Cross-Sample Validation Provides Enhanced Proteome Coverage in Rat Vocal Fold Mucosa

The vocal fold mucosa is a biomechanically unique tissue comprised of a densely cellular epithelium, superficial to an extracellular matrix (ECM)-rich lamina propria. Such ECM-rich tissues are challenging to analyze using proteomic assays, primarily due to extensive crosslinking and glycosylation of the majority of high Mr ECM proteins. In this study, we implemented an LC-MS/MS-based strategy to characterize the rat vocal fold mucosa proteome. Our sample preparation protocol successfully solubilized both proteins and certain high Mr glycoconjugates and resulted in the identification of hundreds of mucosal proteins. A straightforward approach to the treatment of protein identifications attributed to single peptide hits allowed the retention of potentially important low abundance identifications (validated by a cross-sample match and de novo interpretation of relevant spectra) while still eliminating potentially spurious identifications (global single peptide hits with no cross-sample match). The resulting vocal fold mucosa proteome was characterized by a wide range of cellular and extracellular proteins spanning 12 functional categories

A Patient-Specific in silico Model of Inflammation and Healing Tested in Acute Vocal Fold Injury

The development of personalized medicine is a primary objective of the medical community and increasingly also of funding and registration agencies. Modeling is generally perceived as a key enabling tool to target this goal. Agent-Based Models (ABMs) have previously been used to simulate inflammation at various scales up to the whole-organism level. We extended this approach to the case of a novel, patient-specific ABM that we generated for vocal fold inflammation, with the ultimate goal of identifying individually optimized treatments. ABM simulations reproduced trajectories of inflammatory mediators in laryngeal secretions of individuals subjected to experimental phonotrauma up to 4 hrs post-injury, and predicted the levels of inflammatory mediators 24 hrs post-injury. Subject-specific simulations also predicted different outcomes from behavioral treatment regimens to which subjects had not been exposed. We propose that this translational application of computational modeling could be used to design patient-specific therapies for the larynx, and will serve as a paradigm for future extension to other clinical domains

Voice disorders and mental health in teachers: a cross-sectional nationwide study

International audienceBACKGROUND:Teachers, as professional voice users, are at particular risk of voice disorders. Among contributing factors, stress and psychological tension could play a role but epidemiological data on this problem are scarce. The aim of this study was to evaluate prevalence and cofactors of voice disorders among teachers in the French National Education system, with particular attention paid to the association between voice complaint and psychological status.METHODS:The source data come from an epidemiological postal survey on physical and mental health conducted in a sample of 20,099 adults (in activity or retired) selected at random from the health plan records of the national education system. Overall response rate was 53%. Of the 10,288 respondents, 3,940 were teachers in activity currently giving classes to students. In the sample of those with complete data (n = 3,646), variables associated with voice disorders were investigated using logistic regression models. Studied variables referred to demographic characteristics, socio-professional environment, psychological distress, mental health disorders (DSM-IV), and sick leave.RESULTS:One in two female teachers reported voice disorders (50.0%) compared to one in four males (26.0%). Those who reported voice disorders presented higher level of psychological distress. Sex- and age-adjusted odds ratios [95% confidence interval] were respectively 1.8 [1.5-2.2] for major depressive episode, 1.7 [1.3-2.2] for general anxiety disorder, and 1.6 [1.2-2.2] for phobia. A significant association between voice disorders and sick leave was also demonstrated (1.5 [1.3-1.7]).CONCLUSION:Voice disorders were frequent among French teachers. Associations with psychiatric disorders suggest that a situation may exist which is more complex than simple mechanical failure. Further longitudinal research is needed to clarify the comorbidity between voice and psychological disorders

The Multifunctional LigB Adhesin Binds Homeostatic Proteins with Potential Roles in Cutaneous Infection by Pathogenic Leptospira interrogans

Leptospirosis is a potentially fatal zoonotic disease in humans and animals caused by pathogenic spirochetes, such as Leptospira interrogans. The mode of transmission is commonly limited to the exposure of mucous membrane or damaged skin to water contaminated by leptospires shed in the urine of carriers, such as rats. Infection occurs during seasonal flooding of impoverished tropical urban habitats with large rat populations, but also during recreational activity in open water, suggesting it is very efficient. LigA and LigB are surface localized proteins in pathogenic Leptospira strains with properties that could facilitate the infection of damaged skin. Their expression is rapidly induced by the increase in osmolarity encountered by leptospires upon transition from water to host. In addition, the immunoglobulin-like repeats of the Lig proteins bind proteins that mediate attachment to host tissue, such as fibronectin, fibrinogen, collagens, laminin, and elastin, some of which are important in cutaneous wound healing and repair. Hemostasis is critical in a fresh injury, where fibrinogen from damaged vasculature mediates coagulation. We show that fibrinogen binding by recombinant LigB inhibits fibrin formation, which could aid leptospiral entry into the circulation, dissemination, and further infection by impairing healing. LigB also binds fibroblast fibronectin and type III collagen, two proteins prevalent in wound repair, thus potentially enhancing leptospiral adhesion to skin openings. LigA or LigB expression by transformation of a nonpathogenic saprophyte, L. biflexa, enhances bacterial adhesion to fibrinogen. Our results suggest that by binding homeostatic proteins found in cutaneous wounds, LigB could facilitate leptospirosis transmission. Both fibronectin and fibrinogen binding have been mapped to an overlapping domain in LigB comprising repeats 9–11, with repeat 11 possibly enhancing binding by a conformational effect. Leptospirosis patient antibodies react with the LigB domain, suggesting applications in diagnosis and vaccines that are currently limited by the strain-specific leptospiral lipopolysaccharide coats

Alteração vocal auto-referida em professores: prevalência e fatores associados

OBJETIVO: Estimar a prevalência de alteração vocal auto-referida em professores e identificar fatores associados. MÉTODOS: Estudo transversal com amostra de 393 professores do ensino fundamental de Florianópolis, SC, por meio de questionário autoaplicado em 2009. Foi realizada análise multivariável de regressão de Poisson estimando-se as razões de prevalência e intervalos de 95% de confiança. RESULTADOS: A prevalência de alteração vocal foi de 47,6% (IC95% 42,6;52,5). Após o ajuste, permaneceram associados à maior prevalência de alteração vocal ser do sexo feminino e a presença de rinite/sinusite e faringite. CONCLUSÕES: Foi observada elevada prevalência de alteração vocal auto-referida entre os professores estudados.OBJETIVO: Estimar la prevalencia de alteración vocal auto-referida en profesores e identificar factores asociados. MÉTODOS: Estudio transversal con muestra de 393 profesores de enseñanza fundamental de Florianópolis, Sur de Brasil, por medio de cuestionario auto-aplicado en 2009. Se realizó análisis multivariable de regresión de Poisson, estimándose las tasas de prevalencia e intervalos de 95% de confianza. RESULTADOS: La prevalencia de alteración vocal fue de 47,6% (IC95% 42,6;52,5). Posterior al ajuste, permanecieron asociados a la mayor prevalencia de alteración vocal ser del sexo femenino y la presencia de rinitis/sinusitis y faringitis. CONCLUSIONES: Se observó elevada prevalencia de alteración vocal auto-referida entre los profesores estudiados.OBJECTIVE: To estimate the prevalence of self-reported voice problems and to identify associated factors. METHODS: A cross-sectional study was carried out in a sample of 393 public elementary and middle school teachers in Florianópolis, Southern Brazil, in 2009. A self-administered questionnaire was used. A multivariable Poisson regression model was performed to estimate prevalence ratios and their related 95% confidence intervals. RESULTS: The prevalence of voice problems was 47.6% (95%CI 42.6;52.5). In the final adjusted analysis the following variables remained associated with a higher prevalence of voice problems: being female and the presence of rhinitis/sinusitis and pharyngitis. CONCLUSIONS: A high prevalence of self-reported voice problems was found among the teachers studied

Adapted to Roar: Functional Morphology of Tiger and Lion Vocal Folds

Vocal production requires active control of the respiratory system, larynx and vocal tract. Vocal sounds in mammals are produced by flow-induced vocal fold oscillation, which requires vocal fold tissue that can sustain the mechanical stress during phonation. Our understanding of the relationship between morphology and vocal function of vocal folds is very limited. Here we tested the hypothesis that vocal fold morphology and viscoelastic properties allow a prediction of fundamental frequency range of sounds that can be produced, and minimal lung pressure necessary to initiate phonation. We tested the hypothesis in lions and tigers who are well-known for producing low frequency and very loud roaring sounds that expose vocal folds to large stresses. In histological sections, we found that the Panthera vocal fold lamina propria consists of a lateral region with adipocytes embedded in a network of collagen and elastin fibers and hyaluronan. There is also a medial region that contains only fibrous proteins and hyaluronan but no fat cells. Young's moduli range between 10 and 2000 kPa for strains up to 60%. Shear moduli ranged between 0.1 and 2 kPa and differed between layers. Biomechanical and morphological data were used to make predictions of fundamental frequency and subglottal pressure ranges. Such predictions agreed well with measurements from natural phonation and phonation of excised larynges, respectively. We assume that fat shapes Panthera vocal folds into an advantageous geometry for phonation and it protects vocal folds. Its primary function is probably not to increase vocal fold mass as suggested previously. The large square-shaped Panthera vocal fold eases phonation onset and thereby extends the dynamic range of the voice