EpiGe: A machine-learning strategy for rapid classification of medulloblastoma using PCR-based methyl-genotyping.

Molecular classification of medulloblastoma is critical for the treatment of this brain tumor. Array-based DNA methylation profiling has emerged as a powerful approach for brain tumor classification. However, this technology is currently not widely available. We present a machine-learning decision support system (DSS) that enables the classification of the principal molecular groups-WNT, SHH, and non-WNT/non-SHH-directly from quantitative PCR (qPCR) data. We propose a framework where the developed DSS appears as a user-friendly web-application-EpiGe-App-that enables automated interpretation of qPCR methylation data and subsequent molecular group prediction. The basis of our classification strategy is a previously validated six-cytosine signature with subgroup-specific methylation profiles. This reduced set of markers enabled us to develop a methyl-genotyping assay capable of determining the methylation status of cytosines using qPCR instruments. This study provides a comprehensive approach for rapid classification of clinically relevant medulloblastoma groups, using readily accessible equipment and an easy-to-use web-application.t.

What are the Symptoms that Characterize the Clinical Condition of Vocal Fatigue? A Scoping Review and Meta-Analysis.

INTRODUCTION: Vocal fatigue is a clinical manifestation associated with a perception of negative vocal adjustment. It is related to the increase in the sensation of excessive effort when speaking and the lack of conditioning of the muscles and structures that involve vocal production. Because it has a complex and multifactorial diagnosis, there is still no consensus on the symptoms most commonly found in this clinical condition. OBJECTIVE: To review and analyze the symptoms that characterize the clinical condition of vocal fatigue. METHODS: This study consists of a scoping review carried out in the Cochrane Library, Embase, Lilacs, and Medline databases. Observational studies or clinical trials from the last 10 years. Studies with participants younger than 18 years of age were excluded; as well as research that did not describe symptoms of vocal fatigue or that presented vocal fatigue as a symptom; studies with patients with neurological, psychiatric, syndromic conditions, or head and neck cancer. The Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies NHLBI-NIH scale was used to assess the methodological quality of selected observational studies and the PEDro scale for the analysis of experimental studies. The steps were performed by three blinded evaluators. Subsequently, meta-analyses of global means were executed for each factor under study; a comparison of the difference in the mean score for each factor between exposed and unexposed; a comparison of the difference in the average score, among non-professional voice users, for each factor between exposed and unexposed. RESULTS: In the searches performed, 956 articles were found and 29 articles were selected according to the eligibility criteria. Of these, 93.11% of the studies were observational and 6.89% were clinical trials. Regarding the gender and age group of the study samples, women aged between 30 and 45 years were predominant. As for the occupational use of voice, 68.97% of the samples were composed of professional voice users and 31.03% of non-professional voice users, with most professional voice users being teachers and non-professional voice users, individuals with dysphonia or vocal complaint. To assess vocal fatigue symptoms, 28 studies used the Vocal Fatigue Index (VFI) protocol, and only one study used another assessment protocol, Self-Administered Voice Rating. All studies were classified as regular, according to the scale used. As for the meta-analyses performed, the mean scores of the VFI factors were higher among professional voice users when compared to non-professional voice users and higher in dysphonic individuals compared to non-dysphonic individuals. CONCLUSION: The vocal fatigue symptoms found in this review were common in the populations of professional voice users and non-professional voice users and dysphonic and non-dysphonic individuals. These symptoms were related to vocal recovery after rest, physical discomfort, and restricted vocal use.

Efeitos de um programa de fonoterapia da voz em grupo de pacientes com disfonia: estudo piloto / Effects of a voice therapy program in a group of patients with dysphonia: a pilot study

RESUMO Objetivo Identificar os efeitos de um programa de fonoterapia da voz em grupo de pacientes com disfonia, por meio de avaliações perceptivo-auditiva e autopercepção vocal. Métodos Estudo-piloto de ensaio clínico não controlado, com amostra de conveniência. O estudo contou com 22 participantes com diagnóstico otorrinolaringológico de disfonia. Dentre eles, 15 mulheres e sete homens, com média de idade de 59,4 ± 12,53. Foram realizadas dez sessões de terapia fonoaudiológica em grupos de cinco a seis pessoas, com abordagens diretas e indiretas, baseadas no Programa Integral de Reabilitação Vocal (PIRV). Os participantes foram avaliados individualmente, antes e após a realização do programa terapêutico. A avaliação incluiu análise de autopercepção com a Escala de Sintomas Vocais (ESV) e perceptivo-auditiva da qualidade vocal com a escala Grade, Roughness, Breathness, Asteny, Strain, (GRBAS), realizadas por fonoaudiólogos especialistas em voz. Resultados Após o programa terapêutico, observou-se diferença significativa na pontuação de grau geral de alteração da ESV (p=0,002) e também nas subescalas Limitação (p=0,002) e Emocional (p=0,006), indicando autopercepção de redução dos sintomas vocais após intervenção. No entanto, destaca-se que não foram encontrados resultados significativos na comparação pré e pós-tratamento com relação à qualidade vocal. Conclusão O programa de fonoterapia da voz teve efeitos estatisticamente significativos em relação aos sintomas vocais autorrelatados, sinalizando um caminho promissor de abordagem eclética para a terapia vocal em grupo.

ABSTRACT Purpose To identify the effects of a phonotherapy program in a group of patients with dysphonia through auditory-perceptual and vocal self-perception assessments. Methods Pilot study: an uncontrolled clinical trial with a convenience sample. Twenty-two patients with an otorhinolaryngological diagnosis of dysphonia participated in the study, including 15 women and 7 men, with a mean age of 59.4 ± 12.53, who underwent 10 speech therapy sessions in groups of 5 to 6 people, with direct and indirect therapy based on the Comprehensive Vocal Rehabilitation Program (CVRP). Patients were individually assessed before and after the therapeutic program, the assessment included auditory-perceptual analysis with the Vocal Symptoms Scale (VSS) and auditory-perceptual analysis of voice quality GRBAS, performed by speech-language pathologists specializing in voice. Results After the therapeutic program, there was a significant difference in the score for the general degree of change in the VSS (p=0.002), and also in the limitation (p=0.002) and emotional (p=0.006) subscales, indicating selfperceived reduction in vocal symptoms after intervention. However, no significant results were found in the pre- and posttreatment comparison regarding vocal quality. Conclusion The study demonstrated that the voice therapy program had statistically significant effects in relation to self-reported vocal symptoms, thus signaling a promising path for an eclectic approach to group vocal therapy.

MIF/CXCR4 signaling axis contributes to survival, invasion, and drug resistance of metastatic neuroblastoma cells in the bone marrow microenvironment.

BACKGROUND: The bone marrow (BM) is the most common site of dissemination in patients with aggressive, metastatic neuroblastoma (NB). However, the molecular mechanisms underlying the aggressive behavior of NB cells in the BM niche are still greatly unknown. In the present study, we explored biological mechanisms that play a critical role in NB cell survival and progression in the BM and investigated potential therapeutic targets. METHODS: Patient-derived bone marrow (BM) primary cultures were generated using fresh BM aspirates obtained from NB patients. NB cell lines were cultured in the presence of BM conditioned media containing cell-secreted factors, and under low oxygen levels (1% O2) to mimic specific features of the BM microenvironment of high-risk NB patients. The BM niche was explored using cytokine profiling assays, cell migration-invasion and viability assays, flow cytometry and analysis of RNA-sequencing data. Selective pharmacological inhibition of factors identified as potential mediators of NB progression within the BM niche was performed in vitro and in vivo. RESULTS: We identified macrophage migration inhibitory factor (MIF) as a key inflammatory cytokine involved in BM infiltration. Cytokine profiling and RNA-sequencing data analysis revealed NB cells as the main source of MIF in the BM, suggesting a potential role of MIF in tumor invasion. Exposure of NB cells to BM-conditions increased NB cell-surface expression of the MIF receptor CXCR4, which was associated with increased cell viability, enhanced migration-invasion, and activation of PI3K/AKT and MAPK/ERK signaling pathways. Moreover, subcutaneous co-injection of NB and BM cells enhanced tumor engraftment in mice. MIF inhibition with 4-IPP impaired in vitro NB aggressiveness, and improved drug response while delayed NB growth, improving survival of the NB xenograft model. CONCLUSIONS: Our findings suggest that BM infiltration by NB cells may be mediated, in part, by MIF-CXCR4 signaling. We demonstrate the antitumor efficacy of MIF targeting in vitro and in vivo that could represent a novel therapeutic target for patients with disseminated high-risk NB.

Análise do índice de desvantagem vocal para o canto de coristas idosos / Analysis of the singing voice handicap index for elderly choristers

RESUMO Objetivo Analisar o índice de desvantagem vocal para o canto de coristas idosos e verificar a sua relação com perfil, hábitos e condições de saúde dos participantes. Método Foram incluídos 110 indivíduos com 60 anos ou mais, participantes de coros amadores. Os coristas foram entrevistados a fim de verificar dados como idade, tempo de canto coral, classificação vocal e a presença de hábitos e condições de saúde adversas à produção vocal. Posteriormente, responderam o questionário "Índice de Desvantagem Vocal para o Canto (IDV-C)" que avalia a autopercepção do indivíduo em relação às experiências no uso da voz cantada. Resultados O escore do IDV-C teve uma mediana de 25, sendo a pontuação mínima 0 e a máxima 86. Os itens mais pontuados estavam relacionados aos aspectos físicos no uso da voz cantada: "Não consigo cantar agudo" (Q10) e "Minha garganta fica seca quando canto" (Q13). Verificou-se que os idosos com mais de 75 anos apresentaram maior desvantagem vocal para o canto ao comparar com os mais jovens (p=0,020). As coristas classificadas como contralto também apresentaram maior escore do IDV-C (p=0,023), assim como os indivíduos que relataram beber pouca água (p=0,007). Conclusão Os coristas deste estudo apresentaram um índice de desvantagem vocal para o canto compatível com vozes saudáveis para o canto. Ao verificar a relação do escore do IDV-C com as características dos participantes e a respeito dos hábitos e condições de saúde, constatou-se que os coristas idosos com mais de 75 anos, as coristas contralto e aqueles que afirmaram beber pouca água apresentaram escores maiores de desvantagem vocal para o canto.

ABSTRACT Purpose To analyze the singing voice handicap index in elderly choristers and verify its relationship with the profile, habits and health conditions of the participants. Methods 110 individuals aged 60 years or older, participating in amateur choirs, were included. Choir singers were interviewed in order to verify data such as age, time in choir singing, vocal classification, and the presence of habits and health conditions adverse to voice production. Subsequently, they answered the questionnaire "Singing Voice Handicap Index (SVHI)", which assesses the individual's self-perception in relation to experiences in the use of the singing voice. Results The SVHI score had a median of 25, with a minimum score of 0 and a maximum score of 86. The most scored items were related to physical aspects in the use of singing voice: "I am unable to use my 'high voice'" (Q10) and "My throat is dry when I sing"(Q13). It was found that older adults over 75 years of age had a greater voice handicap when compared to younger ones (p=0.020). Choir singers classified as contralto also had a higher SVHI score (p=0.023), as well as individuals who reported drinking little water (p=0.007). Conclusion The choristers in this study presented a singing voice handicap index compatible with healthy singing voices. When verifying the relationship of the SVHI score with the characteristics of the participants and with respect to habits and health conditions, it was found that the elderly choir singers over 75 years old, the contralto choir singers, and those who claimed to drink little water had higher scores for the singing voice handicap.

Analysis of the singing voice handicap index for elderly choristers. / Análise do índice de desvantagem vocal para o canto de coristas idosos.

PURPOSE: To analyze the singing voice handicap index in elderly choristers and verify its relationship with the profile, habits and health conditions of the participants. METHODS: 110 individuals aged 60 years or older, participating in amateur choirs, were included. Choir singers were interviewed in order to verify data such as age, time in choir singing, vocal classification, and the presence of habits and health conditions adverse to voice production. Subsequently, they answered the questionnaire "Singing Voice Handicap Index (SVHI)", which assesses the individual's self-perception in relation to experiences in the use of the singing voice. RESULTS: The SVHI score had a median of 25, with a minimum score of 0 and a maximum score of 86. The most scored items were related to physical aspects in the use of singing voice: "I am unable to use my 'high voice'" (Q10) and "My throat is dry when I sing"(Q13). It was found that older adults over 75 years of age had a greater voice handicap when compared to younger ones (p=0.020). Choir singers classified as contralto also had a higher SVHI score (p=0.023), as well as individuals who reported drinking little water (p=0.007). CONCLUSION: The choristers in this study presented a singing voice handicap index compatible with healthy singing voices. When verifying the relationship of the SVHI score with the characteristics of the participants and with respect to habits and health conditions, it was found that the elderly choir singers over 75 years old, the contralto choir singers, and those who claimed to drink little water had higher scores for the singing voice handicap.

OBJETIVO: Analisar o índice de desvantagem vocal para o canto de coristas idosos e verificar a sua relação com perfil, hábitos e condições de saúde dos participantes. MÉTODO: Foram incluídos 110 indivíduos com 60 anos ou mais, participantes de coros amadores. Os coristas foram entrevistados a fim de verificar dados como idade, tempo de canto coral, classificação vocal e a presença de hábitos e condições de saúde adversas à produção vocal. Posteriormente, responderam o questionário "Índice de Desvantagem Vocal para o Canto (IDV-C)" que avalia a autopercepção do indivíduo em relação às experiências no uso da voz cantada. RESULTADOS: O escore do IDV-C teve uma mediana de 25, sendo a pontuação mínima 0 e a máxima 86. Os itens mais pontuados estavam relacionados aos aspectos físicos no uso da voz cantada: "Não consigo cantar agudo" (Q10) e "Minha garganta fica seca quando canto" (Q13). Verificou-se que os idosos com mais de 75 anos apresentaram maior desvantagem vocal para o canto ao comparar com os mais jovens (p=0,020). As coristas classificadas como contralto também apresentaram maior escore do IDV-C (p=0,023), assim como os indivíduos que relataram beber pouca água (p=0,007). CONCLUSÃO: Os coristas deste estudo apresentaram um índice de desvantagem vocal para o canto compatível com vozes saudáveis para o canto. Ao verificar a relação do escore do IDV-C com as características dos participantes e a respeito dos hábitos e condições de saúde, constatou-se que os coristas idosos com mais de 75 anos, as coristas contralto e aqueles que afirmaram beber pouca água apresentaram escores maiores de desvantagem vocal para o canto.

Vocal parameters, muscle palpation, self-perception of voice symptoms, pain, and vocal fatigue in women with muscle tension dysphonia. / Parâmetros vocais, palpação muscular e autopercepção de sintomas vocais, dor e fadiga vocal em mulheres com disfonia por tensão muscular.

PURPOSE: To identify muscle tension dysphonia (MTD) signs and symptoms, as well as to analyze the results of vocal parameters, the physical clinical examination of muscle palpation, the self-perception of vocal symptoms, vocal pain, and fatigue of women with MTD and compare them with women with healthy voices. METHODS: a cross-sectional study with 45 women (23 with MTD and 22 controls), similar median age between groups. The speech-language and otorhinolaryngological evaluation determined the diagnosis of MTD. All participants responded to the Voice Symptoms Scale (VoiSS), Vocal Fatigue Index (VFI), and Nordic Musculoskeletal Questionnaire (NMQ) protocols. They were also assessed by a palpatory evaluation of the perilaryngeal musculature, auditory-perceptual evaluation, and acoustic analysis of the voice fundamental frequency. The speech sample included sustained vowels "a", "i" and "e" and connected speech, recorded in a silent environment, and submitted to auditory-perceptual evaluation by three judges. In the acoustic analysis, the fundamental frequency and maximum phonation times were extracted. RESULTS: The MTD group had worse results in VoiSS, VFI, and NMQ, in addition to greater resistance to palpation and a high vertical position of the larynx. The vocal parameters also showed greater deviation in the MTD group, except for the fundamental frequency. There was no relationship between vocal symptoms, fatigue, or pain with the general degree of dysphonia in the MTD group, indicating important symptoms in mild or moderate vocal deviations. CONCLUSION: women with MTD presented vocal symptoms, vocal fatigue, muscle pain, resistance to palpation and deviated vocal parameters when compared to vocally healthy women.

OBJETIVO: identificar sinais e sintomas de DTM, bem como analisar os resultados de parâmetros vocais, do exame clínico físico de palpação muscular, da autopercepção de sintomas vocais, dor e fadiga vocal de mulheres com DTM e comparar com mulheres vocalmente saudáveis. MÉTODOS: estudo transversal com 45 mulheres (23 com DTM e 22 controles), mediana de idade similar entre os grupos. A avaliação fonoaudiológica e otorrinolaringológica determinaram o diagnóstico de DTM. Todas as participantes responderam aos protocolos Escala de Sintomas Vocais (ESV), Índice de Fadiga Vocal (IFV) e Questionário Nórdico de Sintomas Osteomusculares (QNSO). Elas também foram avaliadas pelo exame de palpação da musculatura perilaríngea, avaliação perceptivo-auditiva e análise acústica da voz da frequência fundamental. A amostra de fala incluiu vogais "a", "i" e "é" sustentadas e fala encadeada, gravada em ambiente silente, e submetida à avaliação perceptivo-auditiva por três juízes. Na análise acústica, a frequência fundamental e tempos máximos de fonação foram extraídos. RESULTADOS: O grupo DTM apresentou piores resultados na ESV, na IFV e no QNSO, além de maior resistência à palpação e posição vertical de laringe alta. Os parâmetros vocais também apresentaram maior desvio na DTM, exceto para a frequência fundamental. Não houve relação entre sintomas vocais, fadiga ou dor com o grau geral da disfonia no grupo DTM, indicando sintomas importantes em desvios vocais leves ou moderados. CONCLUSÃO: mulheres com DTM apresentaram sintomas vocais, fadiga vocal, dor muscular, resistência à palpação e parâmetros vocais desviados quando comparadas às mulheres vocalmente saudáveis.

Transcutaneous Electrical Nerve Stimulation in Dysphonic Patients: A Systematic Review.

OBJECTIVE: This paper aims to systematically review the application methods and clinical outcomes of transcutaneous electrical nerve stimulation (TENS) in the rehabilitation of dysphonic patients. METHODS: The study consists of a systematic review performed in the Medline (via PubMed), Cochrane Library, Scopus and Lilacs databases, using a search strategy related to the research theme. Inclusion criteria involve experimental studies that investigated the effects of TENS on dysphonic patients, published in the last 15 years in Portuguese, English or Spanish. The Physiotherapy Evidence-Based Database was used to evaluate the methodological quality of the articles. RESULTS: In the first search, 100 publications were found, 57 of which were duplicated and 23 did not address TENS as an intervention. According to the exclusion criteria of the remaining 20 studies, eight were selected for this review. The studies showed a pattern regarding the application of TENS. Of the studies analyzed, 87.5% had effective results after the intervention. Regarding pain, studies have found a reduction of this symptom in the neck, shoulders, back, masseter, and larynx. In the perceptual analysis, an improvement was verified in the parameters of tension, breathiness, roughness, instability, and asthenia. In addition, different types of vocal symptoms such as pain, burning, lump in the throat and effort to speak were reduced after TENS. CONCLUSION: Although the studies included in this review indicate that there were changes related to the reduction of vocal symptoms, reduction of pain and improvement of vocal quality after the application of TENS in dysphonic patients, studies with a higher level of evidence and rigorous assessments of methodological quality are necessary so that findings are more robust and replicable in clinical practice.

Parâmetros vocais, palpação muscular e autopercepção de sintomas vocais, dor e fadiga vocal em mulheres com disfonia por tensão muscular / Vocal parameters, muscle palpation, self-perception of voice symptoms, pain, and vocal fatigue in women with muscle tension dysphonia

RESUMO Objetivo identificar sinais e sintomas de DTM, bem como analisar os resultados de parâmetros vocais, do exame clínico físico de palpação muscular, da autopercepção de sintomas vocais, dor e fadiga vocal de mulheres com DTM e comparar com mulheres vocalmente saudáveis. Métodos estudo transversal com 45 mulheres (23 com DTM e 22 controles), mediana de idade similar entre os grupos. A avaliação fonoaudiológica e otorrinolaringológica determinaram o diagnóstico de DTM. Todas as participantes responderam aos protocolos Escala de Sintomas Vocais (ESV), Índice de Fadiga Vocal (IFV) e Questionário Nórdico de Sintomas Osteomusculares (QNSO). Elas também foram avaliadas pelo exame de palpação da musculatura perilaríngea, avaliação perceptivo-auditiva e análise acústica da voz da frequência fundamental. A amostra de fala incluiu vogais "a", "i" e "é" sustentadas e fala encadeada, gravada em ambiente silente, e submetida à avaliação perceptivo-auditiva por três juízes. Na análise acústica, a frequência fundamental e tempos máximos de fonação foram extraídos. Resultados O grupo DTM apresentou piores resultados na ESV, na IFV e no QNSO, além de maior resistência à palpação e posição vertical de laringe alta. Os parâmetros vocais também apresentaram maior desvio na DTM, exceto para a frequência fundamental. Não houve relação entre sintomas vocais, fadiga ou dor com o grau geral da disfonia no grupo DTM, indicando sintomas importantes em desvios vocais leves ou moderados. Conclusão mulheres com DTM apresentaram sintomas vocais, fadiga vocal, dor muscular, resistência à palpação e parâmetros vocais desviados quando comparadas às mulheres vocalmente saudáveis.

ABSTRACT Purpose To identify muscle tension dysphonia (MTD) signs and symptoms, as well as to analyze the results of vocal parameters, the physical clinical examination of muscle palpation, the self-perception of vocal symptoms, vocal pain, and fatigue of women with MTD and compare them with women with healthy voices. Methods a cross-sectional study with 45 women (23 with MTD and 22 controls), similar median age between groups. The speech-language and otorhinolaryngological evaluation determined the diagnosis of MTD. All participants responded to the Voice Symptoms Scale (VoiSS), Vocal Fatigue Index (VFI), and Nordic Musculoskeletal Questionnaire (NMQ) protocols. They were also assessed by a palpatory evaluation of the perilaryngeal musculature, auditory-perceptual evaluation, and acoustic analysis of the voice fundamental frequency. The speech sample included sustained vowels "a", "i" and "e" and connected speech, recorded in a silent environment, and submitted to auditory-perceptual evaluation by three judges. In the acoustic analysis, the fundamental frequency and maximum phonation times were extracted. Results The MTD group had worse results in VoiSS, VFI, and NMQ, in addition to greater resistance to palpation and a high vertical position of the larynx. The vocal parameters also showed greater deviation in the MTD group, except for the fundamental frequency. There was no relationship between vocal symptoms, fatigue, or pain with the general degree of dysphonia in the MTD group, indicating important symptoms in mild or moderate vocal deviations. Conclusion women with MTD presented vocal symptoms, vocal fatigue, muscle pain, resistance to palpation and deviated vocal parameters when compared to vocally healthy women.

A Novel Method for Rapid Molecular Subgrouping of Medulloblastoma.

Purpose: The classification of medulloblastoma into WNT, SHH, group 3, and group 4 subgroups has become of critical importance for patient risk stratification and subgroup-tailored clinical trials. Here, we aimed to develop a simplified, clinically applicable classification approach that can be implemented in the majority of centers treating patients with medulloblastoma.Experimental Design: We analyzed 1,577 samples comprising previously published DNA methylation microarray data (913 medulloblastomas, 457 non-medulloblastoma tumors, 85 normal tissues), and 122 frozen and formalin-fixed paraffin-embedded medulloblastoma samples. Biomarkers were identified applying stringent selection filters and Linear Discriminant Analysis (LDA) method, and validated using DNA methylation microarray data, bisulfite pyrosequencing, and direct-bisulfite sequencing.Results: Using a LDA-based approach, we developed and validated a prediction method (EpiWNT-SHH classifier) based on six epigenetic biomarkers that allowed for rapid classification of medulloblastoma into the clinically relevant subgroups WNT, SHH, and non-WNT/non-SHH with excellent concordance (>99%) with current gold-standard methods, DNA methylation microarray, and gene signature profiling analysis. The EpiWNT-SHH classifier showed high prediction capacity using both frozen and formalin-fixed material, as well as diverse DNA methylation detection methods. Similarly, we developed a classifier specific for group 3 and group 4 tumors, based on five biomarkers (EpiG3-G4) with good discriminatory capacity, allowing for correct assignment of more than 92% of tumors. EpiWNT-SHH and EpiG3-G4 methylation profiles remained stable across tumor primary, metastasis, and relapse samples.Conclusions: The EpiWNT-SHH and EpiG3-G4 classifiers represent a new simplified approach for accurate, rapid, and cost-effective molecular classification of single medulloblastoma DNA samples, using clinically applicable DNA methylation detection methods. Clin Cancer Res; 24(6); 1355-63. ©2018 AACR.

Effects of Voice Therapy on Muscle Tension Dysphonia: A Systematic Literature Review.

The present study aimed to carry out a systematic review of the effects of voice therapy on individuals diagnosed with muscle tension dysphonia (MTD) or hyperfunctional dysphonia. This is a systematic literature review on the databases Medline (via PubMed), Cochrane Library, Scopus, and Lilacs using a search strategy related to the theme of the study. The selection included clinical trials that assessed the effects of speech therapy intervention on patients diagnosed with MTD or hyperfunctional dysphonia published over the last 10 years in Portuguese, English, or Spanish. The Physiotherapy Evidence-Based Database (PEDro) Scale was used to assess the methodology of the studies. Of the 634 publications, 12 studies were included in this review, of which three were excluded due to a low score on the PEDro Scale, resulting in a final number of nine publications. Regarding the techniques approached, semioccluded vocal tract exercises (22.22%), nasal sound and frequency modulation (22.22%), maximum phonation time (MPT) technique and vocal hygiene (11.11%), vocal function exercises (11.11%), respiratory exercises along with phonoarticulatory sounds (11.11%), manual laryngeal therapy (11.11%), and manual laryngeal therapy associated with respiratory exercises (11.11%) were identified. These techniques promoted the following effects: improvement in intraoral and subglottal pressure, positive alterations in the glottal contact quotient, significant changes in fundamental frequency measures, increased MPT, and reduced voice roughness. Methodology was identified to be a shortcoming in the studies. The clinical trials reviewed showed positive results in using the therapeutic techniques selected in the speech therapy approach.

Effects of a Voice Therapy Program for Patients with Muscle Tension Dysphonia.

OBJECTIVE: This study aimed to verify the effects of a voice therapy program focusing on patients with muscle tension dysphonia (MTD). PATIENTS AND METHODS: The sample comprised 30 participants diagnosed with MTD, 8 men and 22 women, none of whom was a voice professional. The assessments and reassessments employed the perceptual-auditory protocol GRBASI, measures of maximum phonation times, s/z ratio, and acoustic voice analysis. The voice therapy program included indirect and direct therapy approaches. RESULTS: All parameters assessed using the GRBASI protocol improved following treatment, particularly in regard to lowering voice strain, which is important when treating MTD. The average overall maximum phonation times increased from 8.15 to 10.8 s, while the average s/z ratio did not significantly change. Among the various acoustic parameters, a positive difference was observed for vocal jitter and shimmer. CONCLUSIONS: The therapeutic approach adopted in this study proved effective in the treatment of primary and secondary MTD. Speech therapy favored lower phonation effort, lowered vocal strain, and adequacy of adjustment of laryngeal muscles.

Índice de Desvantagem Vocal pré e pós-intervenção vocal em pacientes disfônicos / Voice Handicap Index check pre and post vocal intervention in patients with dysphonia

RESUMO Objetivo: Caracterizar e mensurar a autopercepção vocal de pacientes pré e pós-tratamento fonoaudiológico, por meio do protocolo de Índice de Desvantagem Vocal (IDV). Métodos: Trata-se de um estudo transversal, com utilização do banco de dados de pacientes atendidos em um setor de Fonoaudiologia. Resultados: A amostra foi composta por 23 pacientes, sendo 16 (69,6%) do gênero feminino e sete (30,4%) do gênero masculino. A média de idade foi de 58 anos, a média do tempo de terapia foi de três meses e o número de sessões foi de 11 atendimentos. Dentre os tipos de disfonia encontrados, a orgânica foi a mais frequente (47,8%), seguida da funcional (30,7%) e da organofuncional (21,7%). A mediana do escore total do protocolo apresentou diminuição no período pré-intervenção, em relação ao período pós-intervenção, significando menor desvantagem vocal. Além disso, 80% das questões do protocolo apresentaram diferença significativa, quando comparadas pré e pós-fonoterapia da voz. Conclusão: Houve diferença na percepção da voz após a intervenção fonoaudiológica, indicada por meio da redução dos escores nos itens do IDV. Os achados demonstraram a importância do uso do protocolo IDV na prática clínica, auxiliando o profissional fonoaudiólogo no direcionamento do tratamento e no entendimento do comportamento vocal de pacientes disfônicos. Sugere-se futuras pesquisas, tendo em vista a eficácia do instrumento.

ABSTRACT Purpose: Characterize and measure the voice self-perception of patients pre and post speech therapy treatment using the Índice de Desvantagem Vocal (IDV) protocol, adapted from the Voice Handicap Index (VHI) protocol. Methods: This is a cross-sectional study using a database of patients seen in a speech therapy service. Results: The sample comprised 23 patients, 16 (69.6%) of whom female and seven (30.4%) male. The mean age was 58 years and the mean therapy duration was three months with 11 sessions. Among the types of dysphonia found, organic was the most frequent (47.8%) followed by functional (30.7%) and organic-functional (21.7%). The protocol's total score median decreased prior to intervention compared to the post-intervention period, which means a lower voice handicap. Moreover, 80% of the protocol's questions significantly differed when compared pre and post speech therapy. Conclusion: A difference was found in voice perception after speech therapy intervention, indicated by lower scores in the IDV items. The findings show the importance of using the IDV protocol in clinical practice to help the speech therapist target the treatment and understand the voice behavior of dysphonic patients. Further research is suggested given the instrument's efficacy.

DNA methylation fingerprint of neuroblastoma reveals new biological and clinical insights.

AIM: To define the DNA methylation landscape of neuroblastoma and its clinicopathological impact. MATERIALS & METHODS: Microarray DNA methylation data were analyzed and associated with functional/regulatory genome annotation data, transcriptional profiles and clinicobiological parameters. RESULTS: DNA methylation changes in neuroblastoma affect not only promoters but also intragenic and intergenic regions at cytosine-phosphate-guanine (CpG) and non-CpG sites, and target functional chromatin domains of development and cancer-related genes such as CCND1. Tumors with diverse clinical risk showed differences affecting CpG and, remarkably, non-CpG sites. Non-CpG methylation observed essentially in clinically favorable cases was associated with the differentiation status of neuroblastoma and expression of key genes such as ALK. CONCLUSION: This epigenetic fingerprint of neuroblastoma provides new insights into the pathogenesis and clinical behavior of this pediatric tumor.

Evaluation of quality of life of patients with sickle cell disease in a General Hospital of Goiás, Brazil

INTRODUÇÃO: A doença falciforme é a doença hereditária mais frequente no nosso país. O portador apresenta acometimentos físico, emocional e social, e sua qualidade de vida pode estar comprometida. OBJETIVO: Avaliar a qualidade de vida dos doentes falciformes em tratamento no Hospital das Clínicas da Universidade de Goiás. MÉTODO: Foram entrevistados 60 sujeitos entre 14 e 60 anos, doentes falciformes, em tratamento no Hospital das Clínicas. Aplicou-se o WHOQOL-Bref (instrumento avaliativo de qualidade de vida da Organização Mundial de Saúde - OMS), o questionário étnico-racial e o sociodemográfico. A significância foi definida por um erro padrão de 5 por cento (p < 0,05). Os sujeitos eram do sexo feminino em 53,3 por cento e solteiros em 71,7 por cento. A média da idade foi de 27 anos e o nível educacional até o primeiro grau completo foi de 51,7 por cento. RESULTADOS: A maioria considerou-se parda (46,7 por cento) e a minoria, negra (11,7 por cento). Apenas 6,7 por cento disseram ser vítimas de preconceito devido à cor e 33,3 por cento disseram ser vítimas de preconceito devido à doença. Os sujeitos relataram ligação entre doença e sua cor em 48,3 por cento. A qualidade de vida foi avaliada negativa em 6,7 por cento e, em 70 por cento, positiva. Apresentaram satisfação negativa quanto à saúde 23,3 por cento dos sujeitos e, em 48,3 por cento, a satisfação foi positiva. Os escores do WHOQOL-Bref, de 0 a 100 foram: domínio físico (57,32), psicológico (66,03), social (69,86) e ambiental (52,76). CONCLUSÃO: Houve correlação significativa entre preconceito devido à doença e nível educacional, e entre idade e todos os domínios. A doença falciforme limita a vida do portador, com comprometimento da qualidade de vida. A doença está perdendo o caráter de "black related disease", coincidindo com a miscigenação racial brasileira.

INTRODUCTION: Sickle cell disease is the most common inherited disease in Brazil. Patients are known to suffer physical, emotional and social impairment and their quality of life may well be involved. METHOD: The quality of life of sickle cell disease patients treated in Hospital das Clínicas of the Universidade Federal de Goiás was evaluated. Sixty patients with ages ranging from 14 to 60 years old were interviewed. The WHOQOL-Bref (a quality of life validation instrument of the World Health Organization), and the ethnical-racial, and sociodemographic questionnaires were administered. A standard error of 5 percent (p-value < 0.05) was considered acceptable. RESULTS: The mean age of the participants was 27 years old, 53.3 percent of the patients were women, 71.7 percent were single and 51.7 percent had completed elementary school. The majority classified themselves as mulattos (46.7 percent) and the minority Blacks (11.7 percent). Only 6.7 percent considered themselves victims of racial discrimination because of their skin color but 33.3 percent considered themselves victims of discrimination due to sickle cell disease. The patients 48.3 percent reported an association between their disease and their skin color. The quality of life was considered bad by 6.7 percent and good by 70 percent. A total of 48.3 percent considered their lives to be satisfactory and 23.3 percent to be unsatisfactory. The scores obtained from the WHOQOL-Bref (from 0 to 100) were: 57.32 for physical, 66.03 for psychological, 69.86 for social and 52.76 for environmental domains. There were significant correlations of discrimination due to the disease with educational level and age with all the WHOQOL-Bref domains. CONCLUSION: Sickle cell disease significantly limits the quality of life of patients. Also, sickle cell disease, coinciding with the racial miscegenation, is losing its "black-related disease" character in Brazil.