RESUMO
OBJECTIVE: The 22q11.2 deletion syndrome is among the most common head-and-neck-related syndromes. The literature has examined many of the phenotypic features of 22q11.2 deletion syndrome; however, few studies have explored the manifestation of cervical spine abnormalities. In this study, we compared the cervical spines of individuals with and without 22q11.2 deletion syndrome using diagnostic imaging. DESIGN: A retrospective case-control study, with age- and sex-matched control participants who underwent flexion/extension x-rays and either a computed tomography or MRI scan. SETTING: PARTICIPANTS presented to the velopharyngeal insufficiency clinic at Victoria Hospital in London, Ontario, Canada, a tertiary care center. PARTICIPANTS: Sixteen pediatric patients (Assuntos
Vértebras Cervicais/anormalidades
, Deleção Cromossômica
, Cromossomos Humanos Par 22
, Doenças da Coluna Vertebral/congênito
, Adolescente
, Estudos de Casos e Controles
, Vértebras Cervicais/diagnóstico por imagem
, Feminino
, Humanos
, Masculino
, Ontário
, Estudos Retrospectivos
, Doenças da Coluna Vertebral/diagnóstico por imagem
, Síndrome
RESUMO
Nonsynaptic clusters of postsynaptic proteins have been documented; however, their role remains elusive. We monitored the trafficking of several candidate proteins implicated in synaptogenesis, when nonsynaptic clusters of scaffold proteins are most abundant. We find a protein complex consisting of two populations that differ in their content, mobility, and involvement in synapse formation. One subpopulation is mobile and relies on actin transport for delivery to nascent and existing synapses. These mobile clusters contain the scaffolding proteins PSD-95, GKAP, and Shank. A proportion of mobile clusters that exhibits slow movement and travels short distances contains neuroligin-1. The second group consists of stationary nonsynaptic scaffold complexes that mainly contain neuroligin-1, can recruit synaptophysin-containing axonal transport vesicles, and are readily transformed to functional presynaptic contacts that recycle the vital dye FM 4-64. These results postulate a mechanism whereby preformed scaffold protein complexes serve as predetermined postsynaptic hotspots for establishment of new functional excitatory synapses.
Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Proteínas de Membrana/fisiologia , Proteínas do Tecido Nervoso/fisiologia , Neurônios/citologia , Fosfoproteínas Fosfatases/fisiologia , Sinapses/fisiologia , Actinas/fisiologia , Animais , Moléculas de Adesão Celular Neuronais , Células Cultivadas , Diagnóstico por Imagem/métodos , Proteína 4 Homóloga a Disks-Large , Fosfatases de Especificidade Dupla , Embrião de Mamíferos , Proteínas de Fluorescência Verde/metabolismo , Hipocampo/citologia , Imuno-Histoquímica/métodos , Proteínas de Membrana/metabolismo , Modelos Neurológicos , Proteínas do Tecido Nervoso/classificação , Proteínas do Tecido Nervoso/metabolismo , Nocodazol/farmacologia , Terminações Pré-Sinápticas/efeitos dos fármacos , Terminações Pré-Sinápticas/fisiologia , Transporte Proteico/efeitos dos fármacos , Compostos de Piridínio/farmacocinética , Compostos de Amônio Quaternário/farmacocinética , RNA Interferente Pequeno/farmacologia , Ratos , Ratos Wistar , Fatores de Tempo , Proteínas Vesiculares de Transporte de Glutamato/metabolismoRESUMO
OBJECTIVES: To compare the circulating microRNA (miRNA) expression profiles between sudden sensory neural hearing loss (SSNHL) patients and age-matched normal hearing controls. STUDY DESIGN: Prospective cohort multi-center study. METHODS: Patients presenting within 28 days of onset of SSNHL were prospectively recruited along with contemporaneous age-matched controls. Pooled sera of four patient (n = 09, mean age = 53.0 years; 07, 55.0; 10, 52.9; 10, 51.6) and two control (09, 51.2 and 03, 50.0) groups were assessed using a TaqMan Low Density Array. The patients' sera were also divided into two pools, untreated (04, 57.7) and treated (32, 52.6) for additional analysis. miRNA expression level was derived from cycle threshold (Ct) values normalized to a global mean. Inter-group mean Ct differences with fold changes ≥2.0 and ≤0.5 at P < .05 were considered significant. Bioinformatic databases were used to identify putative target mRNAs or validated genes and their functional annotations. RESULTS: Thirty-six SSNHL patients (mean age 53.0 ± standard deviation (SD) 15.2 years) and 12 controls (50.9 ± 11.9) were studied. Eight miRNAs hsa-miR-590-5p/ -186-5p/ -195-5p/ -140-3p/ -128-3p/ -132-3p/ -375-3p, and -30a-3p were identified as significantly differentially expressed in SSNHL patients. Most of these miRNAs were abundantly identified in the nervous system and the putative target messenger RNAs (mRNAs) were enriched in signaling pathways such as phosphatidyl inositol 3 kinase/protein Kinase B (PI3K/Akt), Ras and mitogen-activated protein kinase (MAPK). CONCLUSION: These findings suggest the possible cellular signaling pathways that underlie the disruption of auditory signal transmission in SSNHL. LEVEL OF EVIDENCE: 2 Laryngoscope, 130:E416-E422, 2020.
Assuntos
Predisposição Genética para Doença/genética , Perda Auditiva Súbita/genética , MicroRNAs/sangue , Adulto , Idoso , Percepção Auditiva/genética , Estudos de Casos e Controles , Feminino , Marcadores Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Transdução de Sinais/genéticaRESUMO
OBJECTIVES: To assess patient adherence to nasal spray regimens after endoscopic sinus surgery (ESS) and to study factors that predict adherence. METHODS: A three-arm, randomized, blinded, controlled trial was conducted at a tertiary care academic hospital, studied via a prospective longitudinal survey, of 60 consecutive chronic rhinosinusitis patients managed with ESS and started on one of three postoperative nasal spray regimens. Structured telephone interviews were conducted after surgery over a 12-month period using a validated questionnaire that assessed both spray adherence and barriers to adherence. Patient demographics, time post-ESS, preoperative Sino-Nasal Outcome Test (SNOT) scores, Lund-Mackay scores, adherence risk factors, and polyp grades were used as covariates with logistic regression. RESULTS: Overall, 57.4% of patients were nonadherent. Logistic regression showed that preoperative SNOT scores (p = .018, 95% CI = 0.84-0.98), time post-ESS (p = .016, 95% CI = 1.02-1.22), and the presence of an adherence risk factor (p = .03, 95% CI = 1.18-26.99) significantly predicted whether a patient was adherent and correctly classified 70.4% of all patients. Age, gender, and nasal spray regimen did not predict adherence (p > .05). CONCLUSION: The majority of patients were nonadherent to post-ESS nasal sprays, irrespective of which nasal spray regimen they were on. Preoperative SNOT scores, time post-ESS, and the presence of an adherence risk factor predicted adherence. With this knowledge, otolaryngologists can selectively employ strategies to improve adherence in high-risk patients and possibly improve ESS outcomes.
Assuntos
Adesão à Medicação , Procedimentos Cirúrgicos Otorrinolaringológicos , Seios Paranasais/cirurgia , Cuidados Pós-Operatórios/métodos , Complicações Pós-Operatórias/prevenção & controle , Rinite/cirurgia , Sinusite/cirurgia , Administração Intranasal , Adulto , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Endoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sprays Nasais , Prognóstico , Rinite/complicações , Sinusite/complicações , Inquéritos e Questionários , Adulto JovemRESUMO
OBJECTIVE: To assess the efficacy of a hearing conservation program in changing acoustic risk-taking and hearing conservation behaviors in elementary school children. STUDY DESIGN: Prospective, randomized, mixed design controlled study. METHODS: Participants were grade-six students from 16 Vancouver School Board schools. Differences between the intervention and control group responses on a behavioral questionnaire were measured at baseline, and then at 2 weeks and 6 months after administration of a hearing conservation program (Sound Sense™). RESULTS: The intervention resulted in significant interactions for improved earplug use at dances (P = .019), rock concerts (P = .001), with percussion musical instruments (P = .002), and electric guitars (P = .028) at 2 weeks postintervention relative to baseline. Improvements in children's earplug use at dances (P = .041), rock concerts (P = .0024), and with power lawn mowers (P = .043) at 6 months postintervention relative to baseline were also observed. Behavior in the intervention group compared to control group improved in earplug use with any "other noises" at 2 weeks (P = .001), and 6 months (P = .022) relative to baseline. There was a tendency in the intervention group to reduce the duration of use of personal music devices at 2 weeks and 6 months after the hearing conservation program, which was nonsignificant. CONCLUSION: The Sound Sense™ hearing conservation program improved earplug use practices in elementary school children in the short and long term. The development, implementation and evaluation of a community-based health promotion project around hearing loss can serve as a tremendous opportunity for students to develop their knowledge and skills in health advocacy.
Assuntos
Dispositivos de Proteção das Orelhas , Educação em Saúde , Perda Auditiva Provocada por Ruído/prevenção & controle , Adolescente , Canadá , Criança , Avaliação Educacional , Feminino , Comportamentos Relacionados com a Saúde , Perda Auditiva Provocada por Ruído/diagnóstico , Perda Auditiva Provocada por Ruído/etiologia , Humanos , Masculino , Música , Instituições AcadêmicasRESUMO
OBJECTIVE: To evaluate the intermediate and longer-term perceptual and objective speech outcomes in velopharyngeal insufficiency (VPI) patients treated with a superiorly based pharyngeal flap. DESIGN: Retrospective review. SETTING: Tertiary care centre, London, Ontario. METHODS: Forty consecutive VPI patients (mean age 14.5 years) from 2004 to 2008 who had a first time superiorly based pharyngeal flap were included. The modified Hogan flap and lateral port control technique was used with a 70° endoscope to provide intraoperative coaxial and magnified lateral port visualization. MAIN OUTCOME MEASURES: The American Cleft Palate-Craniofacial Association (ACPA) perceptual speech assessment and nasalance measured via nasometry using the MacKay-Kummer Simplified Nasometric Assessment Procedures Revised (SNAP-R). A comparison of mean outcomes from the pretreatment versus an intermediate (ACPA 4.3 months; SNAP-R 4.0 months) and longer-term (ACPA 19.5 months) posttreatment time point was performed, and the distribution of successful outcomes was assessed. RESULTS: Mean perceptual scores improved significantly early after surgery (p < .0001; n â=â 33) and in the longer term (p < .01; n â=â 21), with high success rates for hypernasality (87.9% and 80.9%; p < .0001), audible nasal emission (90.9% and 90.5%; p < .0001), overall intelligibility (75.7% and 81.0%; p < .01), and compensatory articulation (81.8% and 85.7%; p < .01). Likewise, significant improvements were observed in posttreatment nasal (n â=â 38; p < .01) and mean oral SNAP-R scores (n â=â 39; p < .001), which demonstrated success rates of 100% (p < .0001) and 73% (p < .0001), respectively. Overcorrection was not observed in perceptual and nasometric testing. CONCLUSION: The modified Hogan flap and lateral port control technique with the use of a 70° endoscope is highly successful in treating VPI. These results indicate that speech outcome improvement occurs early after surgery and is maintained over time.
Assuntos
Faringe/cirurgia , Retalhos Cirúrgicos , Insuficiência Velofaríngea/cirurgia , Adolescente , Criança , Humanos , Inteligibilidade da Fala , Resultado do Tratamento , Insuficiência Velofaríngea/fisiopatologia , Qualidade da VozRESUMO
PURPOSE OF REVIEW: Bilateral Ménière's disease treatment can be extremely challenging and, like its unilateral variant, remains highly controversial. There are few articles in the literature that have focused specifically on the treatment of bilateral Ménière's disease, despite significant numbers of unilateral cases evolving toward bilaterality - a process which complicates management and is not simple to foresee. This study reviews the most up-to-date concepts in its diagnosis and treatment, with a special focus on recent advances. RECENT FINDINGS: Recent advances in electrocochleography, vestibular-evoked myogenic potential, and intratympanic gadolinium-based contrast agent MRI may have the potential to diagnose bilateral endolymphatic hydrops, and predict unilateral to bilateral Ménière's disease progression. Although more prospective studies are necessary, recent studies show that intermittent pressure therapy (Meniett device), intratympanic steroids, and endolymphatic sac surgery appear to be efficacious and well tolerated nonablative management options. Moreover, triple semicircular canal occlusion surgery has recently been used successfully in Ménière's disease. SUMMARY: Bilateral Ménière's disease can be challenging to diagnose via clinical suspicion and pure-tone audiometry alone. Therefore, adjunctive diagnostic tools including electrocochleography, vestibular-evoked myogenic potential, and intratympanic gadolinium-based contrast agent MRI are of even greater value, and may predict progression to bilaterality - allowing better optimization of treatment. Ablative treatments are relatively contraindicated due to the risks of bilateral vestibular and cochlear hypofunction. Nonablative treatments such as the Meniett device, intratympanic steroids, and endolymphatic sac surgery appear to be efficacious, and useful alternatives after conservative measures fail. Systemic aminoglycoside therapy is reserved for only the most severe and intractable cases.