Rehabilitation Treatment Specification System: Content and Criterion Validity Across Evidence-Based Voice Therapies for Muscle Tension Dysphonia.

PURPOSE: Systematically improving voice therapy outcomes is challenging as the clinician actions (i.e., active ingredients) responsible for improved patient functioning (i.e., targets) are relatively unknown. The theory-driven Rehabilitation Treatment Specification System (RTSS) and standard, voice-specific terminology based on the RTSS (RTSS-Voice) may help address this problem. This qualitative study evaluated if the RTSS and RTSS-Voice can describe four evidence-based voice therapies for muscle tension dysphonia without missing critical aspects (content validity) and identify commonalities and differences across them (criterion validity). METHOD: Qualitative interviews were completed between the clinicians (protocol experts) who developed and/or popularized the vocal function exercises, laryngeal reposturing, circumlaryngeal massage, and conversation training therapies as well as RTSS experts to produce RTSS specifications that met two consensus criteria: (a) The protocol expert agreed that the specification represented their treatment theory, and (b) the RTSS experts agreed that the specifications correctly adhered to both the RTSS framework and the RTSS-Voice's standard terminology. RESULTS: The RTSS and RTSS-Voice comprehensively described voice therapy variations across and within the four diverse treatment programs, needing only the addition of one new target: overall auditory-perceptual severity. CONCLUSIONS: The RTSS and RTSS-Voice exhibited strong content validity. The standard RTSS-Voice terminology helped identify, for the first time, commonalities and differences in treatment ingredients, targets, and mechanisms of action across four treatments developed for the same patient population. In the long term, the RTSS and RTSS-Voice could provide the framework for an ever-growing collection of clinically meaningful and evidence-based therapy algorithms with potential to improve research, education, and clinical care. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.25537624.

Prevalence of Anxiety as a Variable in Treatment Outcomes for Individuals With Chronic Refractory Cough.

PURPOSE: Anxiety is a mental state characterized by an intense sense of tension, worry, or apprehension relative to something adverse that might happen in the future. Anxiety is a known comorbidity in cough patients, yet its prevalence among those with chronic refractory cough (CRC) is unknown. Anxiety is not typically assessed during evaluation for CRC, but treatments for CRC such as neuromodulators and behavioral cough suppression therapy (BCST) may potentially attenuate anxiety. This preliminary study investigates the potential prevalence of anxiety in CRC and its possible role in treatment outcomes. METHOD: CRC patients seen in a specialty clinic at the University of Utah or the University of Montana completed the Leicester Cough Questionnaire (LCQ) pre- and post-BCST treatment. Participants were dichotomized into positive anxiety screen (PAS) and negative anxiety screen (NAS) groups based on presence or absence of documented anxiety within electronic medical records at the University of Utah and based on a Generalized Anxiety Disorder-7 score > 5 at the University of Montana. RESULTS: Of the 86 total participants, 37 (43%) were in the PAS group (29 females, Mage = 56 ± 13) and 49 (57%) were in the NAS group (36 females, Mage = 64 ± 14). Eighty-nine percent of CRC participants with a PAS reported a clinically meaningful improvement in LCQ total score following treatment compared to 65% of NAS participants. Furthermore, mean pre- to posttreatment change scores on the LCQ were significantly greater within the PAS group (p = .002, Cohen's d = 0.7, indicating a moderate to large effect size). CONCLUSION: This preliminary study suggests that (a) anxiety may be prevalent among those with CRC and (b) those patients who screen positive for anxiety report greater benefit from BCST.

Exploring Personality and Perceived Present Control as Factors in Postsurgical Voice Rest: A Case Comparison.

OBJECTIVE: This case comparison explored the relation between personality, perceived present control, and postoperative voice rest (as estimated by self-report and objective voice use) following surgery for benign vocal fold lesions. METHOD: Two participants were included. Both participants were diagnosed with benign vocal fold pathology, underwent phonosurgery, and were assigned to either complete voice rest (CVR) or relative voice rest (RVR) postoperatively. During voice rest (VR), a visual analog scale (VAS) and a dosimeter (the Vocalog2) were used daily to estimate self-perceived and objective voice use, respectively. The participants also completed questionnaires on voice-related demographics, the Voice Handicap Index (VHI), Ten-Item Personality Inventory (TIPI), and Perceived Present Control (PPC). After 7 days of CVR or RVR, participants completed a postoperative questionnaire and a final VAS for overall voice use. RESULTS: A wide discrepancy was observed in one of two participant's subjective perception of voice use (using the VAS) versus objective dosimetry data wherein she reported significantly more voice use than was observed objectively. Differences in personality and PPC between the participants did not appear to affect their voice use following the VR protocols. CONCLUSION: The amount of voice use in both VR protocols for these two participants suggests that personality and PPC did not affect their adherence to recommendations of VR. Patients may perceive their voice use differently across time, which might play a role in their adherence to voice rest recommendations: voice use measured as instances versus a unit of time (seconds).

Emotional Adjustment in Children with Vocal Fold Nodules.

INTRODUCTION: Vocal fold nodules (VNs) in children are benign, bilateral, callous-like lesions at the junction of the anterior third and posterior two-thirds of the true vocal folds. Chronic, repetitive, and intense vocal behavior is often cited as the primary etiology; however, difficulties with emotional adjustment may predispose some children towards extreme and possibly phonotraumatic vocal activity, thereby contributing secondarily to the development of VNs. OBJECTIVES: This case-control study examined the association between features of emotional adjustment and VNs in children. METHODS: Parents of children with VNs (N = 40, Mage = 7.5, SDage = 2.03) and two medical control groups [ie, voice disordered, but not VNs (VDCs; N = 40, Mage= 7.09, SDage = 2.01) and vocally normal controls (VNCs; N = 40, Mage = 7.6, SDage = 1.54)] participated in the study. Features of emotional adjustment were assessed using two inventories: the Parent Rating scale for Reactive and Proactive Aggression and the Revised Child Anxiety and Depression Scale - Parent version. RESULTS: As compared with the VNCs, children with VNs were significantly more aggressive (P = 0.042, Cohen's d = 0.47) whereas the VDCs were more depressed (P = 0.013, Cohen's d = 0.60). Furthermore, VDCs experienced more separation anxiety than VNs (P = 0.038, Cohen's d = 0.45) and VNCs (P = 0.021, Cohen's d = 0.55). No other significant between-group differences were identified between the VNs and VDCs. CONCLUSIONS: When present, elevated aggression may represent a risk factor for VNs formation in children, and possibly influence treatment outcomes. Therefore, the current results highlight the importance of understanding the role of emotional adjustment in the evaluation and treatment of dysphonia in children.

Behavioral Treatment Approaches to Lowering Pitch in the Female Voice.

PURPOSE: To assess the outcomes of three voice therapy treatment approaches with an emphasis on lowering speaking pitch. Transmasculine and cisgender individuals may desire to lower their speaking pitch, yet there has not been a method described in the literature to do this effectively using only behavioral techniques. METHOD: To investigate these approaches, we enrolled 32 adult cisgender females and randomly assigned them to one of four treatment groups: vocal function exercises (VFE), resonant voice therapy (RVT), lip-rounding therapy (LRT), and a control group. Participants received individual instruction and feedback on the given exercise program, and they continued to practice daily for 4 weeks. RESULTS: Acoustic recordings were collected before treatment, immediately after the first session, and after 4 weeks of treatment. Results showed a lower minimum pitch in the physiological range, lower speaking fundamental frequency (SFF) in reading, and lower SFF in spontaneous speech-with treatment groups performing better than the control group. Additionally, participants' self-rating of the vocal effort expended to speak in a low pitch decreased over the treatment period. CONCLUSIONS: Each treatment approach (VFE, RVT, and LRT) was successful in lowering the speaking pitch of cisgender females. These methods would likely be useful for clients seeking to speak in a lower pitch. Future research may expand results to include clinical populations, such as transmasculine individuals.

Self-regulation in children with vocal fold nodules: A multilevel analysis.

INTRODUCTION: Vocal fold nodules (VNs) represent the most common cause of voice disorders in children. Phonotrauma related to chronic, repetitive, intense vocal activity is often cited as the proximate cause of VNs. However, diminished self-regulation (SR) may predispose some children toward extreme phonotraumatic voice use, thereby contributing secondarily to their development. This case-control study examined the association between features of SR and VNs in children. METHOD: Parents of children with VNs (N = 40, Age Mean = 7.5, SD = 2.03 years) and vocally normal, medical controls (VNCs; N = 40, Age Mean = 7.6, SD = 1.54 years) completed the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF2; Gioia, Isquith, Guy & Kenworthy, 2015), an inventory that evaluates components of SR in children. RESULTS: Children with VNs, as compared with the vocally normal control group, were described as (i) impulsive (i.e., scoring significantly worse on the Behavior Regulation Index, BRI; P < 0.001, Cohen's d = 0.86), and (ii) emotionally dysregulated (i.e., scoring significantly worse on the Emotional Regulation Index, ERI; P < 0.001, Cohen's d = 0.81). CONCLUSIONS: Diminished SR in some children with VNs may contribute to phonotraumatic vocal behaviors and potentially attenuate the effectiveness of voice therapy.

Relationships Among Personality, Daily Speaking Voice Use, and Phonotrauma in Adult Female Singers.

PURPOSE: This study sought to determine whether personality traits related to extraversion and impulsivity are more strongly associated with singers with nodules compared to vocally healthy singers and to understand the relationship between personality and the types of daily speaking voice use. METHOD: Weeklong ambulatory voice recordings and personality inventories were obtained for 47 female singers with nodules and 47 vocally healthy female singers. Paired t tests investigated trait differences between groups. Relationships between traits and weeklong speaking voice measures (vocal dose, sound pressure level [SPL], neck surface acceleration magnitude [NSAM], fundamental frequency, cepstral peak prominence [CPP], and the ratio of the first two harmonic magnitudes [H 1 -H 2]) were examined using pairwise Pearson r coefficients. Multiple regressions were performed to estimate voice parameters that correlated with two or more traits. RESULTS: Singers with nodules scored higher on the Social Potency scale (reflecting a tendency toward social dominance) and lower on the Control scale (reflecting impulsivity) compared to the vocally healthy singers. In vocally healthy singers, vocal dose measures were positively correlated with a combination of Wellbeing (i.e., happiness) and Social Potency, mean SPL was positively correlated with Wellbeing, SPL variability was positively correlated with Social Potency and negatively with Harm Avoidance, and CPP mean was positively correlated with Wellbeing. Singers with nodules had a negative correlation between NSAM skewness and Social Potency. Both groups had negative correlations between H 1 -H 2 mean and Social Potency and Social Closeness. CONCLUSIONS: Singers with nodules are more socially dominant and impulsive than vocally healthy singers. Personality traits are related to daily speaking voice use, particularly in vocally healthy singers. Individuals with higher levels of traits related to happiness and social dominance and lower Harm Avoidance tended to speak more, with higher laryngeal forces, with more SPL variability, and with more pressed glottal closure, which could increase risk of phonotrauma.

Personality in Children With Vocal Fold Nodules: A Multitrait Analysis.

Purpose Vocal fold nodules (VNs) are bilateral, symmetrical, callous-like lesions secondary to phonotrauma and possibly related to specific personality traits. This case-control study examined the relation between personality and VNs in children within the context of the Trait Theory of VNs. Method Parents of children with VNs (N = 39, M = 7.43, SD = 2.01 years) and two medical control groups (i.e., voice disordered controls, but not VNs [VDCs; N = 40, M = 7.09, SD = 2.01 years] and vocally normal controls [VNCs; N = 40, M = 7.6, SD = 1.54 years]) completed the Inventory of Child Individual Differences, a personality instrument that describes the Big Five superfactors as well as 15 lower order personality traits. Results Children with VNs, as compared with VNCs, were (a) emotionally reactive (i.e., higher N-Neuroticism, p < .005, Cohen's d = 0.53), (b) Antagonistic, Strong-Willed, and less Compliant (i.e., lower A-Agreeableness, p < .014, Cohen's d = 0.59), and (c) Distractible and Disorganized (i.e., lower C-Conscientiousness, p < .009, Cohen's d = 0.62). Both voice disordered groups displayed elevated scores on the personality superfactor of Neuroticism (N; and the "Negative Emotions" lower order trait). Conclusions The combination of personality traits identified in this study (i.e., high N, low A and C) may play a central role in VNs development and possibly attenuate voice therapy success. Children with VNs displayed a similar personality typology as women with VNs, with the exception of elevated Extraversion (E), thereby providing support for the relevance of the Trait Theory of VNs in both children and adults. Clinicians treating children with voice disorders, including VNs, should consider their underlying personality traits in assessment and management.

Voice Therapy According to the Rehabilitation Treatment Specification System: Expert Consensus Ingredients and Targets.

Purpose Clinical trials have demonstrated that standardized voice treatment programs are effective for some patients, but identifying the unique individual treatment ingredients specifically responsible for observed improvements remains elusive. To address this problem, the authors used a taxonomy of voice therapy, the Rehabilitation Treatment Specification System (RTSS), and a Delphi process to develop the RTSS-Voice (expert consensus categories of measurable and unique voice treatment ingredients and targets). Method Initial targets and ingredients were derived from a taxonomy of voice therapy. Through six Delphi Rounds, 10 vocal rehabilitation experts rated the measurability and uniqueness of individual treatment targets and ingredients. After each round, revisions (guided by the experts' feedback) were finalized among a primary reader (a voice therapy expert) and two external readers (rehabilitation experts outside the field of voice). Consensus was established when the label and definition of an ingredient or target reached a supramajority threshold (≥ 8 of 10 expert agreement). Results Thirty-five target and 19 ingredient categories were agreed to be measurable, unique, and accurate reflections of the rules and terminology of the RTSS. Operational definitions for each category included differences in the way ingredients are delivered and the way individual targets are modified by those ingredients. Conclusions The consensus labels and operationalized ingredients and targets making up the RTSS-Voice have potential to improve voice therapy research, practice, and education/training. The methods used to develop these lists may be useful for other speech, language, and hearing treatment specifications. Supplemental Material https://doi.org/10.23641/asha.15243357.

Acoustic Variability in the Healthy Female Voice Within and Across Days: How Much and Why?

Purpose The aims of this study were (1) to quantify variability in voice production (as measured acoustically) within and across consecutive days in vocally healthy female speakers, (2) to identify which acoustic measures are sensitive to this variability, and (3) to identify participant characteristics related to such voice variability. Method Participants included 45 young women with normal voices who were stratified by age, specifically 18-23, 24-29, and 30-35 years. Following an initial acoustic and auditory-perceptual voice assessment, participants performed standardized field voice recordings 3 times daily across a 7-day period. Acoustic analyses involved 32 cepstral-, spectral-, and time-based measures of connected speech and sustained vowels. Relationships among acoustic data and select demographic, health, and lifestyle (i.e., participant-based) factors were also examined. Results Significant time-of-day effects were observed for acoustic analyses within speakers (p < .05), with voices generally being worse in the morning. No significant differences were observed across consecutive days. Variations in voice production were associated with several participant factors, including improved voice with increased voice use; self-perceived poor voice function, minimal or no alcohol consumption, and extroverted personality; and worse voice with regular or current menstruation, depression, and anxiety. Conclusions This acoustic study provides essential information regarding the nature and extent to which healthy voices vary throughout the day and week. Participant-based factors that were associated with improved voice over time included increased voice use, self-perceived poor voice function, minimal or no alcohol consumption, and extroverted personality. Factors associated with worse voice production over time included regular or current menstruation, and depression and anxiety.

Management of functional communication, swallowing, cough and related disorders: consensus recommendations for speech and language therapy.

Communication problems (eg, dysphonia, dysfluency and language and articulation disorders), swallowing disorders (dysphagia and globus), cough and upper airway symptoms, resulting from functional neurological disorder (FND), are commonly encountered by speech and language professionals. However, there are few descriptions in the literature of the most effective practical management approaches. This consensus document aims to provide recommendations for assessment and intervention that are relevant to both adults and young people. An international panel of speech and language professionals with expertise in FND were approached to take part. Participants responded individually by email to a set of key questions regarding best practice for assessment and interventions. Next, a video conference was held in which participants discussed and debated the answers to these key questions, aiming to achieve consensus on each issue. Drafts of the collated consensus recommendations were circulated until consensus was achieved. FND should be diagnosed on the basis of positive clinical features. Speech and language therapy for FND should address illness beliefs, self-directed attention and abnormal movement patterns through a process of education, symptomatic treatment and cognitive behavioural therapy within a supportive therapeutic environment. We provide specific examples of these strategies for different symptoms. Speech and language professionals have a key role in the management of people with communication and related symptoms of FND. It is intended that these expert recommendations serve as both a practical toolkit and a starting point for further research into evidence-based treatments.

A Field-Based Approach to Establish Normative Acoustic Data for Healthy Female Voices.

Purpose The primary aim of this study was to obtain high-quality acoustic normative data in natural field environments for female voices. A secondary aim was to examine acoustic measurement variability in field environments. Method This study employed a within-subject repeated-measures experimental design that included 45 young female adults with normal voices. Participants were stratified by age (18-23, 24-29, and 30-35 years). After initial evaluation and instruction, participants completed voice recordings during seven consecutive days using a standard protocol, including both connected speech and sustained vowels. Thirty-two cepstral-, spectral-, and time-based acoustic measures were acquired using Praat and the Analysis of Dysphonia in Speech and Voice. Results Among the 958 total recordings, greater than 90% satisfied inclusion criteria based on protocol compliance, peak clipping, and signal-to-noise ratio. Significant differences were observed for age (p < .05). For 19 acoustic measures, values improved significantly as signal-to-noise ratio increased. Cepstral- and spectral-based measures demonstrated less measurement variability as compared with time-based measures. Conclusions With adequate training, field audio recordings represent a viable option for clinical voice management. The significant age effects observed in this study support the need for more specific criteria when collecting and applying normative data. Cepstral- and spectral-based measures demonstrated the least measurement variability. This study provides additional evidence for multiparameter acoustic voice measurement, specifically toward ecologically valid sampling in natural environments. Future studies should expand on these findings in other populations with normal and disordered voices.

Rehabilitation Treatment Specification System: Methodology to Identify and Describe Unique Targets and Ingredients.

Although significant advances have been made in measuring the outcomes of rehabilitation interventions, comparably less progress has been made in measuring the treatment processes that lead to improved outcomes. A recently developed framework called the Rehabilitation Treatment Specification System (RTSS) has potential to identify which clinician actions (ie, ingredients) actively improve specific patient functions (ie, targets). However, the RTSS does not provide methodology for standardly identifying specific unique targets or ingredients. Without a method to evaluate the uniqueness of an individual target or ingredient, it is difficult to know whether variations in treatment descriptions are synonymous (ie, different words describing the same treatment) or meaningfully different (eg, different words describing different treatments or variations of the same treatment). A recent project used vocal rehabilitation ingredients and targets to create RTSS-based lists of unique overarching target and ingredient categories with underlying dimensions describing how individual ingredients and targets vary within those categories. The primary purpose of this article is to describe the challenges encountered during the project and the methodology developed to address those challenges. Because the methodology was based on the RTSS's broadly applicable framework, it can be used across all areas of rehabilitation regardless of the discipline (speech-language pathology, physical therapy, occupational therapy, psychology, etc) or impairment domain (language, cognition, ambulation, upper extremity training, etc). The resulting standard operationalized lists of targets and ingredients have high face and content validity. The lists may also facilitate implementation of the RTSS in research, education, interdisciplinary communication, and everyday treatment.

Evidence of Possible Irritable Larynx Syndrome in Obstructive Sleep Apnea: An Epidemiologic Approach.

OBJECTIVE: "Irritable larynx syndrome" (ILS) often refers to a constellation of laryngeal-based symptoms including chronic cough (CC), diurnal dyspnea, and dysphonia. In patients with OSA, we examined: (1) the frequency, severity, comorbidity, risks and triggers of each problem, (2) whether these symptoms were compatible with stereotypic ILS and (3) the role of CPAP in their expression. STUDY DESIGN: Cross-sectional, descriptive epidemiology study. SETTING: Sleep-Wake Center at University of Utah Health Care, Salt Lake City, UT. SUBJECTS AND METHODS: Ninety-four individuals with OSA (53 men, 41 women; mean age 54.7 ± 12.8 yrs.) underwent an extensive telephone interview that addressed study objectives. RESULTS: Long-term CC, daytime breathing and voice problems were common, especially among women despite less severe OSA. Women, more than men, reported all three chronic conditions alone or in combination: CC (44% vs 11.3%), diurnal dyspnea (41.5% vs 13.2%) and voice disorders (41.5% vs 13.2%). Symptoms were not associated with age, BMI or Apnea Hypopnea Index after adjusting for sex. Although evidence supporting stereotypic ILS symptomatology was inconsistent, those participants with a voice disorder were 3.3 (95% CI = 1.8-6.0) times more likely to report CC and 2.4 (95% CI = 1.3-4.4) times more likely to experience diurnal dyspnea. Esophageal reflux, post-nasal drip, and frequent sinus infections were significantly associated with all three conditions. Triggers that provoked or made symptoms worse varied by condition and sex. Nightly, humidified CPAP use was associated with fewer symptoms overall and improved quality of life. CONCLUSIONS: Symptoms suggestive of possible ILS are common in OSA, especially among women, and lessened by nightly CPAP use.

Perceived Control, Voice Handicap, and Barriers to Voice Therapy.

OBJECTIVE: To characterize the associations of perceived control with voice outcomes and self-reported likelihood of attending voice therapy using a national practice-based research network. STUDY DESIGN: Cross-sectional study of prospectively enrolled adult patients seen for dysphonia. SETTING: Creating Healthcare Excellence through Education and Research (CHEER) network of community and academic practice sites. SUBJECTS AND METHODS: Data collected included patient-reported demographics, outcome measures of voice (Voice Handicap Index-10), perceived control (present control subscale of voice-specific Perceived Control over Stressful Events Scale), personality (Ten Item Personality Inventory), likelihood of attending voice therapy if recommended, and barriers to attending voice therapy. RESULTS: Patients (N = 247) were enrolled over 12 months from 10 sites, of whom 170 received a recommendation for voice therapy. The majority (85%) of this group planned to attend voice therapy. Voice-specific perceived control and VHI-10 were inversely related (r = -0.31, P < 0.001), even when controlling for personality. No study variables were associated with self-reported likelihood of attending voice therapy, but perceived control was the most consistent correlate of specific barriers to attending voice therapy (eg, "hard to translate into everyday use") and was inversely related to these barriers. CONCLUSIONS: Patients scoring higher on a voice-specific measure of perceived control reported less voice handicap, independent of personality, and higher perceived control was associated with having fewer concerns about voice therapy goals and process. Perceived control is a potential target for intervention in patients with voice disorders.

Rescue of SARS-CoV-2 from a Single Bacterial Artificial Chromosome.

Infectious coronavirus (CoV) disease 2019 (COVID-19) emerged in the city of Wuhan (China) in December 2019, causing a pandemic that has dramatically impacted public health and socioeconomic activities worldwide. A previously unknown coronavirus, severe acute respiratory syndrome CoV-2 (SARS-CoV-2), has been identified as the causative agent of COVID-19. To date, there are no U.S. Food and Drug Administration (FDA)-approved vaccines or therapeutics available for the prevention or treatment of SARS-CoV-2 infection and/or associated COVID-19 disease, which has triggered a large influx of scientific efforts to develop countermeasures to control SARS-CoV-2 spread. To contribute to these efforts, we have developed an infectious cDNA clone of the SARS-CoV-2 USA-WA1/2020 strain based on the use of a bacterial artificial chromosome (BAC). Recombinant SARS-CoV-2 (rSARS-CoV-2) was readily rescued by transfection of the BAC into Vero E6 cells. Importantly, BAC-derived rSARS-CoV-2 exhibited growth properties and plaque sizes in cultured cells comparable to those of the natural SARS-CoV-2 isolate. Likewise, rSARS-CoV-2 showed levels of replication similar to those of the natural isolate in nasal turbinates and lungs of infected golden Syrian hamsters. This is, to our knowledge, the first BAC-based reverse genetics system for the generation of infectious rSARS-CoV-2 that displays features in vivo similar to those of a natural viral isolate. This SARS-CoV-2 BAC-based reverse genetics will facilitate studies addressing several important questions in the biology of SARS-CoV-2, as well as the identification of antivirals and development of vaccines for the treatment of SARS-CoV-2 infection and associated COVID-19 disease.IMPORTANCE The pandemic coronavirus (CoV) disease 2019 (COVID-19) caused by severe acute respiratory syndrome CoV-2 (SARS-CoV-2) is a major threat to global human health. To date, there are no approved prophylactics or therapeutics available for COVID-19. Reverse genetics is a powerful approach to understand factors involved in viral pathogenesis, antiviral screening, and vaccine development. In this study, we describe the feasibility of generating recombinant SARS-CoV-2 (rSARS-CoV-2) by transfection of a single bacterial artificial chromosome (BAC). Importantly, rSARS-CoV-2 possesses the same phenotype as the natural isolate in vitro and in vivo This is the first description of a BAC-based reverse genetics system for SARS-CoV-2 and the first time that an rSARS-CoV-2 isolate has been shown to be phenotypically identical to a natural isolate in a validated animal model of SARS-CoV-2 infection. The BAC-based reverse genetics approach will facilitate the study of SARS-CoV-2 and the development of prophylactics and therapeutics for the treatment of COVID-19.

Exploring the Neural Bases of Primary Muscle Tension Dysphonia: A Case Study Using Functional Magnetic Resonance Imaging.

Primary muscle tension dysphonia (pMTD) is a voice disorder that occurs in the absence of laryngeal pathology. Dysregulated activity of the paralaryngeal muscles is considered the proximal cause; however, the central origin of this aberrant laryngeal muscle activation is unclear. The Trait Theory (Roy and Bless, 2000a,b) proposed that specific personality traits can predispose one to laryngeal motor inhibition and pMTD, and this inhibition is mediated by a hyperactive "behavioral inhibition system (BIS)" composed of limbic system structures (and associated prefrontal connections). This case study used functional magnetic resonance imaging to detect brain activation changes associated with successful management of pMTD, thereby evaluating possible neural correlates of this poorly understood disorder. METHOD: A 61-year-old woman with moderate-to-severe pMTD underwent functional magnetic resonance imaging scans before and immediately after successful treatment using manual circumlaryngeal techniques. Experimental stimuli were blocks of repeated vowel production and overt sentence reading. RESULTS: Significantly greater activation was observed pre- versus posttreatment in all regions of interest during sentence production, that is, periaqueductal gray, amygdala, hypothalamus, anterior cingulate cortex, hippocampus, dorsolateral prefrontal cortex, Brodmann area 10, and premotor and inferior sensorimotor cortex. CONCLUSIONS: Our findings are compatible with overactivation of neural regions associated with the BIS (cingulate cortex, amygdala, hypothalamus, periaqueductal gray) and motor inhibition networks (eg, [pre-]supplementary motor area) along with the dorsolateral prefrontal cortex and medial prefrontal cortex. Heightened input from limbic regions combined with dysfunctional prefrontal regulation may interfere with laryngeal motor preparation, initiation, and execution thereby contributing to disordered voice in pMTD.

Associations between Community-Acquired Pneumonia and Proton Pump Inhibitors in the Laryngeal/Voice-Disordered Population.

OBJECTIVES: To examine the relationship between community-acquired pneumonia (CAP) and proton pump inhibitor (PPI) treatment among patients with laryngeal/voice disorders. STUDY DESIGN: Retrospective cohort analysis. SETTING: Large national administrative US claims database. SUBJECTS AND METHODS: Patients were included if they were ≥18 years old; had outpatient treatment for a laryngeal/voice disorder from January 1, 2010, to December 31, 2014 (per International Classification of Diseases, Ninth Revision, Clinical Modification codes); had 12 months of continuous enrollment prior to the index date (ie, first diagnosis of laryngeal/voice disorder); had no preindex diagnosis of CAP; and had prescription claims captured from 1 year preindex to end of follow-up. Patient demographics, comorbid conditions, index laryngeal diagnosis, number of unique preindex patient encounters, and CAP diagnoses during the postindex 3 years were collected. Two models-a time-dependent Cox regression model and a propensity score-based approach with a marginal structural model-were separately performed for patients with and without pre-index date PPI prescriptions. RESULTS: A total of 392,355 unique patients met inclusion criteria; 188,128 (47.9%) had a PPI prescription. The 3-year absolute risk for CAP was 4.0% and 5.3% among patients without and with preindex PPI use, respectively. For patients without and with pre-index date PPI use, the CAP occurrence for a person who had already received a PPI is 30% to 50% higher, respectively, than for a person who had not yet had a PPI but may receive one later. CONCLUSIONS: Patients without and with pre-index date PPI use experienced a roughly 30% to 50% increased likelihood of CAP, respectively, as compared with patients who had not had PPI prescriptions.

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

OBJECTIVES: This systematic review examined the evidence linking vocal nodule development in children to personality traits, psychological factors, and associated behavioral tendencies. METHODS: Four 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. RESULTS: Four 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. CONCLUSIONS: Fair 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.