The Impact of Synchronized Cochlear Implant Sampling and Stimulation on Free-Field Spatial Hearing Outcomes: Comparing the ciPDA Research Processor to Clinical Processors.

OBJECTIVES: Bilateral cochlear implant (BiCI) listeners use independent processors in each ear. This independence and lack of shared hardware prevents control of the timing of sampling and stimulation across ears, which precludes the development of bilaterally-coordinated signal processing strategies. As a result, these devices potentially reduce access to binaural cues and introduce disruptive artifacts. For example, measurements from two clinical processors demonstrate that independently-running processors introduce interaural incoherence. These issues are typically avoided in the laboratory by using research processors with bilaterally-synchronized hardware. However, these research processors do not typically run in real-time and are difficult to take out into the real-world due to their benchtop nature. Hence, the question of whether just applying hardware synchronization to reduce bilateral stimulation artifacts (and thereby potentially improve functional spatial hearing performance) has been difficult to answer. The CI personal digital assistant (ciPDA) research processor, which uses one clock to drive two processors, presented an opportunity to examine whether synchronization of hardware can have an impact on spatial hearing performance. DESIGN: Free-field sound localization and spatial release from masking (SRM) were assessed in 10 BiCI listeners using both their clinical processors and the synchronized ciPDA processor. For sound localization, localization accuracy was compared within-subject for the two processor types. For SRM, speech reception thresholds were compared for spatially separated and co-located configurations, and the amount of unmasking was compared for synchronized and unsynchronized hardware. There were no deliberate changes of the sound processing strategy on the ciPDA to restore or improve binaural cues. RESULTS: There was no significant difference in localization accuracy between unsynchronized and synchronized hardware (p = 0.62). Speech reception thresholds were higher with the ciPDA. In addition, although five of eight participants demonstrated improved SRM with synchronized hardware, there was no significant difference in the amount of unmasking due to spatial separation between synchronized and unsynchronized hardware (p = 0.21). CONCLUSIONS: Using processors with synchronized hardware did not yield an improvement in sound localization or SRM for all individuals, suggesting that mere synchronization of hardware is not sufficient for improving spatial hearing outcomes. Further work is needed to improve sound coding strategies to facilitate access to spatial hearing cues. This study provides a benchmark for spatial hearing performance with real-time, bilaterally-synchronized research processors.

Auditory motion tracking ability of adults with normal hearing and with bilateral cochlear implants.

Adults with bilateral cochlear implants (BiCIs) receive benefits in localizing stationary sounds when listening with two implants compared with one; however, sound localization ability is significantly poorer when compared to normal hearing (NH) listeners. Little is known about localizing sound sources in motion, which occurs in typical everyday listening situations. The authors considered the possibility that sound motion may improve sound localization in BiCI users by providing multiple places of information. Alternatively, the ability to compare multiple spatial locations may be compromised in BiCI users due to degradation of binaural cues, and thus result in poorer performance relative to NH adults. In this study, the authors assessed listeners' abilities to distinguish between sounds that appear to be moving vs stationary, and track the angular range and direction of moving sounds. Stimuli were bandpass-filtered (150-6000 Hz) noise bursts of different durations, panned over an array of loudspeakers. Overall, the results showed that BiCI users were poorer than NH adults in (i) distinguishing between a moving vs stationary sound, (ii) correctly identifying the direction of movement, and (iii) tracking the range of movement. These findings suggest that conventional cochlear implant processors are not able to fully provide the cues necessary for perceiving auditory motion correctly.

Generalizability of clinically measured acoustic reflexes to brief sounds.

Middle ear muscle contractions (MEMC) can be elicited in response to high-level sounds, and have been used clinically as acoustic reflexes (ARs) during evaluations of auditory system integrity. The results of clinical AR evaluations do not necessarily generalize to different signal types or durations. The purpose of this study was to evaluate the likelihood of observing MEMC in response to brief sound stimuli (tones, recorded gunshots, noise) in adult participants (N = 190) exhibiting clinical ARs and excellent hearing sensitivity. Results revealed that the presence of clinical ARs was not a sufficient indication that listeners will also exhibit MEMC for brief sounds. Detection rates varied across stimulus types between approximately 20% and 80%. Probabilities of observing MEMC also differed by clinical AR magnitude and latency, and declined over the period of minutes during the course of the MEMC measurement series. These results provide no support for the inclusion of MEMC as a protective factor in damage-risk criteria for impulsive noises, and the limited predictability of whether a given individual will exhibit MEMC in response to a brief sound indicates a need to measure and control for MEMC in studies evaluating pharmaceutical interventions for hearing loss.

Mixed stimulation rates to improve sensitivity of interaural timing differences in bilateral cochlear implant listeners.

Normal hearing listeners extract small interaural time differences (ITDs) and interaural level differences (ILDs) to locate sounds and segregate targets from noise. Bilateral cochlear implant listeners show poor sensitivity to ITDs when using clinical processors. This is because common clinical stimulation approaches use high rates [∼1000 pulses per-second (pps)] for each electrode in order to provide good speech representation, but sensitivity to ITDs is best at low rates of stimulation (∼100-300 pps). Mixing rates of stimulation across the array is a potential solution. Here, ITD sensitivity for a number of mixed-rate configurations that were designed to preserve speech envelope cues using high-rate stimulation and spatial hearing using low rate stimulation was examined. Results showed that ITD sensitivity in mixed-rate configurations when only one low rate electrode was included generally yielded ITD thresholds comparable to a configuration with low rates only. Low rate stimulation at basal or middle regions on the electrode array yielded the best sensitivity to ITDs. This work provides critical evidence that supports the use of mixed-rate strategies for improving ITD sensitivity in bilateral cochlear implant users.

The Effect of Microphone Placement on Interaural Level Differences and Sound Localization Across the Horizontal Plane in Bilateral Cochlear Implant Users.

OBJECTIVE: This study examined the effect of microphone placement on the interaural level differences (ILDs) available to bilateral cochlear implant (BiCI) users, and the subsequent effects on horizontal-plane sound localization. DESIGN: Virtual acoustic stimuli for sound localization testing were created individually for eight BiCI users by making acoustic transfer function measurements for microphones placed in the ear (ITE), behind the ear (BTE), and on the shoulders (SHD). The ILDs across source locations were calculated for each placement to analyze their effect on sound localization performance. Sound localization was tested using a repeated-measures, within-participant design for the three microphone placements. RESULTS: The ITE microphone placement provided significantly larger ILDs compared to BTE and SHD placements, which correlated with overall localization errors. However, differences in localization errors across the microphone conditions were small. CONCLUSIONS: The BTE microphones worn by many BiCI users in everyday life do not capture the full range of acoustic ILDs available, and also reduce the change in cue magnitudes for sound sources across the horizontal plane. Acute testing with an ITE placement reduced sound localization errors along the horizontal plane compared to the other placements in some patients. Larger improvements may be observed if patients had more experience with the new ILD cues provided by an ITE placement.

Lateralization of interaural timing differences with multi-electrode stimulation in bilateral cochlear-implant users.

Bilateral cochlear implant (BiCI) users have shown variability in interaural time difference (ITD) sensitivity at different places along the cochlea. This paper investigates perception of multi-electrode binaural stimulation to determine if auditory object formation (AOF) and lateralization are affected by variability in ITD sensitivity when a complex sound is encoded with multi-channel processing. AOF and ITD lateralization were compared between single- and multi-electrode configurations. Most (7/8) BiCI users perceived a single auditory object with multi-electrode stimulation, and the range of lateralization was comparable to single-electrode stimulation, suggesting that variability in single-electrode ITD sensitivity does not compromise AOF with multi-electrode stimulation.

Sound frequency-invariant neural coding of a frequency-dependent cue to sound source location.

The century-old duplex theory of sound localization posits that low- and high-frequency sounds are localized with two different acoustical cues, interaural time and level differences (ITDs and ILDs), respectively. While behavioral studies in humans and behavioral and neurophysiological studies in a variety of animal models have largely supported the duplex theory, behavioral sensitivity to ILD is curiously invariant across the audible spectrum. Here we demonstrate that auditory midbrain neurons in the chinchilla (Chinchilla lanigera) also encode ILDs in a frequency-invariant manner, efficiently representing the full range of acoustical ILDs experienced as a joint function of sound source frequency, azimuth, and distance. We further show, using Fisher information, that nominal "low-frequency" and "high-frequency" ILD-sensitive neural populations can discriminate ILD with similar acuity, yielding neural ILD discrimination thresholds for near-midline sources comparable to behavioral discrimination thresholds estimated for chinchillas. These findings thus suggest a revision to the duplex theory and reinforce ecological and efficiency principles that hold that neural systems have evolved to encode the spectrum of biologically relevant sensory signals to which they are naturally exposed.

Evidence for a neural source of the precedence effect in sound localization.

Normal-hearing human listeners and a variety of studied animal species localize sound sources accurately in reverberant environments by responding to the directional cues carried by the first-arriving sound rather than spurious cues carried by later-arriving reflections, which are not perceived discretely. This phenomenon is known as the precedence effect (PE) in sound localization. Despite decades of study, the biological basis of the PE remains unclear. Though the PE was once widely attributed to central processes such as synaptic inhibition in the auditory midbrain, a more recent hypothesis holds that the PE may arise essentially as a by-product of normal cochlear function. Here we evaluated the PE in a unique human patient population with demonstrated sensitivity to binaural information but without functional cochleae. Users of bilateral cochlear implants (CIs) were tested in a psychophysical task that assessed the number and location(s) of auditory images perceived for simulated source-echo (lead-lag) stimuli. A parallel experiment was conducted in a group of normal-hearing (NH) listeners. Key findings were as follows: 1) Subjects in both groups exhibited lead-lag fusion. 2) Fusion was marginally weaker in CI users than in NH listeners but could be augmented by systematically attenuating the amplitude of the lag stimulus to coarsely simulate adaptation observed in acoustically stimulated auditory nerve fibers. 3) Dominance of the lead in localization varied substantially among both NH and CI subjects but was evident in both groups. Taken together, data suggest that aspects of the PE can be elicited in CI users, who lack functional cochleae, thus suggesting that neural mechanisms are sufficient to produce the PE.

Effect of multi-electrode configuration on sensitivity to interaural timing differences in bilateral cochlear-implant users.

Recent psychophysical studies in bilateral cochlear implant users have shown that interaural timing difference (ITD) sensitivity with electrical stimulation varies depending on the place of stimulation along the cochlear array. While these studies have measured ITD sensitivity at single electrode places separately, it is important to understand how ITD sensitivity is affected when multiple electrodes are stimulated together because multi-electrode stimulation is required for representation of complex sounds. Multi-electrode stimulation may lead to poorer overall performance due to interference from places with poor ITD sensitivity, or from channel interaction due to electrical current spread. Alternatively, multi-electrode stimulation might result in overall good sensitivity if listeners can extract the most reliable ITD cues available. ITD just noticeable differences (JNDs) were measured for different multi-electrode configurations. Results showed that multi-electrode ITD JNDs were poorer than ITD JNDs for the best single-electrode pair. However, presenting ITD information along the whole array appeared to produce better sensitivity compared with restricting stimulation to the ends of the array, where ITD JNDs were comparable to the poorest single-electrode pair. These findings suggest that presenting ITDs in one cochlear region only may not be optimal for maximizing ITD sensitivity in multi-electrode stimulation.

Biophysics of directional hearing in the American alligator (Alligator mississippiensis).

Physiological and anatomical studies have suggested that alligators have unique adaptations for spatial hearing. Sound localization cues are primarily generated by the filtering of sound waves by the head. Different vertebrate lineages have evolved external and/or internal anatomical adaptations to enhance these cues, such as pinnae and interaural canals. It has been hypothesized that in alligators, directionality may be enhanced via the acoustic coupling of middle ear cavities, resulting in a pressure difference receiver (PDR) mechanism. The experiments reported here support a role for a PDR mechanism in alligator sound localization by demonstrating that (1) acoustic space cues generated by the external morphology of the animal are not sufficient to generate location cues that match physiological sensitivity, (2) continuous pathways between the middle ears are present to provide an anatomical basis for coupling, (3) the auditory brainstem response shows some directionality, and (4) eardrum movement is directionally sensitive. Together, these data support the role of a PDR mechanism in crocodilians and further suggest this mechanism is a shared archosaur trait, most likely found also in the extinct dinosaurs.

Lymphoepithelioma-like carcinoma of the endometrium: immunophenotypic characterization of a rare tumor with microsatellite instability testing.

This report describes the clinicopathologic features of a primary lymphoepithelioma-like carcinoma of the endometrium, representing only the fourth reported case of this tumor at this location. In addition to its classic morphologic features, focal clear cells were also identified within the tumor, thereby expanding the morphologic spectrum of the neoplasm at this location. A comprehensive immunohistochemical characterization of the tumor was performed, as was microsatellite instability testing. The tumor was diagnosed in a 79-year-old woman and was surgically/pathologically staged as IB by the International Federation of Gynecology and Obstetrics (FIGO) criteria. The tumor displayed typical morphologic features (tumor cells with a syncytial appearance in an inflammatory background) with the exception of the aforementioned polygonal cells with well-defined cell membranes and cytoplasmic clarity in <1% of the tumor. The epithelial component showed strong and diffuse immunoreactivity for CAM 5.2, p53, p16, E-cadherin, cytokeratin (CK) 7, vimentin, CKAE1/3, and epithelial membrane antigen. The MIB-1 proliferative index in these regions was about 70%. Approximately 10% to 30% of lesional cells showed strong immunoreactivity for CK903, S100, MOC31, CD138, but the pattern of positivity was patchy and discontinuous. The epithelial cells were entirely negative for CK5/6, smooth muscle actin, p504S, CK20, synaptophysin, chromogranin, CD56, CD99, WT-1, thyroid transcription factor-1, p63, CD117 (c-kit), CD34, calretinin, desmin, estrogen receptor, progesterone receptor, FLI-1, ALK-1, D2-40, cytomegalovirus antigen, Epstein-Barr virus-encoded RNA-1, Epstein-Barr virus, monoclonal carcinoembryonic antigen, and HER2/neu. The foci with clear cells were not immunophenotypically distinct from the non-clear cell areas and had an approximately similar proliferative index. The inflammatory component was mixed (lymphocytes, histiocytes, plasma cells, neutrophils) but was composed predominantly of CD45/CD3/CD8 T lymphocytes, with a CD3 to CD20 ratio of approximately 10:1 and CD8 to CD4 T-cell ratio of approximately 3:1. Numerous (>100 positive cells per 10 high-power fields) S100-positive tumor-infiltrating Langerhans cells were present. The tumor DNA did not exhibit microsatellite instability at any of the loci analyzed. In summary, the limited data available suggest that lymphoepithelioma-like carcinoma is a distinct histotype of endometrial carcinoma that is typically seen in postmenopausal women, seems to be unrelated to the Epstein-Barr virus, and has an uncertain prognosis. Differential diagnostic and pathogenetic considerations are discussed within the context of the lesional morphologic and immunophenotypic profile as described herein and in previously reported cases.

The sound source distance dependence of the acoustical cues to location and their encoding by neurons in the inferior colliculus: implications for the Duplex theory.

For over a century, the Duplex theory has posited that low- and ­high-frequency sounds are localized using two different acoustical cues, interaural time (ITDs) and level (ILDs) differences, respectively. Psychophysical data have generally supported the theory for pure tones. Anatomically, ITDs and ILDs are separately encoded in two parallel brainstem pathways. Acoustically ILDs are a function of location and frequency such that lower and higher frequencies exhibit smaller and larger ILDs, respectively. It is well established that neurons throughout the auditory neuraxis encode high-frequency ILDs. Acoustically, low-frequency ILDs are negligible (∼1­2 dB); however, humans are still sensitive to them and physiological studies often report low-frequency ILD-sensitive neurons. These ­latter findings are at odds with the Duplex theory. We suggest that these discrepancies arise from an inadequate characterization of the acoustical environment. We hypothesize that low-frequency ILDs become large and useful when sources are located near the head. We tested this hypothesis by making measurements of the ILDs in chinchillas as a function of source distance and the sensitivity to ILDs in 103 neurons in the inferior colliculus (IC). The ILD sensitivity of IC neurons was found to be frequency independent even though far-field acoustical ILDs were frequency dependent. However, as source distance was decreased, the magnitudes of low-frequency ILDs increased. Using information theoretic methods, we ­demonstrate that a population of IC neurons can encode the full range of acoustic ILDs across frequency that would be experienced as a joint function of source location and distance.

Effects of unilateral eye closure on middle ear muscle contractions.

Middle ear muscle contractions (MEMCs) are most commonly considered a response to high-level acoustic stimuli. However, MEMCs have also been observed in the absence of sound, either as a response to somatosensory stimulation or in concert with other motor activity. The relationship between MEMCs and non-acoustic sources is unclear. This study examined associations between measures of voluntary unilateral eye closure and impedance-based measures indicative of middle ear muscle activity while controlling for demographic and clinical factors in a large group of participants (N=190) with present clinical acoustic reflexes and no evidence of auditory dysfunction. Participants were instructed to voluntarily close the eye ipsilateral to the ear canal containing a detection probe at three levels of effort. Orbicularis oculi muscle activity was measured using surface electromyography. Middle ear muscle activity was inferred from changes in total energy reflected in the ear canal using a filtered (0.2 to 8 kHz) click train. Results revealed that middle ear muscle activity was positively associated with eye muscle activity. MEMC occurrence rates for eye closure observed in this study were generally higher than previously published rates for high-level brief acoustic stimuli in the same participant pool suggesting that motor activity may be a more reliable elicitor of MEMCs than acoustic stimuli. These results suggest motor activity can serve as a confounding factor for auditory exposure studies as well as complicate the interpretation of any impulsive noise damage risk criteria that assume MEMCs serve as a consistent, uniform protective factor. The mechanism linking eye and middle ear muscle activity is not understood and is an avenue for future research.

Postnatal development of cochlear microphonic and compound action potentials in a precocious species, Chinchilla lanigera.

The development of sound-evoked responses in Chinchilla lanigera was studied from postnatal ages P0-1 (first 24 h) to adult. Cochlear microphonic (CMs) and compound action potentials (CAPs), representing ensemble sound-evoked activities of hair cells and auditory nerve fibers, respectively, were present as early as age P0-1. The data indicate that CM thresholds and sensitivities were generally adult-like (i.e., fall into adult ranges) at birth, but suprathreshold CM amplitudes remained below adult ranges through P28. CAP thresholds reached adult-like values between P7-P14, but the suprathreshold CAP amplitude continued to increase until ∼P28. The results confirm the auditory precociousness of the chinchilla.

Pathologic Features of Down Syndrome Myelodysplastic Syndrome and Acute Myeloid Leukemia: A Report From the Children's Oncology Group Protocol AAML0431.

CONTEXT.­: Detailed diagnostic features of acute myeloid leukemia in Down syndrome are lacking, leading to potential misdiagnoses as standard acute myeloid leukemia occurring in patients with Down syndrome. OBJECTIVE.­: To evaluate diagnostic features of acute myeloid leukemia and myelodysplastic syndrome in patients with Down syndrome. DESIGN.­: Diagnostic bone marrow samples from 163 patients enrolled in the Children's Oncology Group study AAML0431 were evaluated by using central morphologic review and institutional immunophenotyping. Results were compared to overall survival, event-free survival, GATA1 mutation status, cytogenetics, and minimal residual disease results. RESULTS.­: Sixty myelodysplastic syndrome and 103 acute myeloid leukemia samples were reviewed. Both had distinctive features compared to those of patients without Down syndrome. They showed megakaryocytic and erythroid but little myeloid dysplasia, and marked megakaryocytic hyperplasia with unusual megakaryocyte morphology. In acute myeloid leukemia cases, megakaryoblastic differentiation of blasts was most common (54 of 103, 52%); other cases showed erythroblastic (11 of 103, 11%), mixed erythroid/megakaryoblastic (20 of 103, 19%), or no differentiation (10 of 103, 10%). Myelodysplastic syndrome and acute myeloid leukemia cases had similar event-free survival and overall survival. Leukemic subgroups showed interesting, but not statistically significant, trends for survival and minimal residual disease. Cases with institutional diagnoses of French American British M1-5 morphology showed typical features of Down syndrome disease, with survival approaching that of other cases. CONCLUSIONS.­: Myelodysplastic syndrome and acute myeloid leukemia in Down syndrome display features that allow discrimination from standard cases of disease. These distinctions are important for treatment decisions, and for understanding disease pathogenesis. We propose specific diagnostic criteria for Down syndrome-related subtypes of acute myeloid leukemia and myelodysplastic syndrome.

Human middle-ear muscles rarely contract in anticipation of acoustic impulses: Implications for hearing risk assessments.

The current study addressed the existence of an anticipatory middle-ear muscle contraction (MEMC) as a protective mechanism found in recent damage-risk criteria for impulse noise exposure. Specifically, the experiments reported here tested instances when an exposed individual was aware of and could anticipate the arrival of an acoustic impulse. In order to detect MEMCs in human subjects, a laser-Doppler vibrometer (LDV) was used to measure tympanic membrane (TM) motion in response to a probe tone. Here we directly measured the time course and relative magnitude changes of TM velocity in response to an acoustic reflex-eliciting (i.e. MEMC eliciting) impulse in 59 subjects with clinically assessable MEMCs. After verifying the presence of the MEMC, we used a classical conditioning paradigm pairing reflex-eliciting acoustic impulses (unconditioned stimulus, UCS) with various preceding stimuli (conditioned stimulus, CS). Changes in the time-course of the MEMC following conditioning were considered evidence of MEMC conditioning, and any indication of an MEMC prior to the onset of the acoustic elicitor was considered an anticipatory response. Nine subjects did not produce a MEMC measurable via LDV. For those subjects with an observable MEMC (n = 50), 48 subjects (96%) did not show evidence of an anticipatory response after conditioning, whereas only 2 subjects (4%) did. These findings reveal that MEMCs are not readily conditioned in most individuals, suggesting that anticipatory MEMCs are not prevalent within the general population. The prevalence of anticipatory MEMCs does not appear to be sufficient to justify inclusion as a protective mechanism in auditory injury risk assessments.

The Danger Zone for Noise Hazards Around the Black Hawk Helicopter.

BACKGROUND: During ground operations, rotary-wing aircraft engines and subsystems produce noise hazards that place airfield personnel at risk for hearing damage. The noise exposure levels outside the aircraft during various operating conditions, and the distances from aircraft at which they drop to safe levels, are not readily available. The current study measured noise levels at various positions around the UH-60 Black Hawk helicopter for three operating conditions typically used when the aircraft is on the ground. METHODS: Microphones were positioned systematically around the helicopter and A-weighted sound pressure levels (SPLs) were computed from the recordings. In addition, the 85-dBA SPL contour around the aircraft was mapped. The resulting A-weighted SPLs and contour mapping were used to determine the noise hazard area around the helicopter. RESULTS: Measurements reported here show noise levels of 105 dB or greater in all operating conditions. The fueling location at the left rear of the aircraft near the auxiliary power unit (APU) is the area of greatest risk for noise-induced hearing loss (NIHL). Additionally, sound field contours indicate noise hazard areas (>85 dBA SPL) can extend beyond 100 ft from the helicopter. CONCLUSIONS: This report details the areas of greatest risk for auditory injury around the UH-60 Black Hawk helicopter. Our findings suggest the area of hazardous noise levels around the aircraft can extend to neighboring aircraft, particularly on the side of the aircraft where the APU is located. Hearing protection should be worn whenever the aircraft is operating, even if working at a distance.Jones HG, Greene NT, Chen MR, Azcona CM, Archer BJ, Reeves ER. The danger zone for noise hazards around the Black Hawk helicopter. Aerosp Med Hum Perform. 2018; 89(6):547-551.

Spatial variation in signal and sensory precision both constrain auditory acuity at high frequencies.

Sensory performance is constrained by the information in the stimulus and the precision of the involved sensory system(s). Auditory spatial acuity is robust across a broad range of sound frequencies and source locations, but declines at eccentric lateral angles. The basis of such variation is not fully understood. Low-frequency auditory spatial acuity is mediated by sensitivity to interaural time difference (ITD) cues. While low-frequency spatial acuity varies across azimuth and some physiological models predict strong medial bias in the precision of ITD sensitivity, human psychophysical ITD sensitivity appears to vary only slightly with reference ITD magnitude. Correspondingly, recent analyses suggest that spatial variation in human low-frequency acuity is well-accounted for by acoustic factors alone. Here we examine the matter of high-frequency auditory acuity, which is mediated by sensitivity to interaural level difference (ILD) cues. Using two different psychophysical tasks in human subjects, we demonstrate decreasing ILD acuity with increasing ILD magnitude. We then demonstrate that the multiplicative combination of spatially variant sensory precision and physical cue information (local slope of the ILD cue) provides improved prediction of classic high-frequency spatial acuity data. Finally, we consider correlates of magnitude dependent acuity in neurons that are sensitive to ILDs.

HuR, an RNA-binding protein, involved in the control of cellular differentiation.

HuR is an RNA-binding protein that resides predominantly in the nucleus but shuttles to the cytosol carrying mRNAs containing a uridylate-rich region in the 3'untranslated region. Data suggest that HuR is involved in the control of the differentiation process through a tightly regulated selection of mRNAs to be shuttled to the cytosol for translation. In this review, the function of HuR in the differentiation process of preadipocytes is examined in the context of specific mRNAs selected by HuR for translocation to the cytosol.

Preoperative use of enoxaparin compared with unfractionated heparin increases the incidence of re-exploration for postoperative bleeding after open-heart surgery in patients who present with an acute coronary syndrome: clinical investigation and reports.

BACKGROUND: Enoxaparin has become an attractive therapy for use during acute coronary syndrome (ACS) because of its potential superior efficacy over unfractionated heparin (UFH), its longer activity, and its subcutaneous route of administration. However, because a significant number of patients presenting with ACS may be sent directly to open heart surgery while still on anticoagulation, it is important to understand any potential bleeding risks that may be associated with the use of enoxaparin under these circumstances. METHODS: From 1998 to 2001, 1159 consecutive patients presenting with an acute coronary syndrome who received either UFH (n=1008) or enoxaparin (n=151) before proceeding to open heart surgery for urgent therapy during the same hospitalization were included in this study. Incidence of perioperative bleeding as evidenced by the units of blood products (packed red blood cells or platelets) transfused or the need for surgical re-exploration for postoperative bleeding was recorded. RESULTS: Average age was 65+/-11 and 67+/-11 years for patients receiving UFH and enoxaparin, respectively (P=0.005). Seventy-five percent of those receiving UFH and 64% of those receiving enoxaparin (P<0.005) were males. After discharge, the incidence of rehospitalization for hemorrhage requiring return to surgery for re-exploration was 7.9% in the enoxaparin group and 3.7% in the UFH group (adjusted hazard ratio=2.6, P=0.03). The use of blood products did not differ between groups (UFH=2.7+/-6.5 U and enoxaparin=2.3+/-4.5 U; P=NS). CONCLUSION: The preoperative use of enoxaparin compared with UFH in patients presenting with an ACS who undergo open-heart surgery during the same hospitalization is associated with a significantly increased incidence of re-exploration for postoperative bleeding. Further study is needed to understand the mechanism of this phenomenon and to develop appropriate guidelines to address this potentially important issue.