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Sleep plays an important role in memory consolidation within multiple memory systems including contextual fear extinction memory, but little is known about the mechanisms that underlie this process. Here, we show that fear extinction training in rats, which extinguished conditioned fear, increased both slow-wave sleep and rapid-eye movement (REM) sleep. Surprisingly, 24 h later, during memory testing, only 57% of the fear-extinguished animals retained fear extinction memory. We found that these animals exhibited an increase in phasic pontine-wave (P-wave) activity during post-training REM sleep, which was absent in the 43% of animals that failed to retain fear extinction memory. The results of this study provide evidence that brainstem activation, specifically potentiation of phasic P-wave activity, during post-training REM sleep is critical for consolidation of fear extinction memory. The results of this study also suggest that, contrary to the popular hypothesis of sleep and memory, increased sleep after training alone does not guarantee consolidation and/or retention of fear extinction memory. Rather, the potentiation of specific sleep-dependent physiological events may be a more accurate predictor for successful consolidation of fear extinction memory. Identification of this unique mechanism will significantly improve our present understanding of the cellular and molecular mechanisms that underlie the sleep-dependent regulation of emotional memory. Additionally, this discovery may also initiate development of a new, more targeted treatment method for clinical disorders of fear and anxiety in humans that is more efficacious than existing methods such as exposure therapy that incorporate only fear extinction.
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Ondas Encefálicas/fisiologia , Extinção Psicológica/fisiologia , Medo , Memória/fisiologia , Ponte/fisiologia , Sono REM/fisiologia , Análise de Variância , Animais , Córtex Cerebral/fisiologia , Condicionamento Psicológico/fisiologia , Estimulação Elétrica/efeitos adversos , Eletroencefalografia , Eletromiografia , Reação de Congelamento Cataléptica/fisiologia , Modelos Lineares , Masculino , Ratos , Ratos Sprague-Dawley , Tempo de Reação/fisiologia , Fases do Sono , Fatores de Tempo , VigíliaRESUMO
BACKGROUND: Activation of Kv7 potassium channels may decrease the reactivity of mesolimbic dopaminergic neurons that are implicated in mediating the reinforcing effects of ethanol. OBJECTIVES: The objective of this study was to determine whether the administration of the Kv7 potassium channel opener retigabine would decrease ethanol intake in Long Evans rats. METHODS: A limited access two-bottle choice model of alcohol (10% solution) consumption was used in this study. A separate group of animals was tested to evaluate the actions of retigabine on sucrose (5% solution) consumption to determine whether this drug might produce non-selective impairment of the ability of rats to drink liquids. Animals were treated with either vehicle or increasing doses (2.5-7.5 mg/kg SC) of retigabine administered over a 3-day period. RESULTS: Compared to vehicle, retigabine at a dose of 7.5 mg/kg produced a reduction in the amount of ethanol consumed. These effects did not occur in association with significant changes in water consumption. A significant time effect was found for the actions of retigabine in sucrose-drinking rats with a trend for an increase in sucrose intake with the highest dose of retigabine administered. CONCLUSIONS: These results indicate that the administration of retigabine may produce a decrease in ethanol consumption by rats at doses that do not significantly reduce the drinking of either water or a sucrose solution. These findings are consistent with the hypothesis that activation of Kv7 channels facilitates the reduction of alcohol consumption in the rat.
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Consumo de Bebidas Alcoólicas/tratamento farmacológico , Carbamatos/farmacologia , Comportamento de Ingestão de Líquido/efeitos dos fármacos , Moduladores de Transporte de Membrana/farmacologia , Fenilenodiaminas/farmacologia , Canais de Potássio/agonistas , Animais , Carbamatos/uso terapêutico , Comportamento de Escolha/efeitos dos fármacos , Masculino , Moduladores de Transporte de Membrana/uso terapêutico , Fenilenodiaminas/uso terapêutico , Ratos , Ratos Long-EvansRESUMO
Ovarian cancer is a deadly female cancer with high rates of recurrence. The primary treatment strategy for patients is platinum-based therapy regimens that almost universally develop resistance. Consequently, new therapeutic avenues are needed to overcome the plateau that current therapies have on patient outcomes. We describe a gene amplification involving both HSF1 and MYC, wherein these two genes on chromosome 8q are co-amplified in over 7% of human tumors that is enriched to over 30% of patients with ovarian cancer. We further found that HSF1 and MYC transcriptional activity is correlated in human tumors and ovarian cancer cell lines, suggesting they may cooperate in ovarian cancer cells. CUT&RUN for HSF1 and MYC in co-amplified ovarian cancer cells revealed that HSF1 and MYC have overlapping binding at a substantial number of locations throughout the genome where their binding peaks are near identical. Consistent with these data, a protein-protein interaction between HSF1 and MYC was detected in ovarian cancer cells, implying these two transcription factors have a molecular cooperation. Further supporting their cooperation, growth of HSF1-MYC co-amplified ovarian cancer cells were found to be dependent on both HSF1 and MYC. In an attempt to identify a therapeutic target that could take advantage of this dependency on both HSF1 and MYC, PLK1 was identified as being correlated with HSF1 and MYC in primary human tumor specimens, consistent with a previously established effect of PLK1 on HSF1 and MYC protein levels. Targeting PLK1 with the compound volasertib (BI-6727) revealed a greater than 200-fold increased potency of volasertib in HSF1-MYC co-amplified ovarian cancer cells compared to ovarian cancer cells wild-type HSF1 and MYC copy number, which extended to several growth assays, including spheroid growth. Volasertib, and other PLK1 inhibitors, have not shown great success in clinical trials and this study suggests that targeting PLK1 may be viable in a precision medicine approach using HSF1-MYC co-amplification as a biomarker for response.
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OBJECTIVES: Evaluate potential effects of calcium channel blockers (CCB) and bisphosphonates (BP) on residual hearing following cochlear implantation. METHODS: Medications of 303 adult hearing preservation (HP) candidates (low frequency pure tone average [LFPTA] of 125, 250, and 500â Hz ≤80â dB HL) were reviewed. Postimplantation LFPTA of patients taking CCBs and BPs were compared to controls matched by age and preimplantation LFPTA. RESULTS: Twenty-six HP candidates were taking a CCB (N = 14) or bisphosphonate (N = 12) at implantation. Median follow-up was 1.37 years (range 0.22-4.64y). Among subjects with initial HP, 29% (N = 2 of 7) CCB users compared to 50% (N = 2 of 4) controls subsequently lost residual hearing 3-6 months later (OR = 0.40, 95% CI = 0.04-4.32, p = 0.58). None of the four BP patients with initial HP experienced delayed loss compared to 50% (N = 2 of 4) controls with initial HP (OR = 0.00, 95% CI = 0.00-1.95, P = 0.43). Two CCB and one BP patients improved to a LFPTA <80 dB HL following initial unaided thresholds that suggested loss of residual hearing. DISCUSSION: There were no significant differences in the odds of delayed loss of residual hearing with CCBs or BPs. CONCLUSION: Further investigation into potential otoprotective adjuvants for maintaining residual hearing following initial successful hearing preservation is warranted, with larger cohorts and additional CCB/BP agents.
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OBJECTIVE: To report speech recognition outcomes and processor use based on timing of cochlear implant (CI) activation. STUDY DESIGN: Retrospective cohort. SETTING: Tertiary referral center. PATIENTS: A total of 604 adult CI recipients from October 2011 to March 2022, stratified by timing of CI activation (group 1: ≤10 d, n = 47; group 2: >10 d, n = 557). MAIN OUTCOME MEASURES: Average daily processor use; Consonant-Nucleus-Consonant (CNC) and Arizona Biomedical (AzBio) in quiet at 1-, 3-, 6-, and 12-month visits; time to peak performance. RESULTS: The groups did not differ in sex ( p = 0.887), age at CI ( p = 0.109), preoperative CNC ( p = 0.070), or preoperative AzBio in quiet ( p = 0.113). Group 1 had higher median daily processor use than group 2 at the 1-month visit (12.3 versus 10.7 h/d, p = 0.017), with no significant differences at 3, 6, and 12 months. The early activation group had superior median CNC performance at 3 months (56% versus 46%, p = 0.007) and 12 months (60% versus 52%, p = 0.044). Similarly, the early activation group had superior median AzBio in quiet performance at 3 months (72% versus 59%, p = 0.008) and 12 months (75% versus 68%, p = 0.049). Both groups were equivalent in time to peak performance for CNC and AzBio. Earlier CI activation was significantly correlated with higher average daily processor use at all follow-up intervals. CONCLUSION: CI activation within 10 days of surgery is associated with increased early device usage and superior speech recognition at both early and late follow-up visits. Timing of activation and device usage are modifiable factors that can help optimize postoperative outcomes in the CI population.
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Implante Coclear , Implantes Cocleares , Percepção da Fala , Adulto , Humanos , Estudos Retrospectivos , Percepção da Fala/fisiologia , Fala , Resultado do TratamentoRESUMO
Genetically engineered mouse models (GEMM) have fundamentally changed how ovarian cancer etiology, early detection, and treatment is understood. MYC, an oncogene, is amongst the most amplified genes in high-grade serous ovarian cancer (HGSOC), but it has not previously been utilized to drive HGSOC GEMMs. We coupled Myc and dominant negative mutant p53-R270H with a fallopian tube epithelium-specific promoter Ovgp1 to generate a new GEMM of HGSOC. Female mice developed lethal cancer at an average of 14.5 months. Histopathological examination of mice revealed HGSOC characteristics including nuclear p53 and nuclear MYC in clusters of cells within the fallopian tube epithelium and ovarian surface epithelium. Unexpectedly, nuclear p53 and MYC clustered cell expression was also identified in the uterine luminal epithelium, possibly from intraepithelial metastasis from the fallopian tube epithelium (FTE). Extracted tumor cells exhibited strong loss of heterozygosity at the p53 locus, leaving the mutant allele. Copy number alterations in these cancer cells were prevalent, disrupting a large fraction of genes. Transcriptome profiles most closely matched human HGSOC and serous endometrial cancer. Taken together, these results demonstrate the Myc and Trp53-R270H transgene was able to recapitulate many phenotypic hallmarks of HGSOC through the utilization of strictly human-mimetic genetic hallmarks of HGSOC. This new mouse model enables further exploration of ovarian cancer pathogenesis, particularly in the 50% of HGSOC which lack homology directed repair mutations. Histological and transcriptomic findings are consistent with the hypothesis that uterine serous cancer may originate from the fallopian tube epithelium.
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Commonly available alcohols of varying lengths and degree of branching were used to synthesize iron oxide, Fe3O4, and cobalt iron oxide, CoFe2O4, nanoparticles by means of a simple solvothermal decomposition of iron (III) acetylacetonates and cobalt (II) acetylacetonates. Depending on the solvent employed resulting Fe3O4 and CoFe2O4 nanoparticles ranged in size from approximately 5-16 nm and approximately 4-8 nm, respectively. All alcohols utilized resulted in the formation of nanoparticles with a spinel crystal structure, with the exception of methanol. Use of tert-butanol and phenol resulted in nearly spherical agglomerations of individual nanoparticles ranging between 100-250 nm. The resulting structures and morphologies of all samples were confirmed by X-ray diffraction and electron microscopy. Mass specific moments are reported based on SQUID magnetometry, and ranged from 57.5(5)-76.4(3) emu/g for Fe3O4 and 47.7(7)-67.0(4) emu/g CoFe2O4.
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OBJECTIVE: To evaluate cochlear implant (CI) magnet-related MRI artifact shape and size, as well as imaging indications and clinical adequacy of scans. METHODS: A retrospective chart review was performed for patients undergoing CI and subsequent MRI head imaging from 2014 to 2020 at a single institution. Indications and adequacy of each scan was recorded, and interpretability compared by indication. Magnet-related artifact size was determined by performing ellipsoid modeling at axial slice of greatest signal loss. Artifact radius in centimeters was calculated for 5 sequence categories, and size compared between sequences, manufacturers, and by time from implantation. RESULTS: Twenty patients underwent 58 head MRI scans. Approximately 76% of MRIs (n = 44) for 70% of patients (n = 14) were performed for indications known of prior to implantation; the remainder were performed during workup of new issues. Desired structures were interpretable in 23 (52%) of known-indication MRIs and 8 (57%) of new-indication MRIs, without significant difference (P = .751). Magnet-related artifact magnitude, compared to the reference T1-weighted fast spin echo (FSE) (4.47 cm), was similar in T2 FSE (4.57 cm, P = .068) and T1 gradient echo (GRE) sequences (4.79 cm, P = .28), but significantly greater in T2 GRE (6.86, P < .0001) and DWI (7.56 cm, P < .0001) sequences. CONCLUSIONS: DWI and T2 GRE sequences are less useful in MRI evaluation of CI patients. With a more favorable artifact profile, T1 FSE, T2 FSE, and T1 GRE sequences more likely yield clinically useful information. The large proportion of scans performed for known pathology represents an opportunity to optimize for magnet location preoperatively.
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Implantes Cocleares , Humanos , Estudos Retrospectivos , Artefatos , Imãs , Imageamento por Ressonância Magnética/métodosRESUMO
TITLE: Facial Paralysis in Skull Base Osteomyelitis - Comparison of Surgical and Nonsurgical Management. OBJECTIVE: To compare outcomes of surgical and nonsurgical management in cases of facial paresis secondary to skull base osteomyelitis. METHODS: A 14 patients presenting with skull base osteomyelitis complicated by facial nerve paresis at a single tertiary referral center from 2009 to 2019 were retrospectively reviewed. Patients were treated with medical therapy with or without surgical intervention, consisting of mastoidectomy and debridement with or without facial nerve decompression. House-Brackmann (HB) Grade was the main outcome measure. RESULTS: A 14 patients (average age 68 years, range 58-82 years, 71% male) were analyzed, with 5 undergoing facial nerve decompression (36%), 5 undergoing mastoidectomy without facial nerve decompression (36%), and 4 undergoing medical management alone (28%). Of the 4 patients who underwent medical therapy alone, none experienced significant improvement in facial function. Of the 5 patients who underwent facial nerve decompression, 3 patients experienced improved facial function. Of the 5 patients who underwent mastoidectomy without decompression, 4 experienced improved facial function. There was no clear link between the severity of infection and the severity of facial paresis. When comparing HB score changes before and after treatment across groups, there was no statistically significant difference seen (p = 0.47). CONCLUSIONS: Mastoidectomy and debridement with or without facial nerve decompression may improve facial nerve outcomes when compared to isolated medical management, although differences were not of statistical significance. The best facial nerve recoveries occurred in patients undergoing surgery within 14 days of the onset of paralysis. LEVEL OF EVIDENCE: 4 - Case Series Laryngoscope, 133:179-183, 2023.
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Paralisia Facial , Osteomielite , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Paralisia Facial/etiologia , Paralisia Facial/cirurgia , Estudos Retrospectivos , Nervo Facial/cirurgia , Base do Crânio/cirurgia , Osteomielite/complicações , Osteomielite/cirurgia , Descompressão Cirúrgica , Resultado do TratamentoRESUMO
OBJECTIVE: To characterize the incidence of sigmoid sinus occlusion (SSO) following translabyrinthine (TL) surgery for posterior fossa tumor resection and determine the association with cerebrospinal fluid (CSF) leak. STUDY DESIGN: Retrospective case series. SETTING: Tertiary referral center. METHODS: Patients undergoing TL surgery for vestibular schwannoma from 2012 to 2020 were included. Demographic data, medical history, preoperative tumor length and volume, and postoperative complications including CSF leak were recorded. Neuroradiology review of postoperative magnetic resonance imaging was used to determine the presence or absence of flow through the sigmoid sinus. RESULTS: Of 205 patients undergoing TL, 21 (10.2%) experienced CSF leak postoperatively. Overall 56 (27%) demonstrated SSO on immediate postoperative magnetic resonance imaging. CSF leaks were more likely in those with SSO (19.6%) than those without SSO (6.7%; odds ratio, 3.54 [95% CI, 1.25-10.17]). Tumor volume and body mass index were not significantly associated with CSF leak. In total, 105 (51%) patients had some degree of sigmoid sinus thrombosis, but nonocclusive thrombosis was not associated with CSF leak. CONCLUSION: SSO after TL approaches is common and appears to be significantly associated with postoperative CSF leak development. Minimizing manipulation of the sigmoid sinus during TL surgery and compression after surgery may have a role in preventing CSF leak.
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Vazamento de Líquido Cefalorraquidiano , Neuroma Acústico , Humanos , Estudos Retrospectivos , Vazamento de Líquido Cefalorraquidiano/epidemiologia , Vazamento de Líquido Cefalorraquidiano/etiologia , Neuroma Acústico/cirurgia , Neuroma Acústico/complicações , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Índice de Massa CorporalRESUMO
OBJECTIVE: We reviewed a cohort of patients with untreated sporadic vestibular schwannoma (VS) and examined the relationship between high-frequency hearing loss (HFHL) in the non-VS ear and long-term hearing outcomes in the VS-affected ear. We hypothesized that the progression of HFHL is associated with accelerated hearing decline in sporadic VS. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary center. PATIENTS: We studied 102 patients with sporadic VS diagnosed from 1999 to 2015 with ≥5 years of observation (median, 6.92; interquartile range, 5.85-9.29). Sixty-six patients had AAO-HNS class A/B hearing at presentation and were included in analysis. INTERVENTIONS: Audiometry, serial magnetic resonance imaging for observation of VS. MAIN OUTCOME MEASURES: Four-frequency pure tone average (PTA) and word recognition scores (WRS) in the VS-affected ear. Decline in high-frequency PTA (average of thresholds at 4000, 6000, and 8,000 Hz) was defined as ≥10 dB during the study period. Decline in WRS was defined as ≥10%. RESULTS: Compared with those without, patients with progressive HFHL in the non-VS ear were more likely to experience a decline in WRS in the VS ear (80% vs. 54%, p = 0.031). However, the same group showed no difference (52% vs. 41%, p = 0.40) in decline in PTA of the VS ear. CONCLUSIONS: Patients with observed VS who experience progressive HFHL in the non-VS ear are more likely to experience significant declines in speech understanding in the VS-affected ear over time. Patients with a history of presbycusis may have an increased risk of losing serviceable hearing because of sporadic VS.
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Neuroma Acústico , Presbiacusia , Humanos , Neuroma Acústico/complicações , Presbiacusia/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento , Audição , Audiometria de Tons PurosRESUMO
OBJECTIVE: To investigate whether revision surgery with the same device results in a change in three key indicators of electrode positioning: scalar location, mean modiolar distance (M¯), and angular insertion depth (AID). METHODS: Retrospective analysis of a cochlear implant database at a university-based tertiary medical center. Intra-operative CT scans were obtained after initial and revision implantation. Electrode array (EA) position was calculated using auto-segmentation techniques. Initial and revision scalar location, M¯, and AID were compared. RESULTS: Mean change in M¯ for all ears was -0.07â mm (SD 0.24â mm; P = 0.16). The mean change in AID for all ears was -5° (SD 67°; P = 0.72). Three initial implantations with pre-curved EAs resulted in a translocation from Scala Tympani (ST) to Scala Vestibuli (SV). Two remained translocated after revision, while one was corrected when revised with a straight EA. An additional five translocations occurred after revision. CONCLUSIONS: In this study examining revision cochlear implantation from a single manufacturer, we demonstrated no significant change in key indicators of EA positioning, even when revising with a different style of electrode. However, the revision EA is not necessarily confined by the initial trajectory and there may be an increased risk of translocation.
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Implante Coclear , Implantes Cocleares , Humanos , Estudos Retrospectivos , Cóclea , ReimplanteRESUMO
OBJECTIVE: To report our experience for adults undergoing cochlear implantation (CI) for single-sided deafness (SSD). METHODS: This is a retrospective case series for adults with SSD who underwent CI between January 2013 and May 2021 at our institution. CNC and AzBio speech recognition scores, Tinnitus Handicap Inventory (THI), Speech, Spatial, and Qualities of Hearing Scale (SSQ12), datalogging, and the Cochlear Implant Quality of Life (CIQOL)-10 Global measure were utilized. RESULTS: Sixty-six adults underwent CI for SSD (median 51.3 years, range 20.0-74.3 years), and 57 (86.4%) remained device users at last follow-up. Compared to pre-operative performance, device users demonstrated significant improvement in speech recognition scores and achieved peak performance at six months post-activation for CNC (8.0% increased to 45.6%, p < 0.0001) and AzBio in quiet (12.2% increased to 59.5%, p < 0.0001). THI was decreased at 6 months post-implantation (58.1-14.6, p < 0.0001), with 77% of patients reporting improved or resolved tinnitus. Patients demonstrated improved SSQ12 scores as well as the disease-specific CIQOL-10 Global questionnaire. Duration of deafness was not associated with significant differences in speech recognition performance. Average daily wear time was positively associated with CNC and AzBio scores as well as post-operative CIQOL-10 scores. CONCLUSIONS: Herein we present the largest cohort of adult CI recipients with SSD with data on speech recognition scores, tinnitus measures, and SSQ12. Novel insights regarding the correlation of datalogging, duration of deafness, and CI-specific quality of life (CIQOL-10) metrics are discussed. Data continue to support CI as an efficacious treatment option for SSD. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2362-2370, 2023.
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Implante Coclear , Implantes Cocleares , Perda Auditiva Unilateral , Percepção da Fala , Zumbido , Adulto , Humanos , Zumbido/cirurgia , Estudos Retrospectivos , Qualidade de Vida , Perda Auditiva Unilateral/cirurgia , Resultado do Tratamento , Percepção da Fala/fisiologiaRESUMO
OBJECTIVE: Compare incidence of sigmoid sinus wall abnormalities (SSWAs) and other radiographic abnormalities in patients with pulsatile tinnitus (PT) versus controls. STUDY DESIGN: Retrospective case-control. SETTING: Tertiary referral center. PATIENTS: Adults with PT and high-resolution computed tomography imaging were compared with adults undergoing cochlear implant workup including high-resolution computed tomography imaging. MAIN OUTCOME MEASURES: Incidence of SSWA in PT cohort (n = 141) compared with control (n = 149, n = 298 ears). Secondary outcome measures included differences in demographics and in other radiographic abnormalities between cohorts. RESULTS: Patients with PT had a higher incidence of SSWA (34% versus 9%, p < 0.001) and superior canal dehiscence (23% versus 12%, p = 0.017) than controls. Spearman product component correlations demonstrated that ipsilateral PT was weakly associated with SSWA ( r = 0.354, p < 0.001). When SSWA was present in the PT cohort (n = 48 patients, n = 59 ears), in 31 cases (64.6%), the SSWA correlated with PT laterality (e.g., left SSWA, left PT); in 12 (25.0%), SSWA partially correlated with PT laterality (e.g., bilateral SSWA, right PT); and in 5 (10.4%), the SSWA did not correlate with PT laterality (e.g., right SSWA, left PT). CONCLUSIONS: For our patients with both PT and SSWA, the SSWA is likely a contributing factor in approximately 65% of cases. For a third of patients with PT and concomitant SSWA, the association between the two is either not causative or not solely causative. Surgeons counseling patients with PT and SSWA may be optimistic overall regarding sigmoid resurfacing procedures but must appreciate the possibility of treatment failure, likely because of untreated comorbid conditions.
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Zumbido , Adulto , Humanos , Zumbido/diagnóstico por imagem , Zumbido/etiologia , Zumbido/cirurgia , Estudos de Casos e Controles , Estudos Retrospectivos , Cavidades Cranianas/diagnóstico por imagem , Cavidades Cranianas/cirurgia , Tomografia Computadorizada por Raios XRESUMO
The pedunculopontine tegmentum nucleus (PPT) is critically involved in the regulation of wakefulness (W) and rapid eye movement (REM) sleep, but our understanding of the mechanisms of this regulation remains incomplete. The present study was designed to determine the role of PPT intracellular calcium/calmodulin kinase (CaMKII) signaling in the regulation of W and sleep. To achieve this aim, three different concentrations (0.5, 1.0, and 2.0 nmol) of the CaMKII activation inhibitor, KN-93, were microinjected bilaterally (100 nl/site) into the PPT of freely moving rats, and the effects on W, slow-wave sleep (SWS), REM sleep, and levels of phosphorylated CaMKII (pCaMKII) expression in the PPT were quantified. These effects, which were concentration-dependent and affected wake-sleep variables for 3 h, resulted in decreased W, due to reductions in the number and duration of W episodes; increased SWS and REM sleep, due to increases in episode duration; and decreased levels of pCaMKII expression in the PPT. Regression analyses revealed that PPT levels of pCaMKII were positively related with the total percentage of time spent in W (R(2) = 0.864; n = 28 rats; p < 0.001) and negatively related with the total percentage of time spent in sleep (R(2) = 0.863; p < 0.001). These data provide the first direct evidence that activation of intracellular CaMKII signaling in the PPT promotes W and suppresses sleep. These findings are relevant for designing a drug that could treat excessive sleepiness by promoting alertness.
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Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/antagonistas & inibidores , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/fisiologia , Núcleo Tegmental Pedunculopontino/enzimologia , Inibidores de Proteínas Quinases/administração & dosagem , Vigília/fisiologia , Animais , Benzilaminas/administração & dosagem , Masculino , Microinjeções , Núcleo Tegmental Pedunculopontino/efeitos dos fármacos , Distribuição Aleatória , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Fases do Sono/efeitos dos fármacos , Fases do Sono/fisiologia , Sulfonamidas/administração & dosagem , Vigília/efeitos dos fármacosRESUMO
OBJECTIVE: To analyze the relationship of electrode array (EA) type and position on hearing preservation longevity following cochlear implantation. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary referral center. PATIENTS: Adult cochlear implant recipients between 2013 and 2019 with hearing preserved postoperatively and postoperative CT scans. INTERVENTIONS: CT scan analysis of EA position. Stepwise regression to determine influence of EA position, EA type, and patient demographics on postoperative low frequency hearing. MAIN OUTCOME MEASURES: Low frequency pure tone average (LFPTA), LFPTA shift, angular insertion depth, base insertion depth, scalar position, mean perimodiolar distance. RESULTS: Of 792 cochlear implant recipients, 121 had preoperative LFPTA <80 dB HL with 60 of the 121 (49.6%) implanted with straight, 32 (26.4%) with precurved, styletted, and 29 (24.0%) implanted precurved, nonstyletted EA. Mean follow up was 28.6 months (range 1-103). There was no statistically significant difference in activation, 6- and 12-month, and last follow-up LFPTA (125, 250, and 500 Hz) shift based on EA type (straight p = 0.302, precurved, styletted p = 0.52, precurved, nonstyletted p = 0.77). Preoperative LFPTA and age of implantation were significant predictors of LFPTA shift at activation, accounting for 30.8% of variance ( F [2, 113] = 26.603, p < 0.0001). LFPTA shift at activation, scalar position, and base insertion depth were significant predictors of variability and accounted for 39.1% of variance in LFPTA shift at 6 months ( F [3, 87] = 20.269, p < 0.0001). Only LFPTA shift at 12 months was found to be a significant predictor of LFPTA shift at last follow up, accounting for 41.0% of variance ( F [1, 48] = 32.653, p < 0.0001). CONCLUSIONS: Patients had excellent long-term residual hearing regardless of EA type. Age, preoperative acoustic hearing, and base insertion depth may predict short term preservation, while 12-month outcomes significantly predicted long-term hearing preservation.
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Implante Coclear , Implantes Cocleares , Adulto , Audição/fisiologia , Testes Auditivos , Humanos , Estudos RetrospectivosRESUMO
OBJECTIVE: To compare outcomes of endoscope-assisted middle cranial fossa MCF) repair of superior semicircular canal dehiscence (SSCD) compared to microscopic MCF repair. STUDY DESIGN: Retrospective cohort. SETTING: Tertiary medical center neurotology practice. METHODS: Retrospective chart review and cohort study of patients who underwent surgical repair of SSCD via MCF approach from 2010 to 2019 at our institution. Patients were categorized according to use of endoscope intraoperatively. Pre- and post-operative symptom number was calculated from 8 patient-reported symptoms. Pre- and post-operative changes in symptom number were assessed using paired t-tests. Single-predictor binary logistic regression was used to compare final reported symptoms between cohorts. Linear regression was performed to assess air-bone gap (ABG) changes postoperatively between cohorts. RESULTS: Forty-six patients received surgical management for SSCD. Of these, 27 (59%) were male and 19 (41%) were female. Bilateral SSCD was present in 14 cases (29%), of which 3 underwent surgical management bilaterally, for a total of 49 surgical ears. Surgery was performed on the right ear in 19 cases (39%) and on the left in 30 cases (61%). Forty ears (82%) underwent microscopic repair while 9 (18%) underwent endoscope-assisted repair. Microscopic and endoscope-assisted MCF repair both demonstrated significantly improved symptom number postoperatively (P < .001 for each). There was no significant difference in change in ABG between the 2 cohorts. On average, patient-reported symptoms and audiometrically-tested hearing improved postoperatively in both groups. CONCLUSION: While endoscopic-assisted MCF repair has the potential to provide better visualization of medial and downslope defects, repair via this technique yields similar results and is equivalent to MCF repair utilizing the microscope alone.
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Deiscência do Canal Semicircular , Canais Semicirculares , Estudos de Coortes , Endoscópios , Feminino , Humanos , Masculino , Estudos Retrospectivos , Canais Semicirculares/cirurgiaRESUMO
OBJECTIVE: Over the last decade there has been a trend toward observation for small nongrowing vestibular schwannoma (VS). Even without tumor growth, patients commonly experience ipsilateral hearing decline, and hearing rehabilitation remains challenging. This study analyzes hearing and speech performance outcomes after cochlear implantation (CI) in observed VS. STUDY DESIGN: Retrospective review. SETTING: Tertiary referral center. METHODS: Chart review was used to include patients with observed VS who had undergone ipsilateral CI, pre- and postimplantation audiometry, and speech performance. Tumor size pre- and postimplantation was measured with volumetric analysis. RESULTS: Seven patients with ipsilateral VS and CI were identified. Preimplantation tumor volume was 0.11 to 1.02 cm3. Five subjects were implanted with a straight electrode and two with a perimodiolar electrode. The average preimplant pure tone average was 91.3 dB (range, 80-117 dB) and 61.2 dB (range, 12-118 dB) for the implanted and nonimplanted ears, respectively. In all subjects with at least 1 year of listening experience (n = 6), consonant-nucleus-consonant word scores improved at 6 months and 1 year in the CI-alone and bimodal listening conditions. AzBio scores in quiet also improved at 6 months and 1 year. Of subjects with serial pre- and postoperative magnetic resonance imaging, volumetric analysis demonstrated no tumor growth. CONCLUSION: Our results demonstrate that CI is a successful option for subjects with small nongrowing VS. All subjects had improved performance postimplantation. VS may continue to be observed with serial magnetic resonance imaging given increasing conditionality among CI manufacturers and ability to assess cerebellopontine angle extension despite implant artifact.
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Implante Coclear , Implantes Cocleares , Neuroma Acústico , Percepção da Fala , Audiometria de Tons Puros , Implante Coclear/métodos , Audição , Humanos , Neuroma Acústico/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the prevalence of vestibular migraine (VM) in a cohort of patients with radiologic confirmation of superior canal dehiscence (SCD) and to compare management of superior canal dehiscence syndrome (SCDS) in patients with and without comorbid VM. STUDY DESIGN: Retrospective review of a SCD database. SETTING: University-based tertiary medical center. PATIENTS: Ninety-one patients identified with SCD from 2009 to 2017. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Coincidence of VM and SCD, and resolution of symptoms. RESULTS: Ninety-one patients with SCD met the inclusion and exclusion criteria. VM was diagnosed in 36 (39.6%) patients. Of those receiving medical therapy for VM alone, five (45.5%) reported symptom resolution, five (45.5%) reported partial improvement, one (9.1%) had no change, and none worsened. Fifteen patients (41.7%) were treated with both surgery (for SCD) and medical therapy (for VM). Seven (46.7%) reported symptom resolution, seven (46.7%) reported partial improvement, and one (6.7%) worsened. There was no statistically significant difference in symptom resolution between SCD + VM patients who were treated medically compared with those treated with medical therapy and surgery (p = 0.951). There was no significant difference in symptom resolution after surgery between SCD + VM and SCD-only cohorts (p = 0.286). CONCLUSIONS: This is the first study describing the incidence of VM in a cohort of patients with SCDS. The symptoms of VM confound those of SCDS and unrecognized or undertreated VM may contribute to surgical failure in SCDS. Therefore, we recommend a high index of suspicion for VM in patients with SCDS and a trial of medical therapy in the setting of suspected VM.
Assuntos
Transtornos de Enxaqueca , Deiscência do Canal Semicircular , Humanos , Transtornos de Enxaqueca/complicações , Transtornos de Enxaqueca/terapia , Estudos Retrospectivos , Canais Semicirculares/cirurgia , Vertigem/etiologiaRESUMO
OBJECTIVE: To characterize the influence of expanding indications on the profile of adults undergoing cochlear implantation (CI) at a high-volume CI center. STUDY DESIGN: Retrospective review. SETTING: Tertiary referral center. PATIENTS: 774 adults undergoing CI evaluation from August 2015 to August 2020. MAIN OUTCOME MEASURES: Demographics; audiometry; speech recognition; speech, spatial, and qualities of hearing scale (SSQ-12). RESULTS: Of 745 (96.3%) patients qualifying for implantation, 642 (86.6%) pursued surgery. Median age at evaluation was 69 years; 56.3% were men; 88.2% were Caucasian. Median distance to our center was 95 miles. The majority (51.8%) had public insurance (Medicare, Medicaid), followed by private (47.8%) and military (0.4%). Mean PTA, CNC, and AzBio in quiet and noise for the ear to be implanted were 85.2 dB HL, 15.0%, and 19.2% and 3.5%, respectively. Hybrid/EAS criteria were met by 138 (18.5%) CI candidates, and 436 (77.0%) unilateral CI recipients had aidable contralateral hearing for bimodal hearing configurations. Younger age (odds ratio [OR], 0.96; 95% confidence interval, 0.93-0.99) and non-Caucasian race (OR, 6.95; 95% confidence interval, 3.22-14.98) predicted candidacy. Likelihood of surgery increased for Caucasian (OR, 8.08; 95% confidence interval, 4.85-13.47) and married (OR, 2.28; 95% confidence interval, 1.50-3.47) patients and decreased for those with public insurance (OR, 0.45; 95% confidence interval, 0.29-0.69). A lower SSQ-12 score predicted both candidacy and surgery. CONCLUSION: Despite expansions in criteria, speech understanding remained extremely low at CI evaluation. Younger age and non-Caucasian race predicted candidacy, and Caucasian, married patients with private insurance and lower SSQ scores were more likely to pursue surgery.