The first influenza pandemic in the new millennium: lessons learned hitherto for current control efforts and overall pandemic preparedness

Influenza viruses pose a permanent threat to human populations due to their ability to constantly adapt to impact immunologically susceptible individuals in the forms of epidemic and pandemics through antigenic drifts and antigenic shifts, respectively. Pandemic influenza preparedness is a critical step in responding to future influenza outbreaks. In this regard, responding to the current pandemic and preparing for future ones requires critical planning for the early phases where there is no availability of pandemic vaccine with rapid deployment of medical supplies for personal protection, antivirals, antibiotics and social distancing measures. In addition, it has become clear that responding to the current pandemic or preparing for future ones, nation states need to develop or strengthen their laboratory capability for influenza diagnosis as well as begin preparing their vaccine/antiviral deployment plans. Vaccine deployment plans are the critical missing link in pandemic preparedness and response. Rapid containment efforts are not effective and instead mitigation efforts should lead pandemic control efforts. We suggest that development of vaccine/antiviral deployment plans is a key preparedness step that allows nations identify logistic gaps in their response capacity.     

Mutation-induced spatial differences in neuraminidase structure and sensitivity to neuraminidase inhibitors

Neuraminidase(NA), a major surface glycoprotein of influenza virus with well-defined active sites, is an ideal platform for the development of antiviral drugs. However, a growing number of NA mutations have drug resistance to today's inhibitors. Numerous efforts are made to explore the resistance mechanisms through understanding the structural changes in mutated NA proteins and the associated different binding profiles of inhibitors, via x-ray, nuclear magnetic resonance,electron microscopy, and molecular dynamics methods. This review presents the architectural features of mutated NA proteins, as well as the respective inhibitor sensitivities arising from these spatial differences. Finally, we summarize the resistance mechanisms of today's neuraminidase inhibitors and the outlook for the development of novel inhibitors.     

Strobovideolaryngoscopic Findings in Singing Teachers

Professional voice users often present to otolaryngologists and laryngologists with specific voice complaints. The contributions of pathologic lesions to the patients' vocal complaints are not always clear on examination, and often, premorbid examinations of the larynx are not available for review. This study examines the incidence of laryngeal pathology among singing teachers. At a national convention of singing teachers, volunteers were recruited for a "free strobovideolaryngoscopic examination." All volunteers completed a detailed questionnaire of their vocal and medical history and underwent strobovideolaryngoscopic examination. Strobovideolaryngoscopic examinations were completed in 20 volunteers, 7 of whom had voice complaints and 13 of whom perceived their voices to be normal. Vocal fold masses were common among the asymptomatic singing teachers. Evidence of reflux laryngitis was a common finding among both symptomatic and asymptomatic singing teachers. Asymmetries in vocal fold hypomobility were more common among those with voice complaints than was the presence of vocal fold masses in the population studied.     

From Bulk to Nanoparticles: An Overview of Antiviral Materials,Its Mechanisms,and Applications

Infectious diseases caused by viruses are a global health concern and have become prominent in light of the recent COVID-19 pandemic. Considering the limitations of drugs and prophylactic methods used in current medicine, antiviral materials are a useful strategy in preventing the spread of viruses and enhancing treatment efficiency. Thus, this review highlights the state-of-the-art antiviral materials, describes the scientific landscape of the primary antiviral materials used based on bibliometric analysis, presents their mechanisms of action, and discusses their clinical applications. The mechanisms of action underlying the broad-spectrum antiviral properties of metals, ceramics, polymers, and composites are also discussed. Polyanions, polycations, oxides, and metal-based materials, from bulk to nanoparticles, have good potential in antiviral applications that may help prepare the world for future viral breakouts.     

Personality,Psychological Factors,and Behavioral Tendencies in Children With Vocal Nodules: A Systematic Review

ObjectivesThis systematic review examined the evidence linking vocal nodule development in children to personality traits, psychological factors, and associated behavioral tendencies.MethodsFour electronic databases—PubMed, Scopus, ScienceDirect, EBSCO Host—as well as the reference lists from articles (including online sources) were searched. After screening for relevance, eight comparative, case-control studies were identified that met inclusion criteria. The quality of each study was evaluated by two raters using a modified, standardized checklist.ResultsFour studies were rated as “good quality” and four were “fair”. The questionnaires used to measure personality or psychological factors varied widely among the studies, and the results linking personality dispositions (and associated behavioral inclinations) to vocal nodule development in children were mixed.ConclusionsFair to good quality evidence exists to suggest that psychological factors or personality traits related to extraversion and impulsivity (and their related behavioral inclinations) might predispose children to vocal nodules and deserve further attention. Clinical implications, limitations of the current systematic review, and recommendations for future research are also discussed.     

Response of Asthma-Related Voice Dysfunction to Allergen Immunotherapy: A Case Report of Confirmation by Methacholine Challenge

Professional singers and other serious voice users are particularly susceptible to alterations in their vocal apparatus. As the support for vocalization, lung function is an essential element of the production of speech and song. Patients have been described who presented with voice complaints along with minimal or no abnormalities on spirometry, but responded to conventional bronchodilator and other asthma therapy. It was proposed that this represented an exercise-induced asthmalike condition, brought on by the hyperventilation associated with performing. The objective of this study was to establish whether improvement in vocalization while performing correlated with a decrease in nonspecific bronchial reactivity.We concluded that resolution of vocal complaints in conjunction with a decrease in methacholine reactivity supports the hypothesis that these patients do have an exercise-induced asthmalike condition brought on by airway drying. As with other patients with asthma, it appears to respond to allergy-directed therapy.     

Patterns in the vocalizations of male harbor seals

Comparative analyses of the roar vocalization of male harbor seals from ten sites throughout their distribution showed that vocal variation occurs at the oceanic, regional, population, and subpopulation level. Genetic barriers based on the physical distance between harbor seal populations present a likely explanation for some of the observed vocal variation. However, site-specific vocal variations were present between genetically mixed subpopulations in California. A tree-based classification analysis grouped Scottish populations together with eastern Pacific sites, rather than amongst Atlantic sites as would be expected if variation was based purely on genetics. Lastly, within the classification tree no individual vocal parameter was consistently responsible for consecutive splits between geographic sites. Combined, these factors suggest that site-specific variation influences the development of vocal structure in harbor seals and these factors may provide evidence for the occurrence of vocal dialects.     

A report on alterations to the speaking and singing voices of four women following hormonal therapy with virilizing agents

Four women aged between 27 and 58 years sought otolaryngological examination due to significant alterations to their voices, the primary concerns being hoarseness in vocal quality, lowering of habitual pitch, difficulty projecting their speaking voices, and loss of control over their singing voices. Otolaryngological examination with a mirror or flexible laryngoscope revealed no apparent abnormality of vocal fold structure or function, and the women were referred for speech pathology with diagnoses of functional dysphonia. Objective acoustic measures using the Kay Visipitch indicated significant lowering of the mean fundamental frequency for each woman, and perceptual analysis of the patients' voices during quiet speaking, projected voice use, and comprehensive singing activities revealed a constellation of features typically noted in the pubescent male. The original diagnoses of a functional dysphonia were queried, prompting further exploration of each woman's medical history, revealing in each case onset of vocal symptoms shortly after commencing treatment for conditions with medications containing virilizing agents (eg, Danocrine (danazol), Deca-Durabolin (nandrolene decanoate), and testosterone). Although some of the vocal symptoms decreased in severity with the influences from 6 months voice therapy and after withdrawal from the drugs, a number of symptoms remained permanent, suggesting each subject had suffered significant alterations in vocal physiology, including muscle tissue changes, muscle coordination dysfunction, and propioceptive dysfunction. This retrospective study is presented in order to illustrate that it was both the projected speaking voice and the singing voice that proved so highly sensitive to the virilization effects. The implications for future prospective research studies and responsible clinical practice are discussed.     

Paradoxical vocal fold motion: Presentation and treatment options

Paradoxical vocal fold motion is a rare disorder in which adduction of the folds occurs on inspiration. The disorder presents with signs of airway obstruction and often airway distress, so proper diagnosis by the otorhinolaryngologist is critical to subsequent management. We present a retrospective review of 10 patients with the diagnosis of paradoxical vocal fold motion seen over a 6-year period. Eight patients were females, and 6 required an acute airway intervention at presentation; 3 patients eventually underwent tracheotomy for respiratory decompensation. Six patients had a prior diagnosis of asthma, and this was determined to contribute to their respiratory status. Five patients were treated with botulinum toxin and 2 with flexible nasolaryngoscopic biofeedback, which improved the outcome. A review of the literature confirms a female predominance of patients presenting with paradoxical adduction and airway distress, often with a history of asthma and psychopathology. Our experience with botulinum toxin and biofeedback suggests that these procedures are viable treatment options in the management of patients with this disorder.     

Current Understanding and Review of the Literature: Vocal Fold Scarring

Vocal fold scarring is the greatest cause of poor voice after vocal fold injury. Scarring causes a disruption of the viscoelastic layered structure of the lamina propria, an increase in stiffness of the vibratory structure, and glottic incompetence. Current treatments for this complex condition are inconsistent and often produce suboptimal results. Research investigating this condition has dramatically increased over the last several years. The literature has been directed toward understanding vocal fold scarring at the biological level and translating this to the clinical forum. We present an up-to-date, thorough, and scholarly review of the literature in vocal fold scarring since 1996.     

Vocal quality characteristics in children with cleft palate: a multiparameter approach

The main purpose of the present study was to examine the vocal quality and to investigate the effects of gender on vocal quality in 28 children with a unilateral or bilateral cleft palate. In this study, the vocal quality was determined using videolaryngostroboscopic and perceptual evaluations, aerodynamic, voice range, acoustic, and dysphonia severity index (DSI) measurements. The DSI is based on the weighted combination of four voice measurements and ranges from +5 to -5 for, respectively, normal and severely dysphonic voices. Additional objectives were to compare the vocal quality characteristics of children with cleft palate with the available normative data and to investigate the impact of the cleft type on vocal quality. Gender-related vocal quality differences were found. The male cleft palate children showed an overall vocal quality of +0.62 with the presence of a perceptual slight grade of hoarseness and roughness. The female vocal quality had a DSI value of +2.4 reflecting a perceptually normal voice. Irrespective of the type of cleft, all subjects demonstrated a significantly lower DSI-value in comparison with the available normative data. The results of the present study have provided valuable insights into the vocal quality characteristics of cleft palate children.     

Superior laryngeal nerve paresis and paralysis

Superior laryngeal nerve paresis and paralysis are relatively common but often difficult to diagnose with certainty. They are most commonly caused by viral infections, though other etiologies must be considered. A thorough history and physical examination, including strobovideolaryngoscopy and laryngeal electromyography, are needed for definitive diagnosis. It is essential to establish the diagnosis accurately to differentiate an apparent superior laryngeal nerve paresis from other conditions, such as myasthenia gravis. Laryngeal electromyography is used to confirm clinical impressions, as a guide for therapy, and as one measure of recovery. In our experience, accurate and early diagnosis assure the best phonatory outcome by directing therapy that will prevent or eliminate compensatory vocal abuses, which may themselves lead to even more serious vocal injury.     

Sex hormones and the female voice

In the following, the authors examine the relationship between hormonal climate and the female voice through discussion of hormonal biochemistry and physiology and informal reporting on a study of 197 women with either premenstrual or menopausal voice syndrome. These facts are placed in a larger historical and cultural context, which is inextricably bound to the understanding of the female voice. The female voice evolves from childhood to menopause, under the varied influences of estrogens, progesterone, and testosterone. These hormones are the dominant factor in determining voice changes throughout life. For example, a woman's voice always develops masculine characteristics after an injection of testosterone. Such a change is irreversible. Conversely, male castrati had feminine voices because they lacked the physiologic changes associated with testosterone. The vocal instrument is comprised of the vibratory body, the respiratory power source and the oropharyngeal resonating chambers. Voice is characterized by its intensity, frequency, and harmonics. The harmonics are hormonally dependent. This is illustrated by the changes that occur during male and female puberty: In the female, the impact of estrogens at puberty, in concert with progesterone, produces the characteristics of the female voice, with a fundamental frequency one third lower than that of a child. In the male, androgens released at puberty are responsible for the male vocal frequency, an octave lower than that of a child. Premenstrual vocal syndrome is characterized by vocal fatigue, decreased range, a loss of power and loss of certain harmonics. The syndrome usually starts some 4-5 days before menstruation in some 33% of women. Vocal professionals are particularly affected. Dynamic vocal exploration by televideoendoscopy shows congestion, microvarices, edema of the posterior third of the vocal folds and a loss of its vibratory amplitude. The authors studied 97 premenstrual women who were prescribed a treatment of multivitamins, venous tone stimulants (phlebotonics), and anti-edematous drugs. We obtained symptomatic improvement in 84 patients. The menopausal vocal syndrome is characterized by lowered vocal intensity, vocal fatigue, a decreased range with loss of the high tones and a loss of vocal quality. In a study of 100 menopausal women, 17 presented with a menopausal vocal syndrome. To rehabilitate their voices, and thus their professional lives, patients were prescribed hormone replacement therapy and multi-vitamins. All 97 women showed signs of vocal muscle atrophy, reduction in the thickness of the mucosa and reduced mobility in the cricoarytenoid joint. Multi-factorial therapy (hormone replacement therapy and multi-vitamins) has to be individually adjusted to each case depending on body type, vocal needs, and other factors.     

Vocal Fatigue—Do Young Speech-Language Pathologists Practice What They Preach?

PurposeSpeech-Language Pathologists can be categorized as Level II professional voice users who play the roles of voice therapist or vocal coach to treat voice problems. SLPs may be at the risk of experiencing vocal fatigue due to vocal loading and other contributing factors. The present study was undertaken to find the percentage of SLPs reporting vocal fatigue, the probable factors resulting in vocal fatigue, the measures that are taken to avoid/reduce the occurrence of vocal fatigue, its effect on their professional and personal life and the measures taken to tackle it.ResultsThe results of this study are based on data collected from 142 SLPs and 50 controls using a questionnaire. 71.13% SLPs reported that they experience vocal fatigue. Some of the contributing factors that are mainly reported are long durations of voice use, voice use for recreational purposes, speaking loudly, frequent throat clearing, lack of adequate hydration and working in noisy or air-conditioned environments. The major symptoms reported were dryness in throat, tightness in neck and shoulder, choking sensation, effortful speech and pain in the throat. 59% SLPs reported that vocal fatigue affected their professional life while 44% SLPs reported that it affects their personal life also to varying degrees. Measures taken to avoid/ reduce the occurrence of vocal fatigue included vocal warm up, break in between sessions, and play activities. Only a few SLPs took intervention measures like ENT consultation, voice therapy, and home remedies.ConclusionSLPs are inevitably at high risk of experiencing vocal fatigue which, if left untreated, will lead to organic voice problems. However, many young SLPs who experience vocal fatigue reported vocal abuse, do not follow vocal hygiene program and do not follow evidence-based preventive or intervention practices to treat vocal fatigue.     

Two-dimensional model of vocal fold vibration for sound synthesis of voice and soprano singing

Voiced sounds were simulated with a computer model of the vocal fold composed of a single mass vibrating both parallel and perpendicular to the airflow. Similarities with the two-mass model are found in the amplitudes of the glottal area and the glottal volume flow velocity, the variation in the volume flow waveform with the vocal tract shape, and the dependence of the oscillation amplitude upon the average opening area of the glottis, among other similar features. A few dissimilarities are also found in the more symmetric glottal and volume flow waveforms in the rising and falling phases. The major improvement of the present model over the two-mass model is that it yields a smooth transition between oscillations with an inductive load and a capacitive load of the vocal tract with no sudden jumps in the vibration frequency. Self-excitation is possible both below and above the first formant frequency of the vocal tract. By taking advantage of the wider continuous frequency range, the two-dimensional model can successfully be applied to the sound synthesis of a high-pitched soprano singing, where the fundamental frequency sometimes exceeds the first formant frequency.     

Laryngeal Manifestations of Postpoliomyelitis Syndrome

Postpoliomyelitis syndrome (PPS) is a disease that may occur in survivors of acute poliomyelitis several decades after their initial infection. It can present as dysphonia, with vocal weakness and fatigue. Swallowing, respiratory, and other laryngopharyngeal symptoms may be manifestations of the disease or they may represent worsening of previously stable and compensated deficits. Three cases of laryngeal changes in PPS with videostroboscopic and laryngeal electromyography findings highlight the features of this disorder. We review possible etiologies of laryngeal PPS, diagnostic criteria, and treatment, as well as the current literature.     

Vocal Nodules and Laryngeal Morphology

Our purpose was to study the occurrence of vocal fold nodules under conditions of habitual vocal abuse associated with increased laryngeal muscle tension, to identify the existence of a relationship between vocal nodules and laryngeal morphology. We studied one group of 30 subjects with vocal nodules, 18 to 50 years old, who were compared with two control groups, one of females and one of males, consisting of 30 subjects each. The parameters evaluated were: type of vocal folds coaptation, glottic proportion (GP) and abduction angle (AA), obtained by videotelelaryngoscopy. In the nodules group, the larynges presented a mean value of GP similar to that of the female group, both of which were lower than the mean GP value of the male group. On the other hand, the mean AA was lower than the one in the female group, and closer to the one in the male group. We concluded that vocal nodules were present only in larynges with a predominantly young female morphology, with functional limitations of abduction.     

Three-dimensional vocal tract imaging and formant structure: varying vocal register, pitch, and loudness

Although advances in techniques for image acquisition and analysis have facilitated the direct measurement of three-dimensional vocal tract air space shapes associated with specific speech phonemes, little information is available with regard to changes in three-dimensional (3-D) vocal tract shape as a function of vocal register, pitch, and loudness. In this study, 3-D images of the vocal tract during falsetto and chest register phonations at various pitch and loudness conditions were obtained using electron beam computed tomography (EBCT). Detailed measurements and differences in vocal tract configuration and formant characteristics derived from the eight measured vocal tract shapes are reported.     

Physiological mechanisms of vocal frequency control: The role of tension

Control of fundamental frequency by the human voice may be accomplished using a variety of physiological mechanisms. Most of these mechanisms are myoelastic and include the length, mass, and longitudinal tension of the vocal folds. In this paper, a review of some of the data concerning the mechanisms for the creation of tension in the vocal folds is presented. The physiological mechanisms for the development of passive tension are reviewed and the potential contribution of passive tension in the control of fundamental frequency is discussed. Some of the mechanisms for the development of active muscle tension are described and the biomechanical characteristics of muscle are considered in the effort to explain the physiological control of fundamental frequency in the human voice     

Vocal tract area functions and formant frequencies in opera tenors' modal and falsetto registers

According to recent model investigations, vocal tract resonance is relevant to vocal registers. However, no experimental corroboration of this claim has been published so far. In the present investigation, ten professional tenors' vocal tract configurations were analyzed using MRI volumetry. All subjects produced a sustained tone on the pitch F4 (349 Hz) on the vowel /a/ (1) in modal and (2) in falsetto register. The area functions were estimated from the MRI data and their associated formant frequencies were calculated. In a second condition the same subjects repeated the same tasks in a sound treated room and their formant frequencies were estimated by means of inverse filtering. In both recordings similar formant frequencies were observed. Vocal tract shapes differed between modal and falsetto register. In modal as compared to falsetto the lip opening and the oral cavity were wider and the first formant frequency was higher. In this sense the presented results are in agreement with the claim that the formant frequencies differ between registers.