Effect of artificial mucus properties on the characteristics of airborne bioaerosol droplets generated during simulated coughing

The effect of viscoelastic properties and surface tension of artificial mucus simulant samples on the size distribution and volume concentration of bioaerosol droplets generated during simulated coughing was investigated through in vitro experiments. The mucus simulant samples had viscoelastic properties in a similar range as those of real human airway mucus. The mucus simulant gels were prepared by mixing various proportions of 0.5–1.7% locust bean gum solution and 0.1 M sodium tetraborate (XLB) solution. Surface tension of one set of samples was varied by adding different amounts of SDS (sodium dodecyl sulfate) surfactant while the measurement of surface tension was performed using ADSA (axisymmetric drop shape analysis) method. The viscoelastic properties of the samples were measured using a Bohlin Gemini 200 HR (Malvern, UK) nano-rheometer with peltier plate assembly. An artificial cough machine was used to simulate human cough, generating aerosol droplets in a model trachea attached to the front of the cough machine. The size distribution and volume concentration of the droplets generated through simulated cough were measured using a laser diffraction particle sizer (SprayTec, Malvern, USA). The surface tension was found to have negligible effect on the characteristic of generated droplets within the range of this investigation. The experimental results showed a decrease in particle size as the samples changed from a viscous fluid type to a viscoelastic to an elastic solid type sample. The volume concentration also changed significantly as the viscoelasticity of the samples was varied.     

Bacterial protein structures reveal phylum dependent divergence

Protein sequence space is vast compared to protein fold space. This raises important questions about how structures adapt to evolutionary changes in protein sequences. A growing trend is to regard protein fold space as a continuum rather than a series of discrete structures. From this perspective, homologous protein structures within the same functional classification should reveal a constant rate of structural drift relative to sequence changes. The clusters of orthologous groups (COG) classification system was used to annotate homologous bacterial protein structures in the Protein Data Bank (PDB). The structures and sequences of proteins within each COG were compared against each other to establish their relatedness. As expected, the analysis demonstrates a sharp structural divergence between the bacterial phyla Firmicutes and Proteobacteria. Additionally, each COG had a distinct sequence/structure relationship, indicating that different evolutionary pressures affect the degree of structural divergence. However, our analysis also shows the relative drift rate between sequence identity and structure divergence remains constant.     

Estimating protein-ligand binding affinity using high-throughput screening by NMR

Many of today's drug discovery programs use high-throughput screening methods that rely on quick evaluations of protein activity to rank potential chemical leads. By monitoring biologically relevant protein-ligand interactions, NMR can provide a means to validate these discovery leads and to optimize the drug discovery process. NMR-based screens typically use a change in chemical shift or line width to detect a protein-ligand interaction. However, the relatively low throughput of current NMR screens and their high demand on sample requirements generally makes it impractical to collect complete binding curves to measure the affinity for each compound in a large and diverse chemical library. As a result, NMR ligand screens are typically limited to identifying candidates that bind to a protein and do not give any estimate of the binding affinity. To address this issue, a methodology has been developed to rank binding affinities for ligands based on NMR screens that use 1D (1)H NMR line-broadening experiments. This method was demonstrated by using it to estimate the dissociation equilibrium constants for twelve ligands with the protein human serum albumin (HSA). The results were found to give good agreement with previous affinities that have been reported for these same ligands with HSA.     

Validity and Reliability of the Reflux Symptom Index (RSI)

Laryngopharyngeal reflux (LPR) is present in up to 50% of patients with voice disorders. Currently, there is no validated instrument that documents symptom severity in LPR. We developed the reflux symptom index (RSI), a self-administered nine-item outcomes instrument for LPR. The purpose of this investigation was to evaluate the psychometric properties of the RSI. For validity assessment, 25 patients with LPR were evaluated prospectively before and six months after b.i.d. treatment with proton pump inhibitors (PPI). Each patient completed the RSI as well as the 30-item voice handicap index (VHI). For reliability assessment, the study patients were given the RSI on two separate occasions before the initiation of treatment. Normative RSI data were derived from 25 age-matched and gender-matched controls taken from an existing database of asymptomatic individuals without any evidence of LPR. The mean RSI (+/- standard deviation) of patients with LPR improved from 21.2 (+/- 10.7) to 12.8 (+/- 10.0), and the mean VHI improved from 52.2 (+/- 24.7) to 41.5 (+/- 25.0) after 6 months of therapy (p = 0.001 and 0.065, respectively). Of the three VHI subscales (emotional, physical, functional), only the functional subscale improved significantly (p = 0.037). Patients who experienced a five point or better improvement in RSI were 11 times more likely to experience a five-point improvement in VHI (95% confidence interval = 1.7, 76.8). For reliability assessment, the first and second pretreatment RSIs were 19.9 (+/- 11.1) and 20.9 (+/- 9.6), respectively (correlation coefficient = 0.81, p < 0.001). The single-item correlation coefficients ranged from 0.41 to 0.91 (p < 0.05 for all items). The mean pretreatment RSI in patients with LPR was significantly higher than controls (21.2 versus 11.6; p < 0.001). The mean RSI of patients with LPR after 6 months of PPI therapy approached that of asymptomatic controls (p > 0.05). The RSI is easily administered, highly reproducible, and exhibits excellent construct and criterion-based validity.     

Fibronectin: An Interesting Vocal Fold Protein

A great deal of information is accruing regarding the function of the extracellular matrix. Once thought to be simply a structural entity to surround cells, it is now known to do much more. Fibronectin in particular has received specific attention. Fibronectin is a ubiquitous glycoprotein found most abundantly in the extracellular matrix of regenerating, healing, and embryonic tissue. Vast evidence supports the fact that fibronectin participates in many diverse functions throughout the body that are relevant to vocal fold biology. This article introduces the structure of fibronectin and its isoforms and provides an introduction to some of the many functions it plays. It also reviews the evidence about fibronectin's place in vocal folds and vocal fold pathology. It discusses fibronectin's presence in vocal nodules, vocal polyps, vocal scarring, and Reinke's edema, and reviews the data on its role in mucosal wave impairment. Lastly, it discusses preliminary microarray data that show gene expression for fibronectin to be upregulated in true vocal folds when compared to false vocal folds.     

Short-Term Therapeutic Trial of Proton Pump Inhibitors in Suspected Extraesophageal Reflux

Pharyngoesophageal gastric acid reflux is thought to initiate chronic posterior laryngitis. The gold standard for measuring gastric reflux is dual-channel 24-hour pH monitoring. This is a time-consuming, inconvenient, expensive method that is not available in all areas. New therapeutic regimes that make use of proton pump inhibitors (PPIs) have proven to be therapeutically efficient for control of acid reflux. Twenty-four consecutive patients with chronic voice disorders and signs of posterior laryngitis were selected for therapy. Twenty-four hour pH monitoring was performed independently before the therapy. The trial therapy consisted of all patients receiving pantoprazole, 40 mg once daily for 6 weeks. Immediately following the therapy a statistically significant (p < 0.05) improvement was observed in all patients. This improvement was analyzed retrospectively by comparison with the results of 24-hour pH monitoring. In 71% of the patients the 24-hour pH-monitoring gave a positive result showing a high number of patients with extraesophageal reflux in our study group. Patients with positive results of pH-monitoring responded in a statistically significant manner (p < 0.05) to the pantoprazole therapy, whereas those patients without detected reflux did not. A 3-month follow-up of the patients with a positive result of the pH-monitoring confirmed the improvement. No patients reported adverse effects. A 6-week treatment with pantoprazole can be clinically justified. It helps to save time and reduce costs, allows for selection of reflux-negative patients for alternative therapy, and may prevent inadequate treatment of patients with false-negative pH monitoring. Twenty-four hour pH monitoring is still recommended for patients unresponsive to this trial therapy.     

Electrophysiologic monitoring of the recurrent laryngeal nerves may not predict bilateral vocal fold immobility after thyroid surgery

Two cases of bilateral vocal fold immobility (VFI) after identification and preservation of the recurrent laryngeal nerves (RLNs) required tracheotomy until vocal fold recovery. The first patient underwent thyroid surgery without preoperative or postoperative evaluation of the vocal folds, administration of postoperative intravenous steroids, or electrophysiologic monitoring of the RLNs, whereas the second patient underwent a thyroid procedure in which all of the aforementioned were executed. Preoperative and postoperative clinical evaluation of the RLNs is strongly suggested in patients undergoing thyroid surgery, especially revision surgery. Patients potentially undergoing total thyroidectomy should be counseled about the remote chance of airway obstruction and should be properly selected for this operation. Subclinical stretching of the RLNs or ischemia from the endotracheal tube cuff can result in unilateral VFI, and rarely bilateral VFI, requiring reintubation, tracheotomy, or vocal fold lateralization. Electrophysiologic monitoring may not always predict bilateral VFI.     

Stability and convergence of the spectral Lagrange-Galerkin method for mixed periodic/non-periodic convection-dominated diffusion problems

We present a convergence analysis of the spectral Lagrange-Galerkinmethod for mixed periodic/non-periodic convection-diffusionproblems. The scheme is unconditionally stable, independentof the diffusion coefficient, even in the case when numericalquadrature is used. The theoretical predictions are illustratedby a series of numerical experiments. For the periodic case,our results present a significant improvement on those givenby Süli & Ware (1991) SIAM J. Numer.Anal.28, 423-445).     

Tests of significance using selected sample quantiles

Large sample tests of significance for the location parameter, the scale parameter, and quantiles for a location-scale family of distributions based on a few optimally chosen sample quantiles are considered.     

Effects of Testosterone Replacement on a Male Professional Singer

Testosterone has been known to play an important role in the development of the postpubertal male voice for many centuries. In fact, the prevention of pubertal development of the voice by castrating young male singers was a well-known practice, especially in Italy beginning in the sixteenth century. The “castrati” were well known for their clear, high-pitched voices. Because of the resulting small larynx and vocal folds, castrati apparently produced a distinctive resonance as well as the high pitch, which cannot be matched even by the counter tenors of today. Busy voice labs occasionally see males with sex hormone deficiencies secondary to chromosomal or gonadal problems. This is a presentation of an unusual patient who was a trained tenor singer and was found to have hypogonadism on a premarital health examination. Administration of replacement testosterone resulted in significant vocal register and voice quality changes.