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Background: Certain environmental exposures have been linked to the development of parkinsonism. We report four cases in which the onset of chronic parkinsonism occurred immediately or soon after surgery or childbirth. Results: Exposure to certain anesthetic agents in susceptible individuals or the physiological changes associated with surgery or childbirth may have contributed to or precipitated the development of parkinsonism. Conclusion: Clinicians should be aware that postoperative or postpartum settings are potential precipitants of chronic parkinsonism. More research is needed to clarify contributing factors.

A 32-year-old male diagnosed with transverse myelitis in 2013 came to our clinic in 2015 with complaints of paraplegia, sensory disturbances, pain, exertional dyspnea, poor quality of sleep, emotional instability, and depression. This was a recurrent attack that had been exacerbated by post-traumatic stress. Owing to pain and functional disabilities, he was struggling to actively participate in the treatment modalities offered at our center. A modified protocol of electroacupuncture was planned for a period of 21 days, every day, with each session lasting for 30 minutes. Assessments based on the brief version of World Health Organization Brief Quality of Life (WHO Brief QOL) questionnaire, Pittsburgh sleep quality index, visual analog scale, and a disease-specific physical examination showed momentous improvement in functional health status as well as mental well-being. The quality of life showed significant improvement particularly in the physical and psychological dimensions of WHO Brief QOL. The patient reported a reduction in pain, dyspnea, and fatigue accompanied by an improvement in the quality of sleep and mood. This case report suggests that acupuncture can play a vital role in amelioration of symptoms, thereby improving the health status in patients with transverse myelitis.

Proper biobanking is essential for obtaining reliable data, particularly for next-generation sequencing approaches. Diseased vascular tissues, having extended atherosclerotic pathologies, represent a particular challenge due to low RNA quality. In order to address this issue, we isolated RNA from vascular samples collected in our Swiss Vascular Biobank (SVB); these included abdominal aortic aneurysm (AAA), peripheral arterial disease (PAD), healthy aorta (HA), and muscle samples. We used different methods, investigated various admission solutions, determined RNA integrity numbers (RINs), and performed expression analyses of housekeeping genes ( ACTB, GAPDH ), ribosomal genes ( 18S , 28S ), and long non-coding RNAs ( MALAT1 , H19 ). Our results show that RINs from diseased vascular tissue are low (2-4). If the isolation of primary cells is intended, as in our SVB, a cryoprotective solution is a better option for tissue preservation than RNAlater. Because RNA degradation proceeds randomly, controls with similar RINs are recommended. Otherwise, the data might convey differences in RNA degradation rather than the expressions of the corresponding genes. Moreover, since the 18S and 28S genes in the diseased vascular samples were degraded and corresponded with the low RINs, we believe that DV200, which represents the total RNA's disintegration state, is a better decision-making aid in choosing samples for omics analyses.

Background: Mental Health Literacy (MHL) has become a focus of research in recent decades, as a prerequisite for early identification and intervention for mental health problems. Although several instruments have been developed for assessing MHL, there is a need for brief and psychometrically sound measures to capture important aspects of MHL in large and diverse adult samples. The present study aimed to: (1) provide a revised and shorter version of a previously validated questionnaire for assessing MHL; and (2) examine the psychometric properties of the MHLq-SVa in student samples from six different countries (China, India, Indonesia, Portugal, Thailand, and United States)., Methods: The study involved 2180 senior school and undergraduate students, aged between 17 and 25 years old, from China, India, Indonesia, Portugal, Thailand, and the United States. Participants responded to the Mental Health Literacy Questionnaire for young adults (MHLq-ya), in their native language, following its translation and adaptation for each culture. The MHLq-ya comprises 29 items, organized into four dimensions: Knowledge of mental health problems; Erroneous beliefs/stereotypes; First-aid skills and help-seeking behavior; Self-help strategies. Confirmatory factor analyses and internal consistency analyses were performed on the combined data., Results: Data from the different countries supported a shorter version of the questionnaire (MHLq-SVa), composed of 16 items that fit with previously defined dimensions. Internal consistency and between-factor correlations further supported the adequacy of the instrument's psychometric properties., Conclusion: The study provided preliminary support for the construct validity and reliability of the MHLq-SVa as a measure for assessing MHL in young adults from six different countries and languages. Future studies are needed to further validate the measure and undertake multicultural comparisons of MHL in diverse samples from around the globe., (© 2022. The Author(s).)

Human listeners are assumed to apply different strategies to improve speech recognition in background noise. Young listeners with normal hearing (NH), e.g., have been shown to follow the voice of a particular speaker based on the fundamental (F0) and formant frequencies, which are both influenced by the gender, age, and size of the speaker. However, the auditory and cognitive processes that underlie the extraction and discrimination of these voice cues across speakers may be subject to age-related decline. The present study aimed to examine the utilization of F0 and formant cues for voice discrimination (VD) in older adults with hearing expected for their age. Difference limens (DLs) for VD were estimated in 15 healthy older adults (65-78 years old) and 35 young adults (18-35 years old) using only F0 cues, only formant frequency cues, and a combination of F0 + formant frequencies. A three-alternative forced-choice paradigm with an adaptive-tracking threshold-seeking procedure was used. Wechsler backward digit span test was used as a measure of auditory working memory. Trail Making Test (TMT) was used to provide cognitive information reflecting a combined effect of processing speed, mental flexibility, and executive control abilities. The results showed that (a) the mean VD thresholds of the older adults were poorer than those of the young adults for all voice cues, although larger variability was observed among the older listeners; (b) both age groups found the formant cues more beneficial for VD, compared to the F0 cues, and the combined (F0 + formant) cues resulted in better thresholds, compared to each cue separately; (c) significant associations were found for the older adults in the combined F0 + formant condition between VD and TMT scores, and between VD and hearing sensitivity, supporting the notion that a decline with age in both top-down and bottom-up mechanisms may hamper the ability of older adults to discriminate between voices. The present findings suggest that older listeners may have difficulty following the voice of a specific speaker and thus implementing doing so as a strategy for listening amid noise. This may contribute to understanding their reported difficulty listening in adverse conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zaltz and Kishon-Rabin.)

Judgment is the ability to make sound decisions after consideration of relevant information, possible solutions, likely outcomes, and contextual factors. Loss of judgment is common in patients with mild cognitive impairment (MCI) and dementia. The Test of Practical Judgment (TOP-J) evaluates practical judgment in adults and the elderly, with 15- and 9-item versions that require individuals to listen to scenarios about everyday problems and report their solutions., Objective: Adaptation of TOP-J for a Brazilian sample, preparation of a reduced version and verification of the accuracy of both., Methods: Eighty-five older adults, including 26 with MCI, 20 with Alzheimer's disease (AD), 15 with frontotemporal dementia behavioral variant (FTDbv) and 24 controls, underwent neuropsychological assessment including the Brazilian adaptation of the TOP-J (TOP-J-Br)., Results: On both TOP-J-Br versions, controls outperformed MCI, AD and FTDbv patients (p<0.001) and MCI outperformed AD and FTDbv (p<0.001). For the TOP-J/15-Br, the best cutoff for distinguishing controls and patients had a sensitivity of 91.7%, specificity of 59.0% and area under the curve of 0.8. For the TOP-J/9-Br, the best cutoff for distinguishing controls and patients had a sensitivity of 79.9%, specificity of 72.1% and area under the curve of 0.82., Conclusion: The TOP-J/15-Br, and particularly the TOP-J/9-Br, showed robust psychometric properties and the potential for clinical utility in Brazilian older adults at various stages of neurodegenerative cognitive decline., Competing Interests: Disclosure: The authors report no conflicts of interest.

Introduction: Composite scores may be useful to summarize overall language or visuospatial functioning in studies of older adults., Methods: We used item response theory to derive composite measures for language (ADNI-Lan) and visuospatial functioning (ADNI-VS) from the cognitive battery administered in the Alzheimer's Disease Neuroimaging Initiative (ADNI). We evaluated the scores among groups of people with normal cognition, mild cognitive impairment (MCI), and Alzheimer's disease (AD) in terms of responsiveness to change, association with imaging findings, and ability to differentiate between MCI participants who progressed to AD dementia and those who did not progress., Results: ADNI-Lan and ADNI-VS were able to detect change over time and predict conversion from MCI to AD. They were associated with most of the pre-specified magnetic resonance imaging measures. ADNI-Lan had strong associations with a cerebrospinal fluid biomarker pattern., Discussion: ADNI-Lan and ADNI-VS may be useful composites for language and visuospatial functioning in ADNI., Competing Interests: The authors declare that they have no conflicts of interest., (© 2020 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Investigating variables associated with mental health literacy in the college-age population takes us one step closer to providing intervention for this vulnerable group, where growing rates of psychological disorders are a serious public concern. This study adds to the existing literature by incorporating, within a single model, multi-faceted variables (demographic, psychological, and academic) that contribute to mental health literacy in demographically and ethnically diverse college students., Methods: Participants were undergraduate students enrolled at nine different colleges that are part of a large, urban, public university system. A total of 1213 respondents (62.0% female, 73.3% non-white) completed an in-person assessment of mental health literacy and answered questions about demographics, college experience, and mental health experience. Data were analyzed to identify which variables best discriminated between high, mid-level, and low performers on this assessment., Results: Discriminant correspondence analysis revealed that the difference between high and low performers (accounting for 90.27% of the total variance) was driven by participants who had taken at least one course related to clinical psychology and who typically majored in psychology and applied health science fields. These participants were more likely to report being white, female, between the ages of 28-32, and in the fourth year or later of their undergraduate program. In addition, high performers were more likely to have been diagnosed and/or treated for a psychological disorder, have more experience with psychological disorders through personal, family, or peer history, and have families who are open to discussing mental health issues., Conclusion: The main contributor to variation in mental health literacy scores was having taken a clinical psychology course, followed by majoring in psychology. Importantly, our findings identified not only the high performers, but also the low performers, for whom an increase in knowledge and awareness of mental health is crucial to overall psychological well-being. These results have important implications for the design of educational interventions aimed at improving mental health literacy at the college level, especially for students who otherwise would not have been exposed to this information from coursework or their major.

We observed that World Trade Center (WTC) exposure, post-traumatic stress disorder (PTSD) symptoms and depressive symptoms were associated with subjective cognitive concerns in Fire Department of the City of New York (FDNY) rescue/recovery workers. This follow-up study examined whether PTSD symptoms and/or depressive symptoms mediate the observed association between WTC exposure and subjective cognitive concerns. We included WTC-exposed FDNY workers who completed the Cognitive Function Instrument (CFI), measuring self-perceived cognitive decline ( N = 9516). PTSD symptoms and depressive symptoms were assessed using the PCL-S and CES-D, respectively. Multivariable linear regression estimated the association between WTC exposure and CFI score, adjusting for confounders. Mediation analyses followed the methods of Vanderweele (2014). Participants' average age at CFI assessment was 56.6 ± 7.6 years. Higher-intensity WTC exposure was associated with worse CFI score, an effect that was entirely mediated by PTSD symptoms (%mediated: 110.9%; 95%CI: 83.1-138.9). When substituting depressive symptoms for PTSD symptoms, the WTC exposure-CFI association was largely mediated (%mediated: 82.1%; 95%CI: 60.6-103.7). Our findings that PTSD symptoms and depressive symptoms mediate the association between WTC exposure and subjective cognitive concerns indicate that in the absence of these symptoms, WTC exposure in rescue/recovery workers would not be associated with subjective cognition. Interventions targeting PTSD and depression may have additional value in mitigating cognitive decline in WTC-exposed populations.

Cochlear implants (CIs) are the state-of-the-art therapy for individuals with severe to profound hearing loss, providing them with good functional hearing. Nevertheless, speech understanding in background noise remains a significant challenge. The purposes of this study were to: (1) conduct a novel within-study comparison of speech-in-noise performance across ages in different populations of CI and normal hearing (NH) listeners using an adaptive sentence-in-noise test, and (2) examine the relative contribution of sensory information and cognitive-linguistic factors to performance. Forty CI users (mean age 20 years) were divided into "early-implanted" <4 years ( n = 16) and "late-implanted" >6 years ( n = 11), all prelingually deafened, and "progressively deafened" ( n = 13). The control group comprised 136 NH subjects (80 children, 56 adults). Testing included the Hebrew Matrix test, word recognition in quiet, and linguistic and cognitive tests. Results show poorer performance in noise for CI users across populations and ages compared to NH peers, and age at implantation and word recognition in quiet were found to be contributing factors. For those recognizing 50% or more of the words in quiet ( n = 27), non-verbal intelligence and receptive vocabulary explained 63% of the variance in noise. This information helps delineate the relative contribution of top-down and bottom-up skills for speech recognition in noise and can help set expectations in CI counseling.

Cochlear implant (CI) users find it extremely difficult to discriminate between talkers, which may partially explain why they struggle to understand speech in a multi-talker environment. Recent studies, based on findings with postlingually deafened CI users, suggest that these difficulties may stem from their limited use of vocal-tract length (VTL) cues due to the degraded spectral resolution transmitted by the CI device. The aim of the present study was to assess the ability of adult CI users who had no prior acoustic experience, i.e., prelingually deafened adults, to discriminate between resynthesized "talkers" based on either fundamental frequency (F0) cues, VTL cues, or both. Performance was compared to individuals with normal hearing (NH), listening either to degraded stimuli, using a noise-excited channel vocoder, or non-degraded stimuli. Results show that (a) age of implantation was associated with VTL but not F0 cues in discriminating between talkers, with improved discrimination for those subjects who were implanted at earlier age; (b) there was a positive relationship for the CI users between VTL discrimination and speech recognition score in quiet and in noise, but not with frequency discrimination or cognitive abilities; (c) early-implanted CI users showed similar voice discrimination ability as the NH adults who listened to vocoded stimuli. These data support the notion that voice discrimination is limited by the speech processing of the CI device. However, they also suggest that early implantation may facilitate sensory-driven tonotopicity and/or improve higher-order auditory functions, enabling better perception of VTL spectral cues for voice discrimination.

Many studies have examined the contribution of different spectral bands to speech intelligibility, measuring recognition scores of filtered speech stimuli. For a given filter bandwidth, the influence of filter properties on such experiments has been studied mainly with respect to transition band slopes. The objective of the present study was to determine whether nominal transition band slope is a sufficient characterization of filter properties. Several types of filters, both finite impulse response and infinite impulse response types were examined in three experiments to determine if details of the transition band behavior, as well as group delay properties, had any influence on recognition scores. The results of a total of 72 participants showed that for 1/3 octave passbands, differences between filters having the same nominal transition band slopes, but of different types, were large and statistically significant. Linearity of phase response, however, did not influence the results. Further experiments using passband widths of 1/2 and 2/3 octaves revealed that only for the latter the difference in recognition scores between filter types ceased to be significant. These results have important implications for studies which involve filtered speech as well as models that employ different types of filters to emulate peripheral auditory processing.

Context: Damage to the auditory system by loud sounds can be avoided by hearing protection devices (HPDs) such as earmuffs, earplugs, or both for maximum attenuation. However, the attenuation can be limited by air conduction (AC) leakage around the earplugs and earmuffs by the occlusion effect (OE) and by skull vibrations initiating bone conduction (BC)., Aims: To assess maximum attenuation by HPDs and possible flanking pathways to the inner ear., Subjects and Methods: AC attenuation and resulting thresholds were assessed using the real ear attenuation at threshold (REAT) procedure on 15 normal-hearing participants in four free-field conditions: (a) unprotected ears, (b) ears covered with earmuffs, (c) ears blocked with deeply inserted customized earplugs, and (d) ears blocked with both earplugs and earmuffs. BC thresholds were assessed with and without earplugs to assess the OE., Results: Addition of earmuffs to earplugs did not cause significantly greater attenuation than earplugs alone, confirming minimal AC leakage through the external meatus and the absence of the OE. Maximum REATs ranged between 40 and 46 dB, leading to thresholds of 46-54 dB HL. Furthermore, calculation of the acoustic impedance mismatch between air and bone predicted at least 60 dB attenuation of BC., Conclusion: Results do not support the notion that skull vibrations (BC) contributed to the limited attenuation provided by traditional HPDs. An alternative explanation, supported by experimental evidence, suggests transmission of sound to inner ear via non-osseous pathways such as skin, soft tissues, and fluid. Because the acoustic impedance mismatch between air and soft tissues is smaller than that between air and bone, air-borne sounds would be transmitted to soft tissues more effectively than to bone, and therefore less attenuation is expected through soft tissue sound conduction. This can contribute to the limited attenuation provided by traditional HPDs. The present study has practical implications for hearing conservation protocols., Competing Interests: There are no conflicts of interest.

Aim: To evaluate the impact of unilateral hearing loss (UHL) on early aural/oral communication skills of infants by comparing performance to infants with bilateral normal hearing (BNH)., Method: Thirty-four infants with UHL (median age 9.4mo, 25th-75th centile 7.34-12.15) and 331 control infants with BNH (median age 9mo, 6.0-13.38) were divided into two subgroups based on risk factors known to cause developmental delay: low risk and high risk. Early auditory skills and preverbal vocalizations were assessed using two parent questionnaires: the Infant-Toddler Meaningful Auditory Integration Scale and the Production of Infants Scale Evaluation., Results: Of the infants with UHL, 21% showed delays in auditory behaviour and 41% delays in preverbal vocalizations, compared to their peers with BNH (p<0.01). After adjusting for risk level, delayed auditory behaviour and preverbal vocalizations were approximately four and nine times more common in infants with UHL compared to BNH respectively (p<0.01)., Interpretation: This is the first study to show that infants with UHL are at higher risk of delay in early aural/oral communication abilities compared to infants with BNH even in the absence of other known risk factors for developmental delay. This has important implications for early intervention and habilitation of infants with UHL, in order to reduce some of the negative long-term consequences of what was once considered 'minor' hearing loss., (© 2015 Mac Keith Press.)

The pattern of generalization of learning gains to untrained conditions in adult human perceptual skill learning has been used as an effective behavioral probe for studying the functional organization of the learning system. Learning gains were previously reported to generalize symmetrically between the ears for tonal stimuli. However, given the open question concerning the specialization of the hemispheres in the processing of speech sounds, it is not clear whether symmetrical interaural generalization will follow training on such stimuli. Here the effect of monaural single-session training on the identification of consonant-vowel stimuli in noise was examined. Participants showed similar robust gains in performance at 24 h post-training in both trained ears. There was, however, an asymmetrical generalization of the learning gains from the trained to the untrained ear, with more transfer from the right-trained to the left-untrained ear than vice versa. Training and transfer gains were retained for both ears over an interval of several months, although for the untrained ear a brief exposure was necessary to relearn the task. These results provide first-time evidence for an asymmetry in interaural generalization for speech sounds following training and provide further support to the lateralization of speech sounds along the auditory system.

The mechanism of human hearing under water is debated. Some suggest it is by air conduction (AC), others by bone conduction (BC), and others by a combination of AC and BC. A clinical bone vibrator applied to soft tissue sites on the head, neck, and thorax also elicits hearing by a mechanism called soft tissue conduction (STC) or nonosseous BC. The present study was designed to test whether underwater hearing at low intensities is by AC or by osseous BC based on bone vibrations or by nonosseous BC (STC). Thresholds of normal hearing participants to bone vibrator stimulation with their forehead in air were recorded and again when forehead and bone vibrator were under water. A vibrometer detected vibrations of a dry human skull in all similar conditions (in air and under water) but not when water was the intermediary between the sound source and the skull forehead. Therefore, the intensities required to induce vibrations of the dry skull in water were significantly higher than the underwater hearing thresholds of the participants, under conditions when hearing by AC and osseous BC is not likely. The results support the hypothesis that hearing under water at low sound intensities may be attributed to nonosseous BC (STC).

This study was designed to characterize the effect of background noise on the identification of syllables using behavioral and electrophysiological measures. Twenty normal-hearing adults (18-30 years) performed an identification task in a two-alternative forced-choice paradigm. Stimuli consisted of naturally produced syllables [da] and [ga] embedded in white noise. The noise was initiated 1000 ms before the onset of the speech stimuli in order to separate the auditory event related potentials (AERP) response to noise onset from that to the speech. Syllables were presented in quiet and in five SNRs: +15, +3, 0, -3, and -6 dB. Results show that (1) performance accuracy, d', and reaction time were affected by the noise, more so for reaction time; (2) both N1 and P3 latency were prolonged as noise levels increased, more so for P3; (3) [ga] was better identified than [da], in all noise conditions; and (4) P3 latency was longer for [da] than for [ga] for SNR 0 through -6 dB, while N1 latency was longer for [ga] than for [da] in most listening conditions. In conclusion, the unique stimuli structure utilized in this study demonstrated the effects of noise on speech recognition at both the physical and the perceptual processing levels.

Large gains in performance, evolving hours after practice has terminated, were reported in a number of visual and some motor learning tasks, as well as recently in an auditory nonverbal discrimination task. It was proposed that these gains reflect a latent phase of experience-triggered memory consolidation in human skill learning. It is not clear, however, whether and when delayed gains in performance evolve following training in an auditory verbal identification task. Here we show that normal-hearing young adults trained to identify consonant-vowel stimuli in increasing levels of background noise showed significant, robust, delayed gains in performance that became effective not earlier than 4 h post-training, with most participants improving at more than 6 h post-training. These gains were retained for over 6 mo. Moreover, although it has been recently argued that time including sleep, rather than time per se, is necessary for the evolution of delayed gains in human perceptual learning, our results show that 12 h post-training in the waking state were as effective as 12 h, including no less than 6 h night's sleep. Altogether, the results indicate, for the first time, the existence of a latent, hours-long, consolidation phase in a human auditory verbal learning task, which occurs even during the awake state.

This study evaluated the cognitive profiles of children with idiopathic generalized epilepsy (IGE), uniformly treated with valproic acid with well-controlled seizures. Twenty-four were neuropsychologically evaluated. They comprised: 14 females, 10 males: 12 with generalized tonic-clonic seizures (GTCS), mean age 14y 4mo, SD ly 7mo, range 12y to 16y 4 mo; 12 with absence seizures (AS]) mean age 14y 5mo, SD ly 10mo, range 11y to 16y 4mo, with intellectual abilities within the normal range and age-appropriate scholastic skills, and 20 healthy controls (12 females, 8 males; mean age 14y 5mo, SD 1y 10mo, range 10y 7mo to 16y 7mo). As a group, children with IGE performed significantly poorer in all tests (non-verbal and verbal attention, verbal learning and memory, word fluency, and controlled sequential fine motor responses) excluding non-verbal memory. Analysis according to type of seizure revealed that both patient groups (AS and GTCS) had an attention deficit, whereas only children with AS showed deficits in verbal learning and memory, word fluency, and controlled fine motor responses. These results suggest a long-term risk of learning impairment for children with IGE, even if they have normal intelligence and their seizures are well controlled.

Purpose: Auditory processing of increasing acoustic and linguistic complexity was assessed in children with idiopathic generalized epilepsy (IGE) by using auditory event-related potentials (AERPs) as well as reaction time and performance accuracy., Methods: Twenty-four children with IGE [12 with generalized tonic-clonic seizures (GTCSs), and 12 with absence seizures (ASs)] with average intelligence and age-appropriate scholastic skills, uniformly medicated with valproic acid (VPA), and 20 healthy controls, performed oddball discrimination tasks that consisted of the following stimuli: (a) pure tones; (b) nonmeaningful monosyllables that differed by their phonetic features (i.e., phonetic stimuli); and (c) meaningful monosyllabic words from two semantic categories (i.e., semantic stimuli)., Results: AERPs elicited by nonlinguistic stimuli were similar in healthy and epilepsy children, whereas those elicited by linguistic stimuli (i.e., phonetic and semantic) differed significantly in latency, amplitude, and scalp distribution. In children with GTCSs, phonetic and semantic processing were characterized by slower processing time, manifested by prolonged N2 and P3 latencies during phonetic processing, and prolongation of all AERPs latencies during semantic processing. In children with ASs, phonetic and semantic processing were characterized by increased allocation of attentional resources, manifested by enhanced N2 amplitudes. Semantic processing also was characterized by prolonged P3 latency. In both patient groups, processing of linguistic stimuli resulted in different patterns of brain-activity lateralization compared with that in healthy controls. Reaction time and performance accuracy did not differ among the study groups., Conclusions: AERPs exposed linguistic-processing deficits related to seizure type in children with IGE. Neurologic follow-up should therefore include evaluation of linguistic functions, and remedial intervention should be provided, accordingly.

The relationship between auditory perception and vocal production has been typically investigated by evaluating the effect of either altered or degraded auditory feedback on speech production in either normal hearing or hearing-impaired individuals. Our goal in the present study was to examine this relationship in individuals with superior auditory abilities. Thirteen professional musicians and thirteen nonmusicians, with no vocal or singing training, participated in this study. For vocal production accuracy, subjects were presented with three tones. They were asked to reproduce the pitch using the vowel /a/. This procedure was repeated three times. The fundamental frequency of each production was measured using an autocorrelation pitch detection algorithm designed for this study. The musicians' superior auditory abilities (compared to the nonmusicians) were established in a frequency discrimination task reported elsewhere. Results indicate that (a) musicians had better vocal production accuracy than nonmusicians (production errors of 1/2 a semitone compared to 1.3 semitones, respectively); (b) frequency discrimination thresholds explain 43% of the variance of the production data, and (c) all subjects with superior frequency discrimination thresholds showed accurate vocal production; the reverse relationship, however, does not hold true. In this study we provide empirical evidence to the importance of auditory feedback on vocal production in listeners with superior auditory skills.

The effect of auditory feedback on speech production was investigated in five postlingually deafened adults implanted with the 22-channel Nucleus device. Changes in speech production were measured before implant and 1, 6, and 24 months postimplant. Acoustic measurements included: F1 and F2 of vowels in word-in-isolation and word-in-sentence context, voice-onset-time (VOT), spectral range of sibilants, fundamental frequency (F0) of word-in-isolation and word-in-sentence context, and word and sentence duration. Perceptual ratings of speech quality were done by ten listeners. The significant changes after cochlear implantation included: a decrease of F0, word and sentence duration, and F1 values, and an increase of voiced plosives' voicing lead (from positive to negative VOT values) and fricatives' spectral range. Significant changes occurred until 2 years postimplant when most measured values fell within Hebrew norms. Listeners were found to be sensitive to the acoustic changes in the speech from preimplant to 1, 6, and 24 months postimplant. Results suggest that when hearing is restored in postlingually deafened adults, calibration of speech is not immediate and occurs over time depending on the age-at-onset of deafness, years of deafness, and perception skills. The results also concur with hypothesis that the observed changes of some speech parameters are an indirect consequence of intentional changes in other articulatory parameters.

Viral replication was inhibited in a dose-dependent manner after administration of the phosphorothioate oligonucleotide TTGGGGTT (ISIS 5320) to human immunodeficiency virus type 1 (HIV-1)-infected SCID-hu Thy/Liv mice. Potent in vivo antiviral activity was observed against the T-cell-tropic molecular clone NL4-3; the agent was found to have weak activity against one primary HIV-1 isolate, and the agent was inactive against a second primary isolate.

Pathogenic organisms are frequently attenuated after long-term culture in vitro. The mechanisms of the attenuation process are not clear, but probably involve mutations of functions required for replication and pathogenicity in vivo. To identify these functions, a direct comparison must be made between attenuated genomes and those that remain pathogenic in vivo. In this study, we used the heterochimeric SCID-hu Thy/Liv mouse as an in vivo model to define human immunodeficiency virus type 1 (HIV-1) determinants which are uniquely required for replication in vivo. The Lai/IIIB isolate and its associated infectious molecular clones (e.g., HXB2) were found to infect T cell lines but failed to replicate in the SCID-hu Thy/Liv model. When a lab worker was accidentally infected by Lai/IIIB, however, HIV-1 was isolated only from infection of primary PBMC, and not from infection of T cell lines. We hypothesized that the lab worker was exposed to a heterogeneous viral stock which had been attenuated by passage in immortalized T cell lines. Either a rare family member from this stock was selected for in vivo replication or, alternatively, an attenuated genotype dominant in vitro may have reverted to become more infectious in vivo. To address this hypothesis, we have used the SCID-hu Thy/Liv model to study the replication of HXB2 and of HXB2 recombinant viruses with HIV-1 fragments isolated from the infected lab worker. HXB2 showed no or very low levels of replication in the Thy/Liv organ. Replacement of its subgenomic fragment encoding the envelope gene with a corresponding fragment from the lab worker isolate generated a recombinant virus (HXB2/LW) which replicated actively in SCID-hu mice. The NEF mutation in the HXB2 genome is still present in HXB2/LW. Thus, the LW sequences encode HIV-1 determinants which enhance HIV replication in vivo in a NEF-independent mechanism. The specific determinants have been mapped to the V1-V3 regions of the HIV-1 genome. Six unique mutations in the V3 loop region of HXB2/LW have been identified which contribute to the increased replication in vivo.

In two experiments, subjects repeated video-recorded sentences presented via speechreading with and without enhancement by a sensory input derived from the acoustic speech signal. Enhancement was measured as percentage increase in recognized words. In experiment 1, tactile presentation of fundamental frequency (F0) provided, after training, for three of four postlingually deafened adults a mean enhancement of 11%. In experiment 2, using six hearing adults, the auditory presentation of F0 provided a mean enhancement of 50%. This value fell, but only to 37%, when the F0 signal was derived from the processor of the tactile aid used in experiment 1. From these experiments it can be concluded that the unexpectedly small enhancement found in experiment 1 is probably due both to the fact that this tactile aid was not providing effective access to all of the information available in the F0 contour and to limitations related to the tactile processing ability of the kinaesthetic system.

Human immunodeficiency virus (HIV) disease is typified by declining CD4+ T lymphocyte counts in the peripheral circulation, a loss which may be secondary to accelerated destruction, to suppressed differentiation, and/or to sequestration of circulating cells into tissue spaces. As it is hard to distinguish between these possibilities in human subjects, the pathogenic mechanisms associated with HIV infection are unclear. In particular, little is known about the events that occur within infected lymphoid organs in which most CD4 T lymphocytes mature and function. To obtain a better description of HIV pathogenesis in vivo, we have implanted human haematolymphoid organs into the immunodeficient SCID mouse to create the SCID-hu mouse. We have previously shown that these organ systems promote long-term multilineage human haematopoiesis and are permissive for infection with HIV. Here we report that human thymopoiesis is suppressed by HIV infection, thereby precluding regeneration of the peripheral T-cell compartment.

The SCID-hu mouse, engrafted with human hematolymphoid organs, is permissive for infection with the human immunodeficiency virus (HIV). This mouse model was used to test compounds for antiviral efficacy. Two weeks after infection with HIV, 100 percent (40/40) of SCID-hu mice were positive for HIV by the polymerase chain reaction. When first treated with 3'-azido-3'-deoxythymidine (AZT), none (0/17) were HIV-positive by this assay. However, AZT-treated SCID-hu mice did have a few infected cells; after AZT treatment was stopped, viral spread was detected by polymerase chain reaction in such mice. Thus, the SCID-hu mouse provides a means to directly compare new antiviral compounds with AZT and to further improve antiviral efficacy.

A patient who developed chronic cholestatic jaundice during the 1st year of life and eventually died of liver cell failure at the age of 18 years is described. During the terminal illness Kayser-Fleischer-like rings were observed and the serum concentrations of total copper and ceruloplasmin were elevated. At autopsy, a mixed macronodular and micronodular cirrhosis was found and cholangiography and dissection of bile ducts revealed no obstructive lesion of the biliary tract. There was no family history of hepatobiliary disease. Liver biopsies obtained at the ages of 5 and 7 years showed accumulation of bile droplets in hepatocytes, normal-appearing bile ducts, no significant fibrosis, and intact lobular architecture. Striking features of the terminal cirrhosis were the presence of Mallory bodies and a marked excess of copper in the liver (2,175 mug per g dry weight). The latter two findings, as well as the elevated serum concentrations of total copper and ceruloplasmin, may be attributable to chronic cholestasis per se. This study emphasizes the clinical and therapeutic problems posed by chronic cholestasis of unknown etiology in childhood.

A case is described of presumed quinidine hepatotoxicity, characterized by the development of fever, abnormal serum transaminase values, which improved after cessation of the drug but recurred after a challenge dose, and centrizonal hepatocellular necrosis detected on liver biopsy. Morphological changes on electron microscopy, consistent with a drug reaction, are also described. Pertinent features of previous case reports are analyzed, and the histological findings by light microscopy of the present and past cases are discussed. It is suggested that the development of unexplained fever within 1 month of quinidine administration should lead to consideration of possible hepatotoxicity.

Human monoclonal antibodies (HMAbs) to human cytomegalovirus (HCMV) have been developed by using electric field-induced cell fusion of human B lymphocytes to the human-mouse cell line SBC-H20. By this procedure, multiple hybridomas have been produced that secrete IgG 1 HMAbs with distinct patterns of indirect immunofluorescence on HCMV-infected cells. HMAbs Z01 and X20 immunoprecipitated a major protein at 64 kDa. HMAb Z02 immunoprecipitated a major protein of 48-50 kDa. HMAb Z10 identified a single protein at 65 kDa and HMAb X16 identified proteins at 100, 65, and 36-38 kDa. The HMAbs demonstrated varying degrees of virus-neutralizing activity. The production of HMAbs to HCMV provides an important approach to studying the human host response to HCMV by elucidating biologically relevant antigens and epitopes. In addition, HMAbs are a potentially unlimited source of relevant human antibodies for treating life-threatening HCMV infection.