Inner ear delivery: Challenges and opportunities Szeto, Betsy; Chiang, Harry; Valentini, Chris ...
Laryngoscope investigative otolaryngology,
February 2020, Letnik:
5, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Objectives
The treatment of inner ear disorders remains challenging due to anatomic barriers intrinsic to the bony labyrinth. The purpose of this review is to highlight recent advances and strategies ...for overcoming these barriers and to discuss promising future avenues for investigation.
Data Sources
The databases used were PubMed, EMBASE, and Web of Science.
Results
Although some studies aimed to improve systemic delivery using nanoparticle systems, the majority enhanced local delivery using hydrogels, nanoparticles, and microneedles. Developments in direct intracochlear delivery include intracochlear injection and intracochlear implants.
Conclusions
In the absence of a systemic drug that targets only the inner ear, the best alternative is local delivery that harnesses a combination of new strategies to overcome anatomic barriers. The combination of microneedle technology with hydrogel and nanoparticle delivery is a promising area for future investigation.
Level of Evidence
NA
Microneedle-mediated intracochlear injection through the round window membrane (RWM) will facilitate intracochlear delivery, not affect hearing, and allow for full reconstitution of the RWM within 48 ...hours.
We have developed polymeric microneedles that allow for in vivo perforation of the guinea pig RWM and aspiration of perilymph for diagnostic analysis, with full reconstitution of the RWM within 48 to 72 hours. In this study, we investigate the ability of microneedles to deliver precise volumes of therapeutics into the cochlea and assess the subsequent consequences on hearing.
Volumes of 1.0, 2.5, or 5.0 μL of artificial perilymph were injected into the cochlea at a rate of 1 μL/min. Compound action potential (CAP) and distortion product otoacoustic emission were performed to assess for hearing loss (HL), and confocal microscopy was used to evaluate the RWM for residual scarring or inflammation. To evaluate the distribution of agents within the cochlea after microneedle-mediated injection, 1.0 μL of FM 1-43 FX was injected into the cochlea, followed by whole mount cochlear dissection and confocal microscopy.
Direct intracochlear injection of 1.0 μL of artificial perilymph in vivo , corresponding to about 20% of the scala tympani volume, was safe and did not result in HL. However, injection of 2.5 or 5.0 μL of artificial perilymph into the cochlea produced statistically significant high-frequency HL persisting 48 hours postperforation. Assessment of RWMs 48 hours after perforation revealed no inflammatory changes or residual scarring. FM 1-43 FX injection resulted in distribution of the agent predominantly in the basal and middle turns.
Microneedle-mediated intracochlear delivery of small volumes relative to the volume of the scala tympani is feasible, safe, and does not cause HL in guinea pigs; however, injection of large volumes induces high-frequency HL. Injection of small volumes of a fluorescent agent across the RWM resulted in significant distribution within the basal turn, less distribution in the middle turn, and almost none in the apical turn. Microneedle-mediated intracochlear injection, along with our previously developed intracochlear aspiration, opens the pathway for precision inner ear medicine.
Three studies examine the relation between power distance belief (PDB), the tendency to accept and expect inequalities in society; power, the control one has over valued resources; and charitable ...giving. Results suggest that the effect of PDB depends on the power held by the donor. In low-PDB contexts, people high (vs. low) in psychological power tend to be more self-focused (vs. other-focused), and this leads them to be less charitable. In high-PDB contexts, however, people high (vs. low) in psychological power tend to be more other-focused (vs. self-focused), and this leads them to be more charitable. The authors also explore several boundary conditions for these relationships and conclude with the implications of these findings.
Research suggests that cognitive busyness and need for closure have similar effects on a host of consumer phenomena, leading some researchers to treat the two variables as substitutes. We propose ...that cognitive busyness and need for closure have distinct roots and can have different effects. We examine their distinction in the context of cultural differences in the two types of socially desirable responding—impression management and self‐deceptive enhancement. Our findings indicate that high (vs. low) cognitive busyness weakens the relationship between culture and impression management, but not that between culture and self‐deceptive enhancement. In contrast, high (vs. low) need for closure strengthens both relationships. The article concludes with a discussion of the theoretical, methodological, and practical implications of these findings.
Traditional clinical approaches diagnose disorders of the nervous system using standardized observational criteria. Although aiming for homogeneity of symptoms, this method often results in highly ...heterogeneous disorders. A standing question thus is how to automatically stratify a given random cohort of the population, such that treatment can be better tailored to each cluster's symptoms, and severity of any given group forecasted to provide neuroprotective therapies. In this work we introduce new methods to automatically stratify a random cohort of the population composed of healthy controls of different ages and patients with different disorders of the nervous systems. Using a simple walking task and measuring micro-fluctuations in their biorhythmic motions, we combine non-linear causal network connectivity analyses in the temporal and frequency domains with stochastic mapping. The methods define a new type of internal motor timings. These are amenable to create personalized clinical interventions tailored to self-emerging clusters signaling fundamentally different types of gait pathologies. We frame our results using the principle of reafference and operationalize them using causal prediction, thus renovating the theory of internal models for the study of neuromotor control.
Hearing loss is a disabling condition that increases with age and has been linked to difficulties in walking and increased risk of falls. The purpose of this study is to investigate changes in gait ...parameters associated with hearing loss in a group of older adults aged 60 or greater. Custom-engineered footwear was used to collect spatiotemporal gait data in an outpatient clinical setting. Multivariable linear regression was used to determine the relationship between spatiotemporal gait parameters and high and low frequency hearing thresholds of the poorer hearing ear, the left ear, and the right ear, respectively, adjusting for age, sex, race/ethnicity, and the Dizziness Handicap Inventory-Screening version score. Worsening high and low frequency hearing thresholds were associated with increased variability in double support period. Effects persisted after adjusting for the effects of age and perceived vestibular disability and were greater for increases in hearing thresholds for the right ear compared to the left ear. These findings illustrate the importance of auditory feedback for balance and coordination and may suggest a right ear advantage for the influence of auditory feedback on gait.
Music enjoyment with cochlear implantation Prevoteau, Charlotte; Chen, Stephanie Y.; Lalwani, Anil K.
Auris, nasus, larynx,
October 2018, 2018-Oct, 2018-10-00, 20181001, Letnik:
45, Številka:
5
Journal Article
Recenzirano
Since the advent of cochlear implant (CI) surgery in the 1960s, there have been remarkable technological and surgical advances enabling excellent speech perception in quiet with many CI users able to ...use the telephone. However, many CI users struggle with music perception, particularly with the pitch-based and melodic elements of music. Yet remarkably, despite poor music perception, many CI users enjoy listening to music based on self-report questionnaires, and prospective studies have suggested a disassociation between music perception and enjoyment. Music enjoyment is arguably a more functional measure of one’s listening experience, and thus enhancing one’s listening experience is a worthy goal. Recent studies have shown that re-engineering music to reduce its complexity may enhance enjoyment in CI users and also delineate differences in musical preferences from normal hearing listeners.
With its comprehensive review of the sciences and the clinical practice of otolaryngology-head and neck surgery, this fourth edition will be invaluable for medical students, housestaff, physicians of ...all specialties, nurses, physician assistants, and ancillary health care personnel. The book has been designed to meet the clinician's need for an immediate refresher in the clinic as well as to serve as an accessible text for thorough review of the specialty for the boards. The concise presentation is ideally suited for rapid acquisition of information by the busy practitioner.
The elderly are at increased risk of both hearing loss (HL) and osteoporosis. Bone mineral density (BMD) has been putatively linked to HL. However, the roles of serum calcium concentrations and ...vitamin D status have yet to be elucidated.
The purpose of this study was to examine the relation between vitamin D status, parathyroid hormone (PTH), total calcium, BMD, and HL in a nationally representative sample of elderly adults.
Using the NHANES (2005–2010), audiometry and BMD data of 1123 participants aged ≥70 y were analyzed in a cross-sectional manner. HL was defined as pure tone averages >25 dB HL at 500, 1000, and 2000 Hz (low frequency); 500, 1000, 2000, and 4000 Hz (speech frequency); and 3000, 4000, 6000, and 8000 Hz (high frequency) in either ear. Multivariable logistic regression was used to examine the relation between HL and total 25-hydroxyvitamin D 25(OH)D, PTH, total calcium, and BMD, adjusting for covariates.
In multivariable analyses, total 25(OH)D < 20 ng/mL was found to be associated with greater odds of low-frequency HL (OR: 2.02; 95% CI: 1.28, 3.19) and speech-frequency HL (OR: 1.96; 95% CI: 1.12, 3.44). A 1-unit decrease in femoral neck BMD (OR: 4.55; 95% CI: 1.28, 16.67) and a 1-unit decrease in total spine BMD (OR: 6.25; 95% CI: 1.33, 33.33) were found to be associated with greater odds of low-frequency HL. Serum PTH and total calcium were not found to be associated with HL.
In the elderly, low vitamin D status was associated with low-frequency and speech-frequency HL. Low vitamin D status may be a potential risk factor for age-related HL.
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