Adult Ear Research Articles

Reflection function, reflectance, and area function measurements in ears of children and adults.

The main experiment concerned time-domain measurements of the acoustical reflection function (RF) of the human ear in adults and children (aged 5 to 8 years) using a probe inserted into the ear canal. This RF was used to calculate the area function of the ear canal versus distance along its centerline. Acoustical reflectance was calculated in the frequency domain from the RF, as was the difference in sound pressure level near the tympanic membrane relative to the probe tip. Group responses in area function, total ear-canal length, absorbance and group delay, and admittance magnitude and phase were analyzed based on sex, ear, and age. Responses were compared between children/adults and younger/older adults relative to age 50 years. Ear and sex were never significant. Significant differences were observed in children compared to adults in the area function, absorbance and group delay, and admittance magnitude and phase (0.25-4 kHz). Group delay differed between younger and older adults. A second experiment assessed level dependence of responses to better understand limitations in probe performance observed in the main experiment. These results show the utility of time-domain measurements of the area function and derived reflectance to understand sound-transmission differences across age at frequencies important to middle-ear function.

Extended scope audiology clinic – a review of its outcomes and re-presentation to the ear nose and throat service

Objective To evaluate the role of Extended Scope (ES) audiologists in managing adult Ear Nose and Throat (ENT)/Otology waitlists and analyse patient re-presentation rate to the ENT service within 12 months of being discharged from the clinic. Design A retrospective cohort study assessing the efficacy of ES audiologists, measuring the discharge rate from ENT waitlists, the rate of escalation to ENT care, and the rate and reasons for any re-presentations to care. Study sample 394 adult patients. Results Of the referred patients, 95% (n = 374) were deemed suitable for ES care. Of these, 75% were discharged without further ENT intervention, 20% required escalation to ENT, and 5% were returned to the waitlist. Only one patient re-presented for care within 12 months. The inclusion of patients with CHL/MHL and vestibular symptoms marked an expansion from our previous work. The re-presentation rate was notably lower compared to other allied health ES clinics. Conclusion The ES Audiology clinic demonstrates a high discharge rate with a low incidence of patient re-presentation, highlighting the ES audiologists’ efficiency in managing non-urgent ENT cases. The study supports the continued use and expansion of ES roles to ensuring timely and quality care for patients on ENT waitlists.

Targeted genome editing restores auditory function in adult mice with progressive hearing loss caused by a human microRNA mutation.

Mutations in microRNA-96 (MIR96) cause autosomal dominant deafness-50 (DFNA50), a form of delayed-onset hearing loss. Genome editing has shown efficacy in hearing recovery through intervention in neonatal mice, yet editing in the adult inner ear is necessary for clinical applications, which has not been done. Here, we developed a genome editing therapy for the MIR96 mutation 14C>A by screening different CRISPR systems and optimizing Cas9 expression and the sgRNA scaffold for efficient and specific mutation editing. AAV delivery of the KKH variant of Staphylococcus aureus Cas9 (SaCas9-KKH) and sgRNA to the cochleae of presymptomatic (3-week-old) and symptomatic (6-week-old) adult Mir9614C>A/+ mutant mice improved hearing long term, with efficacy increased by injection at a younger age. Adult inner ear delivery resulted in transient Cas9 expression without evidence of AAV genomic integration, indicating the good safety profile of our in vivo genome editing strategy. We developed a dual-AAV system, including an AAV-sgmiR96-master carrying sgRNAs against all known human MIR96 mutations. Because mouse and human MIR96 sequences share 100% homology, our approach and sgRNA selection for efficient and specific hair cell editing for long-term hearing recovery lay the foundation for the development of treatment for patients with DFNA50 caused by MIR96 mutations.

Relationship Between Serum Brain-Derived Neurotrophic Factor and Neurotrophin-3 Levels and Hearing Thresholds in Patients With Age-Related Hearing Loss.

Age-related hearing loss (ARHL) is a general term used to describe the sensorineural type of hearing loss occurring in both ears in older adults. Neurotrophins are the most promising candidates for supporting the auditory nerve by increasing neuronal survival. This study aimed to help elucidate the pathophysiology of ARHL by determining whether any relationship exists between brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) levels in serum samples from patients diagnosed with ARHL. Seventy-seven individuals, a study group of 41 patients diagnosed with ARHL, and a control group of 36 participants without hearing loss were evaluated. Serum samples were collected and used to measure serum BDNF and NT-3 levels with the new Nepenthe enzyme-linked immunosorbent assay method. Median pure-tone average results in the 2000, 4000, and 6000 Hz ranges were 52.5 (44.3-67.3) dB HL in the ARHL group and 13.5 (11.1-17.1) dB HL in the control group. The difference was statistically significant (p = .001). Although NT-3 and BDNF levels were both lower in ARHL patients than in participants without hearing loss, only the BDNF levels were significantly (p = .002) lower. Mean left and right ear word recognition scores were also lower in ARHL patients than in control groups. The ARHL group was further divided into two subgroups based on word recognition scores to evaluate significant differences in BDNF and NT-3 levels. No statistically significant difference was observed in BDNF and NT-3 levels between these subgroups. However, there was a significant difference in word recognition scores. Low BDNF levels in the ARHL group suggest that BDNF may play a role in the pathogenesis of ARHL. Patients with low (ARHL1) and high (ARHL2) word recognition scores were compared for the first time in the literature in terms of BDNF and NT-3 levels. However, the results were not statistically significant. This article is a preliminary study and was written to provide guidance for our next comprehensive project.

Temporal Swelling Following Cochlear Implantation: Frequency, Treatment, and Outcomes.

To investigate the frequency, treatment, and outcomes of postoperative delayed-onset swelling around cochlear implants. Retrospective, observational, nonrandomized group study. Academic medical center. Among 354 patients (516 ears) who underwent cochlear implantation (CI) at our hospital between May 2009 and October 2022, 329 (472 ears: 138 children [246 ears] and 191 adults [226 ears]) with a follow-up period of >3 months were included. Physical examination and computed tomography of the head were performed. In total, 5.5% (26/472 ears) had a history of delayed-onset swelling around the implant. This complication occurred in 9.8% (24/246 ears) of children and 0.9% (2/226 ears) of adults. The mean time to onset of swelling was 50 (range, 5.5-147) months following CI. In 60% (21/35) of the cases, the cause was unknown, whereas in 25.7% (9/35) and 11.5% (4/35) of cases, it was head trauma and acute inflammation, respectively. Conservative treatment (observation, antibiotics, and/or strong magnetic compression) was adapted in 91.4% (32/35) of cases. After conservative treatment, revision CI surgery was performed in one ear. Additionally, recurrent swelling was observed in 23.1% (6/26 ears) of swelling cases. The results suggest that delayed-onset swelling around implants occurs more frequently in children than in adults because of the higher incidence rates of head trauma and acute otitis media in children. In most cases, conservative treatment was adequate; however, careful follow-up is necessary. Our findings can serve as a reference for optimizing care and intervention options after CI.

Bioengineering Full-scale auricles using 3D-printed external scaffolds and decellularized cartilage xenograft

Reconstruction of the human auricle remains a formidable challenge for plastic surgeons. Autologous costal cartilage grafts and alloplastic implants are technically challenging, and aesthetic and/or tactile outcomes are frequently suboptimal. Using a small animal “bioreactor”, we have bioengineered full-scale ears utilizing decellularized cartilage xenograft placed within a 3D-printed external auricular scaffold that mimics the size, shape, and biomechanical properties of the native human auricle. The full-scale polylactic acid ear scaffolds were 3D-printed based upon data acquired from 3D photogrammetry of an adult ear. Ovine costal cartilage was processed either through mincing (1 mm3) or zesting (< 0.5 mm3), and then fully decellularized and sterilized. At explantation, both the minced and zested neoears maintained the size and contour complexities of the scaffold topography with steady tissue ingrowth through 6 months in vivo. A mild inflammatory infiltrate at 3 months was replaced by homogenous fibrovascular tissue ingrowth enveloping individual cartilage pieces at 6 months. All ear constructs were pliable, and the elasticity was confirmed by biomechanical analysis. Longer-term studies of the neoears with faster degrading biomaterials will be warranted for future clinical application. Statement of significanceAccurate reconstruction of the human auricle has always been a formidable challenge to plastic surgeons. In this article, we have bioengineered full-scale ears utilizing decellularized cartilage xenograft placed within a 3D-printed external auricular scaffold that mimic the size, shape, and biomechanical properties of the native human auricle. Longer-term studies of the neoears with faster degrading biomaterials will be warranted for future clinical application.

Comparing Hearing Loss in Children with Adults Living with Sickle Cell Disease and Sickle Cell Traits.

Hearing loss is a neurological sequelae associated with sickle cell disease (SCD) and probably sickle cell trait (SCT) in children and adults but remains understudied. This study aimed to compare the hearing impairment among children and adults living with SCD or SCT. A comparative cross-sectional study conducted in four departments with SCD outpatient clinic in a tertiary hospital in Nigeria. Participants with Sickle cell disease (HbSS) and Sickle cell trait (HbAS) (cohort) and HbAA (control) had comprehensive ear and hearing assessments for sensorineural hearing loss. Audiometric results were categorized according to WHO classifications and data analysed with Statistical Analysis System (SAS 9.4). A total of 212 participants (106 cohort and control, respectively), aged 6 months to 55 years, were enrolled. Of these, 35% of children with SCD and 25% with SCT had hearing impairment, while 30% of adults with SCD, 36.1% with SCT, and 11% with HbAA had hearing impairment. There was asymmetry in the hearing impairment, with the left ear more affected in children and the right ear in adults. The odds ratio (OD) of hearing impairment was higher in HbSS (2.48 (95% confidence interval (CI):1.51-4.14); P = 0.0004) and HbAS (2.28 (95% CI: 1.1-4.58); P = 0.02) participants compared with HbAA but was not statistically significant when adjusted for frequency of hospitalization, crises, blood transfusion and routine drugs in HbAS (P = 0.49) unlike HbSS (P = 0.03). The prevalence of hearing loss among children and adults with SCD is higher than in those with HbA genotype. The frequency of hospitalization, crises, blood transfusion and taking routine drugs may influence hearing impairment in SCT but may not in SCD.

Spectacle Frame: An Unusual Aural Foreign Body in an Adult Patient

Foreign body in the ear in adults mostly consists of animate objects. However, sometimes isolated cases of weird objects are reported in literature. A case is being reported where the patient had used a piece of spectacle frame for scratching the ear to relieve itching and it got lodged in the medial end of the external auditory canal.

Investigation of Age and Gender Effects on the Middle Ear With Wideband Tympanometry in Adults.

Several studies have reported the effects of age and gender on the middle ear of adults using wideband acoustic immittance (WAI) that measures middle ear function over a range of frequencies rather than the traditional measures with a single probe tone. Although these results are often based on WAI measurements under ambient pressure, using WAI under varying ear-canal pressures (wideband tympanometry [WBT]) may be able to provide more information about age and gender effects on the middle ear. The aim of this study is to examine the effects of age and gender on the middle ear with WBT in three different age groups consisting of young, middle-aged, and older adults. A total of 95 adults with normal middle ear function were assessed, including 32 young adults (16 men, 16 women, aged 20 to 39 years), 31 middle-aged adults (15 men, 16 women, aged 41 to 60 years), and 32 older adults (16 men, 16 women, aged 65 to 82 years). WBT measurements were performed from 226 to 8000 Hz using Interacoustics Titan. Energy absorbance data at tympanometric peak pressure (EA TPP ) and ambient pressure (EA AP ) at 1/3 octave frequencies, and resonance frequency (RF) data were analyzed according to age and gender variables. Analysis results showed that the mean EA TPP was significantly higher from 500 to 794 Hz and at 5040 and 6350 Hz, and significantly lower from 1587 to 3175 Hz in older adults compared with young adults. The mean EA AP was significantly lower from 1587 to 3175 Hz, and significantly higher at 5040 and 6350 Hz in older adults compared with young adults. There was no significant difference in the mean EA TPP and mean EA AP at any frequency between young and middle-aged adults, and middle-aged and older adults. RF was significantly lower in older adults compared with young adults. In all age groups, men had higher mean EA TPP and mean EA AP at lower frequencies and lower mean EA TPP and mean EA AP at higher frequencies than women. Men had slightly lower RF than women in young and older adults, while men had significantly lower RF than women in middle-aged adults. This study demonstrated that there are possible age and gender effects on the middle ear that may affect the mechanical transmission of sound. It may be useful to consider this finding in clinical evaluation in adults of different ages and genders, and to establish age- and gender-specific WBT norms in the adult population.

A reference for ear-canal absorbance based on semi-anechoic waveguides.

Wideband acoustic immittance (WAI), in particular, ear-canal absorbance, is a useful clinical tool for assessing the middle-ear status and diagnosing conductive hearing disorders. However, little evidence documents the measurement accuracy of WAI in human ears, and, because its clinical adoption is still in its infancy, no international standards exist to define appropriate requirements for commercial instrumentation. A challenge from a standardization point of view is the lack of an absorbance reference, i.e., an acoustic load similar to the adult ear canal with a known absorbance. This paper explores various approaches to providing such an acoustic load to quantify WAI measurement accuracy. The approaches considered here include standardized and inexpensive occluded-ear simulators, and a family of semi-anechoic waveguides with different step discontinuities in cross-sectional area. These semi-anechoic waveguides could be included in a future WAI standard. In addition, a means of monitoring the stability of WAI calibrations over time is proposed, utilizing a single inexpensive occluded-ear simulator.

Evaluation of an Investigational Hearing Screening Device (HeLe) to Demonstrate Acoustic Brainstem Response among Normal-hearing Adults.

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

Whole mount of adult ear skin as a model to study vascular malformations.

Genetic analysis in human patients has linked mutations in PIK3CA, the catalytic subunit of PI-3'Kinase, to sporadic incidences of vascular malformations. We have developed a mouse model with inducible and endothelial-specific expression of PIK3CAH1047R , resulting in the development of vascular malformations. Systemic induction of this mutation in adult mice results in rapid lethality, limiting our ability to track and study these lesions; therefore, we developed a topical and local induction protocol using the active metabolite of tamoxifen, 4OH-T, on the ear skin of adults. This approach allows us to successfully model the human disease in a mature and established vascular bed and track the development of vascular malformations. To validate the utility of this model, we applied a topical rapamycin ointment, as rapamycin is therapeutically beneficial to patients in clinical trials. We found that the induced ear lesions showed significant attenuation after treatment, which was easily quantified. These data collectively provide evidence of a new model to study vascular malformations in adult tissues, which should be particularly useful in environments lacking specialized small-animal imaging facilities.

Delivery of gene therapy through a cerebrospinal fluid conduit to rescue hearing in adult mice.

Inner ear gene therapy has recently effectively restored hearing in neonatal mice, but it is complicated in adulthood by the structural inaccessibility of the cochlea, which is embedded within the temporal bone. Alternative delivery routes may advance auditory research and also prove useful when translated to humans with progressive genetic-mediated hearing loss. Cerebrospinal fluid flow via the glymphatic system is emerging as a new approach for brain-wide drug delivery in rodents as well as humans. The cerebrospinal fluid and the fluid of the inner ear are connected via a bony channel called the cochlear aqueduct, but previous studies have not explored the possibility of delivering gene therapy via the cerebrospinal fluid to restore hearing in adult deaf mice. Here, we showed that the cochlear aqueduct in mice exhibits lymphatic-like characteristics. In vivo time-lapse magnetic resonance imaging, computed tomography, and optical fluorescence microscopy showed that large-particle tracers injected into the cerebrospinal fluid reached the inner ear by dispersive transport via the cochlear aqueduct in adult mice. A single intracisternal injection of adeno-associated virus carrying solute carrier family 17, member 8 (Slc17A8), which encodes vesicular glutamate transporter-3 (VGLUT3), rescued hearing in adult deaf Slc17A8-/- mice by restoring VGLUT3 protein expression in inner hair cells, with minimal ectopic expression in the brain and none in the liver. Our findings demonstrate that cerebrospinal fluid transport comprises an accessible route for gene delivery to the adult inner ear and may represent an important step toward using gene therapy to restore hearing in humans.

The Impact of Daily Processor Use on Adult Cochlear Implant Outcomes: Reexamining the Roles of Duration of Deafness and Age at Implantation.

To quantify the roles and relationships between age at implantation, duration of deafness (DoD), and daily processor use via data logging on speech recognition outcomes for postlingually deafened adults with cochlear implants. Retrospective case review. Cochlear implant (CI) program at a tertiary medical center. Six-hundred fourteen postlingually deafened adult ears with CIs (mean age, 63 yr; 44% female) were included. A stepwise multiple regression analysis was completed to investigate the combined effects of age, DoD, and daily processor use on CI-aided speech recognition (Consonant-Nucleus-Consonant monosyllables and AzBio sentences). Results indicated that only daily processor use was significantly related to Consonant-Nucleus-Consonant word scores ( R2 = 0.194, p < 0.001) and AzBio in quiet scores ( R2 = 0.198, p < 0.001), whereas neither age nor DoD was significantly related. In addition, there was no significant relationship between daily processor use, age at implantation, or DoD and AzBio sentences in noise ( R2 = 0.026, p = 0.005). Considering the clinical factors of age at implantation, DoD, and daily processor use, only daily processor use significantly predicted the ~20% of variance in postoperative outcomes (CI-aided speech recognition) accounted for by these clinical factors.

A single-cell level comparison of human inner ear organoids with the human cochlea and vestibular organs

Inner ear disorders are among the most common congenital abnormalities; however, current tissue culture models lack the cell type diversity to study these disorders and normal otic development. Here, we demonstrate the robustness of human pluripotent stem cell-derived inner ear organoids (IEOs) and evaluate cell type heterogeneity by single-cell transcriptomics. To validate our findings, we construct a single-cell atlas of human fetal and adult inner ear tissue. Our study identifies various cell types in the IEOs including periotic mesenchyme, type I and type II vestibular hair cells, and developing vestibular and cochlear epithelium. Many genes linked to congenital inner ear dysfunction are confirmed to be expressed in these cell types. Additional cell-cell communication analysis within IEOs and fetal tissue highlights the role of endothelial cells on the developing sensory epithelium. These findings provide insights into this organoid model and its potential applications in studying inner ear development and disorders.

Rescue of auditory function by a single administration of AAV-TMPRSS3 gene therapy in aged mice of human recessive deafness DFNB8

Patients with mutations in the TMPRSS3 gene suffer from recessive deafness DFNB8/DFNB10. For these patients, cochlear implantation is the only treatment option. Poor cochlear implantation outcomes are seen in some patients. To develop biological treatment for TMPRSS3 patients, we generated a knockin mouse model with a frequent human DFNB8 TMPRSS3 mutation. The Tmprss3A306T/A306T homozygous mice display delayed onset progressive hearing loss similar to human DFNB8 patients. Using AAV2 as a vector to carry a human TMPRSS3 gene, AAV2-hTMPRSS3 injection in the adult knockin mouse inner ear results in TMPRSS3 expression in the hair cells and the spiral ganglion neurons. A single AAV2-hTMPRSS3 injection in Tmprss3A306T/A306T mice of an average age of 18.5months leads to sustained rescue of the auditory function to a level similar to wild-type mice. AAV2-hTMPRSS3 delivery rescues the hair cells and the spiral ganglions neurons. This study demonstrates successful gene therapy in an aged mouse model of human genetic deafness. It lays the foundation to develop AAV2-hTMPRSS3 gene therapy to treat DFNB8 patients, as a standalone therapy or in combination with cochlear implantation.

Light at the end of the tunnel of Corti

Light at the end of the tunnel of Corti

Measurements of ear-canal geometry from high-resolution CT scans of human adult ears

Description of the ear canal’s geometry is essential for describing peripheral sound flow, yet physical measurements of the canal’s geometry are lacking and recent measurements suggest that older-adult-canal areas are systematically larger than previously assumed. Methods to measure ear-canal geometry from multi-planar reconstructions of high-resolution CT images were developed and applied to 66 ears from 47 subjects, ages 18–90 years. The canal’s termination, central axis, entrance, and first bend were identified based on objective definitions, and the canal’s cross-sectional area was measured along its canal’s central axis in 1–2 mm increments. In general, left and right ears from a given subject were far more similar than measurements across subjects, where areas varied by factors of 2–3 at many locations. The canal areas varied systematically with age cohort at the first-bend location, where canal-based measurement probes likely sit; young adults (18–30 years) had an average area of 44mm2 whereas older adults (61–90 years) had a significantly larger average area of 69mm2. Across all subjects ages 18–90, measured means ± standard deviations included: canals termination area at the tympanic annulus 56±8mm2; area at the canal’s first bend 53±18mm2; area at the canal’s entrance 97±24mm2; and canal length 31.4±3.1mm2.

Uncommon congenital swellings around external ear in adults

Congenital cyst around external ear appearing in adulthood is rare condition. Such lesions arising around the external auditory canal that requires surgical excision are uncommon and their clinical and surgical management is often difficult because these anomalies have variable relationship with facial nerve. In this study, we investigated characteristics of congenital cysts of the external ear by analyzing their clinical and histo-pathological features. Here we described 3 unique cases with localization of an epithelial cyst, type 1 branchial cleft cyst and epidermal inclusion cyst in adults which are uncommon, congenital and rare.

Different For Boys by Patrick Ness

Reviewed by: Different For Boys by Patrick Ness Sarah Sahn Ness, Patrick Different For Boys; illus. by Tea Bendix. Walker, 2023 [104p] Trade ed. ISBN 9781536228892 $18.99 Reviewed from digital galleys R* Gr. 10-12 What does it mean to lose your virginity? Is it when you ______? Or ______? Such questions preoccupy Ant Stevenson, because he’s done everything that would qualify, but he still feels like a virgin—maybe because Charlie has made it clear that fooling around together doesn’t make them gay. They’ve been sleeping together for almost a year, since Charlie spent Christmas with Ant’s family to escape his mom’s drunkenness, but while they can ____, kissing is off the table, and at school Charlie will go right back to his homophobic bullying of their classmate Jack. This spare, affecting novella takes place over the first week of eleventh grade, zeroing in on the dynamics between Ant, Charlie, Jack, and Josh, who just returned after having moved away seven years earlier. Josh encourages Ant to try out for the football team with him, which makes Charlie jealous at the same time he’s threatened by Ant’s desire for greater intimacy. Ant is forced to reckon with the disconnect between the Charlie he knows behind closed doors and the Charlie who’s only become a bigger bully to Jack since sleeping with Ant. Ant’s first-person narration moves between the present day, his history with Charlie and Jack, and his reflections on love, sex, and friendship with appealing raw-edged frankness and humor, complemented by Tea Bendix’s sketch and collage artwork. Black boxes hide swearing and explicit sexual content, which invites scathing comment from Ant—“we’re too young to read about the stuff we actually do”—skewering adult preoccupations with vulgarity as he also ponders what can and can’t be spoken, and what truths are appropriate for adult eyes and ears. “Parents say they want to know the truth . . . but they never really mean it,” he tells Jack; likewise, some moments may belong behind black boxes because he chooses to keep them private, like losing his virginity, which Ant decides is something he gets to define for himself. Ness takes on the often under-explored social dynamics among teenage boys with nuance and subtlety that will leave readers thinking long after they turn the final page. Copyright © 2023 The Board of Trustees of the University of Illinois