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ALK mutations occur in 10% of primary neuroblastomas and represent a major target for precision treatment. In combination with MYCN amplification, ALK mutations infer an ultra-high-risk phenotype resulting in very poor patient prognosis. To open up opportunities for future precision drugging, a deeper understanding of the molecular consequences of constitutive ALK signaling and its relationship to MYCN activity in this aggressive pediatric tumor entity will be essential. We show that mutant ALK downregulates the 'HMG-box transcription factor 1' (HBP1) through the PI 3 K-AKT-FOXO3a signaling axis. HBP1 inhibits both the transcriptional activating and repressing activity of MYCN, the latter being mediated through PRC2 activity. HBP1 itself is under negative control of MYCN through miR-17~92. Combined targeting of HBP1 by PI 3 K antagonists and MYCN signaling by BET- or HDAC-inhibitors blocks MYCN activity and significantly reduces tumor growth, suggesting a novel targeted therapy option for high-risk neuroblastoma.

Purpose The aim of this study was to compare the effect of a short-term intensive voice therapy (IVT) with a long-term traditional voice therapy (TVT) on the vocal quality, vocal capacities, psychosocial impact, vocal tract discomfort, laryngological anatomy/physiology, and session attendance of patients with dysphonia. An additional comparison was made between an individual IVT (IVT-I) and a group IVT (IVT-G). Method A longitudinal, prospective controlled trial was used. Forty-six adults diagnosed with dysphonia were assigned to 1 of the 3 treatment groups. The IVT groups practiced with a frequency of 1 hr 20 min a day and a duration of 2 weeks. The TVT group practiced with a frequency of two 30-min sessions a week and a duration of 6 months. Both therapy programs were content-identical and guided by the same voice therapist. A multidimensional voice assessment consisting of both objective (maximum performance task, aerodynamic measurements, voice range profile, acoustic analysis, multiparametric voice quality indices) and subjective (subject's self-report, auditory-perceptual evaluation, flexible videolaryngostroboscopy) outcomes was used to evaluate the participants' voice. Results IVT made an equal progress in only 2 weeks and 12 hr of therapy compared with TVT that needed 6 months and 24 hr of therapy. IVT-I and IVT-G showed comparable results. Session attendance was clearly higher in IVT compared with TVT. Long-term follow-up results (1 year) were positive for the 3 groups, except for the self-reported psychosocial impact that increased in the IVT-I group. Conclusions Short-term IVT is at least equally effective in treating patients with dysphonia as long-term TVT. Group treatment seemed as effective as individual treatment. Attendance and cost-effectiveness are important advantages of IVT. A potential drawback might be an insufficient psychosocial progress. The golden mean between intensive and traditional treatment might therefore be an achievable, effective, and efficient solution for everyday clinical practice. Supplemental Material https://doi.org/10.23641/asha.7761872.

Background: To date, the immediate effects of a semi-occluded vocal tract (SOVT) configuration have been thoroughly demonstrated. However, it is not yet sufficiently confirmed whether a therapy programme (i.e. longer than one session) using SOVT exercises leads to an enhanced phonation and improved vocal quality., Aims: The aim of this study was to investigate the effect of three SOVT therapy programmes: lip trill, water-resistance therapy (WRT) and straw phonation, on the vocal quality, vocal capacities, psychosocial impact and vocal tract discomfort of patients with dysphonia., Methods & Procedures: A blocked-randomized sham-controlled trial was used. Thirty-five patients with dysphonia (mean age = 21 years; 33 women, two men) were assigned to either a lip trill group, a WRT group, a straw phonation group or a control group using blocked randomization. The lip trill, WRT and straw phonation groups practised their respective SOVT exercise across 3 weeks, whereas the control group received a sham treatment across the same time span. A multidimensional voice assessment consisting of both objective (multiparametric indices: Dysphonia Severity Index (DSI), Acoustic Voice Quality Index (AVQI)) and subjective (subject's self-report, auditory-perceptual evaluation) vocal outcomes was performed by a blinded assessor pre- and post-therapy., Outcomes & Results: Lip trill and straw phonation therapy led to a significant improvement in DSI. Auditory-perceptual grade and roughness significantly decreased after straw phonation. Lip trill and WRT both led to a significant decrease in Voice Handicap Index. Subjects reported a better self-perceived vocal quality and a more comfortable voice production after WRT. No changes were found after the sham treatment in the control group., Conclusions & Implications: Results suggest that SOVT therapy programmes including lip trill or straw phonation can improve the objective vocal quality in patients with dysphonia. Auditory-perceptual improvements were found after straw phonation therapy, whereas psychosocial improvements were found after lip trill and WRT. Patients seem to experience more comfort and a better self-perceived vocal quality after WRT. This study supports the use of the three SOVT therapy programmes in clinical practice. They all had a positive impact on one or more outcomes of the multidimensional voice assessment. Strikingly, vocal quality outcomes were not in line with the subject's opinion. Larger-scale investigation is needed to support these preliminary findings., (© 2018 Royal College of Speech and Language Therapists.)

Objective: To evaluate the long-term efficacy of the transobturator vaginal tape inside out (TVT-O) in female dogs with urethral sphincter mechanism incompetence (USMI)., Study Design: Retrospective study., Animals: Incontinent spayed female dogs (n = 12)., Methods: TVT-O tape was inserted in 12 incontinent bitches diagnosed with USMI. Follow-up information was evaluated by a telephone questionnaire, and a continence score was attributed., Results: One year after surgery, 7 of 12 (58%) dogs were completely continent. Two dogs were removed from the long-term analysis (1 dead and 1 lost). At a median follow-up time of 85 months (range, 28-95), 4 of 10 dogs were completely continent without medical treatment. Incontinence recurred in 6 dogs at a median time of 2 months after surgery (range 1-20). Among these 6 dogs, 4 regained continence, and 2 had sporadic episodes of incontinence with additional medical treatment. No postoperative complications were encountered., Conclusion: TVT-O alone was successful in maintaining long-term continence in 40% of the dogs. Additional postoperative medical treatment was effective in restoring continence in another 40% of the dogs., Clinical Significance: TVT-O provides an alternative treatment of USMI in female dogs that is safe and less invasive than standard surgical techniques., (© 2018 The American College of Veterinary Surgeons.)

Oncogenic anaplastic lymphoma kinase (ALK) is one of the few druggable targets in neuroblastoma, and therapy resistance to ALK-targeting tyrosine kinase inhibitors (TKIs) comprises an inevitable clinical challenge. Therefore, a better understanding of the oncogenic signaling network rewiring driven by ALK is necessary to improve and guide future therapies. Here, we performed quantitative mass spectrometry-based proteomics on neuroblastoma cells treated with one of three clinically relevant ALK TKIs (crizotinib, LDK378, or lorlatinib) or an experimentally used ALK TKI (TAE684) to unravel aberrant ALK signaling pathways. Our integrated proximal proteomics (IPP) strategy included multiple signaling layers, such as the ALK interactome, phosphotyrosine interactome, phosphoproteome, and proteome. We identified the signaling adaptor protein IRS2 (insulin receptor substrate 2) as a major ALK target and an ALK TKI-sensitive signaling node in neuroblastoma cells driven by oncogenic ALK. TKI treatment decreased the recruitment of IRS2 to ALK and reduced the tyrosine phosphorylation of IRS2. Furthermore, siRNA-mediated depletion of ALK or IRS2 decreased the phosphorylation of the survival-promoting kinase Akt and of a downstream target, the transcription factor FoxO3, and reduced the viability of three ALK-driven neuroblastoma cell lines. Collectively, our IPP analysis provides insight into the proximal architecture of oncogenic ALK signaling by revealing IRS2 as an adaptor protein that links ALK to neuroblastoma cell survival through the Akt-FoxO3 signaling axis., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Introduction: Despite the established contribution of deregulated microRNA (miRNA) function to carcinogenesis, relatively few miRNA-cancer gene interactions have been validated, making it difficult to appreciate the true complexity of miRNA-cancer gene regulatory networks., Results: In this effort, we identify miRNA interactomes of 17 well-established cancer genes, involved in various cancer types, through a miRNome-wide 3' UTR reporter screening. Using a novel and performant strategy for high-throughput screening data analysis, we identify 390 interactions, quadrupling the size of the known miRNA interactome for the cancer genes under investigation. Clear enrichments of established and predicted interactions underscore the validity of the interactome data set. Interactomes appear to be primarily driven by canonical binding site interactions. Nonetheless, non-canonical binding sites, such as offset 6mer and seed-mismatched or G:U wobble sites, also have regulatory activity, albeit clearly less pronounced. Furthermore, we observe enhanced regulation in the presence of 3' supplementary pairing for both canonical and non-canonical binding sites., Conclusions: Altogether, the cancer gene-miRNA interactome data set represents a unique resource that will aid in the unraveling of regulatory miRNA networks and the dynamic regulation of key protein-coding cancer genes. In addition, it uncovers aspects of the functional miRNA binding site's architecture and the relative contributions of different binding site types.

Background: In contrast with most medical and pharmaceutical therapies, the optimal dosage for voice therapy or training is unknown., Aims: The aim of this study was to compare the effect of a short-term intensive voice training (IVT) with a longer-term traditional voice training (TVT) on the vocal quality and vocal capacities of vocally healthy non-professional voice users., Methods & Procedures: A pre-/post-test randomized control group design with follow-up measurements was used. Twenty healthy female non-professional voice users with a mean age of 21.7 years (range = 20-24 years) were randomly assigned into a short-term IVT group (n = 10) or a longer-term TVT group (n = 10). Both groups received an identical 6-h lasting voice training. Only the distribution of practice varied between the groups: 2 h a day for 3 consecutive days for the IVT group versus two 30-min sessions a week for 6 weeks for the TVT group. In both groups, a voice assessment protocol consisting of subjective (questionnaire, participant's self-report, auditory-perceptual evaluation) and objective (maximum performance task, acoustic analysis, voice range profile, dysphonia severity index) measurements and determinations was used to evaluate the participants' voice pre- and post-training and at 6 weeks follow-up. Groups were compared over time using linear mixed models and generalized linear mixed models. Within-group effects of time were determined using post-hoc pairwise comparisons with Bonferroni corrections., Outcomes & Results: No significant time-by-group interactions were found for any of the outcome measures, indicating no significant differences in evolution over time between the groups. Significant time effects were found for maximum phonation time, lowest intensity, lowest frequency, highest frequency and dysphonia severity index, all improving over time in both groups. More in-depth within-group analyses indicate a preference for the IVT group regarding the evolution of maximum phonation time, lowest frequency and dysphonia severity index, and a preference for the TVT group regarding the evolution of lowest intensity., Conclusions & Implications: Short-term IVT may be equally, or even more, effective in training vocally healthy non-professional voice users compared with longer-term TVT., (© 2017 Royal College of Speech and Language Therapists.)

Objective: To determine the influence of manipulations aimed at increasing the transdiaphragmatic pressure gradient on the gastro-esophageal junction (GEJ) of dogs with brachycephalic airway obstructive syndrome (BAOS), and to identify the manipulation that most improves the detection of GEJ abnormalities and sliding hiatal hernia (SHH) in dogs with BAOS., Study Design: In vivo experimental pilot study and prospective clinical study., Animals: Five purpose-bred Beagles and 20 dogs diagnosed with BAOS., Methods: Respiratory and digestive clinical signs as well as respiratory and GEJ abnormalities were scored. The presence of SHH was investigated using radiography and endoscopy in standard conditions. Endoscopic investigation was repeated after manipulations including manual pressure on the cranial abdomen (MP), Trendelenburg position (30°), or temporary complete endotracheal tube obstruction (ETO)., Results: No SHH was detected in any normal dog under any condition. Sixty-five percent of dogs with BAOS presented with digestive clinical signs, including vomiting and/or regurgitation. SHH was observed in only one dog via radiography and was not detected via endoscopy. Manipulations during endoscopy influenced GEJ abnormalities and allowed the detection of SHH in 2 (30°), 4 (ETO), and 5 (MP) dogs, respectively. Digestive clinical signs correlated with GEJ abnormalities observed only in dogs with ETO (P = .02)., Conclusion: Manipulations aimed at increasing the transdiaphragmatic pressure gradient during endoscopy in BAOS dogs allowed the detection of GEJ abnormalities and SHH that were not detected under standard conditions. Although MP allowed detection of SHH in more dogs than ETO, scores under MP did not correlate with digestive clinical signs. Therefore, ETO may be more accurate manipulation for the detection of GEJ abnormalities in BAOS dogs., (© 2017 The American College of Veterinary Surgeons.)

Background: Neuroblastoma is an aggressive childhood malignancy of the sympathetic nervous system. Despite multi-modal therapy, survival of high-risk patients remains disappointingly low, underscoring the need for novel treatment strategies. The discovery of ALK activating mutations opened the way to precision treatment in a subset of these patients. Previously, we investigated the transcriptional effects of pharmacological ALK inhibition on neuroblastoma cell lines, six hours after TAE684 administration, resulting in the 77-gene ALK signature, which was shown to gradually decrease from 120 minutes after TAE684 treatment, to gain deeper insight into the molecular effects of oncogenic ALK signaling., Aim: Here, we further dissected the transcriptional dynamic profiles of neuroblastoma cells upon TAE684 treatment in a detailed timeframe of ten minutes up to six hours after inhibition, in order to identify additional early targets for combination treatment., Results: We observed an unexpected initial upregulation of positively regulated MYCN target genes following subsequent downregulation of overall MYCN activity. In addition, we identified adrenomedullin (ADM), previously shown to be implicated in sunitinib resistance, as the earliest response gene upon ALK inhibition., Conclusions: We describe the early and late effects of ALK inhibitor TAE684 treatment on the neuroblastoma transcriptome. The observed unexpected upregulation of ADM warrants further investigation in relation to putative ALK resistance in neuroblastoma patients currently undergoing ALK inhibitor treatment., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Objectives: The main objectives of this functional magnetic resonance imaging (fMRI) study are (1) to investigate brain activity during phonation in women with muscle tension dysphonia (MTD) in comparison with healthy controls; and (2) to explain the neurophysiological mechanism of laryngeal hyperfunction/tension during phonation in patients with MTD., Methods: Ten women with MTD and fifteen healthy women participated in this study. The fMRI experiment was carried out using a block design paradigm. Brain activation during phonation and exhalation was analyzed using BrainVoyager software., Results: The statistical analysis of fMRI data has demonstrated that MTD patients control phonation by use of the auditory, motor, frontal, parietal, and subcortical areas similar to phonation control by healthy people. Comparison of phonation tasks in the two groups revealed higher brain activities in the precentral gyrus, inferior, middle and superior frontal gyrus, lingual gyrus, insula, cerebellum, midbrain, and brainstem as well as lower brain activities in the cingulate gyrus, superior and middle temporal gyrus, and inferior parietal lobe in the MTD group. No differences were found between the two groups regarding exhalation control., Conclusions: The findings in this study provide insight into phonation and exhalation control in patients with MTD. The imaging results demonstrated that in patients with MTD, altered (higher/lower) brain activities may result in laryngeal tension and vocal hyperfunction., (Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to determine the short-term effect of 2 semi-occluded vocal tract training programs, "resonant voice training using nasal consonants" versus "straw phonation," on the vocal quality of vocally healthy future occupational voice users., Method: A multigroup pretest-posttest randomized control group design was used. Thirty healthy speech-language pathology students with a mean age of 19 years (range: 17-22 years) were randomly assigned into a resonant voice training group (practicing resonant exercises across 6 weeks, n = 10), a straw phonation group (practicing straw phonation across 6 weeks, n = 10), or a control group (receiving no voice training, n = 10). A voice assessment protocol consisting of both subjective (questionnaire, participant's self-report, auditory-perceptual evaluation) and objective (maximum performance task, aerodynamic assessment, voice range profile, acoustic analysis, acoustic voice quality index, dysphonia severity index) measurements and determinations was used to evaluate the participants' voice pre- and posttraining. Groups were compared over time using linear mixed models and generalized linear mixed models. Within-group effects of time were determined using post hoc pairwise comparisons., Results: No significant time × group interactions were found for any of the outcome measures, indicating no differences in evolution over time among the 3 groups. Within-group effects of time showed a significant improvement in dysphonia severity index in the resonant voice training group, and a significant improvement in the intensity range in the straw phonation group., Conclusions: Results suggest that the semi-occluded vocal tract training programs using resonant voice training and straw phonation may have a positive impact on the vocal quality and vocal capacities of future occupational voice users. The resonant voice training caused an improved dysphonia severity index, and the straw phonation training caused an expansion of the intensity range in this population.

Objective: To determine outcomes after surgical correction of ectopic ureters (EU) and identify prognostic factors for long-term continence., Study Design: Retrospective study., Animals: Forty-seven dogs (36 females and 11 males)., Methods: Medical records (1999-2016) of dogs with surgical correction of EU were reviewed. A continence score (1 = incontinent, 2 = sporadic incontinence, 3 = continent) was attributed preoperatively, at discharge, 1 month postoperatively, and at long-term evaluation., Results: Twenty-eight dogs had unilateral and 19 dogs had bilateral EU (57 intramural and 9 extramural). Nineteen dogs had a pelvic bladder. Neoureterostomy with dissection (n = 50), ureteroneocystotomy (n = 9), or nephroureterectomy (n = 7) were performed. Thirty-three dogs were neutered: 32 before or during the surgery and 1 after surgery. Colposuspension was performed during surgical correction in 15 dogs. Adjuvant medical treatment improved postoperative continence scores. Median continence scores were greater at discharge (3), at 1 month postoperatively (3), and at long-term evaluation (3) than before surgery (1). At long-term evaluation (mean 46.1 months), a score of 1 was observed in 19%, a score of 2 in 7%, and a score of 3 in 74% of the dogs., Conclusion: Overall, good (score 2) to excellent (score 3) long-term outcome was achieved in 81% of dogs. Long-term continence was improved with medical treatment and neutering was not associated with an increased risk of recurrence of incontinence in this population of dogs., (© 2017 The American College of Veterinary Surgeons.)

Objectives: The purpose of this study was to investigate vocal quality, vocal complaints, and risk factors for developing voice disorders in theater actors. Secondly, the impact of one vocal performance on the voice was investigated by comparing objective and subjective vocal quality before and after a theater performance., Study Design: Prospective study of the actors' voice prior to and after a performance METHODS: Speech samples of 26 theater actors (15 men, 11 women, mean age 41.9 years) were recorded before and after a theater performance of one and a half hour and analyzed using the software program Praat. Speech samples consisted of the combination of sustained phonation and continuous speech. For each speech sample, the Acoustic Voice Quality Index was calculated. Auditory perceptual evaluations were performed using the GRBASI scale. Questionnaires were used to inventory vocal symptoms and influencing factors., Results: Acoustic analysis showed a mean Acoustic Voice Quality Index (AVQI) of 3.48 corresponding with a mild dysphonia. Fifty percent of the theater actors reported having (sometimes or regularly) vocal complaints after a performance. The questionnaire revealed a high presence of vocally violent behavior and poor vocal hygiene habits. Objective vocal quality, measured by the AVQI, did not change after a theater performance. The auditory perceptual evaluation of the overall grade of dysphonia showed a subtle amelioration of the vocal quality., Conclusions: The results of this study showed the presence of mild dysphonia, regular vocal complaints, and poor vocal hygiene habits in theater actors. A theater performance did not have an impact on the objective vocal quality., (Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to measure the objective and subjective vocal quality in women aged between 60 and 75 years. Secondly, the impact of a teaching or singing career on the vocal quality was investigated by comparing the vocal quality of retired women with different careers., Study Design: This is a case-control study., Methods: Seventy-three retired women between 60 and 75 years (mean age: 67 years, standard deviation: 4.49) participated in the study and were divided into three groups: women with a teaching career (n = 21), choir singers with a singing career (n = 12), and women with a non-vocal career (n = 40). All subjects underwent the same assessment protocol consisting of objective (aerodynamic, maximum performance, vocal range, acoustic measurements, and the Dysphonia Severity Index) and subjective (the Voice Handicap Index, auditory-perceptual evaluations by three listeners) voice measurements., Results: In all three groups, objective and perceptual voice analysis showed a mild dysphonia. No differences in the Dysphonia Severity Index were found between the three groups. The voices of choir singers with a singing career were perceived significantly less rough than voices of the women with a non-vocal career. Additionally, the lowest frequency of the frequency range was significantly lower in the retired teachers and choir singers than in the controls., Conclusion: The results of this study prudently suggest that a singing or a teaching career compared with a non-vocal career has a positive impact on the vocal frequency range, and that singing has a positive impact on the perceptual vocal quality of the older female voice., (Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: Musical theater performers are a special group of elite vocal performers with a high vocal load as they combine singing, acting, and physical performance. As they are absolutely depending on their voice quality and vocal capacities for their studies and their future profession, an optimal voice production is very important. The purpose of this study was to determine the voice quality of musical theater students. The voice quality of seven students was then reevaluated 1 year after the first assessment., Study Design: Observational study., Methods: Thirty-one musical students (7 men and 24 women) with a mean age of 20 years participated in the study. To determine the voice quality, objective (aerodynamic measurements, voice range profile, acoustic analysis, and Dysphonia Severity Index) and subjective (videolaryngostroboscopy, Voice Handicap Indexes, and questionnaires regarding voice symptoms and risk factors) voice measurements were performed., Results: The median Dysphonia Severity Index in male and female musical students was respectively 5.3 and 5.7, both corresponding with an overall good voice quality. The questionnaires revealed the presence of vocal fatigue, dryness of the throat, vocal tract discomfort, and harmful vocal habits in the majority of students. In 45% of the subjects, videolaryngostroboscopic evaluation of the vocal folds showed an organic lesion. The majority of these lesions are inflammatory lesions (26%). In 68% of the subjects, a certain degree of supraglottic constriction was observed., Conclusion: Despite the overall good voice quality, videolaryngostroboscopy showed a high presence of vocal fold lesions and supraglottic constriction during phonation., (Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This functional magnetic resonance imaging (fMRI) study investigated the brain activity associated with pitch adaptation during phonation in healthy women without voice disorders., Study Design: This is an interventional prospective study., Methods: Sixteen healthy women (mean age: 24.3 years) participated in a blocked design fMRI experiment involving two phonation (comfortable phonation and high-pitched phonation) and exhalation (prolonged exhalation) tasks. BrainVoyager QX Version 2.4 software was used for group-level general linear model analysis (q[FDR] < 0.05)., Results: Analyses showed a significant main effect of phonation with pitch adaptation compared with rest period in the bilateral precentral gyrus, superior frontal gyrus, posterior cingulate gyrus, superior and middle temporal gyrus, insula and cerebellum, left middle and inferior frontal gyrus, right lingual gyrus, cingulate gyrus, and thalamus. Statistical results also identified a significant main effect of exhalation compared with rest period in the bilateral precentral gyrus, cerebellum, right lingual gyrus, thalamus, and left supramarginal gyrus. In addition, a significant main effect of phonation was found in the bilateral superior temporal gyrus and right insula, as well as in the left midbrain periaqueductal gray for high-pitched phonation only., Conclusions: We demonstrated that a blocked design fMRI is sensitive enough to define a widespread network of activation associated with phonation involving pitch variation. The results of this study will be implemented in our future research on phonation and its disorders., (Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: The purpose of this study was to determine the effect of the isolated vocal-facilitating techniques Chant Talk and Pitch Inflections on the phonation of healthy female speech-language pathology (SLP) students., Study Design: A multigroup pretest-posttest design was used., Methods: A homogenous group of 40 healthy female SLP students with a mean age of 18.7 years were randomly assigned into 3 groups: a Chant Talk group (practicing Chant Talk across 18 weeks), a Pitch Inflections group (practicing Pitch Inflections across 18 weeks), and a control group (practicing no facilitating techniques). To compare vocal measures before and after this time span, an identical objective voice assessment protocol (aerodynamic measurement, acoustic analysis, voice range profile, and Dysphonia Severity Index) was performed in the 3 groups., Results: Both Chant Talk and Pitch Inflections groups resulted in a significant decrease of the acoustic measure noise-to-harmonics ratio compared with the control group. The Chant Talk group resulted in a significant increase in the acoustic measure fundamental frequency compared with the control group., Conclusions: The results of this pilot study suggest that the facilitating techniques Chant Talk and Pitch Inflections may improve the objective measure of breathiness (noise-to-harmonics ratio) in healthy female SLP students., (Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to determine how use of the vocal facilitating technique, chewing, affected the phonation of speech-language pathology (SLP) students., Study Design: A pretest-posttest randomized control group design was used., Methods: Twenty-seven healthy female SLP students were randomly assigned into either an experimental group or a control group. The experimental group practiced chewing exercises across 18 weeks, whereas the control group received no vocal facilitating techniques. Both groups completed pre- and post- objective voice assessment measures (aerodynamic measurement, acoustic analysis, voice range profile, and Dysphonia Severity Index). Differences between pre- and post-data were compared between the experimental and control group using an independent sample t test., Results: Compared to the control group, chewing resulted in a significant decrease in jitter and noise-to-harmonic ratio (NHR), a significant increase in fundamental frequency (fo), a significant expansion of the voice range profile, and a significant increase in Dysphonia Severity Index (DSI). Shimmer and maximum phonation time (MPT) were not significantly different between groups., Conclusions: The results of this pilot study suggest that the vocal facilitating technique, chewing, may improve objective vocal measures in healthy female SLP students., (Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: The purpose of this retrospective study was to determine the vocal characteristics of a treatment-seeking population with the primary complaint of vocal fatigue (VF)., Methods: Forty-three men (mean age 42 years, range 19-69) and 145 women (mean age 34 years, range 18-68) were included. None of the subjects had received voice therapy or previous laryngeal surgery. A questionnaire, laryngeal and perceptual evaluations, aerodynamic and acoustic parameters, and the Dysphonia Severity Index (DSI) were used to determine vocal characteristics., Results: In 74% of the subjects, flexible laryngeal videostroboscopic evaluation revealed a vocal pathology, with vocal nodules and muscle tension dysphonia as the most frequently diagnosed pathologies. Vocal abuse/misuse was present in 65% of the subjects. A median DSI value of -0.4 and -0.8 was found in female and male patients, respectively. Aerodynamic and acoustic parameters and DSI scores were significantly different from normative data., Conclusion: VF is a vocal sign with a significant need for medical consultation, especially in future professional voice users. Understanding the occurrence and the influencing variables of VF may help to close the gap between early stages of a vocal problem and the starting point of a well-established disorder., (© 2016 S. Karger AG, Basel.)

Purpose: Activating ALK mutations are present in almost 10% of primary neuroblastomas and mark patients for treatment with small-molecule ALK inhibitors in clinical trials. However, recent studies have shown that multiple mechanisms drive resistance to these molecular therapies. We anticipated that detailed mapping of the oncogenic ALK-driven signaling in neuroblastoma can aid to identify potential fragile nodes as additional targets for combination therapies., Experimental Design: To achieve this goal, transcriptome profiling was performed in neuroblastoma cell lines with the ALK(F1174L) or ALK(R1275Q) hotspot mutations, ALK amplification, or wild-type ALK following pharmacologic inhibition of ALK using four different compounds. Next, we performed cross-species genomic analyses to identify commonly transcriptionally perturbed genes in MYCN/ALK(F1174L) double transgenic versus MYCN transgenic mouse tumors as compared with the mutant ALK-driven transcriptome in human neuroblastomas., Results: A 77-gene ALK signature was established and successfully validated in primary neuroblastoma samples, in a neuroblastoma cell line with ALK(F1174L) and ALK(R1275Q) regulable overexpression constructs and in other ALKomas. In addition to the previously established PI3K/AKT/mTOR, MAPK/ERK, and MYC/MYCN signaling branches, we identified that mutant ALK drives a strong upregulation of MAPK negative feedback regulators and upregulates RET and RET-driven sympathetic neuronal markers of the cholinergic lineage., Conclusions: We provide important novel insights into the transcriptional consequences and the complexity of mutant ALK signaling in this aggressive pediatric tumor. The negative feedback loop of MAPK pathway inhibitors may affect novel ALK inhibition therapies, whereas mutant ALK induced RET signaling can offer novel opportunities for testing ALK-RET oriented molecular combination therapies., (©2015 American Association for Cancer Research.)

Objectives: To describe the complications, short and long-term outcome and owner satisfaction of dogs with cranial cruciate ligament rupture treated with a recently described new osteotomy for the modified Maquet technique (N-MMT)., Materials and Methods: Medical records and radiographs of 82 dogs (84 stifles) were reviewed. Details regarding short-term outcome and complications were recorded from the medical records. Long-term follow-up information was obtained by telephone interview. Historical data and complications were statistically analysed., Results: Major complications occurred in 34/84 stifles. Intra-operative complications occurred in 26/84 stifles, all of which were fissures or fractures of the cortical hinge. Twenty-one of these fractures or fissures were repaired with a figure-of-eight wire. The second most common major complication was late meniscal tears in 3/84 stifles. One dog sustained a complete tibial fracture. Non-displaced fracture of the cortical hinge was the most common postoperative minor complication, which occurred in 5/84 stifles. The median preoperative lameness score was 3 out of 6. Final in-hospital re-evaluation of limb function was available in 58 dogs. The median lameness score at that time was 0 out of 6. Development of osteotomy related complications was not associated with a significant change in the postoperative lameness score., Clinical Significance: Subjectively assessed clinical outcome with the N-MMT was good to excellent in this cohort of dogs. However, a high rate of intra- and postoperative complications of the N-MMT procedure was also present in these dogs.

Objectives: to evaluate in vitro the strength of different compositions of beta-tricalcium phosphate (β-TCP) wedges in comparison with titanium foam and cages. To study the response to cyclic loading of the strongest β-TCP wedge, titanium foam and titanium cage., Methods: Compression test: Twenty-five tibiae were prepared for tibial tuberosity advancement using the modified Maquet technique. Five groups were defined depending on the material used to maintain the tibial tuberosity: Group 1=titanium cage; Group 2=wedges of porous titanium foam with 50% porosity (OrthoFoam®); Group 3=blocks of biphasic synthetic bone (60% hydroxyapatite [HAP] and 40% β-TCP, porosity 80%); Group 4=blocks of biphasic synthetic bone (60% HAP and 40% β-TCP, porosity 70%) and Group 5=blocks of biphasic synthetic bone (65% HAP and 35% β-TCP, porosity 60%). Loads to failure were calculated for each implant. Cyclic study: Five additional tibiaes of group 1, 2 and 5 were fatigue tested from 100 to 500 N at a rate of 4 Hz for 200,000 cycles or until failure., Results: Compression test: For the five groups, the mean load at failure was 1895 N, 1917 N, 178 N, 562 N and 1370 N respectively. Cyclical study: All samples in the three groups tested withstood 200,000 cycles without failure., Clinical Significance: The ideal implant to maintain tibial tuberosity advancement after the modified Maquet technique would be absorbable and allow osteoconduction and osteoinduction. As such, β-TCP wedges have many advantages and our study shows that they can withstand loads in the patellar tendon up to 500 N over 200,000 cycles in vitro and deserve more investigation.

Objectives/hypothesis: The purpose of this study was to investigate the impact of a single session of manual circumlaryngeal therapy on the vocal characteristics of future elite vocal performers (music students)., Study Design: A pretest/post-test control group design was used., Methods: Sixteen music students were randomly divided in an experimental and control group. The experimental group received manual circumlaryngeal therapy for 20 minutes, whereas the control group was instructed to have complete vocal rest for 20 minutes. Immediately before and after the therapy or vocal rest, an identical objective voice assessment protocol (aerodynamic measurement, acoustic analysis, voice range profile, and Dysphonia Severity Index [DSI]) was performed. Vocal parameters were compared before and after manual circumlaryngeal therapy in the experimental group, and before and after vocal rest in the control group using the Wilcoxon signed rank test., Results: In the experimental group a significant difference in DSI was found between the measurement before and after manual circumlaryngeal therapy. The median DSI increased from 6.3 before to 7.2 after manual circumlaryngeal therapy. No differences in DSI were found in the control group between the two measurements., Conclusions: The results of this pilot study prudently suggest that manual circumlaryngeal therapy can also improve vocal capacities in the healthy trained voices of future elite vocal performers., (© 2013 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: Muscle tension dysphonia (MTD) is the pathological condition in which an excessive tension of the (para)laryngeal musculature leads to a disturbed voice. Surface electromyography (sEMG) was used to investigate differences in extralaryngeal muscles' tension in patients with MTD compared with normal speakers. sEMG was examined as a diagnostic tool to differentiate between patients with MTD and controls., Methods: Eighteen patients with MTD and 44 normal speakers were included in the study. All subjects were evaluated with videostroboscopy, voice assessment protocol, and sEMG. sEMG was performed on three locations of the anterior neck. Measurements were taken during silence, phonation tasks, and while reading, with comparisons made between both study groups., Results: Patients with MTD did not express higher levels of sEMG during rest, phonation, or reading compared with normal speakers. There were no significant differences in sEMG values between males and females in both study groups., Conclusion: sEMG was not able to detect an increase in muscle tension in patients with MTD. The results of this study do not support the use of sEMG as a diagnostic tool for distinguishing patients with and without MTD. Clinical examination with laryngeal palpation, videostroboscopy, and dysphonia severity index remain the key investigations., (Copyright © 2013 The Voice Foundation. Published by Mosby, Inc. All rights reserved.)

Background: Teaching is a high-risk occupation for developing voice disorders. The purpose of this study was to investigate previously described vocal risk factors as well as to identify new risk factors related to both the personal life of the teacher (fluid intake, voice-demanding activities, family history of voice disorders, and children at home) and to environmental factors (temperature changes, chalk use, presence of curtains, carpet, or air-conditioning, acoustics in the classroom, and noise in and outside the classroom)., Methods: The study group comprised 994 teachers (response rate 46.6%). All participants completed a questionnaire. Chi-square tests and logistic regression analyses were performed., Results: A total of 51.2% (509/994) of the teachers presented with voice disorders. Women reported more voice disorders compared to men (56.4% versus 40.4%, P < 0.001). Vocal risk factors were a family history of voice disorders (P = 0.005), temperature changes in the classroom (P = 0.017), the number of pupils per classroom (P = 0.001), and noise level inside the classroom (P = 0.001). Teachers with voice disorders presented a higher level of psychological distress (P < 0.001) compared to teachers without voice problems., Conclusion: Voice disorders are frequent among teachers, especially in female teachers. The results of this study emphasize that multiple factors are involved in the development of voice disorders.

Objective: The purpose of this study is to determine objective vocal quality, vocal characteristics, and vocal habits in future speech language pathology (SLP) students and to evaluate the possible impact of a provided vocal counseling procedure. A comparison of vocal data was done in SLP students who had and who had not undergone vocal counseling procedure. It is hypothesized that counseling results in good vocal quality, adequate vocal performance, and appropriate vocal hygiene., Study Design: Randomized controlled study design., Methods: To determine the vocal quality, questionnaires (Voice Handicap Index [VHI]), subjective (videostroboscopic and perceptual evaluations), and instrumental assessment techniques (aerodynamic, vocal range, acoustic measurements, Dysphonia Severity Index [DSI]) were used. Identical voice assessments were made in 71 students who followed and have not (n=83) followed the vocal counseling procedure., Results: The VHI showed the absence of a psychosocial impact of the vocal quality. Thirty percentage of the subjects mentioned hoarseness as the most common vocal complain. Videostroboscopic evaluations revealed normal vocal anatomy and physiology. A significant difference regarding the DSI value was found between the students with (+3.3, 83%) and without (+1.8, 68%) a followed voice counseling procedure., Conclusion: This vocal counseling procedure is added as a standard procedure when future students gain information about the SLP master program. To what extent the presence and content of the vocal education strategy can influence the choice of the profession as an SLP is subject for further research., (Copyright © 2012 The Voice Foundation. Published by Mosby, Inc. All rights reserved.)

Objectives: The main purpose of this study was to investigate the impact of hormone therapy (HT) on vocal characteristics in postmenopausal women by comparing postmenopausal women with HT (n=59) and postmenopausal women without HT (n=46). The second purpose was to investigate the differences in vocal characteristics between two types of HT: estrogen therapy (ET) and estrogen-progestogen therapy (E-PT)., Methods: To determine the vocal characteristics in both groups, objective (aerodynamic measurements, vocal range measurements, acoustic analysis, and a determination of the dysphonia severity index) and subjective assessment techniques (perceptual evaluation, videostroboscopic evaluation, and voice handicap index) were used., Results: The postmenopausal women without HT showed a significantly lower speaking fundamental frequency and were able to phonate lower compared with postmenopausal women with HT. No differences in vocal characteristics were found between postmenopausal women with ET and postmenopausal women with E-PT., Conclusion: HT seems to counteract the vocal changes caused by menopause. The type of HT did not affect the outcome in this study., (Copyright © 2012 The Voice Foundation. Published by Mosby, Inc. All rights reserved.)

The purpose of this study was to investigate the impact of menopause and hormone therapy on nasal resonance by comparing premenopausal women and postmenopausal women with and without hormone therapy. A total of 147 middle-aged Flemish (Dutch)-speaking women participated in the study and were divided into three groups: premenopausal women (n =42), and postmenopausal women with (n =63) and without (n =42) hormone therapy. Nasal resonance scores of isolated sounds and connected speech were measured using the Nasometer. For the isolated sounds as well as for the reading texts, no differences were found in nasal resonance scores between the three groups (ANCOVA). The results of this study indicate that menopause and hormone therapy do not have an impact on the nasal resonance in middle-aged women.

Muscle tension dysphonia (MTD) is the pathological condition in which excessive tension of the (para)laryngeal musculature leads to a disturbed voice. This study was developed to investigate if differences in pressure in the upper esophageal sphincter (UES) were present in patients with MTD in comparison with normal speakers. Concurrently, all patients were screened for gastroesophageal reflux disease (GERD) as an associated cause or aggravating factor in MTD. The study's design was a prospective case-control study. Fourteen patients with MTD (mean age = 40.2 years, range = 22-62 years) and 14 adult controls (mean age = 33.9 years, range = 23-58 years) were studied. A water-perfusion assembly with 22 sensors was positioned to record pressures during phonation. The mean values of the phonation pressures at the UES were measured. All patients underwent a dual-probe 24-h ambulatory pH impedance in order to measure the pH and the height of the refluxes from the lower esophageal sphincter to the hypopharynx. There were no significant differences in the UES pressures of patients with MTD compared to those of normal speakers during phonation tasks and reading. Two patients were identified with GERD. In these patients the refluxate reached the UES but this did not influence the UES pressures. We conclude that this study was not able to detect differences in phonation-induced UES pressures between patients with MTD and normal speakers using a standard water-perfusion high-resolution manometry assembly. Future investigation should be focused on developing probes with closely spaced sensors in the hypopharynx and the esophagus in order to investigate if differences in UES pressures in these study populations are present.

In an initial study it was shown that (without hormonal influences) middle-aged (premenopausal) women show a smaller frequency and intensity range and a lower fundamental frequency of the voice compared to young women. To investigate the impact of menopause on voice and nasal resonance a cross-sectional non-randomized study design was used. Vocal characteristics and nasal resonance in premenopausal and postmenopausal women without hormone therapy (HT) were compared. Postmenopausal women without HT showed a significantly lower speaking fundamental frequency (SFF) and were able to phonate lower compared to postmenopausal women with HT. The mean difference in SFF was 14 Hz. HT can also counteract the menopausal changes in SFF. The lower SFF did not result in vocal complaints. Further research about the impact of menopause and HT on voice should concentrate on elite professional voice users.

Objectives: Aging influences several speech characteristics in middle-aged women. However, the effect of aging on nasal resonance has not been widely investigated, and findings are contradictory. The purpose of this study was to investigate the effect of aging on nasal resonance by comparing young women (between 20 and 28 years of age) with middle-aged women (between 45 and 55 years of age)., Methods: Thirty-one middle-aged women with a mean age of 48 years participated in the subject group. The control group consisted of 22 young women with a mean age of 23 years. To investigate nasal resonance, we used a multiparameter approach by means of the Nasal Severity Index (NSI). Objective acoustic (nasal resonance scores of sounds and connected speech measured with the Nasometer) and aerodynamic measurements (maximum duration time of /s/, vital capacity, and mirror fogging test), as well as perceptual evaluations (Gutzmann /a/-i/test), were performed., Results: The results of this study showed no differences in aerodynamic measurements and nasal resonance scores of connected speech and the sounds /i/, /u/, and /m/. Only the mean nasal resonance score of /a/ and the Gutzmann /a/ test were significantly different between the young and middle-aged women. The mean (+/- SD) NSI scores of the young women (12.93 +/- 17.9) and the middle-aged women (-1.49 +/- 14.4) both corresponded to normal nasal resonance., Conclusions: The results of this study indicate that both young and middle-aged women show a normal nasal resonance. Differences in objective and subjective measurements of nasal resonance were only found in isolated vowels, and not in connected speech.

Objectives: Teachers are at increased risk for developing voice disorders. Occupational risk factors have been extensively examined; however, little attention has been paid to the consequences of the vocal complaints. The objective of this study was to investigate the knowledge that teachers have about vocal care, treatment-seeking behavior, and voice-related absenteeism., Methods: The study group comprised 994 teachers and 290 controls whose jobs did not involve vocal effort. All participants completed a questionnaire inquiring about vocal complaints, treatment-seeking behavior, voice-related absenteeism, and knowledge about vocal care. Comparisons were made between teachers with and without vocal complaints and with the control group., Results: Teachers reported significantly more voice problems than the control population (51.2% vs. 27.4%) (χ2=50.45, df=1, P<0.001). Female teachers reported significantly higher levels of voice disorders than their male colleagues (38% vs 13.2%, χ2=22.34, df=1, P<0.001). Teachers (25.4%) sought medical care and eventually 20.6% had missed at least 1 day of work because of voice problems. Female teachers were significantly more likely to seek medical help (χ2=7.24, df=1, P=0.007) and to stay at home (χ2=7.10, df=1, P=0.008) in comparison with their male colleagues. Only 13.5% of all teachers received information during their education., Conclusions: Voice disorders have an impact on teachers' personal and professional life and imply a major financial burden for society. A substantial number of teachers needed medical help and was obligated to stay at home because of voice problems. This study strongly recommends the implementation of vocal education during the training of teacher students to prepare the vocal professional user., (Copyright © 2011 The Voice Foundation. Published by Mosby, Inc. All rights reserved.)

Aging influences the laryngeal anatomy and physiology, leading to altered vocal quality. In middle-aged women, the voice is affected by a combination of aging and menopausal transition. However, in many studies about vocal aging, the menopausal transition is not taken into account. The purpose of this study was to measure and describe the effect of aging on the vocal characteristics by comparing young women (between 20 and 28 years) and middle-aged premenopausal women (between 45 and 52 years). To determine the vocal characteristics in both groups, objective (aerodynamic measurements, vocal performance measurements, acoustic analysis, and a determination of the Dysphonia Severity Index) and subjective assessment techniques (perceptual evaluation, videostroboscopic evaluation, and Voice Handicap Index) were used. The middle-aged premenopausal women showed a smaller frequency and intensity range, a lower habitual fundamental frequency, and a higher soft phonation index compared with the young women. The results of this study are important when studying the voices of middle-aged women. Vocal characteristics of middle-aged women differ from young women, and these changes cannot only be because of hormonal changes during the menopause., (Copyright © 2011 The Voice Foundation. Published by Mosby, Inc. All rights reserved.)

The objective of this retrospective study was to determine the efficacy of a single daily oral dose of phenylpropanolamine (PPA) in the treatment of urethral sphincter mechanism incompetence (USMI) in bitches. Nine bitches diagnosed with USMI were treated with a single daily dose [1.5 mg/kg body weight (BW)] of PPA for at least 1 month. Urethral pressure profiles (UPP) were performed in 7 dogs before treatment and repeated in 4 of them after treatment. Treatment with PPA resulted in long-term continence in 8/9 bitches. One dog did not respond to PPA and was treated surgically later. Recheck UPPs showed a significant increase in maximal urethral closure pressure in the 4 bitches after treatment with PPA compared to before treatment. In conclusion, long-term continence can be achieved in bitches affected with USMI after administration of a single daily dose of PPA (1.5 mg/kg BW).

Purpose: The purpose of this study was to determine the impact of a specific vocal warm-up (WU) program-focused on the improvement of the dynamics of the extrinsic and intrinsic laryngeal muscles-on the objective vocal quality in Dutch female students who are getting trained to be speech language pathologists (SLPs). Hypothetically, one can assume that the objective vocal quality will increase after vocal WU exercises in SLPs in comparison with the matched control group that receives no WU program., Methods: This was a pretest-posttest control group design study, in which 45 female future SLPs were randomly assigned into two groups. The experimental group received a well-defined vocal WU program, whereas the control group took 30 minutes of vocal rest. Objective assessment techniques (aerodynamic, vocal range, acoustic measurements, and Dysphonia Severity Index [DSI]) were used., Results: After vocal WU, a significant increased DSI value, increased vocal performance (with lower intensity and higher frequency), and increased fundamental frequency (F₀) were measured., Conclusions: Clinically, there is clear evidence that warming up the vocal mechanism is beneficial to the objective vocal quality and the vocal performance in future SLPs. To what extent the repetition of these vocal WU exercises has the possibility to maintain increased objective vocal quality in these future professional voice users is subject to further research., (Copyright © 2011 The Voice Foundation. Published by Mosby, Inc. All rights reserved.)

Objective: The purpose of this study was to measure and describe the effect of menopause on vocal characteristics by comparing premenopausal and postmenopausal women (not taking hormone therapy [HT])., Methods: Thirty-eight postmenopausal women (mean age, 58 y) not taking HT participated in the study. The control group consisted of 34 premenopausal women (mean age, 48 y). To determine the vocal characteristics in both groups, objective (aerodynamic measurements, vocal range measurements, acoustic analysis, electroglottography, and a determination of the Dysphonia Severity Index) and subjective (perceptual evaluation, videostroboscopic evaluation, and Voice Handicap Index) assessment techniques were used., Results: Postmenopausal women showed a good overall vocal quality, with a Dysphonia Severity Index value of 3.3. Significant differences in aerodynamic parameters (vital capacity and phonation quotient), vocal range (lowest frequency), and acoustic parameters (fundamental frequency [F0] during reading, variation of F0, F0 tremor intensity index, and amplitude tremor intensity index) were found between the premenopausal and postmenopausal women. However, when controlling for age, only phonation quotient and F0 during reading were significantly lower in the group of postmenopausal women. For the perceptual evaluation, significant differences in grade of dysphonia, breathiness, and strained vocal quality were found., Conclusions: Postmenopausal women not taking HT had a good overall vocal quality. However, in comparison with premenopausal women, they showed a lower habitual F0 in continuous speech.

Objective: Muscle tension dysphonia (MTD) is a clinical and diagnostic term describing a spectrum of disturbed vocal fold behavior caused by increased tension of the (para)laryngeal musculature. Recent knowledge introduced MTD as a bridge between functional and organic disorders. This review addresses the causal and contributing factors of MTD and evaluates the different treatment options., Methods: We searched MEDLINE (Pubmed, 1950-2009) and CENTRAL (The Cochrane Library, Issue 2, 2009). Studies were included if they reviewed the classification of functional dysphonia or the pathophysiology of MTD. Etiology and pathophysiology of MTD and circumlaryngeal manual therapy (CMT) were obligatory based on reviews and prospective cohort studies because randomized controlled trials (RCTs) are nonexisting. Concerning the treatment options of voice therapy and vocal hygiene, selection was based on RCTs and systematic reviews., Results: Etiological factors can be categorized into three new subgroups: (1) psychological and/or personality factors, (2) vocal misuse and abuse, and (3) compensation for underlying disease. The effective treatment options for MTD are (1) indirect therapy: vocal hygiene and patient education; (2) direct therapy: voice therapy and CMT; (3) medical treatment; and (4) surgery for secondary organic lesions., Conclusions: MTD is the pathological condition in which an excessive tension of the (para)laryngeal musculature, caused by a diverse number of etiological factors, leads to a disturbed voice. Etiological factors range from psychological/personality disorders and vocal misuse/abuse to compensatory vocal habits in case of laryngopharyngeal reflux, upper airway infections, and organic lesions. MTD needs to be approached in a multidisciplinary setting where close cooperation between a laryngologist and a speech language pathologist is possible., (Copyright © 2011 The Voice Foundation. Published by Mosby, Inc. All rights reserved.)

Objectives: To evaluate the clinical efficacy of the transobturator vaginal tape inside-out (TVT-O) in incontinent female dogs affected with urethral sphincter mechanism incompetence (USMI) and to determine its urodynamic and morphologic effects., Study Design: Case series., Animals: Incontinent spayed female dogs (n=7)., Methods: TVT-O tape was inserted in 7 incontinent female dogs diagnosed with USMI. Urethral pressure profilometry (UPP) and vaginourethrograms were performed preoperatively, and 1 and 3 months postoperatively. Clinical efficacy of the technique was evaluated and complications reported. Follow-up information was evaluated by a telephone questionnaire., Results: All dogs were continent immediately after the procedure. Incontinence recurred 2 months after surgery in 1 dog and was treated by phenylpropanolamine administration. At mean follow-up time of 11.3 months, 6 of 7 dogs were continent. An iatrogenic urethral tear occurred intraoperatively in 1 dog. No postoperative complications were encountered. The postoperative UPPs showed significantly increased maximal urethral closure pressure and integrated pressure. Postoperative vaginourethrograms were unremarkable. The surgical procedure did not modify the location of the urinary bladder neck in dogs with a "pelvic urinary bladder" preoperatively., Conclusions: TVT-O was efficient in maintaining short term continence in 6 of 7 dogs affected with USMI., (© Copyright 2010 by The American College of Veterinary Surgeons.)

Objectives: (1) To describe a surgical technique adapted from the "transobturator vaginal tape inside-out" (TVT-O) used in women and to define the trajectory of the tape on canine cadavers, and (2) to determine the urodynamic and morphological effects of the TVT-O in continent bitches., Study Design: Cadaveric and experimental in vivo study., Animals: Fresh female canine cadavers (n=12) and spayed female Beagle dogs (2)., Methods: (1) TVT-O was inserted in 12 cadavers. Dissection was performed and distances between the tape and neighboring structures were recorded. (2) TVT-O was inserted in 2 continent female Beagle dogs. Urethral pressure profilometry and vaginourethrograms were performed preoperatively, immediately after surgery, and 2, 4, and 6 months postoperatively. Histopathology was performed 6 months after surgery., Results: (1) TVT-O tape was consistently located in a perineal space before entering the obturator foramina and was located at a safe distance from major neurovascular structures including the femoral vessels and obturator nerve. (2) TVT-O was performed without any surgical or postoperative complications in 2 continent bitches. Histopathologic examination of the tissues surrounding the tape revealed a mild fibroblastic proliferation with a mild to minimal lymphoplasmacytic inflammatory infiltration., Conclusions: TVT-O is a feasible and accurate procedure that can be performed in continent bitches with a low risk of complications., (© Copyright 2010 by The American College of Veterinary Surgeons.)

Urethral sphincter mechanism incompetence (USMI) is the most common cause of urinary incontinence in dogs. Surgery may be recommended if the animal does not respond to medical treatment or becomes refractory. In this third part of a three-part review, surgical options for the treatment of USMI are described. Colposuspension is the most frequently described procedure and offers a fair prognosis, with about 50% of the dogs being continent after surgery and most of the reminder being improved or more responsive to medical treatment. Urethropexy offers a similar success rate, but with a higher rate of complications. Endoscopic injection of collagen is an attractive technique due to its minimally invasive nature and low risk of adverse effects. Initial results may however deteriorate with time. Other procedures have been reported, but involve a low number of cases and have resulted in variable success rates. In women, stress urinary incontinence is mainly treated by minimally invasive procedures involving vaginal placement of sub-urethral slings., (Copyright © 2009 Elsevier Ltd. All rights reserved.)

Micturition disorders are commonly encountered in veterinary medicine and can be divided into two main categories, namely, urinary incontinence and urinary retention. Various pathologies can affect the bladder and/or urethral contractility causing symptoms of urinary incontinence. In this first part of a three-part review, the different causes of urinary incontinence, the physiology of the lower urinary tract and impaired bladder contractility are reviewed. Since urinary incontinence due to overactive bladder syndrome or detrusor atony is described in both dogs and humans, the different therapeutic targets in the treatment of impaired bladder contractility in human and veterinary medicine are discussed., (Copyright © 2009 Elsevier Ltd. All rights reserved.)

Various pathologies can affect the bladder and/or urethral contractility causing signs of urinary incontinence. In this second part of a three-part review, the pathophysiology of impaired urethral contractility (including urethral hyper- and hypotonicity) in the bitch and in women is discussed. Urethral sphincter mechanism incompetence (USMI) is the most common form of acquired urinary incontinence in bitches and is characterized by a decreased urethral tone. The pathophysiology and current recommended medical treatment options for USMI and cases of modified urethral tonicity due to a neurological disorder or functional outlet obstruction are discussed. Treatment options in human medicine in cases of impaired urethral contractility are described., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

A needle trap (NT) device filled with Carbopack X as a sorbent material is evaluated for the static headspace analysis of benzene, toluene, ethylbenzene, and xylene (BTEX) compounds in aqueous samples. Injection parameters used with the NT device (e.g. volume of carrier gas and time to open the split valve) are evaluated to determine the mechanism involved during the desorption and transferring of the target compounds into the GC column. Furthermore, different parameters affecting the adsorption capacity of the sorbent are studied (e.g. sampling time and temperature, headspace/sample volume ratio, salting-out, and stirring). The evaluation of the method with aqueous samples shows that repeatability and recoveries with the NT device are equivalent to those obtained using solid-phase microextraction with a carboxen/PDMS (CAR/PDMS) coating. LODs obtained with flame ionization detection are in the range of 10-25 μg/L, and in the range of hundredths of μg/L with MS detection. The method developed is satisfactorily applied to the analysis of aqueous samples obtained from wastewater treatment plants.

Objective: To describe outcome of treatment with propofol and phenobarbital for status epilepticus (SE) after portosystemic shunt (PSS) attenuation., Case or Series Summary: Three dogs without preceding seizure activity, were diagnosed with a single extrahepatic PSS. Following standard preoperative medical therapy, an ameroid constrictor was placed surgically. Recovery was uneventful until spontaneous SE developed 46-96 hours after surgery. After unsuccessful seizure control with benzodiazepines, dogs were treated with a bolus of propofol followed by a propofol constant rate infusion. Phenobarbital was concurrently administered and supportive care was optimized. All dogs recovered uneventfully over the next 7-9 days. Over the following months phenobarbital was slowly tapered. All dogs have been free from antiepileptic drugs for several months, without recurrence of neurologic signs., New or Unique Information Provided: In this case series, we describe the treatment of 3 dogs with propofol and phenobarbital for refractory SE following attenuation of a single congenital PSS. After weaning of the propofol constant rate infusion, and tapering and discontinuation of phenobarbital over the following months, all dogs experienced a complete recovery. This study provides evidence that use of propofol in combination with phenobarbital may be efficacious for management of SE in dogs after PSS surgery.

Objectives/hypothesis: This article describes the prevalence of laryngeal pathology in a treatment-seeking population with dysphonia in the Flemish part of Belgium., Study Design: Retrospective investigation., Methods: During a period of 5 years (2004-2008), data were collected from 882 patients who consulted with dysphonia at the ear, nose, and throat department of the University Hospital in Ghent (Belgium). Laryngeal pathology was diagnosed using videostroboscopy. Ages ranged from 4 years to 90 years., Results: Functional voice disorders were most frequently diagnosed (30%), followed by vocal fold nodule (15%), and pharyngolaryngeal reflux (9%). The role of age, gender, and occupation was investigated. Pathologies were significantly more common in females than in males, representing 63.8% and 36.2% of the population, respectively. Professional voice users accounted for 41% of the workforce population, with teachers as main subgroup. In professional voice users, functional dysphonia occurred in 41%, vocal fold nodules in 15%, and pharyngolaryngeal reflux in 11%. Our data were compared with data from other countries., Conclusions: Functional voice disorders were overall the most common cause of voice disorders (except in childhood), followed by vocal fold nodules and pharyngolaryngeal reflux. Professional voice users accounted for almost one half of the active population, with functional voice disorders as the main cause of dysphonia.

The clinical features of brachycephalic airway obstructive disease in 11 brachycephalic dogs are described in this study. The respiratory strategy was assessed before (n=11) and after (n=6) surgery using barometric whole-body plethysmography (BWBP), with the relationship between BWBP variables and the severity of the clinical signs assessed by the use of a respiratory score based on clinical, radiographic and endoscopic findings. Partial collapse of the left main bronchus was a common finding not previously described as part of the brachycephalic airway obstructive disease syndrome. Epiglottic cysts, laryngeal granulomas and nasopharyngeal turbinates in English Bulldogs were other previously unreported findings. No significant correlation between the respiratory score and any of the BWBP variables was detected. Compared to healthy dogs, brachycephalic dogs had a significantly lower Te/Ti ratio (expiratory time over inspiratory time), peak inspiratory flow (PIF) per kg bodyweight (BW), significantly higher peak expiratory flow (PEF) per kgBW, PEF/PIF, and enhanced pause. These variations are compatible with upper airway obstructions primarily in the extrathoracic airways. Following surgery, a significant decrease in PEF/PIF was detected. The study showed that BWBP could be used to characterise the respiratory strategy in brachycephalic dogs before and after surgery., (Copyright 2008 Elsevier Ltd. All rights reserved.)

Open structure rhinoplasty (OSR) is an old technique that has gained in popularity amongst plastic surgeons and otolaryngologists over the past twenty years. Opponents of the external approach cite potential problems such as unnecessary scaring, reduction of tip support, extended operative time and excessive post-operative tip swelling. However, even relatively inexperienced rhinoplastic surgeons embrace this approach, especially in cases with more complex tip deformities and skeletal abnormalities. Concerns about scarring and post-operative tissue reaction due to the more "aggressive" external approach make it necessary to consider the indications for the open approach carefully. Various incisions have been described for open rhinoplasty to reduce scarring, such as the Z, V, reverse V, and W incisions. There should be a strong emphasis on post-operative care in open approach rhinoplasty since open structure rhinoplasty is generally considered to be a more traumatic technique than the endonasal approach. Careful incision and dissection of the skin flap in the right surgical plane and proper suturing are essential to avoid short- and long-term complications. In conclusion, the external approach is preferable in selected cases where extended exposure (asymmetry cases, for example), per-operative assessment (revision cases), grafting and suturing are required. It allows the surgeon to work bimanually during reconstruction and the better per-operative evaluation reduces the revision rate.

During lifetime the female larynx is very sensitive to sex hormone fluctuations. The menopause forms a critical event in a women's life and also affects the laryngeal tissues. The present report gives an overview of the recent literature about the impact of the menopause on the female larynx and vocal quality. The article discusses the symptoms, aetiology and different treatment options for laryngeal changes during the menopause. The literature pertaining to the impact of the menopause on the voice and the larynx was reviewed to provide a critical summary about the menopausal voice, aetiology and therapeutic options. In postmenopausal women laryngeal changes like oedema and muscular and mucosal dystrophy and atrophy were found. For the voice, the most important acoustic changes in postmenopausal women are a decreased vocal frequency range, decreased fundamental frequency and a higher frequency perturbation. Potential direct and indirect causes for these changes are discussed. Hormone replacement therapy is prescribed in some women for the treatment of menopausal complaints. The first reports in the literature point out a tendency towards a positive, organ-conserving effect of hormone treatment on the larynx and probably the voice. The type and the form of application of hormone therapy seem to be important in the outcome of the studies.

Chronic rhinosinusitis is a heterogeneous group of chronic sinus diseases that may consist of clearly different disease entities. Further investigation of the pathomechanisms of chronic rhinosinusitis and the introduction of appropriate disease markers have recently facilitated disease classification. Evaluation of inflammatory cell profiles, the differentiation of T-effector cells, characterization of remodeling processes such as fibrosis or edema formation, and innate or adaptive immunity products such as Toll-like receptors and immunoglobulins all provide tools to identify distinct disease entities within the group of chronic sinus diseases. This disease differentiation will not only increase our knowledge of the pathophysiology of sinusitis but may lead to new diagnostic and therapeutic strategies specifically targeted and adapted to the diagnosed disease entity.