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Purpose: The Minimum Speech Test Battery (MSTB) for adults was introduced in 1996 (Nilsson et al., 1996) and subsequently updated in 2011 (Advanced-Bionics et al., 2011). The MSTB has been widely used by clinicians as a guide for cochlear implant (CI) candidacy evaluations and to document post-operative speech recognition performance. Due to changes in candidacy over the past 10 years, a revision to the MSTB was needed., Method: In 2022, the Institute for Cochlear Implant Training (ICIT) recruited a panel of expert CI audiologists to update and revise the MSTB. This panel utilized a modified Delphi consensus process to revise the test battery and to improve its applicability considering recent changes in CI care., Results: This resulted in the MTSB-Version 3 (MSTB-3), which includes test protocols for identifying not only traditional CI candidates but also possible candidates for electric-acoustic stimulation and patients with single-sided deafness and asymmetric hearing loss. The MSTB-3 provides information that supplements the earlier versions of the MSTB, such as recommendations of when to refer patients for a CI, recommended patient-reported outcome measures, considerations regarding the use of cognitive screeners, and sample report templates for clinical documentation of pre- and post-operative care. Electronic versions of test stimuli, along with all the materials described above, will be available to clinicians via the ICIT website (https://www.cochlearimplanttraining.com)., Conclusion: The goal of the MSTB-3 is to be an evidence-based test battery that will facilitate a streamlined standard of care for adult CI candidates and recipients that will be widely used by CI clinicians.

Measuring seroprevalence over time is a valuable epidemiological tool for improving our understanding of COVID-19 immunity. Due to the large number of collections required for population surveillance as well as concerns about potential infection risk to the collectors, self-collection approaches are being increasingly pursued. To advance this methodology, we collected paired venous and capillary blood samples by routine phlebotomy and Tasso-SST device respectively from 26 participants and measured total immunoglobulin (Ig) and IgG antibodies to the SARS-CoV-2 receptor binding domain (RBD) by enzyme-linked immunosorbent assay (ELISA) on both specimens. Qualitatively, no discrepancies were noted in binary results between Tasso and venipuncture-derived plasma. Furthermore, in vaccinated participants, correlation between Tasso and venous total Ig and IgG specific antibody quantitative levels was high (Total Ig: Spearman ρ = 0.72, 95% CI (0.39,0.90); IgG: Spearman ρ = 0.85, 95% CI (0.54, 0.96)). Our results support the use of Tasso at-home collection devices for antibody testing., Competing Interests: Declaration of Competing Interest The authors declare no potential conflicts of interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

While trifluoromethylthiolation of aryl halides has been extensively explored, the current methods require complex and/or air-sensitive catalysts. Reported here is a method employing a bench-stable Ni(II) salt and an iridium photocatalyst that can mediate the trifluoromethylthiolation of a wide range of electronically diverse aryl and heteroaryl iodides, likely via a Ni(I)/Ni(III) catalytic cycle. The reaction has broad functional group tolerance and potential for application in medicinal chemistry, as demonstrated by a late-stage functionalization approach to access (racemic)-Monepantel.

Objective: This study examined the prevalence and factors associated with non-medical use of prescription stimulants to promote wakefulness. Participants: We surveyed 3,160 university students aged 18-35 between June 2016 and May 2017. Method: Participants reported whether they used prescription stimulants non-medically to stay awake and completed measures of anxiety and depressive symptoms, sleep quality, insomnia, daytime sleepiness, and attitudes toward non-medical prescription drug use. Univariate and multivariate regression models were used. Results: Prevalence of non-medical prescription stimulant use to promote wakefulness was 3.1%. The following factors remained significant in the multivariate model: alcohol, tobacco, and nicotine vapor use, attitude toward non-medical use of prescription medication, poor sleep quality, and daytime sleepiness. Conclusion: Poor sleep, substance use and more liberal attitudes to non-medical prescription drug use were associated with the misuse of stimulants to promote wakefulness. Prevention/intervention programs should promote sleep hygiene and highlight the risks of using prescription drugs non-medically.

Objectives/hypothesis: To identify barriers to and opportunities for referral among children who could be considered for cochlear implantation., Study Design: Retrospective review., Methods: Audiological and medical records were reviewed on all children who had diagnostic or hearing aid care through a statewide healthcare system over 5-year span to identify children who met newly established clinical cochlear implant (CI) referral criteria. Data were collected for 869 potential CI candidates regarding demographic, socio-economic, audiological, medical, and family factors that may influence referral. A binomial logistic regression was completed to investigate the potential contributions of these predictors toward referral for a CI evaluation., Results: Children who met traditional candidacy criteria of severe-to-profound bilateral hearing loss were referred at very high rates, while nontraditional candidates were referred less frequently. Factors influencing referral included race, age, insurance source, hearing thresholds, audiologist, physician, and family request., Conclusions: Results suggest that bilateral traditional candidates are being referred at high percentages; however, current practices and trends in pediatric cochlear implantation should be shared with families and providers to increase referral rates for nontraditional candidates.  LEVEL OF EVIDENCE: 3 Laryngoscope, 131:E2904-E2910, 2021., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc..)

Objectives/hypothesis: Speech recognition with a cochlear implant (CI) tends to be better for younger adults than older adults. However, older adults may take longer to reach asymptotic performance than younger adults. The present study aimed to characterize speech recognition as a function of age at implantation and listening experience for adult CI users., Study Design: Retrospective review., Methods: A retrospective review identified 352 adult CI recipients (387 ears) with at least 5 years of device listening experience. Speech recognition, as measured with consonant-nucleus-consonant (CNC) words in quiet and AzBio sentences in a 10-talker noise masker (10 dB signal-to-noise ratio), was reviewed at 1, 5, and 10 years postactivation., Results: Speech recognition was better in younger listeners, and performance was stable or continued to improve through 10 years of CI listening experience. There was no indication of differences in acclimatization as a function of age at implantation. For the better performing CI recipients, an effect of age at implantation was more apparent for sentence recognition in noise than for word recognition in quiet., Conclusions: Adult CI recipients across the age range examined here experience speech recognition benefit with a CI. However, older adults perform more poorly than young adults for speech recognition in quiet and noise, with similar age effects through 5 to 10 years of listening experience., Level of Evidence: 3 Laryngoscope, 131:2106-2111, 2021., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc..)

BACKGROUND Immune thrombocytopenic purpura (ITP) is an immune response that destroys platelets and increases the risk of bleeding, which can range from bruising to intracranial hemorrhage. ITP is a known complication of coronavirus disease 2019 (COVID-19). In the first studies of the BNT162b2 messenger RNA (mRNA) COVID-19 vaccine, there were no reports of ITP and the incidence of serious adverse events (AEs) was low overall. Here, we present a case of ITP as a complication of the BNT162b2 mRNA COVID-19 vaccine. CASE REPORT Three days after receiving a second dose of the BNT162b2 mRNA COVID-19 vaccine, a 39-year-old woman presented with a petechial rash on her trunk, legs, and arms, and fatigue and muscle aches. At the time of her hospital admission, her platelet count was 1000/µL. A peripheral smear showed profound thrombocytopenia. During the course of the patient's hospitalization, she was treated with 2 units of platelets, 2 infusions of i.v. immunoglobulin, and i.v. methylprednisolone. Her platelet count increased to 92 000/µL on the day of discharge and she was prescribed a tapered dose of oral prednisone. One day later, her rash had resolved and her platelet count was 243 000/µL. The patient recovered completely with no complications. CONCLUSIONS ITP should be considered a severe AE of the BNT162b2 mRNA COVID-19 vaccine. Knowing the early signs and symptoms of ITP will become increasingly important as more of the population receives this vaccine. Quick diagnosis and management are essential to avoid life-threatening bleeding.

Synthetic aromatic polymers are ubiquitous and indispensable to modern life, industry, and the global economy. The direct functionalization of these materials remains a considerable challenge on account of their unreactive aromatic C-H bonds and robust physical properties. Here, we demonstrate that homogeneous gold catalysis offers a mild, chemoselective, and practical approach to functionalize high-volume commodity aromatic polymers. Utilizing a gold-catalyzed intermolecular hydroarylation between a methyl ester functionalized alkyne, methyl propiolate, and nucleophilic arenes within polystyrene (PS) results in direct functionalization of phenyl rings with 1,2-substituted methyl acrylate functional groups. The reactivity and functionalization depend on the steric and electronic environment of the catalyst, counterion pairing, and method of activation. The reactivity is broad in scope, enabling the functionalization of arenes within commercial polysulfone (PSU) and waste polyethylene terephthalate (PET). These reactions open new opportunities to chemically transform aromatic polymers and modify their physical properties., Competing Interests: The authors declare the following competing financial interest(s): E.R.K., S.B.H., and J.D.A. are inventors on a patent application filed by the University of Southern Mississippi for the reactions described in this Communication., (© 2021 The Authors. Published by American Chemical Society.)

Objectives/hypothesis: Results from a prospective trial demonstrated better speech recognition for cochlear implant (CI) recipients implanted with a long lateral wall electrode array compared to subjects with a short array after 1 year of listening experience. As short array recipients may require an extended adaptation period, this study investigated whether differences in speech recognition continued through 4 years of CI use., Study Design: Long-term follow-up of a prospective randomized trial., Methods: Subjects were randomized to receive a MED-EL medium (24 mm) or standard (31.5 mm) array. Linear mixed models compared speech recognition between cohorts with word recognition in quiet and sentence recognition in noise at 1, 3, 6, 12, 24, and 48 months postactivation. Postoperative imaging and electric frequency filters were reviewed to assess the influence of frequency-to-place mismatch and angular separation between neighboring contacts, a metric associated with peripheral spectral selectivity., Results: Long (31.5 mm) array recipients demonstrated superior speech recognition out to 4 years postactivation. There was a significant effect of angular separation between contacts, with more closely spaced contacts associated with poorer speech recognition. There was no significant effect of mismatch, yet this may have been obscured by changes in frequency filters over time., Conclusions: Conventional MED-EL CI recipients implanted with 31.5-mm arrays experience better speech recognition than 24-mm array recipients, initially and with long-term listening experience. The benefit conferred by longer arrays in the present cohort can be partially attributed to more widely spaced electrode contacts, presumably a result of reduced channel interaction., Level of Evidence: 2 Laryngoscope, 131:892-897, 2021., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Adequate counseling from a pharmacist concerning anticoagulation therapy is crucial to the wellbeing of patients. No studies have fully examined the relationship between health literacy, patient-pharmacist communication, and anticoagulation control., Objective(s): To evaluate the relationship between health literacy and the perceived quality of patient-pharmacist communication among those receiving anticoagulation therapy., Methods: This investigation utilized structured telephone interviews to evaluate the relationship between health literacy and perceived quality patient-pharmacist communication among patients receiving anticoagulation therapy. Two hundred-twenty participants prescribed anticoagulation therapy continuously for at least 6-months served as the sample for this study. A previously validated one-item screening tool was utilized to estimate health literacy. The primary outcome was patients' perceptions regarding the general communication process with pharmacists, according to the Interpersonal Process of Care questionnaire., Results: Patients possessing inadequate health literacy reported significantly less favorable ratings for the perceived quality of pharmacist communication on the domains of general clarity (p = 0.02), responsiveness to patient concerns (p=<0.01), empowerment (p = 0.01), and consideration of patients' desire and ability to comply with recommendations (p = 0.01). Inadequate health literacy was found to be independently associated with poorer quality interpersonal processes of care across the domains of responsiveness to patient concerns and empowerment, (β = -0.207, P = <0.01 and β = -0.137, P = 0.04, respectively). Patients with inadequate health literacy did not differ significantly from those with adequate health literacy in terms of time within therapeutic INR range or percent of INRs in therapeutic range over the previous 12 months., Conclusions: Patients receiving anticoagulation therapy and possessing inadequate health literacy appear more likely to percieve poorer communication with pharmacists. This seems especially true as it relates to the percieved time and attention pharmacist devote to the communication encounter, as well as the sense pharmacists provide patients concerning their ability to influence health outcomes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives/hypothesis: To evaluate speech perception outcomes and hearing preservation after cochlear implantation in patients with Meniere's disease (MD)., Study Design: Retrospective chart review., Methods: Fifty-one adult patients, accounting for a total of 63 implants, with MD treated at a tertiary care center were included in the study. Patients with unaided preoperative air-conduction thresholds ≤80 dB at 250 Hz were included in hearing preservation analyses. The primary outcome measure was Consonant-Nucleus-Consonant (CNC) score. Hearing preservation was assessed as follows: 1) maintenance of functional hearing, defined as a postoperative unaided air-conduction threshold ≤80 dB at 250 Hz and 2) low-frequency pure-tone average (LFPTA) shift., Results: Speech perception scores improved significantly postimplantation; specifically, the CNC mean score was 9% preoperatively and increased to 57% by 1 year postoperatively (P < .001). Eighteen ears were included in hearing preservation analysis; the mean preoperative LFPTA was 65 dB (standard deviation [SD] = 10). The mean postoperative LFPTA at activation was 93 dB (SD = 21), and at 1 year was 102 dB (SD = 11). Twenty-seven percent of patients achieved short-term functional hearing preservation, whereas the longer-term outcomes were less favorable (11%)., Conclusions: Speech perception scores improve after implantation in patients with MD. Hearing preservation is possible in patients with MD, albeit at lower rates than reported non-MD populations. Our data suggest that there can be degradation in acoustic hearing over time., Level of Evidence: 4 Laryngoscope, 2019., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Homogeneous gold (Au) complexes have demonstrated tremendous utility in modern organic chemistry; however, their application for the synthesis of polymers remains rare. Herein, we demonstrate the first catalytic application of Au complexes toward the polycondensation of alkyne-containing comonomers and heteroarene nucleophiles. Polymerization occurs through successive intermolecular hydroarylation reactions to produce high molecular weight aromatic copolymers with 1,1-disubstituted alkene backbone linkages. Clear correlations between the rate and degree of polymerization (DP) were established based on catalyst structure and counterion pairing, thus enabling polymerization reactions that proceeded with remarkable efficiency, high reactivity, and exceptional DPs. The reactivity is broad in scope, enabling the copolymerization of highly functionalized aromatic and aliphatic monomers. These results highlight the untapped utility of Au catalysis in providing access to new macromolecular constructs., (© 2020 Wiley-VCH GmbH.)

Objective: To investigate the influence of cochlear implant (CI) use on subjective benefits in quality of life in cases of asymmetric hearing loss (AHL)., Study Design: Prospective clinical trial., Setting: Tertiary academic center., Subjects and Methods: Subjects included CI recipients with AHL (n = 20), defined as moderate-to-profound hearing loss in the affected ear and mild-to-moderate hearing loss in the contralateral ear. Quality of life was assessed with the Speech, Spatial, and Qualities of Hearing Scale (SSQ) pragmatic subscales, which assess binaural benefits. Subjective benefit on the pragmatic subscales was compared to word recognition in quiet and spatial hearing abilities (ie, masked sentence recognition and localization)., Results: Subjects demonstrated an early, significant improvement ( P < .01) in abilities with the CI as compared to preoperative abilities on the SSQ pragmatic subscales by the 1-month interval. Perceived abilities were either maintained or continued to improve over the study period. There were no significant correlations between results on the Speech in Quiet subscale and word recognition in quiet, the Speech in Speech Contexts subscale and masked sentence recognition, or the Localization subscale and sound field localization., Conclusions: CI recipients with AHL report a significant improvement in quality of life as measured by the SSQ pragmatic subscales over preoperative abilities. Reported improvements are observed as early as 1 month postactivation, which likely reflect the binaural benefits of listening with bimodal stimulation (CI and contralateral hearing aid). The SSQ pragmatic subscales may provide a more in-depth insight into CI recipient experience as compared to behavioral sound field measures alone.

Purpose The goal of this work was to evaluate the low-frequency hearing preservation of long electrode array cochlear implant (CI) recipients. Method Twenty-five participants presented with an unaided hearing threshold of ≤ 80 dB HL at 125 Hz pre-operatively in the ear to be implanted. Participants were implanted with a long (31.5-mm) electrode array. The unaided hearing threshold at 125 Hz was compared between the preoperative and postoperative intervals (i.e., initial CI activation, and 1, 3, 6, 9, and 12 months after activation). Results Eight participants maintained an unaided hearing threshold of ≤ 80 dB HL at 125 Hz postoperatively. The majority ( n = 5) demonstrated aidable low-frequency hearing at initial activation, whereas 3 other participants experienced an improvement in unaided low-frequency hearing thresholds at subsequent intervals. Conclusions CI recipients can retain residual hearing sensitivity with fully inserted long electrode arrays, and low-frequency hearing thresholds may improve during the postoperative period. Therefore, unaided hearing thresholds obtained within the initial weeks after surgery may not reflect later hearing sensitivity. Routine measurement of postoperative unaided hearing thresholds-even for patients who did not demonstrate aidable hearing thresholds initially after cochlear implantation-will identify CI recipients who may benefit from electric-acoustic stimulation. Supplemental Material https://doi.org/10.23641/asha.11356637.

A prospective clinical trial evaluated the effectiveness of cochlear implantation in adults with asymmetric hearing loss (AHL). Twenty subjects with mild-to-moderate hearing loss in the better ear and moderate-to-profound hearing loss in the poorer ear underwent cochlear implantation of the poorer hearing ear. Subjects were evaluated preoperatively and at 1, 3, 6, 9, and 12 months post-activation. Preoperative performance was evaluated unaided, with traditional hearing aids (HAs) or with a bone-conduction HA. Post-activation performance was evaluated with the cochlear implant (CI) alone or in combination with a contralateral HA (bimodal). Test measures included subjective benefit, word recognition, and spatial hearing (i.e., localization and masked sentence recognition). Significant subjective benefit was reported as early as the 1-month interval, indicating better performance with the CI compared with the preferred preoperative condition. Aided word recognition with the CI alone was significantly improved at the 1-month interval compared with preoperative performance with an HA and continued to improve through the 12-month interval. Subjects demonstrated early, significant improvements in the bimodal condition on the spatial hearing tasks compared with baseline preoperative performance tested unaided. The magnitude of the benefit was reduced for subjects with AHL when compared with published data on CI users with normal hearing in the contralateral ear; this finding may reflect significant differences in age at implantation and hearing sensitivity across cohorts.

Purpose Three experiments were carried out to evaluate the low-frequency pitch perception of adults with unilateral hearing loss who received a cochlear implant (CI). Method Participants were recruited from a cohort of CI users with unilateral hearing loss and normal hearing in the contralateral ear. First, low-frequency pitch perception was assessed for the 5 most apical electrodes at 1, 3, 6, and 12 months after CI activation using an adaptive pitch-matching task. Participants listened with a coding strategy that presents low-frequency temporal fine structure (TFS) and compared the pitch to that of an acoustic target presented to the normal hearing ear. Next, participants listened with an envelope-only, continuous interleaved sampling strategy. Pitch perception was compared between coding strategies to assess the influence of TFS cues on low-frequency pitch perception. Finally, participants completed a vocal pitch-matching task to corroborate the results obtained with the adaptive pitch-matching task. Results Pitch matches roughly corresponded to electrode center frequencies (CFs) in the CI map. Adaptive pitch matches exceeded the CF for the most apical electrode, an effect that was larger for continuous interleaved sampling than TFS. Vocal pitch matches were variable but correlated with the CF of the 3 most apical electrodes. There was no evidence that pitch matches changed between the 1- and 12-month intervals. Conclusions Relatively accurate and asymptotic pitch perception was observed at the 1-month interval, indicating either very rapid acclimatization or the provision of familiar place and rate cues. Early availability of appropriate pitch cues could have played a role in the early improvements in localization and masked speech recognition previously observed in this cohort. Supplemental Material https://doi.org/10.23641/asha.8862389.

Objective: Hearing preservation after cochlear implantation allows for fitting of acoustic and cochlear implant technologies in the same ear, known as Electric-Acoustic Stimulation (EAS). Cochlear implant recipients with EAS who experience an internal device failure face the additional risk of residual hearing loss during reimplantation. This report reviews the case of an EAS recipient with long-term hearing preservation and significant benefit who experienced a device failure and underwent cochlear reimplantation., Patient: Case study who presented with an internal device failure after nearly 10 years of hearing preservation and significant benefit with an EAS device., Intervention: Reimplantation with hearing preservation electrode array., Main Outcome Measures: Unaided residual hearing and aided speech perception with an EAS device using CNC words in quiet and CUNY sentences in noise., Results: Low-frequency thresholds were similar when comparing residual hearing pre- and post-reimplantation. The patient does not use the acoustic portion of the EAS device due to normal low-frequency hearing sensitivity-even after two cochlear implantation procedures. At the 3-month follow-up interval, the patient demonstrated restoration of aided speech perception performance with the EAS device., Conclusions: Hearing preservation can be maintained with long-term use of EAS devices. Those with preserved low-frequency hearing who experience a device failure may maintain hearing preservation after reimplantation. Normal low-frequency hearing thresholds were maintained in the present case, and the patient continued to listen with the EAS device without the acoustic component. EAS recipients may experience rapid restoration in speech perception after reimplantation in the presence of hearing preservation.

A FDA clinical trial was carried out to evaluate the potential benefit of cochlear implant (CI) use for adults with unilateral moderate-to-profound sensorineural hearing loss. Subjects were 20 adults with moderate-to-profound unilateral sensorineural hearing loss and normal or near-normal hearing on the other side. A MED-EL standard electrode was implanted in the impaired ear. Outcome measures included: (a) sound localization on the horizontal plane (11 positions, -90° to 90°), (b) word recognition in quiet with the CI alone, and (c) masked sentence recognition with the target at 0° and the masker at -90°, 0°, or 90°. This battery was completed preoperatively and at 1, 3, 6, 9, and 12 months after CI activation. Normative data were also collected for 20 age-matched control subjects with normal or near-normal hearing bilaterally. The CI improved localization accuracy and reduced side bias. Word recognition with the CI alone was similar to performance of traditional CI recipients. The CI improved masked sentence recognition when the masker was presented from the front or from the side of normal or near-normal hearing. The binaural benefits observed with the CI increased between the 1- and 3-month intervals but appeared stable thereafter. In contrast to previous reports on localization and speech perception in patients with unilateral sensorineural hearing loss, CI benefits were consistently observed across individual subjects, and performance was at asymptote by the 3-month test interval. Cochlear implant settings, consistent CI use, and short duration of deafness could play a role in this result.

Objectives: The present study evaluated early auditory localization abilities of cochlear implant (CI) recipients with normal or near-normal hearing (NH) in the contralateral ear. The goal of the study was to better understand the effect of CI listening experience on localization in this population., Design: Twenty participants with unilateral hearing loss enrolled in a prospective clinical trial assessing outcomes of cochlear implantation (ClinicalTrials.gov Identifier: NCT02203305). All participants received the MED-EL Standard electrode array, were fit with an ear-level audio processor, and listened with the FS4 coding strategy. Localization was assessed in the sound field using an 11-speaker array with speakers uniformly positioned on a horizontal, semicircular frame. Stimuli were 200-msec speech-shaped noise bursts. The intensity level (52, 62, and 72 dB SPL) and sound source were randomly interleaved across trials. Participants were tested preoperatively, and 1, 3, and 6 months after activation of the audio processor. Performance was evaluated in two conditions at each interval: (1) unaided (NH ear alone [NH-alone] condition), and (2) aided, with either a bone conduction hearing aid (preoperative interval; bone conduction hearing aid + NH condition) or a CI (postoperative intervals; CI + NH condition). Performance was evaluated by comparing root-mean-squared (RMS) error between listening conditions and between measurement intervals., Results: Mean RMS error for the soft, medium, and loud levels were 66°, 64°, and 69° in the NH-alone condition and 72°, 66°, and 70° in the bone conduction hearing aid + NH condition. Participants experienced a significant improvement in localization in the CI + NH condition at the 1-month interval (38°, 35°, and 38°) as compared with the preoperative NH-alone condition. Localization in the CI + NH condition continued to improve through the 6-month interval. Mean RMS errors were 28°, 25°, and 28° in the CI + NH condition at the 6-month interval., Conclusions: Adult CI recipients with normal or near-normal hearing in the contralateral ear experienced significant improvement in localization after 1 month of device use, and continued to improve through the 6-month interval. The present results show that binaural acclimatization in CI users with unilateral hearing loss can progress rapidly, with marked improvements in performance observed after only 1 month of listening experience.

Objective: Patients with moderate-to-profound sensorineural hearing loss in 1 ear and normal hearing in the contralateral ear, known as unilateral hearing loss (UHL) or single-sided deafness (SSD), may experience improved quality of life with the use of a cochlear implant (CI) in the affected ear. Quality of life assessment before and after implantation may reveal changes to aspects of hearing beyond those explicitly evaluated with behavioral measures., Methods: The present report completed 2 experiments investigating quality of life outcomes in CI recipients with UHL. The first experiment assessed quality of life during the 1st year of device use with 3 questionnaires: the Speech, Spatial, and Qualities of Hearing Scale (SSQ), the Abbreviated Profile of Hearing Aid Benefit (APHAB), and the Tinnitus Handicap Inventory. Twenty subjects were evaluated preoperatively and 1, 3, 6, 9, and 12 months post-activation. Quality of life results were compared over the study period using traditional scoring methods and the SSQ pragmatic subscales. Subscales specific to localization and speech perception in noise were compared to behavioral measures at the preoperative and 12-month intervals. The 2nd experiment evaluated quality of life preoperatively and at the 12-month interval for CI recipients with UHL and CI recipients with bilateral hearing loss, including conventional CI users and those listening with electric-acoustic stimulation (EAS). The 3 cohorts differed in CI candidacy criteria, including the amount of residual hearing in the contralateral ear., Results: For subjects with moderate-to-profound UHL, receipt of a CI significantly improved quality of life, with benefits noted as early as 1 month after initial activation. The UHL cohort reported less perceived difficulty at the pre- and postoperative intervals than the conventional CI and EAS cohorts, which may be due to the presence of the normal-hearing ear. Each group experienced a significant benefit in quality of life on the APHAB with CI use., Conclusions: Cochlear implantation in cases of substantial UHL may offer significant improvements in quality of life. Quality of life measures revealed a reduction in perceived tinnitus severity and subjective improvements in speech perception in noise, spatial hearing, and listening effort. While self-report of difficulties were lower for the UHL cohort than the conventional CI and EAS cohorts, subjects in all 3 groups reported an improvement in quality of life with CI use., (© 2018 S. Karger AG, Basel.)

Objective: Assess whether differences in speech perception are observed after exclusive listening experience with high-definition continuous interleaved sampling (HDCIS) versus fine structure processing (FSP) coding strategies., Methods: Subjects were randomly assigned at initial activation of the external speech processor to receive the HDCIS or FSP coding strategy. Frequency filter assignments were consistent across subjects. The speech perception test battery included CNC words in quiet, HINT sentences in quiet and steady noise (+10 dB SNR), AzBio sentences in quiet and a 10-talker babble (+10 dB SNR), and BKB-SIN. Assessment intervals included 1, 3, and 6 months post-activation., Results: Data from 22 subjects (11 with HDCIS and 11 with FSP) were assessed over time. Speech perception performance was not significantly different between groups., Discussion: Speech perception performance was not significantly different after 6 months of listening experience with the HDCIS or FSP coding strategy.

Background: Candidacy criteria for cochlear implantation are expanding to include patients with substantial low-to-mid frequency hearing sensitivity. Postoperative hearing preservation has been achieved in cochlear implant recipients, though with variable outcomes. Previous investigations on postoperative hearing preservation outcomes have evaluated intraoperative procedures. There has been limited review as to whether electric stimulation influences hearing preservation., Purpose: The purpose of this analysis was to evaluate whether charge levels associated with electric stimulation influence postoperative hearing preservation within the first year of listening experience., Research Design: Retrospective analysis of unaided residual hearing and charge levels., Study Sample: Twenty-eight cochlear implant recipients with postoperative residual hearing in the operative ear and at least 12 mo of listening experience with electric-acoustic stimulation (EAS)., Data Collection and Analysis: Assessment intervals included initial cochlear implant activation, initial EAS activation, and 3-, 6-, and 12-mo postinitial EAS activation. A masked low-frequency bone-conduction (BC) pure-tone average (PTA) was calculated for all participants at each assessment interval. Charge levels for each electrode were determined using the most comfortable loudness level and pulse width values. Charge levels associated with different regions of the electrode array were compared to the change in the low-frequency BC PTA between two consecutive intervals., Results: Charge levels had little to no association with the postoperative change in low-frequency BC PTA within the first year of listening experience., Conclusions: Electric charge levels do not appear to be reliably related to the subsequent loss of residual low-frequency hearing in the implanted ear within the first year of EAS listening experience., (American Academy of Audiology.)

Importance: This study reviewed whether advanced age should be a consideration when revision cochlear implantation is warranted., Objective: To examine whether age at revision cochlear implantation is related to postrevision speech perception performance., Design, Setting, and Participants: A retrospective analysis was performed in an academic tertiary care center. Participants included 14 younger adults (<65 years) and 15 older adults (≥65 years) who underwent revision cochlear implantation., Intervention: Revision cochlear implantation., Main Outcomes and Measures: Speech perception performance, as measured with consonant-nucleus-consonant [CNC] words in quiet, at the best prerevision interval as well as the 3- and 6-month postrevision intervals were compared between the 2 cohorts. The CNC word test consists of 10 lists of 50 phonemically balanced monosyllabic words, scored with a range of 0% to 100% correct., Results: Both cohorts experienced a restoration in speech perception scores after revision cochlear implantation compared with their best performance before the revision (mean [SD] CNC word test scores for the younger cohort: 43.9% [25.6%] before revision and 47.7% [21.3%] at 3 months and 47.6% [19.8%] at 6 months after revision; for the older cohort: 36.3% [19.1%] before revision and 35.3% [17.2%] at 3 months and 39.9% [16.3%] at 6 months after revision; F₂,₅₄= 0.93; P = .40). There was no interaction between age at revision surgery and speech perception performance at each assessment interval (F₂,₅₄= 0.51; P = .60)., Conclusions and Relevance: In this study, age at revision cochlear implantation was not related to postrevision speech perception performance. Advanced age should not be considered a contraindication to revision cochlear implantation.

Objective: The purpose of the present study was to assess the influence of electrode insertion length on cochlear implant (CI) performance., Study Design: Prospective randomized allocation of CI patients to receive either a standard (26.4 mm)- or medium (20.9 mm)-length electrode array. The processing strategy and electrode insertion number were held constant. The postoperative testing audiologist was blinded to the map details and array., Setting: Tertiary referral center., Patients: Thirteen adult CI candidates randomized to receive the standard- (n = 7) or medium-length (n = 6) electrode array., Intervention(s): Unilateral CI using standard- or medium-length array from the same implant system., Main Outcome Measures(s): Speech perception was assessed with HINT sentences in quiet and steady-state noise (SNR, +10) and CNC words in quiet at defined intervals. Quality of life was assessed using the Hearing Device Satisfaction Survey and the Abbreviated Profile of Hearing Aid Benefit (APHAB). Music perception was assessed using the Musical Sounds In Cochlear implants (MuSIC) test. Postoperative electrode insertion angle was assessed using reconstructed computed tomographic images., Results: Interim analysis necessitated discontinuation of subject enrollment by the institutional review board. There was a trend (p = 0.07) for improved speech perception performance among standard array patients. This difference was significant when the standard array group was increased retrospectively. Quality of life and music perception differences were not apparent between groups., Conclusion: Longer electrode insertions (and greater insertion angles) appear to offer better speech perception performance in the early postactivation period when using the same implant system.

Objective: Assess surgical complications, postoperative residual hearing, and speech perception outcomes of placement of a middle ear implant on the round window in conductive and mixed hearing loss cases., Study Design: Single-subject, repeated-measures design where each subject served as his or her own control., Setting: Tertiary referral medical systems., Subjects: Eighteen subjects with either conductive or mixed hearing loss who could not benefit from conventional amplification were enrolled in a clinical trial investigating vibratory stimulation of the round window., Intervention: The floating mass transducer (FMT) was positioned in the round window niche., Main Outcome Measures: Unaided residual hearing, and aided sound field thresholds and speech perception abilities were evaluated preoperatively, and at 1, 3, 6, and 10 months post-activation of the external speech processor., Results: Six subjects experienced complications that either required further medical management or resolved on their own. There was no difference in residual bone conduction thresholds or unaided word discrimination over time. All subjects experienced a significant improvement in aided speech perception abilities as compared to preoperative performance., Conclusion: Subjects with conductive and mixed hearing loss with placement of the FMT in the round window niche experienced improved sound field thresholds and speech perception, without compromising residual hearing thresholds. Vibratory stimulation of the round window via a middle ear implant may be an appropriate treatment option for patients with conductive and mixed hearing loss. Additional research is needed on the preferred placement of the FMT, improvement of functional gain, and methods to limit postoperative complications and need for revision surgery.

Objective: To assess the potential influence of 2 different surgical access routes to scala tympani for hearing preservation cochlear implantation on outcomes., Study Design: Retrospective review., Setting: Tertiary care academic center., Patients: Twenty adult subjects participating in a prospective clinical trial on electric-acoustic stimulation. Subjects underwent cochlear implantation with attempted hearing preservation and subsequent ipsilateral electric-acoustic stimulation of the auditory system., Interventions: Eight subjects (40%) were implanted using a round window-related cochleostomy and 12 subjects (60%) via a round window approach., Main Outcome Measures: Postoperative acoustic hearing preservation and speech perception measures were obtained at defined intervals and compared for both groups with and without the use of the external speech processor., Results: The data demonstrate no statistically significant differences in postoperative outcomes for both preservation of residual hearing and unaided and aided speech perception between the cochleostomy and round window groups., Conclusion: The results of this investigation suggest that hearing preservation cochlear implantation can be performed either via a round window-related cochleostomy as well as via the round window membrane itself with similar outcomes in terms of both hearing preservation rates as well as speech perception measures.

Objectives/hypothesis: To report on single-center data of an FDA-approved clinical trial on the objective benefits of cochlear implantation and subsequent ipsilateral Electric-Acoustic Stimulation (EAS)., Study Design: Single-center data from a prospective, multicenter clinical trial., Methods: Eighteen subjects completed the 12-month EAS evaluation and were included in this evaluation. Each patient underwent cochlear implantation using a standardized hearing preservation approach. Both hearing preservation and speech perception abilities were evaluated at various intervals. Speech testing included performance measures obtained in quiet (CNC words) and noise (adaptive CUNY protocol) in three listening conditions: hearing aid (HA) alone, cochlear implant (CI) only, and combined ipsilateral EAS., Results: Various levels of hearing preservation were achieved with cochleostomy and round-window surgical approaches in 17 of the 18 subjects. Mean CNC word scores at the 12-month interval were 14.9 ± 12.1, 45.3 ± 15.4, and 70.7 ± 11.7% correct in the HA only, CI only, and EAS conditions, respectively. Average CUNY scores at 0 dB SNR were 14.6 ± 17.2, 47.1 ± 22.1, and 72.2 ± 21.5 for the three test conditions obtained after 12 months., Conclusions: Data obtained during this clinical trial correlate well with previous reports. Hearing preservation appears successful in a high number of subjects, and combined EAS offers excellent speech perception abilities in quiet and in noise., Level of Evidence: 4., (Copyright © 2013 The American Laryngological, Rhinological, and Otological Society, Inc.)

Objective: The objective of this study is to investigate whether wild-type TP53 status in high-grade serous ovarian carcinoma is associated with poorer survival., Methods: Clinical and genomic data of 316 sequenced samples from The Cancer Genome Atlas (TCGA) ovarian high-grade serous carcinoma study were downloaded from TCGA data portal. Association between wild-type TP53 and survival was analyzed with Kaplan Meier method and Cox regression. The diagnosis of high-grade serous carcinomas was evaluated by reviewing pathological reports and high-resolution hematoxylin and eosin (H&E) images from frozen sections. The authenticity of wild-type TP53 in these tumor samples was assessed by analyzing SNP array data with ASCAT algorithm, reverse phase protein array (RPPA) data and RNAseq data., Results: Fifteen patients with high grade serous ovarian carcinomas were identified to have wild-type TP53, which had significantly shorter survival and higher chemoresistance than those with mutated TP53. The authenticity of wild-type TP53 status in these fifteen patients was supported by SNP array, RPPA, and RNAseq data. Except four cases with mixed histology, the classification as high grade serous carcinomas was supported by pathological reports and H&E images. Using RNAseq data, it was found that EDA2R gene, a direct target of wild-type TP53, was highly up-regulated in samples with wild-type TP53 in comparison to samples with either nonsense or missense TP53 mutations., Conclusion: Although patients with wild-type TP53 ovarian cancer were rare in the TCGA high grade ovarian serous carcinomas cohort, these patients appeared to have a poorer survival and were more chemoresistant than those with mutated TP53. Differentially expressed genes in these TP53 wild-type tumors may provide insight in the molecular mechanism in chemotherapy resistance., (Copyright © 2013 Elsevier Inc. All rights reserved.)

PAX2 is one of nine PAX genes that regulate tissue development and cellular differentiation in embryos. However, the functional role of PAX2 in ovarian cancer is not known. Twenty-six ovarian cancer cell lines with different histology origins were screened for PAX2 expression. Two ovarian cancer cell lines: RMUGL (mucinous) and TOV21G (clear cell), with high PAX2 expression were chosen for further study. Knockdown PAX2 expression in these cell lines was achieved by lentiviral shRNAs targeting the PAX2 gene. PAX2 stable knockdown cells were characterized for cell proliferation, migration, apoptosis, protein profiles, and gene expression profiles. The result indicated that these stable PAX2 knockdown cells had reduced cell proliferation and migration. Microarray analysis indicated that several genes involved in growth inhibition and motility, such as G0S2, GREM1, and WFDC1, were up-regulated in PAX2 knockdown cells. On the other hand, over-expressing PAX2 in PAX2-negative ovarian cell lines suppressed their cell proliferation. In summary, PAX2 could have both oncogenic and tumor suppression functions, which might depend on the genetic content of the ovarian cancer cells. Further investigation of PAX2 in tumor suppression and mortality is warranty.

Importance: A review of a test battery presented in both quiet and noise may clarify what the progression of speech perception abilities is in older adult cochlear implant users and whether the performance declines with advancing age., Objective: To examine whether older adults (≥65 years) with cochlear implants maintain stable speech perception performance after at least 10 years of listening experience with an external speech processor., Design and Setting: Retrospective analysis performed in an academic tertiary care center., Participants: Fourteen older adult cochlear implant recipients with at least 10 years of listening experience., Main Outcome Measures: Speech perception outcomes as measured with Consonant-Nucleus-Consonant words in quiet and Hearing in Noise Test sentences in quiet and steady-state noise were analyzed retrospectively at the 6-month and 1-, 5-, and 10-year postoperative follow-up intervals., Results: Consonant-Nucleus-Consonant word scores remained stable between 6 months and 1 year of listening experience, improved significantly (P < .001) between 1 year and 5 years, and remained stable between 5 years and 10 years. Hearing in Noise Test sentence scores in quiet and noise showed a similar pattern, with stability in performance between the 6-month to 1-year and 5-year to 10-year follow-up intervals, and significantly improved performance (P = .04) between the 1-year and 5-year follow-up intervals., Conclusions and Relevance: On average, patients who undergo cochlear implantation at age 65 years or older do not experience a decline in speech perception performance with extended listening experience and may potentially continue to see improvements beyond the 1-year follow-up interval.

The reaction of ((Ar)L)Co(py) with (t)BuN(3) afforded the isolable three-coordinate Co-imido complex ((Ar)L)Co(N(t)Bu), which is paramagnetic at room temperature. Variable-temperature (VT) (1)H NMR spectroscopy, VT crystallography, and magnetic susceptibility measurements revealed that ((Ar)L)Co(N(t)Bu) undergoes a thermally induced spin crossover from an S = 0 ground state to a quintet (S = 2) state. The reaction of ((Ar)L)Co(py) with mesityl azide yielded an isolable S = 1 terminal imido complex that was converted into the metallacycloindoline ((Ar)L)Co(κ(2)-NHC(6)H(2)-2,4-Me(2)-6-CH(2)) via benzylic C-H activation.

Transamination of divalent transition metal starting materials (M(2)(N(SiMe(3))(2))(4), M = Mn, Co) with hexadentate ligand platforms (R)LH(6) ((R)LH(6) = MeC(CH(2)NPh-o-NR)(3) where R = H, Ph, Mes (Mes = Mesityl)) or (H,Cy)LH(6) = 1,3,5-C(6)H(9)(NHPh-o-NH(2))(3) with added pyridine or tertiary phosphine coligands afforded trinuclear complexes of the type ((R)L)Mn(3)(py)(3) and ((R)L)Co(3)(PMe(2)R')(3) (R' = Me, Ph). While the sterically less encumbered ligand varieties, (H)L or (Ph)L, give rise to local square-pyramidal geometries at each of the bound metal atoms, with four anilides forming an equatorial plane and an exogenous pyridine or phosphine in the apical site, the mesityl-substituted ligand ((Mes)L) engenders local tetrahedral coordination. Both the neutral Mn(3) and Co(3) clusters feature S = (1)/(2) ground states, as determined by direct current (dc) magnetometry, (1)H NMR spectroscopy, and low-temperature electron paramagnetic resonance (EPR) spectroscopy. Within the Mn(3) clusters, the long internuclear Mn-Mn separations suggest minimal direct metal-metal orbital overlap. Accordingly, fits to variable-temperature magnetic susceptibility data reveal the presence of weak antiferromagnetic superexchange interactions through the bridging anilide ligands with exchange couplings ranging from J = -16.8 to -42 cm(-1). Conversely, the short Co-Co interatomic distances suggest a significant degree of direct metal-metal orbital overlap, akin to the related Fe(3) clusters. With the Co(3) series, the S = (1)/(2) ground state can be attributed to population of a single molecular orbital manifold that arises from mixing of the metal- and o-phenylenediamide (OPDA) ligand-based frontier orbitals. Chemical oxidation of the neutral Co(3) clusters affords diamagnetic cationic clusters of the type [((R)L)Co(3)(PMe(2)R)(3)](+). Density functional theory (DFT) calculations on the neutral (S = (1)/(2)) and cationic (S = 0) Co(3) clusters reveal that oxidation occurs at an orbital with contributions from both the Co3 core and OPDA subunits. The predicted bond elongations within the ligand OPDA units are corroborated by the ligand bond perturbations observed by X-ray crystallography.

MicroRNAs coordinate networks of mRNAs, but predicting specific sites of interactions is complicated by the very few bases of complementarity needed for regulation. Although efforts to characterize the specific requirements for microRNA (miR) regulation have made some advances, no general model of target recognition has been widely accepted. In this work, we describe an entirely novel approach to miR target identification. The genomic events responsible for the creation of individual miR loci have now been described with many miRs now known to have been initially formed from transposable element (TE) sequences. In light of this, we propose that limiting miR target searches to transcripts containing a miR's progenitor TE can facilitate accurate target identification. In this report we outline the methodology behind OrbId (Origin-based identification of microRNA targets). In stark contrast to the principal miR target algorithms (which rely heavily on target site conservation across species and are therefore most effective at predicting targets for older miRs), we find OrbId is particularly efficacious at predicting the mRNA targets of miRs formed more recently in evolutionary time. After defining the TE origins of > 200 human miRs, OrbId successfully generated likely target sets for 191 predominately primate-specific human miR loci. While only a handful of the loci examined were well enough conserved to have been previously evaluated by existing algorithms, we find ~80% of the targets for the oldest miR (miR-28) in our analysis contained within the principal Diana and TargetScan prediction sets. More importantly, four of the 15 OrbId miR-28 putative targets have been previously verified experimentally. In light of OrbId proving best-suited for predicting targets for more recently formed miRs, we suggest OrbId makes a logical complement to existing, conservation based, miR target algorithms.

Background: The objective of the study was to determine if initial surgery (IS) or initial chemotherapy (IC) affects rates of optimal surgery and survival in a population with significant medical comorbidities., Methods: Data of all patients with stage III-IV ovarian, peritoneal, and fallopian tube cancers diagnosed from 1995 to 2008 were reviewed. Clinical and pathologic data were abstracted., Results: There were 551 cases for review: 255 (46.3%) received IS, and 296 (53.7%) received IC. Patients who received IC had higher stage (P < 0.001), higher-grade cancers (P < 0.001), higher mean CA-125 (P = 0.015), higher rates of diabetes (P = 0.006), hypertension (P = 0.008), and presurgical embolism (P < 0.022) and were older (P = 0.043). There was no difference with respect to body mass index, albumin, extent of surgery, or intensive care use. Rates of optimal cytoreduction were higher with IC compared with IS (72.7% vs 56.1%, P < 0.001). IS was associated with more blood loss (P = 0.005) and higher rates of postsurgical venous thrombosis (P < 0.001). Optimal cytoreduction predicted survival in both groups. Among optimal patients, IS improved median survival: progression-free survival of 14 months (IS) versus 12 months (IC), P = 0.004; overall survival of 58 months (IS) versus 34 months (IC), P = 0.002. Factors influencing this difference were receipt of IC and history of diabetes; both predictors of mortality: hazard ratios, 1.9 (95% confidence interval, 1.3-2.8; P < 0.001) and 1.8 (95% confidence interval, 1.02-3.1; P = 0.042), respectively., Conclusions: The achievement of optimal cytoreduction continues to be a significant predictor of survival, regardless of treatment approach. Patients selected for IS and in whom optimal cytoreduction was achieved had improvements in both progression-free survival and overall survival. However, the differences could not be explained by surgical effort alone as diabetes was independently associated with mortality.

Loss of Pten in the Kras(G12D);Amhr2-Cre mutant mice leads to the transformation of ovarian surface epithelial (OSE) cells and rapid development of low-grade, invasive serous adenocarcinomas. Tumors occur with 100% penetrance and express elevated levels of wild-type tumor repressor protein 53 (TRP53). To test the functions of TRP53 in the Pten;Kras (Trp53+) mice, we disrupted the Trp53 gene yielding Pten;Kras(Trp53-) mice. By comparing morphology and gene expression profiles in the Trp53+ and Trp53- OSE cells from these mice, we document that wild-type TRP53 acts as a major promoter of OSE cell survival and differentiation: cells lacking Trp53 are transformed yet are less adherent, migratory, and invasive and exhibit a gene expression profile more like normal OSE cells. These results provide a new paradigm: wild-type TRP53 does not preferentially induce apoptotic or senescent related genes in the Pten;Kras(Trp53+) cancer cells but rather increases genes regulating DNA repair, cell cycle progression, and proliferation and decreases putative tumor suppressor genes. However, if TRP53 activity is forced higher by exposure to nutlin-3a (a mouse double minute-2 antagonist), TRP53 suppresses DNA repair genes and induces the expression of genes that control cell cycle arrest and apoptosis. Thus, in the Pten;Kras(Trp53+) mutant mouse OSE cells and likely in human TP53+ low-grade ovarian cancer cells, wild-type TRP53 controls global molecular changes that are dependent on its activation status. These results suggest that activation of TP53 may provide a promising new therapy for managing low-grade ovarian cancer and other cancers in humans in which wild-type TP53 is expressed.

Background: The mechanisms of paraneoplastic thrombocytosis in ovarian cancer and the role that platelets play in abetting cancer growth are unclear., Methods: We analyzed clinical data on 619 patients with epithelial ovarian cancer to test associations between platelet counts and disease outcome. Human samples and mouse models of epithelial ovarian cancer were used to explore the underlying mechanisms of paraneoplastic thrombocytosis. The effects of platelets on tumor growth and angiogenesis were ascertained., Results: Thrombocytosis was significantly associated with advanced disease and shortened survival. Plasma levels of thrombopoietin and interleukin-6 were significantly elevated in patients who had thrombocytosis as compared with those who did not. In mouse models, increased hepatic thrombopoietin synthesis in response to tumor-derived interleukin-6 was an underlying mechanism of paraneoplastic thrombocytosis. Tumor-derived interleukin-6 and hepatic thrombopoietin were also linked to thrombocytosis in patients. Silencing thrombopoietin and interleukin-6 abrogated thrombocytosis in tumor-bearing mice. Anti-interleukin-6 antibody treatment significantly reduced platelet counts in tumor-bearing mice and in patients with epithelial ovarian cancer. In addition, neutralizing interleukin-6 significantly enhanced the therapeutic efficacy of paclitaxel in mouse models of epithelial ovarian cancer. The use of an antiplatelet antibody to halve platelet counts in tumor-bearing mice significantly reduced tumor growth and angiogenesis., Conclusions: These findings support the existence of a paracrine circuit wherein increased production of thrombopoietic cytokines in tumor and host tissue leads to paraneoplastic thrombocytosis, which fuels tumor growth. We speculate that countering paraneoplastic thrombocytosis either directly or indirectly by targeting these cytokines may have therapeutic potential. (Funded by the National Cancer Institute and others.).