and ultrasonication, and separate it from the micronemal membranes, have so far met with limited success as the internal material tends to remain as a disorganized cluster of particles upon release.     

The value of single-shot black-blood MR imaging for mapping of the coronary arteries: a comparison of four different orientations during breath-holding and free breathing

The value of ECG-gated single-shot black-blood MR imaging for rapid visualization of the origin and course of the coronary arteries was investigated. The study population included 28 patients with known or suspected cardiac disease. ECG-gated single-shot black-blood MR acquisitions were acquired in the transverse, coronal, sagittal and LAO orientations, during free breathing and breath-holding. The origin of the left coronary artery was most frequently visualized in the coronal and LAO orientations and the origin of the right coronary artery was most frequently visualized in the LAO orientation. Overall, no significant difference was found for the visualization of the coronary artery segments and the overall image quality among acquisitions during breath-holding and free breathing. ECG-gated single-shot black-blood MR imaging (HASTE) appears to be a time-efficient and robust method for mapping of the entire coronary artery tree, without the need for breath-holding. The LAO orientation provides the most consistent visualization of the origins and major coronary artery segments.     

Third body modeling in fretting using the combined finite-discrete element method

A new approach was developed for modeling the effect of the third body on fretting. This was accomplished using the combined finite-discrete element method (FDEM) in which the third body is analyzed as discrete elements while the first bodies are modeled using finite elements. This approach provides a link between large scale models which treat the mass of wear debris as a single or small number of bodies and small scale models which only study a control volume. The FDEM was used to analyze the behavior of third body particles between flat sliding surfaces. When the third body mass is composed of unconnected particles, it behaves as a Newtonian fluid, but this behavior ceases when the particles are connected into platelets. The FDEM was also used to study the behavior of third body particles inside a Hertzian line contact. As the number of particles and platelet size increase the load carried by the worn slip zone grows larger in relationship to the unworn stick zone.     

Does double electron capture lead to the formation of biradicals? An ECD-SORI-CID study on lacticin 481

We studied lacticin 481, a small lantibiotic with three lanthionine bridges, by electron capture dissociation (ECD) in a Fourier transform ion cyclotron resonance (FTICR) mass spectrometer. Following electron capture, very little fragmentation was observed, but species formed by nondissociative single and multiple electron capture were abundant. Ions formed by double electron capture were subjected to sustained off resonance irradiation collision induced dissociation (SORI-CID) to determine whether stable biradicals were formed. In the SORI-CID spectra of the ions formed by double electron capture, some, but minor, H* radical loss was observed, which was not observed at all for regularly protonated ions. A small part of the ions formed by double electron capture are thus long-lived biradicals. Apart from the observed H* loss, the SORI-CID spectra of ions that captured two electrons was similar to that of regularly protonated ions and quite different from the SORI-CID spectra of radical ions formed by single electron capture. This implies that recombination of the two radical sites is the dominant process in biradical lacticin 481 ions, at least on the time scale of our SORI-CID experiments.     

Unraveling complex small-molecule binding mechanisms by using simple NMR spectroscopy

Heteronuclear NMR spectroscopy provides a unique way to obtain site-specific information about protein-ligand interactions. Usually, such studies rely on the availability of isotopically labeled proteins, thereby allowing both editing of the spectra and ligand signals to be filtered out. Herein, we report that the use of the methyl SOFAST correlation experiment enables the determination of site-specific equilibrium binding constants by using unlabeled proteins. By using the binding of L- and D-tryptophan to serum albumin as a test case, we determined very accurate dissociation constants for both the high- and low-affinity sites present at the protein surface. The values of site-specific dissociation constants were closer to those obtained by isothermal titration calorimetry than those obtained from ligand-observed methods, such as saturation transfer difference. The possibility of measuring ligand binding to serum albumin at physiological concentrations with unlabeled proteins may open up new perspectives in the field of drug discovery.     

Tetramethylnorbornadiene, a versatile alkene for cyclopentenone synthesis through intermolecular Pauson-Khand reactions

1,2,3,4-Tetramethyl-bicyclo[2.2.1]hepta-2,5-diene (TMNBD, for tetramethylnorbornadiene) has been prepared and used successfully as an acetylene equivalent in the synthesis of substituted cyclopentenones. TMNBD is easily accessible on a multigram scale and displays excellent reactivity toward the intermolecular Pauson-Khand reaction. Conjugate additions on the resulting tricyclic compounds proceed with exquisite diastereoselectivity. The retro-Diels-Alder reaction of these TMNBD derivatives occurs under much smoother conditions than those required for its norbornadiene homologues.