Evaluation of clinical predictors of postoperative outcomes in tegmen defect patients with and without concurrent superior semicircular canal dehiscence and cerebrospinal fluid leak.

OBJECTIVES: Tegmen and superior semicircular canal defects have been well studied, yet the factors contributing to their onset and progression are widely debated. The clinical utility of intraoperative intracranial pressure measurements has yet to be tested. This report aims to use intraoperative opening pressure and concurrent superior semicircular canal dehiscence (SSCD) to analyze factors influencing disease course and clinical outcomes in patients with tegmen dehiscence. METHODS: A retrospective analysis of 61 patients who underwent tegmen defect repair was performed. Multiple variables of interest including body mass index (BMI), presence of SSCD, presence of dural venous sinus stenosis, opening pressure, and acetazolamide therapy use were recorded. The cohort was divided into those with or without concurrent SSCD and those presenting with or without cerebrospinal fluid (CSF) leak for analysis. RESULTS: A linear relationship between opening pressure and BMI (p = 0.009) was noted; however, intraoperative opening pressure was not associated with disease outcome. Concurrent SSCD was present in 25 % of patients, while 62 % presented with CSF leak. The concurrent SSCD group exhibited higher opening pressure, higher likelihood of having dural sinus stenosis, and higher likelihood of being discharged on acetazolamide. The CSF leak group had higher likelihood of obstructive sleep apnea and persistent symptoms. CONCLUSIONS: In patients undergoing tegmen defect repair, concurrent SSCD suggests increased disease severity. The presence of preoperative CSF leak predicts persistent symptoms following repair. BMI is linearly correlated with intracranial pressure in these patients.

Cost-Effectiveness of Diffusion Weighted MRI Versus Planned Second-Look Surgery for Cholesteatoma.

OBJECTIVE: To compare the cost-effectiveness of serial non-echo planar diffusion weighted MRI (non-EP DW MRI) versus planned second look surgery following initial canal wall up tympanomastoidectomy for the treatment of cholesteatoma. METHODS: A decision-analytic model was developed. Model inputs including residual cholesteatoma rates, rates of non-EP DW MRI positivity after surgery, and health utility scores were abstracted from published literature. Cost data were derived from the 2022 Centers for Medicare and Medicaid Services fee rates. Efficacy was defined as increase in quality-adjusted life year (QALY). One- and 2-way sensitivity analyses were performed on variables of interest to probe the model. Total time horizon was 50 years with a willingness to pay (WTP) threshold set at $50 000/QALY. RESULTS: Base case analysis revealed that planned second-look surgery ($11 537, 17.30 QALY) and imaging surveillance with non-EP DWMRI ($10 439, 17.26 QALY) were both cost effective options. Incremental cost effectiveness ratio was $27 298/QALY, which is below the WTP threhshold. One-way sensitivity analyses showed that non-EP DW MRI was more cost effective than planned second-look surgery if the rate of residual disease after surgery increased to 48.3% or if the rate of positive MRI was below 45.9%. A probabilistic sensitivity analysis at WTP of $50 000/QALY found that second-look surgery was more cost-effective in 56.7% of iterations. CONCLUSION: Non-EP DW MRI surveillance is a cost-effect alternative to planned second-look surgery following primary canal wall up tympanomastoidectomy for cholesteatoma. Cholesteatoma surveillance decisions after initial canal wall up tympanomastoidectomy should be individualized. LEVEL OF EVIDENCE: V.

Colocalization by cross-correlation, a new method of colocalization suited for super-resolution microscopy.

BACKGROUND: A common goal of scientific microscopic imaging is to determine if a spatial correlation exists between two imaged structures. This is generally accomplished by imaging fluorescently labeled structures and measuring their spatial correlation with a class of image analysis algorithms known as colocalization. However, the most commonly used methods of colocalization have strict limitations, such as requiring overlap in the fluorescent markers and reporting requirements for accurate interpretation of the data, that are often not met. Due to the development of novel super-resolution techniques, which reduce the overlap of the fluorescent signals, a new colocalization method is needed that does not have such strict requirements. RESULTS: In order to overcome the limitations of other colocalization algorithms, I developed a new ImageJ/Fiji plugin, Colocalization by cross-correlation (CCC). This method uses cross-correlation over space to identify spatial correlations as a function of distance, removing the overlap requirement and providing more comprehensive results. CCC is compatible with 3D and time-lapse images, and was designed to be easy to use. CCC also generates new images that only show the correlating labeled structures from the input images, a novel feature among the cross-correlating algorithms. CONCLUSIONS: CCC is a versatile, powerful, and easy to use colocalization and spatial correlation tool that is available through the Fiji update sites. Full and up to date documentation can be found at https://imagej.net/plugins/colocalization-by-cross-correlation . CCC source code is available at https://github.com/andmccall/Colocalization_by_Cross_Correlation .

Prevalence of Cochlear-Facial and Other Non-Superior Semicircular Canal Third Window Dehiscence on High-Resolution Temporal Bone CT.

BACKGROUND AND PURPOSE: The radiologic prevalence of superior semicircular canal dehiscence in the asymptomatic population has been widely studied, but less is known about the rates of other forms of third window dehiscence. Per the existing literature, the radiologic prevalence of cochlear-facial nerve dehiscence, for example, exceeds that seen in histologic studies, suggesting that conventional CT is unreliable for cochlear-facial dehiscence. These studies relied on nonisometric CT acquisitions, however, and underused multiplanar reformatting techniques, leading to false-positive findings. Our purpose was to determine the rate of cochlear-facial dehiscence and other non-superior semicircular canal third window dehiscences on optimized CT in asymptomatic patients. MATERIALS AND METHODS: Sixty-four-channel temporal bone CT scans from 602 patients in emergency departments were assessed for cochlear-facial and other non-superior semicircular canal third window dehiscences by using high-resolution, multiplanar oblique reformats. Confidence intervals for dehiscence prevalence were calculated using the Newcombe 95% interval confidence method. RESULTS: Of 602 patients, 500 were asymptomatic, while 102 had an imaging indication consistent with possible third window syndrome (symptomatic). Eight asymptomatic patients (1.6%) had cochlear-facial dehiscence, while 43 (8.4%) had jugular bulb-vestibular aqueduct dehiscence. There was no statistically significant difference between the prevalence of cochlear-facial dehiscence or jugular bulb-vestibular aqueduct dehiscence in asymptomatic patients compared with symptomatic patients. Cochlear-carotid canal, cochlear-internal auditory canal, and cochlear-petrosal sinus dehiscences were not observed. CONCLUSIONS: Sixty-four-channel CT with multioblique reformatting is sensitive and specific for identifying cochlear-facial dehiscence, with rates similar to those in postmortem series. Jugular bulb-vestibular aqueduct dehiscence is a common incidental finding and is unlikely to produce third window physiology. Other non-superior semicircular canal third window dehiscences are rare in asymptomatic patients.

Multimodal CT imaging of ischemic stroke thrombi identifies scale-invariant radiomic features that reflect clot biology.

BACKGROUND: Biological interpretability of ischemic stroke clot imaging remains challenging. OBJECTIVE: To carry out paired CT/micro-CT imaging of ischemic stroke clots retrieved by thrombectomy with the aim of identifying interpretable image features that are correlated among pretreatment image modalities and post-treatment histopathology. METHODS: We performed multimodal CT imaging and histology for 10 stroke clots retrieved by mechanical thrombectomy. Clots were manually segmented from co-registered, pretreatment CT angiography (CTA) and non-contrast CT (NCCT). For the same cases, retrieved clots were iodine-stained, and imaged with a ScanCo micro-CT 100 (4.9 µm resolution). Afterwards, clots were subjected to histological processing (hematoxylin and eosin staining) and whole slide scanned (40X). Clot radiomic features (RFs) (n=93 per modality, 279 total) were extracted using PyRadiomics and histological composition was computed using Orbit Image Analysis. Correlation analysis was used to test associations between micro-CT and CTA (or NCCT) RFs as well as between RFs and histological composition. Statistical significance was considered at R≥0.65 and q<0.05. RESULTS: From paired RF correlation analysis, we identified 23 scale-invariant RFs with significant correlation between micro-CT and CTA (18), and micro-CT and NCCT (5). Correlation of unpaired RFs identified 377 positively and 36 negatively correlated RFs between micro-CT and CTA, and 168 positively and 41 negatively correlated RFs between micro-CT and NCCT. Scale-invariant RFs computed from CTA and NCCT demonstrated significant correlation with red blood cell and fibrin-platelet components, while micro-CT RFs were found to be correlated with white blood cell percent composition. CONCLUSION: Multimodal CT, radiomic, and histological analysis of stroke clots can help to bridge the gap between pretreatment imaging and clot pathobiology.

Hearing impairment in murine model of Down syndrome.

Hearing impairment is a cardinal feature of Down syndrome (DS), but its clinical manifestations have been attributed to multiple factors. Murine models could provide mechanistic insights on various causes of hearing loss in DS. To investigate mechanisms of hearing loss in DS in the absence of the cadherin 23 mutation, we backcrossed our DS mice, Dp(16)1Yey, onto normal-hearing CBA/J mice and evaluated their auditory function. Body weights of wild type (WT) and DS mice were similar at 3-months of age, but at 9-months, WT weighed 30% more than DS mice. Distortion product otoacoustic emissions (DPOAE), a test of sensory outer hair cell (OHC) function negatively impacted by conductive hearing loss, were reduced in amplitude and sensitivity across all frequencies in DS mice. The middle ear space in DS mice appeared normal with no evidence of infection. MicroCT structural imaging of DS temporal bones revealed a smaller tympanic membrane diameter, oval window, and middle ear space and localized thickening of the bony otic capsule, but no gross abnormalities of the middle ear ossicles. Histological analysis of the cochlear and vestibular sensory epithelium revealed a normal density of cochlear and vestibular hair cells; however, the cochlear basal membrane was approximately 0.6 mm shorter in DS than WT mice so that the total number of hair cells was greater in WT than DS mice. In DS mice, the early and late peaks in the auditory brainstem response (ABR), reflecting neural responses from the cochlear auditory nerve followed by subsequent neural centers in the brainstem, were reduced in amplitude and ABR thresholds were elevated to a similar degree across all frequencies, consistent with a conductive hearing impairment. The latency of the peaks in the ABR waveform were longer in DS than WT mice when compared at the same intensity; however, the latency delays disappeared when the data were compared at the same intensity above thresholds to compensate for the conductive hearing loss. Future studies using wideband tympanometry and absorbance together with detailed histological analysis of the middle ear could illuminate the nature of the conductive hearing impairment in DS mice.

Both consumptive and non-consumptive effects of predators impact mosquito populations and have implications for disease transmission.

Predator-prey interactions influence prey traits through both consumptive and non-consumptive effects, and variation in these traits can shape vector-borne disease dynamics. Meta-analysis methods were employed to generate predation effect sizes by different categories of predators and mosquito prey. This analysis showed that multiple families of aquatic predators are effective in consumptively reducing mosquito survival, and that the survival of Aedes, Anopheles, and Culex mosquitoes is negatively impacted by consumptive effects of predators. Mosquito larval size was found to play a more important role in explaining the heterogeneity of consumptive effects from predators than mosquito genus. Mosquito survival and body size were reduced by non-consumptive effects of predators, but development time was not significantly impacted. In addition, Culex vectors demonstrated predator avoidance behavior during oviposition. The results of this meta-analysis suggest that predators limit disease transmission by reducing both vector survival and vector size, and that associations between drought and human West Nile virus cases could be driven by the vector behavior of predator avoidance during oviposition. These findings are likely to be useful to infectious disease modelers who rely on vector traits as predictors of transmission.

Mosquitoes are often referred to as the deadliest animals on earth because some species spread malaria, West Nile virus or other dangerous diseases when they bite humans and other animals. Adult mosquitoes fly to streams, ponds and other freshwater environments to lay their eggs. When the eggs hatch, the young mosquitoes live in the water until they are ready to grow wings and transform into adults. In the water, the young mosquitoes are particularly vulnerable to being eaten by dragonfly larvae, fish and other predators. When adult females are choosing where to lay their eggs, they can use their sense of smell to detect these predators and attempt to avoid them. Along with eating the mosquitoes, the predators may also reduce mosquito populations in other ways. For example, predators can disrupt feeding among young mosquitoes, which may affect the time that it takes for them to grow into adults or the size of their bodies once they reach the adult stage. Although the impacts of different predators have been tested separately in multiple settings, the overall effects of predators on the ability of mosquitoes to spread diseases to humans remain unclear. To address this question, Russell, Herzog et al. used an approach called meta-analysis on data from previous studies. The analysis found that along with increasing the death rates of mosquitoes, the presence of predators also leads to a reduction in the body size of those mosquitoes that survive, causing them to have shorter lifespans and fewer offspring. Russell, Herzog et al. found that one type of mosquito known as Culex ­ which carries West Nile virus ­ avoided laying its eggs near predators. During droughts, increased predation in streams, ponds and other aquatic environments may lead adult female Culex mosquitoes to lay their eggs closer to residential areas with fewer predators. Russell, Herzog et al. propose that this may be one reason why outbreaks of West Nile virus in humans are more likely to occur during droughts. In the future, these findings may help researchers to predict outbreaks of West Nile virus, malaria and other diseases carried by mosquitoes more accurately. Furthermore, the work of Russell, Herzog et al. provides examples of mosquito predators that could be used as biocontrol agents to decrease numbers of mosquitoes in certain regions.

Pain and Pain Control With Opioid and Nonopioid Medications After Otologic Surgery.

OBJECTIVE: To prospectively analyze pain and pain medication use following otologic surgery. STUDY DESIGN: Prospective cohort study with patient reported pain logs and medication use logs. SETTING: Tertiary academic hospital.Patients: Sixty adults who underwent outpatient otologic surgeries. INTERVENTIONS: Surveys detailing postoperative pain levels, nonopioid analgesic (NOA) use, and opioid analgesic use. MAIN OUTCOME MEASURES: Self-reported pain scores, use of NOA, and use of opioid medications normalized as milligrams morphine equivalents (MME). RESULTS: Thirty-two patients had surgery via a transcanal (TC) approach, and 28 patients had surgery via a postauricular (PA) approach. TC surgery had significantly lower reported pain scores than PA surgery on both postoperative day (POD) 1 (median pain score 2.2, IQR 0-5 vs. median pain score 4.8, IQR 3.4-6.3, respectively; p = 0.0013) and at POD5 (median pain score 0, IQR 0-0 vs. median pain score 2.0, IQR 0-3, respectively; p = 0.0002). Patients also used significantly fewer opioid medications with TC approach than patients who underwent PA approach at POD1 (median total MME 0, IQR 0-5 vs. median total MME 5.0, IQR 0-15, respectively; p = 0.03) and at POD5 (median total MME 0, IQR 0-0 vs. median total MME 0, IQR 0-5, respectively; p = 0.0012). CONCLUSIONS: Surgery with a postauricular approach is associated with higher pain and opioid use following otologic surgery. Patient- and approach-specific opioid prescribing is feasible following otologic surgery.

Data Science in Undergraduate Life Science Education: A Need for Instructor Skills Training.

There is a clear demand for quantitative literacy in the life sciences, necessitating competent instructors in higher education. However, not all instructors are versed in data science skills or research-based teaching practices. We surveyed biological and environmental science instructors (n = 106) about the teaching of data science in higher education, identifying instructor needs and illuminating barriers to instruction. Our results indicate that instructors use, teach, and view data management, analysis, and visualization as important data science skills. Coding, modeling, and reproducibility were less valued by the instructors, although this differed according to institution type and career stage. The greatest barriers were instructor and student background and space in the curriculum. The instructors were most interested in training on how to teach coding and data analysis. Our study provides an important window into how data science is taught in higher education biology programs and how we can best move forward to empower instructors across disciplines.

Scoping review of cochlear implantation in Susac's syndrome.

OBJECTIVE: Scoping review of published literature to establish clinical characteristics and audiologic outcomes in patients diagnosed with Susac's Syndrome(SS) who have undergone cochlear implantation (CI). DATA SOURCES: All published studies of CI in SS and contribution of two of our own patients who have not been reported previously. METHODS: A comprehensive search of MEDLINE (via PubMed) was carried out in March 2020 using the following keywords and related entry terms: Susac's Syndrome, Cochlear Implantation. RESULTS: Our search identified a total of five case reports of CI in SS. With the addition of our two patients reported here, we analyzed characteristics and outcomes in seven patients. Mean age at implantation was 30 years old (range 19-46), with six women and one man implanted. Mean time from onset of hearing loss to implantation was 17 months (range three months to four years). Best reported postoperative speech understanding was reported via different metrics, with six of seven patients achieving open set speech scores of 90% or better, and one subject performing at 68%. Vestibular symptoms were present preoperatively in four of seven patients (57%), with vestibular testing reported in two patients, and showing vestibulopathy in one patient. No complications were reported following cochlear implantation. CONCLUSION: Cochlear implantation is a viable option for hearing rehabilitation in patients with SS, with levels of attainment of open set speech comparable to other populations of CI candidates.

Integration of vestibular and hindlimb inputs by vestibular nucleus neurons: multisensory influences on postural control.

We recently demonstrated in decerebrate and conscious cat preparations that hindlimb somatosensory inputs converge with vestibular afferent input onto neurons in multiple central nervous system (CNS) locations that participate in balance control. Although it is known that head position and limb state modulate postural reflexes, presumably through vestibulospinal and reticulospinal pathways, the combined influence of the two inputs on the activity of neurons in these brainstem regions is unknown. In the present study, we evaluated the responses of vestibular nucleus (VN) neurons to vestibular and hindlimb stimuli delivered separately and together in conscious cats. We hypothesized that VN neuronal firing during activation of vestibular and limb proprioceptive inputs would be well fit by an additive model. Extracellular single-unit recordings were obtained from VN neurons. Sinusoidal whole body rotation in the roll plane was used as the search stimulus. Units responding to the search stimulus were tested for their responses to 10° ramp-and-hold roll body rotation, 60° extension hindlimb movement, and both movements delivered simultaneously. Composite response histograms were fit by a model of low- and high-pass filtered limb and body position signals using least squares nonlinear regression. We found that VN neuronal activity during combined vestibular and hindlimb proprioceptive stimulation in the conscious cat is well fit by a simple additive model for signals with similar temporal dynamics. The mean R2 value for goodness of fit across all units was 0.74 ± 0.17. It is likely that VN neurons that exhibit these integrative properties participate in adjusting vestibulospinal outflow in response to limb state.NEW & NOTEWORTHY Vestibular nucleus neurons receive convergent information from hindlimb somatosensory inputs and vestibular inputs. In this study, extracellular single-unit recordings of vestibular nucleus neurons during conditions of passively applied limb movement, passive whole body rotations, and combined stimulation were well fit by an additive model. The integration of hindlimb somatosensory inputs with vestibular inputs at the first stage of vestibular processing suggests that vestibular nucleus neurons account for limb position in determining vestibulospinal responses to postural perturbations.

Operable, Low-Cost, High-Resolution, Patient-Specific 3D Printed Temporal Bones for Surgical Simulation and Evaluation.

OBJECTIVES: Three-dimensional printed models created on a consumer level printer can be used to practice mastoidectomy and to discern mastoidectomy experience level. Current models in the literature for mastoidectomy are limited by expense or operability. The aims of this study were (1) to investigate the utility of an inexpensive model for mastoidectomy and (2) to assess whether the model can be used as an evaluation tool to discern the experience level of the surgeon performing mastoidectomy. METHODS: Three-dimensional printed temporal bone models from the CT scan of a 7-year old patient were created using a consumer-level stereolithography 3D printer for a raw material cost of $10 each. Mastoidectomy with facial recess approach was performed by 4 PGY-2 residents, 4 PGY-5 residents, and 4 attending surgeons on the models who then filled out an evaluation. The drilled models were collected and then graded in a blinded fashion by 6 attending otolaryngologists. RESULTS: Both residents and faculty felt the model was useful for training (mean score 4.7 out of 5; range: 4-5) and case preparation (mean score: 4.3; range: 3-5). Grading of the drilled models revealed significant differences between junior resident, senior resident, and attending surgeon scores (P = .012) with moderate to excellent interrater agreement (ICC = 0.882). CONCLUSION: The described operable model that is patient-specific was rated favorably for pediatric mastoidectomy case preparation and training by residents and faculty. The model may be used to differentiate between experience levels and has promise for use in formative and summative evaluations.

Cochlear Implant Performance in Adult Patients with Absent Intraoperative Electrically Evoked Compound Action Potentials.

OBJECTIVE: To describe cochlear implant performance outcomes in adult patients in whom no intraoperative electrically evoked compound action potential (ECAP) responses were able to be obtained despite intracochlear electrode placement. STUDY DESIGN: Retrospective case review. SETTING: Academic tertiary center. SUBJECTS AND METHODS: Patients 18 years of age and older undergoing cochlear implantation between May 2010 and September 2018 with absent ECAP measurements intraoperatively with intracochlear electrode positioning were identified. Patient performance on sentence recognition testing using the Hearing in Noise Test (HINT) and AzBio at 6 to 12 months postoperatively was compared to preimplantation scores. Additional collected data included patient demographics, etiology of hearing loss, and preoperative pure-tone average (PTA) and word recognition scores (WRSs). RESULTS: Intraoperative ECAP measurements were unable to be obtained in 15 cochlear implants performed on 14 patients out of 383 cochlear implant cases. Of the patients with absent ECAP measures, the mean ± SD age was 61.7 ± 15.7 years. Causes of hearing loss included congenital hearing loss, meningitis, autoimmune inner ear disease, otosclerosis, presbycusis, and Ménière's disease. The average preoperative PTA was 103.5 ± 17.0 dB. Twelve implanted ears had a WRS of 0% and 9 had a HINT score of 0% prior to surgery. The mean HINT score at 6 to 12 months postimplantation was 57.8% ± 37.8% and had improved by 42.6% ± 35.6% compared to the mean preimplantation HINT score (95% confidence interval, 22.0%-63.1%, P = .001, paired Student t test). CONCLUSION: There is a wide range of cochlear implant performance in patients with absent intraoperative ECAP measures ranging from sound awareness to HINT scores of 100%.

Responses of neurons in the rostral ventrolateral medulla of conscious cats to anticipated and passive movements.

The vestibular system contributes to regulating sympathetic nerve activity and blood pressure. Initial studies in decerebrate animals showed that neurons in the rostral ventrolateral medulla (RVLM) respond to small-amplitude (<10°) rotations of the body, as in other brain areas that process vestibular signals, although such movements do not affect blood distribution in the body. However, a subsequent experiment in conscious animals showed that few RVLM neurons respond to small-amplitude movements. This study tested the hypothesis that RVLM neurons in conscious animals respond to signals from the vestibular otolith organs elicited by large-amplitude static tilts. The activity of approximately one-third of RVLM neurons whose firing rate was related to the cardiac cycle, and thus likely received baroreceptor inputs, was modulated by vestibular inputs elicited by 40° head-up tilts in conscious cats, but not during 10° sinusoidal rotations in the pitch plane that affected the activity of neurons in brain regions providing inputs to the RVLM. These data suggest the existence of brain circuitry that suppresses vestibular influences on the activity of RVLM neurons and the sympathetic nervous system unless these inputs are physiologically warranted. We also determined that RVLM neurons failed to respond to a light cue signaling the movement, suggesting that feedforward cardiovascular responses do not occur before passive movements that require cardiovascular adjustments.

Metachronous Sudden Sensorineural Hearing Loss: Patient Characteristics and Treatment Outcomes.

OBJECTIVES: Idiopathic sudden sensorineural hearing loss (ISSNHL) is a distressing condition that can significantly affect quality of life. Unilateral ISSNHL, occurring first in 1 ear and then the contralateral ear at a separate and discrete time, is a rare presentation that we refer to as metachronous ISSNHL. Our objective was to characterize the presentation of metachronous ISSNHL and report on management and hearing outcomes. STUDY DESIGN: Retrospective case series. SETTING: Otology clinic at an academic tertiary referral center. SUBJECTS AND METHODS: Patients ≥18 years old presenting with metachronous ISSNHL between April 2008 to November 2017 were identified through review of the clinic electronic medical record. Metachronous ISSNHL was defined as unilateral ISSNHL occurring in temporally discrete episodes (>6 months apart) affecting both ears. Patients with identifiable causes for sudden hearing loss were excluded. Patient demographics, comorbidities, management, and audiologic outcomes were recorded. RESULTS: Eleven patients with metachronous ISSNHL were identified out of 558 patients with ISSNHL. In patients with metachronous ISSNHL, the mean ± standard deviation age at the time of ISSNHL in the second ear was 58.6 ± 15.2 years (range, 31-77 years). The mean interval between episodes was 9.6 ± 7.5 years (range, 1-22 years). Patients were treated with systemic and intratympanic steroids with variable hearing recovery; 5 patients with resultant bilateral severe to profound hearing loss underwent successful cochlear implantation. CONCLUSION: Metachronous ISSNHL is uncommon. Treatment is similar to ISSNHL, and cochlear implantation can successfully restore hearing in individuals who do not experience recovery.

Comparison of Spontaneous Temporal Bone Cerebrospinal Fluid Leaks From the Middle and Posterior Fossa.

OBJECTIVES: To compare patients surgically managed for spontaneous cerebrospinal fluid (CSF) leaks of the temporal bone arising from the middle cranial fossa (MCF) and posterior cranial fossa (PCF) and to describe the surgical management of posterior fossa CSF leaks. STUDY DESIGN: Retrospective case review. SETTING: Academic tertiary center. PATIENTS: Adult patients presenting with spontaneous temporal bone CSF leaks undergoing operative repair between January 2010 and August 2018. Patients with a history of trauma, previous mastoid surgery, and iatrogenic CSF leaks were excluded. INTERVENTION: Transmastoid or MCF CSF leak repair. MAIN OUTCOME MEASURES: Patient demographics, body mass index (BMI), comorbidities, presenting features, and lumbar puncture opening pressures were compared between groups and the management of the PCF CSF leaks described. RESULTS: Forty-six patients (26 women, 20 men) were included. The mean age at the time of repair was 58.0 ±â€Š12.9 years (±SD). The origin of the CSF leak was from the PCF in three patients and MCF in 43 patients. All three patients with PCF leaks presented with an acute history of meningitis compared with only seven (16%) in the MCF group. This difference was statistically significant (p = 0.01, Fisher's exact test). There were no statistically significant differences in age, sex, BMI, or lumbar puncture opening pressures. The PCF leaks were repaired using a transmastoid approach with multilayer closure of the bony defect and fat graft obliteration of the mastoid. CONCLUSIONS: Spontaneous CSF leaks arising from the PCF are rare and may present more commonly with meningitis. Identification requires careful review of imaging.

Responses of Neurons in the Medullary Lateral Tegmental Field and Nucleus Tractus Solitarius to Vestibular Stimuli in Conscious Felines.

Considerable evidence shows that the vestibular system contributes to adjusting sympathetic nervous system activity to maintain adequate blood pressure during movement and changes in posture. However, only a few prior experiments entailed recordings in conscious animals from brainstem neurons presumed to convey baroreceptor and vestibular inputs to neurons in the rostral ventrolateral medulla (RVLM) that provide inputs to sympathetic preganglionic neurons in the spinal cord. In this study, recordings were made in conscious felines from neurons in the medullary lateral tegmental field (LTF) and nucleus tractus solitarius (NTS) identified as regulating sympathetic nervous system activity by exhibiting changes in firing rate related to the cardiac cycle, or cardiac-related activity (CRA). Approximately 38% of LTF and NTS neurons responded to static 40° head up tilts with a change in firing rate (increase for 60% of the neurons, decrease for 40%) of ~50%. However, few of these neurons responded to 10° sinusoidal rotations in the pitch plane, in contrast to prior findings in decerebrate animals that the firing rates of both NTS and LTF neurons are modulated by small-amplitude body rotations. Thus, as previously demonstrated for RVLM neurons, in conscious animals NTS and LTF neurons only respond to large rotations that lead to changes in sympathetic nervous system activity. The similar responses to head-up rotations of LTF and NTS neurons with those documented for RVLM neurons suggest that LTF and NTS neurons are components of the vestibulo-sympathetic reflex pathway. However, a difference between NTS/LTF and RVLM neurons was variability in CRA over time. This variability was significantly greater for RVLM neurons, raising the hypothesis that the responsiveness of these neurons to baroreceptor input is adjusted based on the animal's vigilance and alertness.

Candida albicans biofilm development is governed by cooperative attachment and adhesion maintenance proteins.

The opportunistic fungal pathogen Candida albicans is capable of adhering to the oral mucosa despite forces created by salivary flow. Although many fungal adhesion proteins have been identified, less is known about the temporal development of cell adhesion and biofilm growth in a flow environment. In this study, we use a flow system with real-time imaging of C. albicans cells as they adhere and grow. Rates of cell attachment and dispersion of C. albicans knockout strains of putative adhesins, transcription factors, and deletions with a hyperfilamentous phenotype were quantified during 18 h of biofilm development. Cell adhesion under flow is a multi-phase process initiated with cell rolling, then an initial firm attachment to the substrate occurs. After attachment, cells enter a growth phase where cells either commit to adherence or disperse. C. albicans Δeap1, Δhwp2, Δhyr1, and Δihd1 cells had significantly reduced initial attachment and subsequent adhesion, while Δals1/Δals3 had no change in initial attachment but reduced adhesion maintenance. WT cells had increased adhesion during the late growth phase when hyphae were more highly expressed. Hyperfilamentous strains had 10-fold higher total biofilm growth, a result of significantly reduced detachment rates, showing that hyphal morphogenesis is important for adhesion maintenance in the developing biofilm. The rate of C. albicans biomass dispersion was most important for determining the density of the mature biomass. Adhesion maintenance was mediated in part by Ywp1, a protein previously thought to regulate dispersion, thus it functions as an adhesion maintenance protein in C. albicans.

Filamentous Non-albicans Candida Species Adhere to Candida albicans and Benefit From Dual Biofilm Growth.

Non-albicans Candida species (NACS) are often isolated along with Candida albicans in cases of oropharyngeal candidiasis. C. albicans readily forms biofilms in conjunction with other oral microbiota including both bacteria and yeast. Adhesion between species is important to the establishment of these mixed biofilms, but interactions between C. albicans and many NACS are not well-characterized. We adapted a real-time flow biofilm model to study adhesion interactions and biofilm establishment in C. albicans and NACS in mono- and co-culture. Out of five NACS studied, only the filamenting species C. tropicalis and C. dubliniensis were capable of adhesion with C. albicans, while C. parapsilosis, C. lusitaniae, and C. krusei were not. Over the early phase (0-4 h) of biofilm development, both mono- and co-culture followed similar kinetics of attachment and detachment events, indicating that initial biofilm formation is not influenced by inter-species interactions. However, the NACS showed a preference for inter-species cell-cell interactions with C. albicans, and at later time points (5-11 h) we found that dual-species interactions impacted biofilm surface coverage. Dual-species biofilms of C. tropicalis and C. albicans grew more slowly than C. albicans alone, but achieved higher surface coverage than C. tropicalis alone. Biofilms of C. dubliniensis with C. albicans increased surface coverage more rapidly than either species alone. We conclude that dual culture biofilm of C. albicans with C. tropicalis or C. dubliniensis offers a growth advantage for both NACS. Furthermore, the growth and maintenance, but not initial establishment, of dual-species biofilms is likely facilitated by interspecies cell-cell adherence.