Supra-Threshold LS CE-Chirp Auditory Brainstem Response in the Elderly.

INTRODUCTION: Aging deteriorates peripheral and central auditory structures and functions. In elders, for an accurate audiological evaluation, it is important to explore beyond the cochlear receptor. Audiograms provide an estimation of hearing thresholds, while the amplitudes and latencies of supra-threshold auditory brainstem response (ABR) can offer noninvasive measures of the auditory pathways functioning. Regarding ABR, in young populations, level-specific chirp (LS CE-chirp) stimulus has been proposed as an alternative synchronizing method to obtain larger ABR responses than those evoked by clicks. However, the supra-threshold characteristics of chirp evoked ABR, and their association to hearing thresholds is relatively unknown in the elderly. The aim of this study was to evaluate supra-threshold LS CE-chirp ABRs in an aged population by comparing their features with click ABRs, and evaluating their relationship with audiometric hearing thresholds. METHODS: We carried out a cross-sectional study to characterize the hearing of 125 adults aged over 65 years. We determined the audiometric hearing thresholds and supra-threshold ABRs elicited by LS CE-chirp and click stimuli at 80 dB nHL. We evaluated associations by means of partial correlations and covariate adjustment. We performed specific frequencies' analysis and subgroup analysis per hearing level. RESULTS: Wave V responses had significantly shorter latencies and larger amplitudes when elicited by LS CE-chirp as compared to click-evoked responses. Audiometric hearing thresholds correlated with age, but ABR characteristics did not. We found mild correlations between hearing thresholds and ABR characteristics, predominantly at higher frequencies and with chirp. We found scarce evidence of correlation between ABR characteristics and the average of behavioral hearing thresholds between 0.5 to 4 kHz (0.5-4 kHz PTA). After subgroup analysis according to the hearing level, no stronger or more significant correlations were found between ABR characteristics and 0.5-4 kHz PTA. DISCUSSION: In this study, we found that supra-threshold LS CE-chirp ABR presented some of the previously described similitudes and differences with supra-threshold click ABR in younger populations. Although, the average amplitude and latency of wave V evoked by LS CE-chirp were larger and faster than those evoked by clicks, these results should be taken with caution at the individual level, and further studies are required to state that LS CE-chirp ABRs are better than click ABRs in elders for clinical evaluations. We did not find consistent associations between hearing thresholds and supra-threshold wave V features, suggesting that these measures should be considered independently in the elderly.

Hearing loss in school-aged children.

BACKGROUND: Hearing loss is a common disability affecting 5% of the world's population. A lack of opportune diagnosis affects both the individual and society. In order to develop public health policies in the field of hearing health, countries must have information about epidemiology. AIMS/OBJECTIVES: In this review, we describe the information available about prevalence and incidence of hearing loss in school-aged children. MATERIAL AND METHODS: Review of the literature in PubMed. RESULTS: Reported prevalence of hearing loss in school-aged children varied between 0.2% and 7.8%. Several factors could explain the discrepancy in numbers such as definition of hearing loss, cause, and the inclusion of high-frequency hearing loss. The rate of delayed-onset hearing loss at the age of six years old varied between 0.6 and 0.8 per 1000. CONCLUSIONS AND SIGNIFICANCE: The prevalence of hearing loss in school-aged children varied between 0.2% and 7.8%, and the rate of delayed-onset hearing loss at the age of six years old varied between 0.6 and 0.8 per 1000.

Prevalence of Cognitive Impairment and Its Association With Hearing Loss Among Adults Over 50 Years of Age: Results From a Population-Based Survey in Santiago, Chile.

PURPOSE: The purpose of this study was to estimate the prevalence of cognitive impairment and explore its association with hearing loss and other sociodemographic and clinical risk factors, using an objective measurement of hearing levels, in adults over 50 years of age. METHOD: A population-based survey was completed in Santiago, Chile between December 2019 and March 2020. Participants were screened for cognitive impairment using the Short Chilean Mini-Mental State Examination and hearing levels were assessed with tonal audiometry (hearTest). Data on demographic, socioeconomic, and clinical characteristics were collected. RESULTS: A total of 538 persons completed the assessment. The prevalence of cognitive impairment in the 50+ population was 9.3% (95% confidence interval [CI] [5.8, 14.7]). Cognitive impairment was significantly higher in individuals with any level of hearing loss (odds ratio [OR] = 2.19, 95% CI [1.00, 4.80], adjusted for age, sex, education, socioeconomic position [SEP], and head trauma). Subjects with hearing loss and who reported any use of hearing aids (16% of the sample) had a lower risk of cognitive impairment (OR of nonusers 3.64, 95% CI [1.00, 13.28], adjusted for age, sex, education, SEP, and head trauma). CONCLUSION: Strategies for addressing cognitive impairment should further explore the integration of early diagnosis of hearing loss and the regular use of hearing aids.

Prevalence, risk factors and causes of hearing loss among adults 50 years and older in Santiago, Chile: results from a rapid assessment of hearing loss survey.

OBJECTIVE: Among a representative sample of adults aged 50 years and older too (i) determine the prevalence of hearing loss, (ii) evaluate probable causes and risk factors of hearing loss, and (iii) assess the association between hearing loss measured by audiometry and self-report. DESIGN: A population-based survey of adults aged 50 and older in Santiago, Chile using the Rapid Assessment of Hearing Loss (RAHL) survey. STUDY SAMPLE: 538 participants completed a questionnaire, which included questions on socio-demographic and health characteristics and self-reported hearing loss. Hearing and possible cause of hearing loss was assessed using pure tone audiometry (0.5-4.0 kHz), tympanometry, and otoscopy. RESULTS: The prevalence of any level of hearing loss in adults aged 50 years and older was 41% (95% CI 33.2, 49.2). In terms of aetiologies, 89.3% of ears with mild or worse hearing loss were classified as sensorineural. Otoscopy was abnormal in 10.7% of subjects with impacted earwax being the most common finding (4.4%) followed by chronic otitis media (3.5%). Hearing aid usage was 16.6%. Older age, lower socioeconomic position, lack of education, and solvent exposure were significantly associated with hearing loss. CONCLUSION: Hearing loss among individuals aged over 50 years was common in Santiago, Chile.

Speech Perception and Dichotic Listening Are Associated With Hearing Thresholds and Cognition, Respectively, in Unaided Presbycusis.

Presbycusis or age-related hearing loss is a prevalent condition in the elderly population, which affects oral communication, especially in background noise, and has been associated with social isolation, depression, and cognitive decline. However, the mechanisms that relate hearing loss with cognition are complex and still elusive. Importantly, recent studies show that the use of hearing aids in presbycusis, which is its standard management, can induce neuroplasticity and modify performance in cognitive tests. As the majority of the previous studies on audition and cognition obtained their results from a mixed sample of subjects, including presbycusis individuals fitted and not fitted with hearing aids, here, we revisited the associations between hearing loss and cognition in a controlled sample of unaided presbycusis. We performed a cross-sectional study in 116 non-demented Chilean volunteers aged ≥65 years from the Auditory and Dementia study cohort. Specifically, we explored associations between bilateral sensorineural hearing loss, suprathreshold auditory brain stem responses, auditory processing (AP), and cognition with a comprehensive neuropsychological examination. The AP assessment included speech perception in noise (SIN), dichotic listening (dichotic digits and staggered spondaic words), and temporal processing [frequency pattern (FP) and gap-in-noise detection]. The neuropsychological evaluations included attention, memory, language, processing speed, executive function, and visuospatial abilities. We performed an exploratory factor analysis that yielded four composite factors, namely, hearing loss, auditory nerve, midbrain, and cognition. These four factors were used for generalized multiple linear regression models. We found significant models showing that hearing loss is associated with bilateral SIN performance, while dichotic listening was associated with cognition. We concluded that the comprehension of the auditory message in unaided presbycusis is a complex process that relies on audition and cognition. In unaided presbycusis with mild hearing loss (<40 dB HL), speech perception of monosyllabic words in background noise is associated with hearing levels, while cognition is associated with dichotic listening and FP.

The Spanish 12-item version of the Speech, Spatial and Qualities of Hearing scale (Sp-SSQ12): adaptation, reliability, and discriminant validity for people with and without hearing loss.

PURPOSE: Because of the limited number of Spanish validated questionnaires available to assess auditory functionality in daily life situations in adults, the purpose of this study was to investigate the validity and the reliability of the Spanish version of the Speech, Spatial and Qualities of Hearing 12 items scale (sp-SSQ12), adapted from the published Spanish SSQ49, and to provide reference data for normal and hearing-impaired populations. METHODS: The SSQ12 is a self-report questionnaire, consisting of 12 items assessing a range of daily life listening situations. One hundred fifty adults (101 female) with a mean age of 53.9 years (SD 20.3; range 20-88 years) took part in the study. Internal consistency, test-retest reliability, validity, and floor and ceiling effects were investigated. RESULTS: The sp-SSQ12 questionnaire had high internal consistency (Cronbach's alpha = 0.95) and test-retest scores were highly correlated (ICC = 0.79). There was minimal evidence of floor and ceiling effects in our sample. Significant differences were observed overall and for the three subscales between normal and hearing-impaired groups. Although some significant differences in SSQ12 scores between groups of participants from different countries, these differences were minimal. CONCLUSIONS: The sp-SSQ12 questionnaire is a valid and reliable tool that is easy to administer and requires a short time to answer. We recommend the use of this tool for the assessment of functional hearing in the Spanish-speaking population.Implication for rehabilitationHearing loss impacts people's lives in a number of ways that are captured in the SSQ.The sp-SSQ12 is a valid and reliable tool for assessing everyday listening abilities and limitations experienced by Spanish-speaking adults with hearing loss.The sp-SSQ12 can be incorporated in the hearing rehabilitation process as a tool for evaluating and improving hearing assessment and rehabilitation programs.The sp-SSQ12 can help to identify adults who require a comprehensive hearing assessment.

How the COVID-19 pandemic affects specialty training: An analysis of a nationwide survey among otolaryngology residents in Chile. / How the COVID-19 pandemic affects specialty training: An analysis of a nationwide survey among otolaryngology residents in Chile.

INTRODUCTION: Coronavirus disease 2019, or COVID-19, has become a global pandemic. Given that the highest viral load of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is found in the airway, otolaryngologists are at high risk of infection. As a result, multiple recommendations have emerged regarding protective measures for surgical teams, including suspending non-urgent procedures and surgeries. OBJECTIVES: To evaluate the impact of the COVID-19 pandemic on otolaryngology residency training programs nationwide. METHODS: A cross-sectional survey-based study was completed in April 2020. The participants were recruited through an online survey, sent by email to all Chilean otolaryngology residents. Demographics, clinical activities, on-call shifts, COVID-19 infection status, exposure to COVID-19 patients, deployment to other specialties, diagnostic/therapeutic procedures, and surgeries performed were analyzed. Self-reported surgical data logs from previous years were used to compare results. RESULTS: Forty-seven residents completed the survey (84% response rate); 64% of residents refer seeing patients ten days or less during April 2020. Commonly performed procedures such as flexible nasolaryngoscopy, rigid nasal endoscopy, and peritonsillar abscess drainage were not performed by over 40% of the residents in that month. Only 38% participated in surgeries, with an average of 0.6 surgeries as a first surgeon, a dramatic decrease in surgical exposure when comparing the data logs from previous years. Most residents refer the following measures taken by their residency program to improve residency training: bibliographic videoconferences (87%), online clinical case seminars (60%), weekly journal clubs (38%), among others. CONCLUSIONS: Clinical and surgical opportunities decreased dramatically during April 2020. Adjustments to the regular academic curricula should be considered to decrease the negative impact of this pandemic on residency training.

INTRODUCCIÓN: La enfermedad por coronavirus 2019, o COVID-19, se ha convertido en una pandemia. Dada que la mayor carga viral de coronavirus de tipo 2 causante del síndrome respiratorio agudo severo (SARS-CoV-2) se encuentra en la vía aérea, los otorrinolaringólogos tienen un elevado riesgo de infección. Múltiples recomendaciones han surgido con respecto a las medidas de protección, incluidos la suspensión de procedimientos y cirugías electivas. OBJETIVOS: Evaluar el impacto de la pandemia de COVID-19 en los programas de formación de otorrinolaringología a nivel nacional. MÉTODOS: Estudio transversal de encuesta en línea a residentes de otorrinolaringología realizado durante abril de 2020. Se analizaron datos demográficos, actividades clínicas, turnos de llamado, infección por COVID-19, exposición a pacientes COVID-19 positivos, despliegue a otras especialidades, procedimientos y cirugías realizadas. Se utilizaron los portafolios quirúrgicos de años previos para comparar los resultados. RESULTADOS: Completaron la encuesta 47 residentes, con 84% de tasa de respuesta; el 64% refirió haber acudido a su centro asistencial 10 días o menos durante el mes de abril de 2020. Con relación a procedimientos frecuentes tales como nasofibroscopía, endoscopia nasal rígida y drenaje de absceso periamigdalino, no fueron realizados por más del 40% de los residentes en el mes. Solo el 38% participó en cirugías, con un promedio de 0,6 procedimientos como primer cirujano; se constata una drástica disminución al comparar los registros de años anteriores. La mayoría de los residentes refieren estas medidas educativas complementarias: videoconferencias bibliográficas (87%), seminarios de casos clínicos en línea (60%), revisión de artículos (38%), entre otros. CONCLUSIONES: La formación clínica y quirúrgica disminuyó drásticamente durante abril de 2020. Se deben considerar ajustes a los planes de estudio para disminuir el impacto negativo de la pandemia en la formación de los residentes.

Impacto de pandemia COVID-19 en la formación de residentes: análisis de una encuesta nacional a residentes de otorrinolaringología en Chile / How the COVID-19 pandemic affects specialty training: An analysis of a nationwide survey among otolaryngology residents in Chile

Introducción La enfermedad por coronavirus 2019, o COVID-19, se ha convertido en una pandemia. Dada que la mayor carga viral de coronavirus de tipo 2 causante del síndrome respiratorio agudo severo (SARS-CoV-2) se encuentra en la vía aérea, los otorrinolaringólogos tienen un elevado riesgo de infección. Múltiples recomendaciones han surgido con respecto a las medidas de protección, incluidos la suspensión de procedimientos y cirugías electivas. Objetivos Evaluar el impacto de la pandemia de COVID-19 en los programas de formación de otorrinolaringología a nivel nacional. Métodos Estudio transversal de encuesta en línea a residentes de otorrinolaringología realizado durante abril de 2020. Se analizaron datos demográficos, actividades clínicas, turnos de llamado, infección por COVID-19, exposición a pacientes COVID-19 positivos, despliegue a otras especialidades, procedimientos y cirugías realizadas. Se utilizaron los portafolios quirúrgicos de años previos para comparar los resultados. Resultados Completaron la encuesta 47 residentes, con 84% de tasa de respuesta; el 64% refirió haber acudido a su centro asistencial 10 días o menos durante el mes de abril de 2020. Con relación a procedimientos frecuentes tales como nasofibroscopía, endoscopia nasal rígida y drenaje de absceso periamigdalino, no fueron realizados por más del 40% de los residentes en el mes. Solo el 38% participó en cirugías, con un promedio de 0,6 procedimientos como primer cirujano; se constata una drástica disminución al comparar los registros de años anteriores. La mayoría de los residentes refieren estas medidas educativas complementarias: videoconferencias bibliográficas (87%), seminarios de casos clínicos en línea (60%), revisión de artículos (38%), entre otros. Conclusiones La formación clínica y quirúrgica disminuyó drásticamente durante abril de 2020. Se deben considerar ajustes a los planes de estudio para disminuir el impacto negativo de la pandemia en la formación de los residentes.

Introduction Coronavirus disease 2019, or COVID-19, has become a global pandemic. Given that the highest viral load of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is found in the airway, otolaryngologists are at high risk of infection. As a result, multiple recommendations have emerged regarding protective measures for surgical teams, including suspending non-urgent procedures and surgeries. Objectives To evaluate the impact of the COVID-19 pandemic on otolaryngology residency training programs nationwide. Methods A cross-sectional survey-based study was completed in April 2020. The participants were recruited through an online survey, sent by email to all Chilean otolaryngology residents. Demographics, clinical activities, on-call shifts, COVID-19 infection status, exposure to COVID-19 patients, deployment to other specialties, diagnostic/therapeutic procedures, and surgeries performed were analyzed. Self-reported surgical data logs from previous years were used to compare results. Results Forty-seven residents completed the survey (84% response rate); 64% of residents refer seeing patients ten days or less during April 2020. Commonly performed procedures such as flexible nasolaryngoscopy, rigid nasal endoscopy, and peritonsillar abscess drainage were not performed by over 40% of the residents in that month. Only 38% participated in surgeries, with an average of 0.6 surgeries as a first surgeon, a dramatic decrease in surgical exposure when comparing the data logs from previous years. Most residents refer the following measures taken by their residency program to improve residency training: bibliographic videoconferences (87%), online clinical case seminars (60%), weekly journal clubs (38%), among others. Conclusions Clinical and surgical opportunities decreased dramatically during April 2020. Adjustments to the regular academic curricula should be considered to decrease the negative impact of this pandemic on residency training.

Hipoacusia como factor de riesgo para demencia

In the last decades, there has been an increase in life expectancy in the world, with the consequent modification in the proportion of adults over 60 years. This is accompanied by an increase in pathologies for which aging is the main risk factor, such as dementia and hearing loss, which profoundly affect the quality of life of individuals and their family and impact health system costs. Given the lack of disease-modifying treatments for dementia, the study of mechanisms to prevent its occurrence has become a world priority. In the year 2017, the Lancet "Commission for dementia prevention, intervention, and care" proposed a model, in which hearing loss emerged as a new modifiable risk factor for the development of dementia. This result undoubtedly has important consequences for the understanding the multifactorial nature of dementia, our daily clinical practice and public policies aimed at its prevention and treatment. In this article, we review the current evidence supporting the association between dementia and hearing loss, discussing the available strategies for prevention, detection and treatment of hearing loss and its possible impact on the natural course of dementia. A flow chart for the clinical management of different subgroups of patients is proposed.

Reduced suprathreshold auditory nerve responses are associated with slower processing speed and thinner temporal and parietal cortex in presbycusis.

Epidemiological evidence shows an association between hearing loss and dementia in elderly people. However, the mechanisms that connect hearing impairments and cognitive decline are still unknown. Here we propose that a suprathreshold auditory-nerve impairment is associated with cognitive decline and brain atrophy. METHODS: audiological, neuropsychological, and brain structural 3-Tesla MRI data were obtained from elders with different levels of hearing loss recruited in the ANDES cohort. The amplitude of waves I (auditory nerve) and V (midbrain) from auditory brainstem responses were measured at 80 dB nHL. We also calculated the ratio between wave V and I as a proxy of suprathreshold brainstem function. RESULTS: we included a total of 101 subjects (age: 73.5 ± 5.2 years (mean ± SD), mean education: 9.5 ± 4.2 years, and mean audiogram thresholds (0.5-4 kHz): 25.5 ± 12.0 dB HL). We obtained reliable suprathreshold waves V in all subjects (n = 101), while replicable waves I were obtained in 92 subjects (91.1%). Partial Spearman correlations (corrected by age, gender, education and hearing thresholds) showed that reduced suprathreshold wave I responses were associated with thinner temporal and parietal cortices, and with slower processing speed as evidenced by the Trail-Making Test-A and digit symbol performance. Non-significant correlations were obtained between wave I amplitudes and other cognitive domains. CONCLUSIONS: These results evidence that reduced suprathreshold auditory nerve responses in presbycusis are associated with slower processing speed and brain structural changes in temporal and parietal regions.

Computer-aided diagnosis of external and middle ear conditions: A machine learning approach.

In medicine, a misdiagnosis or the absence of specialists can affect the patient's health, leading to unnecessary tests and increasing the costs of healthcare. In particular, the lack of specialists in otolaryngology in third world countries forces patients to seek medical attention from general practitioners, whom might not have enough training and experience for making correct diagnosis in this field. To tackle this problem, we propose and test a computer-aided system based on machine learning models and image processing techniques for otoscopic examination, as a support for a more accurate diagnosis of ear conditions at primary care before specialist referral; in particular, for myringosclerosis, earwax plug, and chronic otitis media. To characterize the tympanic membrane and ear canal for each condition, we implemented three different feature extraction methods: color coherence vector, discrete cosine transform, and filter bank. We also considered three machine learning algorithms: support vector machine (SVM), k-nearest neighbor (k-NN) and decision trees to develop the ear condition predictor model. To conduct the research, our database included 160 images as testing set and 720 images as training and validation sets of 180 patients. We repeatedly trained the learning models using the training dataset and evaluated them using the validation dataset to thus obtain the best feature extraction method and learning model that produce the highest validation accuracy. The results showed that the SVM and k-NN presented the best performance followed by decision trees model. Finally, we performed a classification stage -i.e., diagnosis- using testing data, where the SVM model achieved an average classification accuracy of 93.9%, average sensitivity of 87.8%, average specificity of 95.9%, and average positive predictive value of 87.7%. The results show that this system might be used for general practitioners as a reference to make better decisions in the ear pathologies diagnosis.

[Hearing loss as a risk factor for dementia]. / Hipoacusia como factor de riesgo para demencia.

In the last decades, there has been an increase in life expectancy in the world, with the consequent modification in the proportion of adults over 60 years. This is accompanied by an increase in pathologies for which aging is the main risk factor, such as dementia and hearing loss, which profoundly affect the quality of life of individuals and their family and impact health system costs. Given the lack of disease-modifying treatments for dementia, the study of mechanisms to prevent its occurrence has become a world priority. In the year 2017, the Lancet "Commission for dementia prevention, intervention, and care" proposed a model, in which hearing loss emerged as a new modifiable risk factor for the development of dementia. This result undoubtedly has important consequences for the understanding the multifactorial nature of dementia, our daily clinical practice and public policies aimed at its prevention and treatment. In this article, we review the current evidence supporting the association between dementia and hearing loss, discussing the available strategies for prevention, detection and treatment of hearing loss and its possible impact on the natural course of dementia. A flow chart for the clinical management of different subgroups of patients is proposed.

Decellularized equine carotid artery layers as matrix for regenerated neurites of spiral ganglion neurons.

Today's best solution in compensating for sensorineural hearing loss is the cochlear implant, which electrically stimulates the spiral ganglion neurons in the inner ear. An optimum hearing impression is not ensured due to, among other reasons, a remaining anatomical gap between the spiral ganglion neurons and the implant electrodes. The gap could be bridged via pharmacologically triggered neurite growth toward the electrodes if biomaterials for neurite guidance could be provided. For this, we investigated the suitability of decellularized tissue. We compared three different layers (tunica adventitia, tunica media, and tunica intima) of decellularized equine carotid arteries in a preliminary approach. Rat spiral ganglia explants were cultured on decellularized equine carotid artery layers and neurite sprouting was assessed quantitatively. Generally, neurite outgrowth was possible and it was most prominent on the intima (in average 83 neurites per spiral ganglia explants, followed by the adventitia (62 neurites) and the lowest growth on the media (20 neurites). Thus, decellularized equine carotid arteries showed promising effects on neurite regeneration and can be developed further as efficient biomaterials for neural implants in hearing research.

Comprehensive analysis of HPV expression in laryngeal squamous cell carcinoma.

Role of human papillomavirus (HPV) in laryngeal carcinoma remains controversial. The aim of this study is to evaluate the role of HPV in laryngeal squamous cell carcinoma by determining presence of markers of viral infection. HPV DNA and E6*I mRNA status was determined by type-specific E7 PCR bead-based multiplex genotyping and RT-PCR assays in laryngeal squamous cell carcinoma biopsy samples. p16(INK4a) and COX-2 expression was determined by immunohistochemistry. Four cases out of 32 (13%) were HPV DNA+: HPV 11 (n = 1), HPV 31 (n = 3), HPV 59 (n = 1). One double infection: HPV 11 and HPV 31. p16(INK4a) was overexpressed in three cases (9%) and COX-2 in 17 cases (53%). Two of four HPV DNA+ samples had E6*I mRNA for HPV 31 and overexpressed p16(INK4a) and COX-2. HPV appears to play an active role in a small subset of laryngeal squamous cell carcinoma. p16(INK4a) can be used as a surrogate marker of transcriptionally active HPV infection; COX-2 expression had no correlation with HPV DNA and/or RNA positivity.

Prevalence of the 35delG mutation in the GJB2 gene in two samples of non-syndromic deaf subjects from Chile.

Hearing loss is the most common inherited sensorial deficiency in humans; about 1 in 1000 children suffer from severe or profound hearing loss at birth. Mutations in the GJB2 gene are the most common cause of prelingual, non-syndromic autosomal recessive deafness in many populations; the c.35delG mutation is the most common in Caucasian populations. The frequency of the c.35delG mutation was estimated in two samples of deaf patients from Santiago, Chile. Unrelated non-syndromic sensorioneural deaf patients were examined: Group 1 consisted of 47 unrelated individuals with neurosensory deafness referred to the Chilean Cochlear Implant Program; Group 2 included 66 school children with prelingual deafness attending special education institutions for deaf people. Individuals with profound to moderate isolated neurosensory hearing loss with unknown etiology were included. The presence of the c.35delG mutation was evaluated by the allele-specific polymerase chain reaction method (PCR), and in some cases it was confirmed by direct DNA sequencing of the coding region of the GJB2 gene. Deaf relatives were present in 20.3% of the cases. We found 19.5% (22/113) patients with the c.35delG mutation, 6 of them homozygous; these rates are similar to frequencies found in other Latin American countries.

Prevalence of the 35delG mutation in the GJB2 gene in two samples of non-syndromic deaf subjects from Chile

Hearing loss is the most common inherited sensorial deficiency in humans; about 1 in 1000 children suffer from severe or profound hearing loss at birth. Mutations in the GJB2 gene are the most common cause of prelingual, non-syndromic autosomal recessive deafness in many populations; the c.35delG mutation is the most common in Caucasian populations. The frequency of the c.35delG mutation was estimated in two samples of deaf patients from Santiago, Chile. Unrelated non-syndromic sensorioneural deaf patients were examined: Group 1 consisted of 47 unrelated individuals with neurosensory deafness referred to the Chilean Cochlear Implant Program; Group 2 included 66 school children with prelingual deafness attending special education institutions for deaf people. Individuals with profound to moderate isolated neurosensory hearing loss with unknown etiology were included. The presence of the c.35delG mutation was evaluated by the allele-specific polymerase chain reaction method (PCR), and in some cases it was confirmed by direct DNA sequencing of the coding region of the GJB2 gene. Deaf relatives were present in 20.3% of the cases. We found 19.5% (22/113) patients with the c.35delG mutation, 6 of them homozygous; these rates are similar to frequencies found in other Latin American countries.

Inactivation of the putative suppressor gene DOK1 by promoter hypermethylation in primary human cancers.

The DOK1 gene is a putative tumour suppressor gene located on the human chromosome 2p13 which is frequently rearranged in leukaemia and other human tumours. We previously reported that the DOK1 gene can be mutated and its expression down-regulated in human malignancies. However, the mechanism underlying DOK1 silencing remains largely unknown. We show here that unscheduled silencing of DOK1 expression through aberrant hypermethylation is a frequent event in a variety of human malignancies. DOK1 was found to be silenced in nine head and neck cancer (HNC) cell lines studied and DOK1 CpG hypermethylation correlated with loss of gene expression in these cells. DOK1 expression could be restored via demethylating treatment using 5-aza-2'deoxycytidine. In addition, transduction of cancer cell lines with DOK1 impaired their proliferation, consistent with the critical role of epigenetic silencing of DOK1 in the development and maintenance of malignant cells. We further observed that DOK1 hypermethylation occurs frequently in a variety of primary human neoplasm including solid tumours (93% in HNC, 81% in lung cancer) and haematopoietic malignancy (64% in Burkitt's lymphoma). Control blood samples and exfoliated mouth epithelial cells from healthy individuals showed a low level of DOK1 methylation, suggesting that DOK1 hypermethylation is a tumour specific event. Finally, an inverse correlation was observed between the level of DOK1 gene methylation and its expression in tumour and adjacent non tumour tissues. Thus, hypermethylation of DOK1 is a potentially critical event in human carcinogenesis, and may be a potential cancer biomarker and an attractive target for epigenetic-based therapy.

Human papillomavirus infections in laryngeal cancer.

Although the association and clinical significance of human papillomavirus (HPV) infections with a subset of head and neck cancers, particularly for oropharyngeal carcinoma, has recently been well documented, the involvement of HPV in laryngeal cancer has been inadequately evaluated. Herein we review the currently known associations of HPV infections in diseases of the larynx and their potential for oncogenicity. Using several methods of detection, HPV DNA has been detected in benign (papillomatosis), indolent (verrucous carcinoma), and malignant (squamous cell carcinoma) lesions of the larynx. Consistent with the known oncogenic risk of HPV infections, common HPV types associated with laryngeal papillomatosis include low-risk HPV types 6 and 11, with high-risk HPV types 16 and 18 more commonly present in neoplastic lesions (verrucous carcinoma and squamous cell carcinoma). Although a broad range of prevalence has been noted in individual studies, approximately 25% of laryngeal squamous cell carcinomas harbor HPV infections on meta-analysis, with common involvement of high-risk HPV types 16 (highest frequency) and 18. Preliminary results suggest that these high-risk HPV infections seem to be biologically relevant in laryngeal carcinogenesis, manifested as having viral DNA integration in the cancer cell genome and increased expression of the p16 protein. Despite this knowledge, the clinical significance of these infections and the implications on disease prevention and treatment are unclear and require further investigation.

DNA extraction from formalin-fixed laryngeal biopsies: Comparison of techniques.

CONCLUSION: PCR-quality DNA could be extracted from formalin-fixed paraffin-embedded (FFPE) samples with amplicons of at least 390 bp. Paraffin removal was not a necessary step. Proteinase K digestion was as efficient as the commercial kit for DNA extraction with a lower cost. OBJECTIVES: To compare different DNA extraction protocols for FFPE samples and to describe the suitability of the extracted DNA for PCR reactions. METHODS: For deparaffinization the following techniques were compared: alkaline heat, xylene, and no removal. For DNA extraction, proteinase K digestion and organic extraction were compared. A commercial extraction kit was included as standard. DNA quality was assessed by PCR amplification of the HFE gene, for amplicons of 208 and 390 bp. RESULTS: Extraction with the commercial kit and proteinase K digestion were more efficient than other techniques, with no statistical difference between them for both amplicons. The proteinase K digestion buffer had a cost of U$ 0.2 per sample and the commercial kit of U$7 per sample.

Exploring the relation between human papilloma virus and larynx cancer.

Human papilloma virus (HPV) has a role in benign and malignant pathology of the larynx. In this review we present the biological and epidemiological aspects related to these issues.