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1.
J Occup Environ Hyg ; 21(5): 342-352, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38489754

RESUMO

Traffic enforcers are exposed to various occupational health and safety hazards, including noise pollution, which may lead to occupational hearing loss. This cross-sectional study aimed to estimate the prevalence of hearing loss and to assess the relationship between occupational noise exposure level (ONEL) and abnormalities in air conduction thresholds among Metropolitan Manila Development Authority (MMDA) employees along Epifanio delos Santos Avenue, Philippines. Eight-hour ONELs were measured among 108 participants working with greater than 5 years of service. Participants had hearing evaluations using pure tone audiometry (PTA) to calculate the prevalence of hearing loss. Generalized linear models with a Poisson distribution were fitted to estimate the association between ONEL and audiologic abnormalities, controlling for confounding factors. Approximately 16% of employees had hearing loss. The prevalence of hearing loss was higher with ONEL exposures greater than 85 A-weighted decibels (dBA), with traffic enforcers exposed to higher ONELs than office workers. ONELs greater than 85 dBA were related to audiologic abnormalities at different frequencies in PTA. The prevalence of audiologic abnormalities at 4000 Hz and 6000 Hz was 48% higher (adjusted prevalence ratio [aPR], 1.48; 95% CI, 1.12-1.96) and 25% higher (aPR, 1.25; 95% CI, 1.00-1.55), respectively, among participants with ONELs greater than 85 dBA than with ONELs less than or equal to 85 dBA. Participants exposed to ONELs greater than 85 dBA, more likely traffic enforcers, may have increased risk of audiologic abnormalities. Regular ONEL monitoring is warranted for occupational risk assessment of traffic enforcers. A hearing conservation program may need to be considered for this population. Additional studies are needed to determine trends in hearing deterioration among traffic enforcers.


Assuntos
Audiometria de Tons Puros , Perda Auditiva Provocada por Ruído , Ruído Ocupacional , Exposição Ocupacional , Humanos , Ruído Ocupacional/efeitos adversos , Estudos Transversais , Adulto , Masculino , Perda Auditiva Provocada por Ruído/epidemiologia , Perda Auditiva Provocada por Ruído/etiologia , Exposição Ocupacional/efeitos adversos , Feminino , Pessoa de Meia-Idade , Filipinas/epidemiologia , Prevalência , Doenças Profissionais/epidemiologia , Doenças Profissionais/etiologia , Adulto Jovem
2.
Acta Med Philipp ; 57(9): 116-120, 2023 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-37990697

RESUMO

Objective: Recent advances in epigenetic studies continue to reveal novel mechanisms of gene regulation and control, however little is known on the role of epigenetics in sensorineural hearing loss (SNHL) in humans. We aimed to investigate the methylation patterns of two regions, one in RB1 and another in GJB2 in Filipino patients with SNHL compared to hearing control individuals. Methods: We investigated an RB1 promoter region that was previously identified as differentially methylated in children with SNHL and lead exposure. Additionally, we investigated a sequence in an enhancer-like region within GJB2 that contains four CpGs in close proximity. Bisulfite conversion was performed on salivary DNA samples from 15 children with SNHL and 45 unrelated ethnically-matched individuals. We then performed methylation-specific real-time PCR analysis (qMSP) using TaqMan® probes to determine percentage methylation of the two regions. Results: Using qMSP, both our cases and controls had zero methylation at the targeted GJB2 and RB1 regions. Conclusion: Our study showed no changes in methylation at the selected CpG regions in RB1 and GJB2 in the two comparison groups with or without SNHL. This may be due to a lack of environmental exposures to these target regions. Other epigenetic marks may be present around these regions as well as those of other HL-associated genes.

3.
Healthcare (Basel) ; 11(5)2023 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-36900663

RESUMO

HPV infection is one of the most studied risk factors in cervical cancer-the second most common cancer site and cause of death due to cancer in the Philippines. However, there is a lack of population-based epidemiological data on cervical HPV infection in the Philippines. Local reports on co-infections with other lower genital tract pathogens, commonly reported globally, are also lacking, which emphasizes the need to increase efforts in targeting HPV prevalence, genotype, and distribution. Hence, we aim to determine the molecular epidemiology and natural history of HPV infection among reproductive-age Filipino women using a community-based prospective cohort design. Women from rural and urban centers will be screened until the target sample size of 110 HPV-positive women (55 from rural sites and 55 from urban sites) is reached. Cervical and vaginal swabs will be collected from all screened participants. For HPV-positive patients, HPV genotypes will be determined. One hundred ten healthy controls will be selected from previously screened volunteers. The cases and controls will comprise the multi-omics subset of participants and will be followed up after 6 and 12 months for repeat HPV screening. Metagenomic and metabolomic analyses of the vaginal swabs will also be performed at baseline, after 6 months, and after 12 months. The results of this study will update the prevalence and genotypic distribution of cervical HPV infection among Filipino women, determine whether the current vaccines used for HPV vaccination programs capture the most prevalent high-risk HPV genotypes in the country, and identify vaginal community state types and bacterial taxa associated with the natural history of cervical HPV infection. The results of this study will be used as the basis for developing a biomarker that can help predict the risk of developing persistent cervical HPV infection in Filipino women.

4.
Genet Test Mol Biomarkers ; 27(1): 12-17, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36719978

RESUMO

Background: Many indigenous peoples are at elevated risk for otitis media, however there is limited information on hearing loss due to OM in these communities. An Indigenous Filipino community that has previously been described with an elevated prevalence of OM that is due to rare A2ML1 variants and a common FUT2 variant underwent additional phenological testing. In this study, we describe the audiologic profiles in A2ML1- and FUT2-related otitis media and the validity of otoscopy and genotyping for A2ML1 and FUT2 variants in screening for otitis media and hearing loss. Method: We analyzed A2ML1 and FUT2 genotypes together with demographic, otologic and audiologic data from tympanometry and hearing level assessments of 109 indigenous individuals. Results: We confirmed previous findings of a spectrum of nonsyndromic otitis media as associated with A2ML1 variants. A2ML1 and FUT2 variants were associated with high-frequency hearing loss at 4000 Hz. As expected, young age was associated with flat tympanograms, and eardrum perforations due to chronic otitis media were associated with severe-to-profound hearing loss across frequencies. Adding A2ML1 or FUT2 genotypes improved the validity of otoscopy as a screening test to rule out moderate-to-profound hearing loss. Conclusion: Continued multi-disciplinary management and audiologic follow-up using tympanometry and screening audiometry are needed to document and treat otitis media and prevent permanent hearing loss in the indigenous community.


Assuntos
Surdez , Perda Auditiva , Otite Média , Humanos , alfa-Macroglobulinas/genética , Genótipo , Perda Auditiva/genética , Perda Auditiva/diagnóstico , Otite Média/genética , Otoscopia , Galactosídeo 2-alfa-L-Fucosiltransferase
5.
Acta Med Philipp ; 57(10): 79-88, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-39483179

RESUMO

Background and Objective: The pandemic acted as an accelerator for the development of online teaching formats in anatomy and histology worldwide. The authors introduce a bridging program that reinforces the knowledge and understanding of gross and correlative anatomy and histology acquired in a virtual environment in preparation for its future clinical application. The study aims to evaluate the Learning Enhancement in Anatomy Program (LEAP) conducted among first-year medical students at the College of Medicine, University of the Philippines Manila. Methods: This descriptive cross-sectional study aims to determine the initial experience of implementing a learning enhancement program and assess areas for its improvement. An internally validated questionnaire was given to students after the program to gauge students' reactions (Kirkpatrick Level 1 evaluation). Pre- and post-tests were administered to evaluate knowledge acquisition (Kirkpatrick Level 2 evaluation). Short-term behavioral peer evaluation (Kirkpatrick Level 3 evaluation) was also instituted. Results: One hundred fifty-two (152) students participated in the study. General reactions from students to the LEAP were consistently positive, with a steady majority of the students rating '5' or a 'Strongly Agree' to positive statements regarding the program. Higher ratings for more traditional teaching methods, such as cadavers, formalinized specimens, and bones, compared to virtual systems were apparent. However, inter-student variation in preference for teaching modalities was observed. All stations of the LEAP were evaluated satisfactorily, with most gross anatomy stations rated higher than histology stations. A significant increase was noted in the total post-test scores compared to pre-test scores. This improvement in test scores was observed in the anatomy and histology subcategories and in six of the seven organ system modules. Perceived behavioral outcomes were also generally positive. Conclusion: The LEAP is a worthwhile endeavor, garnering overwhelmingly positive reactions and a significant improvement in test scores. Future studies are necessary to fine-tune teaching and training in a blended learning environment.

6.
Acta Med Philipp ; 57(10): 32-38, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-39483187

RESUMO

Background and Objective: The COVID 19 pandemic has changed the way the human anatomy is taught. A necessary shift towards online instruction, combined with a decrease in cadaver donation has resulted in the need for maximizing formalinized, soft-embalmed, computerized, and plastinated cadaver specimens. Task-oriented activities allow students to demonstrate acquired knowledge and skills. It is the aim of this study to get the perspective of students in the utilization of available laboratory materials. Method: One hundred forty-three students participated in task-oriented activities. Students demonstrated anatomy of the facial nerve, recurrent laryngeal nerve, and phrenic nerve by parotidectomy, thyroidectomy, and posterior neck dissection using formalinized cadaver and VH dissector™. Deep neck and sagittal structures in the plastinated specimen were identified using laser pointers. Ossicular mobility of the middle ear, and endoscopy of the nose and larynx were demonstrated using the soft embalmed cadaver. Students were surveyed on their perceptions on the utility of each cadaver specimen. Results: Formalinized and soft-embalmed cadaver were observed to present the most accurate anatomy, while the virtual dissector and plastinated specimens were seen to be the most sustainable and reusable. Conclusion: Task-oriented learning in head and neck anatomy may use different cadaveric materials with varied accuracy and utility.

7.
Acta Med Philipp ; 57(9): 95-102, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-39483795

RESUMO

Objectives: We present in this article the design and evaluation of a blended learning approach for training community healthcare providers in performing newborn hearing screening (NHS). Methods: We developed a blended learning course for training community healthcare providers on eHealth-enabled NHS, following Bloom's revised taxonomy of educational objectives. The training involved three components: computer-based training (CBT), face-to-face (FTF) training, and on-site coaching. We used surveys and post-training interviews following Level 1 Kirkpatrick's training evaluation model to get initial feedback on the training program. Results: Thirty-one community healthcare providers from five rural health units and a private hearing screening center, with a mean age of 42.2 ± 12.0 years, participated in the pilot. 93.5% of the participants agreed that the program content met stated objectives and was relevant to their practice. The length of the course was perceived to be adequate. Overall satisfaction with the program was rated at 8.5 ± 0.9 (with ten as the highest). The majority expressed that the CBT and FTF course were satisfactory at 93.5% and 100%, respectively. All participants agreed that the course enhanced their knowledge of newborn hearing screening and telehealth. Positive reviews were received from participants on the use of CBT to improve theoretical knowledge before FTF training. Participants declared that FTF training and on-site coaching helped improved NHS skills and implementation. Conclusion: Competent community healthcare providers are critical to strengthening the performance of the health system, and advances in the education and technology sectors offer promising potential in upskilling local healthcare providers. The increasing access of Filipino healthcare providers to improved information and communications technology (ICT) is a significant catalyst for pedagogical innovation, like the use of blended learning in the continuous professional development of health practitioners. As ICTs gradually penetrate the health sector, the challenge we now face is not whether but how we can use innovations in education strategies to benefit healthcare providers.

8.
Acta Med Philipp ; 57(9): 103-115, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-39483793

RESUMO

Objective: Newborn hearing screening (NHS) in the Philippines has been mandated by law since 2009. However, lack of awareness and knowledge about NHS remains a challenge, especially among healthcare providers. This paper describes the pilot implementation of a computer-based training (CBT) course on NHS and teleaudiology among primary healthcare providers (PHCPs) in rural Philippines. Methods: A four-module web-based training course on newborn hearing screening and teleaudiology in an online learning management system (LMS) was field-tested among PHCPs from eight rural communities in the Philippines. Participants were given four weeks to complete the course. Results: Forty-two PHCPs participated in the CBT. Thirty-four (81%) completed the whole course (mean attrition rate of 4.8% per module) at a mean duration of 10.2 days. Baseline data shows that participants had no NHS training, although the majority (83%) had information and communications technology (ICT) training. Comparison of pre- and post-test mean scores showed a 24.0% (p<0.001) significant increase in the post-test in all four modules. Passing rates (i.e., score ≥70%) from pre- to post-test increased by 54.6% (range: 38-80% increase). Usability of the CBT was rated high with a mean score of 4.32 out of 5 (range: 4.13 to 4.47), covering all eight parameters. Participants expressed general satisfaction and a positive attitude on CBT to improve knowledge on NHS and teleaudiology. Conclsion: Even in low resource settings where gaps in ICT infrastructure exist, eLearning can be used as an alternative approach to increase awareness and support training of healthcare providers on newborn hearing screening.

10.
Acta Med Philipp ; 57(9): 54-59, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-39483798

RESUMO

Objective: This pilot human trial demonstrates the ability of the investigational newborn hearing screening device to provide acoustic stimulation to produce evoked potentials, as well as its ability to capture and acquire auditory evoked potentials, especially the auditory brainstem response (ABR) wave V. This pilot study also demonstrates the ease of recognizing and identifying ABR waves in the graphical presentation of the evoked potentials over time. Methods: Fourteen normal-hearing adults or a total of twenty-eight (28) normal-hearing adult ears underwent auditory brainstem response testing using the investigational hearing screening device. A commercially available auditory brainstem response detection device was used to confirm that the acquired ABR waves of the investigational device are normal. The ABR waves displayed by the investigation device were also reviewed by the clinical audiologists to determine their recognizability and identifiability. Results: The pilot trial demonstrates the ability of the investigational newborn hearing screening device in providing acoustic stimulation to produce evoked potentials, and in acquiring and capturing ABR waves, specifically the wave V, among normal-hearing adult ears. The clinical audiologists recognized and identified the ABR wave V among the evoked potentials at 40dB, 60dB, and 80dB acoustic stimulation. About eighty-nine percent (89.2%) of all ears tested had identifiable and recognizable wave V upon acoustic stimulation at 40dB. Conclusion: The investigational hearing screening device: (1) can provide acoustic stimulation to produce evoked potentials, (2) can accurately capture and acquire these evoked potentials, (3) can present these evoked potentials in a voltage per time graphical display which an audiologist and trained HCP can easily read and interpret (diagnostic ABR), and (4) can present wave V auditory brainstem potentials that can be easily identified by an audiologist and trained HCP (screening ABR).

11.
Acta Med Philipp ; 57(9): 73-84, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-39483802

RESUMO

Objectives: This study explores the potential of the HeLe Service Delivery Model, a community-based newborn hearing screening (NHS) program supported by a web-based referral system, in improving provision of hearing care services. Methods: This prospective observational study evaluated the HeLe Service Delivery Model based on records review and user perspectives. We collected system usage logs from July to October 2018 and data on patient outcomes. Semi-structured interviews and review of field reports were conducted to identify implementation challenges and facilitating factors. Descriptive statistics and content analysis were used to analyze quantitative and qualitative data, respectively. Results: Six hundred ninety-two (692) babies were screened: 110 in the RHUs and 582 in the Category A NHS hospital. Mean age at screening was 1.4±1.05 months for those screened in the RHU and 0.46±0.74 month for those in the Category A site. 47.3% of babies screened at the RHU were ≤1 month old in contrast to 86.6% in the Category A hospital. A total of 10 babies (1.4%) received a positive NHS result. Eight of these ten patients were referred via the NHS Appointment and Referral System; seven were confirmed to have bilateral profound hearing loss, while one patient missed his confirmatory testing appointment. The average wait time between screening and confirmatory testing was 17.1±14.5 days. Facilitating factors for NHS implementation include the presence of champions, early technology adopters, legislations, and capacity-building programs. Challenges identified include perceived inconvenience in using information systems, cost concerns for the patients, costly hearing screening equipment, and unstable internet connectivity. The lack of nearby facilities providing NHS diagnostic and intervention services remains a major block in ensuring early diagnosis and management of hearing loss in the community. Conclusion: The eHealth-enabled HeLe Service Delivery Model for NHS is promising. It addresses the challenges and needs of community-based NHS by establishing a healthcare provider network for NHS in the locale, providing a capacity-building program to train NHS screeners, and deploying health information systems that allows for documentation, web-based referral and tracking of NHS patients. The model has the potential to be implemented on a larger scale - a deliberate step towards universal hearing health for all Filipinos.

12.
Acta Med Philipp ; 57(9): 32-38, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-39483803

RESUMO

Objectives: Responding to the reality of neonate patients with delayed childhood development due to late diagnosis of and intervention on hearing impairment, this study aims to determine the features based on time-frequency domain of auditory brainstem response (ABR) signals and to test the protocol on ABR signals from PhysioNet. Methods: This is done by pre-processing, performing time-frequency analysis, and characterizing hearing impairment using the dominant features of the ABR. In this study, normal (N) and hearing impaired (HI) ABR adult human signals were acquired from Physionet.org, a publicly available database. Considering its high signal-to-noise ratio, numerous filters and transformations were applied to extract the ABR. Consequently, the features acquired - dominant frequency and bigrams, were used as data classifiers. Results: Initial results using only N classifiers, that is features from the Normal dataset, and bandpass Chebyshev filter with a lower cut-off frequency of 60 Hz show that the tests yielded low to middle sensitivity. Further tests were done to improve the sensitivity that incorporated the HI classifiers, used data filtered with a low cut-off frequency of 300 Hz, and data divided per stimulus intensity level. Conclusion: Conclusions made are 1) data with both N and HI classifiers have higher sensitivity than those using only N classifiers, 2) data with a Chebyshev cut-off frequency of 300 Hz have a higher sensitivity than those with 60 Hz, and 3) data divided per intensity level have a higher sensitivity than data analyzed as a whole, and that features with stimulus intensity in middle ranges have a better distinction between HI and N patients.

13.
Acta Med Philipp ; 57(9): 21-27, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-39483804

RESUMO

Objective: To determine the accuracy, sensitivity, specificity, positive predictive values, and use of the Reflexive Behavioral "Baah" Test and NHSRC Level 1 and Level 2 Questionnaires in detecting hearing impairment in rural health communities. Methods: This was a prospective cross-sectional study conducted at the rural health unit of five municipalities. Infants less than six months old were screened for hearing impairments using the OAE device (standard), the Reflexive Behavioral "Baah" test, and the NHSRC Level 1 and Level 2 Questionnaires. The "Baah" test and the filling out of the NHSRC Level 1 and 2 Questionnaires were done by trained health workers while OAE was done by an audiologist. Results: A total of 103 babies, with a mean age of 41.9 days at the time of testing and a male to female ratio of 1.02:1 (52 males and 51 females) were tested. A hearing impairment prevalence of 4.9% (5 out of 103) was noted. The "Baah" test showed to have a sensitivity of 60%, specificity of 97.96% and an accuracy rate of 96.12%. The NHSRC Level 1 and Level 2 Questionnaires showed sensitivity, specificity, and accuracy rate of 40%, 67.35% and 66.02%, respectively for the former and 40%, 85.71% and 83.50%, respectively for the latter. Analysis of the complimentary use of the NHSRC Level 1 and Level 2 Questionnaires with the "Baah" test also showed no significant improvement to using the "Baah" test as a stand-alone screening tool with sensitivity, specificity, and accuracy of 60%, 67.35% and 66.99%, respectively for the "Baah" test and Level 1 Questionnaire, and 60%, 83.67% and 82.52%, respectively for the "Baah" test and Level 2 Questionnaire. Conclusion: The Reflexive Behavioral "Baah" test is a potentially accurate, sensitive, specific, and acceptable stand-alone hearing screening test to identify infants with higher risk of hearing impairment in the rural health community setting. On the other hand, the use of the NHSRC Questionnaires as a stand-alone or complementary tool for "Baah" is unnecessary as it results to more false positive and false negative results.

14.
Acta Med Philipp ; 57(9): 28-31, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-39483805

RESUMO

Objective: To assess the usage of the "Baah" Test compared to the AABR (Automated Auditory Brainstem Response) in detecting hearing loss of neonates in the community setting. Methods: This is a retrospective cross-sectional study. The targeted sample population are infants less than a month old who underwent screening at a testing facility in Malolos, Bulacan spanning the years 2011 and 2012. Results: A total of 201 infants were included in the study, with a mean age of 10.77 days with a standard deviation of 7.79. The ratio of males to females was almost equal at 1:1.01. For infants who passed hearing screening on at least one ear, 96% (193 infants) correlated with the results of "Baah" testing. For those with bilateral refer results on AABR, 4 out of the 6 correlated with the "Baah" Test. Conclusion: There is potential in using the "Baah" Test as a tool for hearing loss assessment of infants in situations wherein the usual hearing screening tests are inaccessible. It makes use of little resources, and though it does have its limitations in assessing for unilateral hearing loss (as the test cannot test ears in isolation), it would be able to identify infants likely to have bilateral hearing loss.

15.
Front Cell Infect Microbiol ; 12: 746428, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35521215

RESUMO

Otitis media (OM), defined as infection or inflammation of the middle ear (ME), remains a major public health problem worldwide. Cholesteatoma is a non-cancerous, cyst-like lesion in the ME that may be acquired due to chronic OM and cause disabling complications. Surgery is required for treatment, with high rates of recurrence. Current antibiotic treatments have been largely targeted to previous culturable bacteria, which may lead to antibiotic resistance or treatment failures. For this study, our goal was to determine the microbiota of cholesteatoma tissue in comparison with other ME tissues in patients with long-standing chronic OM. ME samples including cholesteatoma, granulation tissue, ME mucosa and discharge were collected from patients undergoing tympanomastoidectomy surgery for chronic OM. Bacteria were profiled by 16S rRNA gene sequencing in 103 ME samples from 53 patients. Respiratory viruses were also screened in 115 specimens from 45 patients. Differences in bacterial profiles (beta-diversity) and the relative abundances of individual taxa were observed between cholesteatoma and ME sample-types. Additionally, patient age was associated with differences in overall microbiota composition while numerous individual taxa were differentially abundant across age quartiles. No viruses were identified in screened ME samples. Biodiversity was moderately lower in cholesteatoma and ME discharge compared to ME mucosal tissues. We also present overall bacterial profiles of ME tissues by sample-type, age, cholesteatoma diagnosis and quinolone use, including prevalent bacterial taxa. Our findings will be useful for fine-tuning treatment protocols for cholesteatoma and chronic OM in settings with limited health care resources.


Assuntos
Colesteatoma , Microbiota , Otite Média Supurativa , Otite Média , Bactérias/genética , Doença Crônica , Humanos , Infecção Persistente , RNA Ribossômico 16S/genética
16.
Genes (Basel) ; 12(4)2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33924653

RESUMO

Background: Hearing loss remains an important global health problem that is potentially addressed through early identification of a genetic etiology, which helps to predict outcomes of hearing rehabilitation such as cochlear implantation and also to mitigate the long-term effects of comorbidities. The identification of variants for hearing loss and detailed descriptions of clinical phenotypes in patients from various populations are needed to improve the utility of clinical genetic screening for hearing loss. Methods: Clinical and exome data from 15 children with hearing loss were reviewed. Standard tools for annotating variants were used and rare, putatively deleterious variants were selected from the exome data. Results: In 15 children, 21 rare damaging variants in 17 genes were identified, including: 14 known hearing loss or neurodevelopmental genes, 11 of which had novel variants; and three candidate genes IST1, CBLN3 and GDPD5, two of which were identified in children with both hearing loss and enlarged vestibular aqueducts. Patients with variants within IST1 and MYO18B had poorer outcomes after cochlear implantation. Conclusion: Our findings highlight the importance of identifying novel variants and genes in ethnic groups that are understudied for hearing loss.


Assuntos
Redes Reguladoras de Genes , Variação Genética , Perda Auditiva/genética , Perda Auditiva/cirurgia , Osso Temporal/anormalidades , Criança , Pré-Escolar , Implante Coclear , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Miosinas/genética , Proteínas do Tecido Nervoso/genética , Proteínas Oncogênicas/genética , Fenótipo , Diester Fosfórico Hidrolases/genética , Proteínas Supressoras de Tumor/genética
18.
J Med Genet ; 58(7): 442-452, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-32709676

RESUMO

BACKGROUND: Otitis media (OM) susceptibility has significant heritability; however, the role of rare variants in OM is mostly unknown. Our goal is to identify novel rare variants that confer OM susceptibility. METHODS: We performed exome and Sanger sequencing of >1000 DNA samples from 551 multiethnic families with OM and unrelated individuals, RNA-sequencing and microbiome sequencing and analyses of swabs from the outer ear, middle ear, nasopharynx and oral cavity. We also examined protein localisation and gene expression in infected and healthy middle ear tissues. RESULTS: A large, intermarried pedigree that includes 81 OM-affected and 53 unaffected individuals cosegregates two known rare A2ML1 variants, a common FUT2 variant and a rare, novel pathogenic variant c.1682A>G (p.Glu561Gly) within SPINK5 (LOD=4.09). Carriage of the SPINK5 missense variant resulted in increased relative abundance of Microbacteriaceae in the middle ear, along with occurrence of Microbacteriaceae in the outer ear and oral cavity but not the nasopharynx. Eight additional novel SPINK5 variants were identified in 12 families and individuals with OM. A role for SPINK5 in OM susceptibility is further supported by lower RNA counts in variant carriers, strong SPINK5 localisation in outer ear skin, faint localisation to middle ear mucosa and eardrum and increased SPINK5 expression in human cholesteatoma. CONCLUSION: SPINK5 variants confer susceptibility to non-syndromic OM. These variants potentially contribute to middle ear pathology through breakdown of mucosal and epithelial barriers, immunodeficiency such as poor vaccination response, alteration of head and neck microbiota and facilitation of entry of opportunistic pathogens into the middle ear.


Assuntos
Microbiota , Otite Média/genética , Otite Média/microbiologia , Inibidor de Serinopeptidase do Tipo Kazal 5/genética , Adulto , Animais , Bactérias/classificação , Bactérias/genética , Criança , Suscetibilidade a Doenças/microbiologia , Orelha Externa/microbiologia , Orelha Média/microbiologia , Exoma , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Camundongos , Boca/microbiologia , Nasofaringe/microbiologia , Linhagem , Análise de Sequência de DNA , Análise de Sequência de RNA
19.
World Neurosurg ; 142: e260-e270, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32603862

RESUMO

OBJECTIVE: Chondroblastoma is an uncommon benign neoplasm of cartilaginous origin usually involving the long bones. The temporal bone is a rare location for this tumor. The clinical profile, optimal medical and surgical management, and outcomes of treatment for temporal bone chondroblastoma remain unknown. METHODS: We performed a systematic review of the SCOPUS, PubMed, and CENTRAL databases for case reports and case series on patients with histopathologically proven temporal bone chondroblastoma. Data on demographics, clinical manifestation, surgical management, adjuvant treatment, and outcome on last follow-up were collected. RESULTS: A total of 100 cases were reported in the literature, including one described in the current study. The mean age of patients was 42.3 years (range, 2-85 years), with a slight male predilection (1.3:1). The most common clinical manifestations were otologic symptoms (e.g., hearing loss [65%], tinnitus, and otalgia) and a palpable mass. Surgical excision was performed in all cases, with gross total excision achieved in 58%. Radiation therapy was performed in 18% of cases, mostly as adjuvant treatment after subtotal excision. There were no deaths at a median follow-up of 2 years. Among the patients with detailed status on follow-up, 58% had complete neurologic recovery, 38% had partial recovery, and 4% had progression of symptoms as a result of tumor recurrence. CONCLUSIONS: Temporal bone chondroblastoma has a distinct clinical profile from chondroblastoma of long bones. Surgery is the mainstay of treatment, and radiation therapy may be given after subtotal excision. Outcomes are generally favorable after treatment.


Assuntos
Condroblastoma/terapia , Perda Auditiva/fisiopatologia , Procedimentos Neurocirúrgicos , Neoplasias Cranianas/terapia , Osso Temporal/cirurgia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Audiometria de Tons Puros , Criança , Pré-Escolar , Condroblastoma/diagnóstico por imagem , Condroblastoma/patologia , Condroblastoma/fisiopatologia , Dor de Orelha/fisiopatologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Radioterapia Adjuvante , Recuperação de Função Fisiológica , Distribuição por Sexo , Neoplasias Cranianas/diagnóstico por imagem , Neoplasias Cranianas/patologia , Neoplasias Cranianas/fisiopatologia , Zumbido/fisiopatologia , Adulto Jovem
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