Preliminary evidence for therapeutic impact of intravesical glucosamine on protamine sulfate and potassium chloride-induced bladder overactivity in rat model.

PURPOSE: To investigate the protective effect of intravesical glucosamine in treating overactive bladder (OAB). METHODS: Ninety-two female Sprague-Dawley (SD) rats were divided into 4 groups i.e. protamine sulfate (PS), N-acetylcysteine (NAC), and glucosamine-treated PS (GPS), and normal saline control (NC) were used. We induced hyperactivity in rats via intravesical infusion of PS and potassium chloride (KCl), whereas the NC group underwent a sustained intravesical saline infusion for 1 h. N-acetylcysteine (NAC), a potential antioxidant as well as anti-inflammatory agent was employed as positive control. Cystometrography (CMG) was then conducted to determine urodynamic parameters, i.e., leak point pressure (LPP, n = 48) and inter-contractile interval, the duration between two voids (ICI, n = 32). RESULTS: LPP was significantly elevated in the GPS group (mean ± SD: 110.9 ± 6.2 mmHg) compared to the NC (81.0 ± 32.5 mmHg), PS (40.3 ± 10.9 mmHg), and NAC group (70.3 ± 19.4 mmHg). The cystometrogram data also reveals a prolonged ICI in the GPS group (241.3 ± 40.2 s) compared to the NC group (216.0 ± 41.7 s), PS group (128.8 ± 23.6 s), and NAC group (193.8 ± 28.3 s). CONCLUSION: This preliminary study implies the ameliorative impact of GPS treatment on OAB in terms of improved urodynamic parameters, including LPP and ICI.

The impact of photobiomodulation on sleep and life quality in hemodialysis patients: A randomized controlled trial.

The quality of life (QoL) and sleep quality are closely linked to the physical and psychological health of end-stage renal disease (ESRD) patients, especially those underwent hemodialysis (HD) therapy. This study aims to investigate the impact of 830 nm laser treatment on improving QoL and sleep quality in HD patients. Forty ESRD patients participated in this study. 830 nm laser was used to radiate on the palm (at dose of 256.10 J/cm2), ST 36 and KI 1 acupoints (at dose of 109.76 J/cm2) of HD patients, and QoL and sleep quality questionnaires were utilized to assess changes following the treatment. After 830 nm laser radiation, lower global Pittsburgh Sleep Quality Index and Athens Insomnia Scale scores were observed, accompanied by higher physical and mental component summary scores in MOS 36-item short-form health survey version 2 and a global World Health Organization Quality of Life Brief Version score. The laser group also showed significant improvements in QoL and sleep quality indicators. Additionally, pain levels decreased on the third day and after one month according to visual analogue scale. This study revealed the positive effects of 830 nm laser on palm, KI 1 and ST 36 acupoints for improving the QoL and sleep quality in ESRD patients underwent HD treatment. The results suggest that 830 nm laser applied to specific targets could be used as a complementary and alternative approach to increase the QoL and sleep quality in ESRD patients.

An Approach for Personalized Dynamic Assessment of Chronic Kidney Disease Progression Using Joint Model.

Chronic kidney disease (CKD) poses significant challenges to public health and healthcare systems, demanding a comprehensive understanding of its progressive nature. Prior methods have often fallen short in capturing the dynamic and individual variability of renal function. This study aims to address this gap by introducing a novel approach for the individualized assessment of CKD progression. A cohort of 1042 patients, comprising 700 with stage 3a and 342 with stage 3b to stage 5 CKD, treated at a veteran general hospital in Taiwan from 2006 to 2019, was included in the study. A comprehensive dataset spanning 12 years, consisting of clinical measurements, was collected and analyzed using joint models to predict the progression to hemodialysis treatment. The study reveals that the estimated glomerular filtration rate (eGFR) can be considered an endogenous factor influenced by innate biochemical markers. Serum creatinine, blood pressure, and urinary protein excretion emerged as valuable factors for predicting CKD progression. The joint model, combining longitudinal and survival analyses, demonstrated predictive versatility across various CKD severities. This innovative approach enhances conventional models by concurrently incorporating both longitudinal and survival analyses and provides a nuanced understanding of the variables influencing renal function in CKD patients. This personalized model enables a more precise assessment of renal failure risk, tailored to each patient's unique clinical profile. The findings contribute to improving the management of CKD patients and provide a foundation for personalized healthcare interventions in the context of renal diseases.

Applying the reference values of real-ear-to-coupler-difference for deaf and hard-of-hearing children in Taiwan: Cautions and considerations.

Measurement of real-ear-to-coupler differentials (RECDs) is a critical part of the hearing aid (HA) verification process. This study examines the validity of reference RECD values preset by the HA analyzer, Audioscan RM500, for deaf-and-hard-of-hearing (DHH) children in Taiwan. RECD measurements were performed on 658 ears of DHH children. A linear mixed model was used to analyze the reference and measured RECD values. The findings revealed slight disparities between normative RECD values from North America and those observed in Taiwanese DHH children. While generally small (less than 5 dB), these differences imply potential challenges in achieving optimal HA fitting in specific scenarios. Therefore, we recommend individualized RECD/REM measurements for cases of poor auditory performance, certain frequency ranges, or notable variations in ear canal volume. From a clinical perspective, while broadly applicable, the use of North American RECD normative data in Taiwan requires cautious consideration of potential minor variations. This study contributes to current knowledge by affirming the use of a Western RECD database for Taiwanese DHH children. However, we underscore the ongoing importance of individualized HA fitting strategies, particularly for cases with stagnant intervention progress. While built-in RECD reference values can offer preliminary fitting guidance, especially in busy clinical settings, our study sheds light on the circumstances where caution is essential. Audiologists can efficiently allocate their time and effort by focusing on personalized RECD measurements for cases exhibiting suboptimal intervention outcomes, thereby effectively optimizing HA gain settings.

Femtosecond proton transfer in urea solutions probed by X-ray spectroscopy.

Proton transfer is one of the most fundamental events in aqueous-phase chemistry and an emblematic case of coupled ultrafast electronic and structural dynamics1,2. Disentangling electronic and nuclear dynamics on the femtosecond timescales remains a formidable challenge, especially in the liquid phase, the natural environment of biochemical processes. Here we exploit the unique features of table-top water-window X-ray absorption spectroscopy3-6 to reveal femtosecond proton-transfer dynamics in ionized urea dimers in aqueous solution. Harnessing the element specificity and the site selectivity of X-ray absorption spectroscopy with the aid of ab initio quantum-mechanical and molecular-mechanics calculations, we show how, in addition to the proton transfer, the subsequent rearrangement of the urea dimer and the associated change of the electronic structure can be identified with site selectivity. These results establish the considerable potential of flat-jet, table-top X-ray absorption spectroscopy7,8 in elucidating solution-phase ultrafast dynamics in biomolecular systems.

Machine Learning Models for the Prediction of Renal Failure in Chronic Kidney Disease: A Retrospective Cohort Study.

This study assessed the feasibility of five separate machine learning (ML) classifiers for predicting disease progression in patients with pre-dialysis chronic kidney disease (CKD). The study enrolled 858 patients with CKD treated at a veteran's hospital in Taiwan. After classification into early and advanced stages, patient demographics and laboratory data were processed and used to predict progression to renal failure and important features for optimal prediction were identified. The random forest (RF) classifier with synthetic minority over-sampling technique (SMOTE) had the best predictive performances among patients with early-stage CKD who progressed within 3 and 5 years and among patients with advanced-stage CKD who progressed within 1 and 3 years. Important features identified for predicting progression from early- and advanced-stage CKD were urine creatinine and serum creatinine levels, respectively. The RF classifier demonstrated the optimal performance, with an area under the receiver operating characteristic curve values of 0.96 for predicting progression within 5 years in patients with early-stage CKD and 0.97 for predicting progression within 1 year in patients with advanced-stage CKD. The proposed method resulted in the optimal prediction of CKD progression, especially within 1 year of advanced-stage CKD. These results will be useful for predicting prognosis among patients with CKD.

Acrolein plays a culprit role in the pathogenesis of diabetic nephropathy in vitro and in vivo.

Objective: Diabetic nephropathy (DN), also known as diabetic kidney disease (DKD), is a major chronic complication of diabetes and is the most frequent cause of kidney failure globally. A better understanding of the pathophysiology of DN would lead to the development of novel therapeutic options. Acrolein, an α,ß-unsaturated aldehyde, is a common dietary and environmental pollutant. Design: The role of acrolein and the potential protective action of acrolein scavengers in DN were investigated using high-fat diet/ streptozotocin-induced DN mice and in vitro DN cellular models. Methods: Acrolein-protein conjugates (Acr-PCs) in kidney tissues were examined using immunohistochemistry. Renin-angiotensin system (RAS) and downstream signaling pathways were analyzed using quantitative RT-PCR and Western blot analyses. Acr-PCs in DN patients were analyzed using an established Acr-PC ELISA system. Results: We found an increase in Acr-PCs in kidney cells using in vivo and in vitro DN models. Hyperglycemia activated the RAS and downstream MAPK pathways, increasing inflammatory cytokines and cellular apoptosis in two human kidney cell lines (HK2 and HEK293). A similar effect was induced by acrolein. Furthermore, acrolein scavengers such as N-acetylcysteine, hydralazine, and carnosine could ameliorate diabetes-induced kidney injury. Clinically, we also found increased Acr-PCs in serum samples or kidney tissues of DKD patients compared to normal volunteers, and the Acr-PCs were negatively correlated with kidney function. Conclusions: These results together suggest that acrolein plays a role in the pathogenesis of DN and could be a diagnostic marker and effective therapeutic target to ameliorate the development of DN.

Behavioral and Neural Assessments of Auditory Skill Development After Hearing Instrument Fitting in Children: Case Reports and Clinical Implications.

PURPOSE: The purpose of this study was to comprehensively monitor the auditory skill development of children with hearing loss after hearing instrument fitting, and a battery of four assessments was proposed. METHOD: This battery was designed to fill the gap in speech discrimination in clinically available evaluations. The battery includes both behavioral and neural assessments. On the other hand, both tests in structured settings (sound-treated booth) and daily life were included in the battery. The four assessments include visual reinforced infant speech discrimination (VRISD), cortical auditory evoked potentials (CAEP), Auditory Skills Checklist (ASC), and Parents' Evaluation of Aural/Oral Performance of Children (PEACH). RESULTS: Two cases were reported, and their clinical implications were discussed. CONCLUSIONS: The proposed comprehensive assessment battery is suitable for evaluating children who are developmentally appropriate for visual reinforcement audiometry. More importantly, the VRISD assessment fills in the current gap, which is the discrimination stage, for the available clinical tests for assessing auditory developmental stages.

Temperature measurements of liquid flat jets in vacuum.

Sub-µm thin samples are essential for spectroscopic purposes. The development of flat micro-jets enabled novel spectroscopic and scattering methods for investigating molecular systems in the liquid phase. However, the temperature of these ultra-thin liquid sheets in vacuum has not been systematically investigated. Here, we present a comprehensive temperature characterization using optical Raman spectroscopy of sub-micron flatjets produced by two different methods: colliding of two cylindrical jets and a cylindrical jet compressed by a high pressure gas. Our results reveal the dependence of the cooling rate on the material properties and the source characteristics, i.e., nozzle-orifice size, flow rate, and pressure. We show that materials with higher vapor pressures exhibit faster cooling rates, which is illustrated by comparing the temperature profiles of water and ethanol flatjets. In a sub-µm liquid sheet, the temperature of the water sample reaches around 268 K and the ethanol around 253 K close to the flatjet's terminus.

Static and Dynamic Prediction of Chronic Renal Disease Progression Using Longitudinal Clinical Data from Taiwan's National Prevention Programs.

Kidney diseases can cause severe morbidity, mortality, and health burden. Determining the risk factors associated with kidney damage and deterioration has become a priority for the prevention and treatment of kidney disease. This study followed 1042 chronic kidney disease (CKD) patients with Stage 3-5 kidney disease who were treated at a public veteran's hospital through the national prevention program. A total of 12.5 years of records of clinical measurements were collected and analyzed using dynamic and static Cox hazard models to predict the progression to dialysis treatment. The results showed that the statistical significance of several variables in patients with Stage 3-5 CKD was attenuated while the dynamic model was being used. The estimated glomerular filtration rate (eGFR) and urine protein to creatinine ratio (PCR) had the powerful ability to predict the progression of CKD patients with Stage 3a and Stage 3b-5 kidney disease, whereas serum calcium was also predictive for the progression of Stages 3b-5 CKD. Because these two sub-stages of Stage 3 CKD are often associated with differences in routine measurements and the risk analysis of renal dialysis, future research can use this predictive model as a reference while similar prevention programs are implemented.

Femtosecond Soft-X-ray Absorption Spectroscopy of Liquids with a Water-Window High-Harmonic Source.

Femtosecond X-ray absorption spectroscopy (XAS) is a powerful method to investigate the dynamical behavior of a system after photoabsorption in real time. So far, the application of this technique has remained limited to large-scale facilities, such as femtosliced synchrotrons and free-electron lasers (FEL). In this work, we demonstrate femtosecond time-resolved soft-X-ray absorption spectroscopy of liquid samples by combining a sub-micrometer-thin flat liquid jet with a high-harmonic tabletop source covering the entire water-window range (284-538 eV). Our work represents the first extension of tabletop XAS to the oxygen edge of a chemical sample in the liquid phase. In the time domain, our measurements resolve the gradual appearance of absorption features below the carbon K-edge of ethanol and methanol during strong-field ionization and trace the valence-shell ionization dynamics of the liquid alcohols with a temporal resolution of ∼30 fs. This technique opens unique opportunities to study molecular dynamics of chemical systems in the liquid phase with elemental, orbital, and site sensitivity.

Light-wave dynamic control of magnetism.

The enigmatic interplay between electronic and magnetic phenomena observed in many early experiments and outlined in Maxwell's equations propelled the development of modern electromagnetism1. Today, the fully controlled evolution of the electric field of ultrashort laser pulses enables the direct and ultrafast tuning of the electronic properties of matter, which is the cornerstone of light-wave electronics2-7. By contrast, owing to the lack of first-order interaction between light and spin, the magnetic properties of matter can only be affected indirectly and on much longer timescales, through a sequence of optical excitations and subsequent rearrangement of the spin structure8-16. Here we introduce the regime of ultrafast coherent magnetism and show how the magnetic properties of a ferromagnetic layer stack can be manipulated directly by the electric-field oscillations of light, reducing the magnetic response time to an external stimulus by two orders of magnitude. To track the unfolding dynamics in real time, we develop an attosecond time-resolved magnetic circular dichroism detection scheme, revealing optically induced spin and orbital momentum transfer in synchrony with light-field-driven coherent charge relocation17. In tandem with ab initio quantum dynamical modelling, we show how this mechanism enables the simultaneous control of electronic and magnetic properties that are essential for spintronic functionality. Our study unveils light-field coherent control of spin dynamics and macroscopic magnetic moments in the initial non-dissipative temporal regime and establishes optical frequencies as the speed limit of future coherent spintronic applications, spin transistors and data storage media.

Morphomechanical alterations in the medial gastrocnemius muscle in patients with a repaired Achilles tendon: Associations with outcome measures.

BACKGROUND: Functional deficits are found in ankles that have sustained an Achilles rupture. This study sought to evaluate and compare the morphomechanical characteristics of the medial gastrocnemius muscle in the legs of participants within six months of a unilateral Achilles repair to determine any correlations between those characteristics and objective outcomes and self-reported functional levels. METHODS: Fifteen participants were assessed via measurements of muscle morphologies (fascicle length, pennation angle, and muscle thickness) in a resting state, the mechanical properties of the proximal aponeurosis of the medial gastrocnemius muscle, the pennation angle during ramping maximal voluntary isometric contractions (MVIC), the heel raise test, and the Taiwan Chinese version of the Lower Extremity Functional Scale (LEFS-TC) questionnaire. Findings Compared with the non-injured legs, the repaired legs showed a lower muscle fascicle length (mean 4.4 vs. 5.0cm) and thickness (1.7 vs. 1.9cm), lower stiffness of the GM tendon and aponeurosis (174.1 vs. 375.6N/mm), and a greater GM pennation angle (31.2 vs. 28.9°) during 90% MVIC (all p≤0.05). Correlations were found between the morphomechanical results and maximal heel raise heights or the LEFS-TC score, and between the symmetry ratios of the fascicle lengths and the LEFS-TC score. Interpretation There are decreases in fascicle length, muscle thickness and mechanical properties in the medial gastrocnemius muscles of the participants within the first six months after an Achilles repair. These morphomechanical alterations demonstrate associations with functional levels in the lower extremities and indicated the need for early mobilization of the calf muscles after the repair.

Characteristics of Intratendinous Microcirculation Shortly After an Achilles Rupture and Subsequent Treatment Outcomes.

BACKGROUND: Early microcirculatory responses after experimental tenotomy are critical to the healing of tendons and their ultimate tensile strength. The effects of changes in microcirculation on the outcomes of tendon healing, however, have not been determined. OBJECTIVES: To assess microcirculation values in injured Achilles tendons in the first 3 months after surgical repair and to correlate the inter-limb microcirculatory changes with functional outcomes at 3 and 6 months after surgery. DESIGN: Case-control study. SETTING: A university sports physiotherapy laboratory. PARTICIPANTS: Thirteen subjects (median age: 45 years; range: 34.8-51.9 years) with a repaired Achilles tendon were recruited. METHODS OR INTERVENTION: Surgical repair. MAIN OUTCOME MEASUREMENTS: Measurements were obtained at 1, 2, 3, and 6 months after surgery. Bilateral measurements of tendon microcirculation (total hemoglobin [THb] and oxygen saturation [StO2]) were recorded at the first 3 time points, whereas outcome measures of a Taiwan Chinese version of the Victorian Institute of Sport Assessment Scale-Achilles questionnaire, one-leg hopping distance, the star excursion balance test, and the heel raise index were conducted at the third and fourth time points. Correlations between the inter-limb microcirculatory changes, eg, between the measurements at 2 months and 1 month (2-1) after surgery, at 3 months and 2 months (3-2) after surgery, and at 3 months and 1 month (3-1) after surgery, and the outcome measures were investigated. RESULTS: Compared with the noninjured tendons, the repaired Achilles demonstrated greater THb (at 1, 2, and 3 months; P = .017, .008, and .012 respectively) and StO2 (at 3 months; P = .017). Furthermore, the THb2-1 and THb3-2, StO2 2-1, and StO2 3-2 showed correlations with the heel raise index, differences in the star excursion balance test and one-leg hopping distance between the noninjured leg and injured leg, and Taiwan Chinese version of the Victorian Institute of Sport Assessment Scale-Achilles questionnaire scores (rho -0.921 to 0.855). CONCLUSIONS: Changes in the inter-limb microcirculation shortly after Achilles repair were correlated with subsequent symptoms and functional symmetry. LEVEL OF EVIDENCE: III.

Mandarin Tone and Vowel Recognition in Cochlear Implant Users: Effects of Talker Variability and Bimodal Hearing.

OBJECTIVES: For cochlear implant (CI) users with residual low-frequency acoustic hearing in the nonimplanted ear, bimodal hearing combining the use of a CI and a contralateral hearing aid (HA) may provide more salient talker voice cues than CI alone to handle the variability of talker identity across trials. This study tested the effects of talker variability, bimodal hearing, and their interaction on response accuracy and time of CI users' Mandarin tone, vowel, and syllable recognition (i.e., combined Mandarin tone and vowel recognition in this study). DESIGN: Fifteen prelingually deafened native Mandarin-speaking CI users (at age 20 or lower) participated in this study. Four talkers each produced six Mandarin single-vowel syllables in four lexical tones. The stimuli were presented in quiet via a single loudspeaker. To study the effects of talker variability, Mandarin tone, vowel, and syllable recognition was tested in two presentation conditions: with stimuli blocked according to talker (blocked-talker condition) or mixed across talkers from trial to trial (mixed-talker condition). To explore the effects of bimodal hearing, two processor conditions were tested: CI alone or CI + HA. The cumulative response time was recorded as an indirect indicator of the cognitive load or listening effort in each condition. The correlations were computed between demographic/hearing factors (e.g., hearing thresholds in the nonimplanted ear) and bimodal performance/benefits (where bimodal benefits refer to the performance differences between CI alone and CI + HA). RESULTS: Mandarin tone recognition with both CI alone and CI + HA was significantly poorer in the mixed-talker condition than in the blocked-talker condition, while vowel recognition was comparable in the two presentation conditions. Bimodal hearing significantly improved Mandarin tone recognition but not vowel recognition. Mandarin syllable recognition was significantly affected by both talker variability and bimodal hearing. The cumulative response time significantly reduced with CI + HA compared with CI alone, but remained invariant with respect to talker variability. There was no interaction between talker variability and bimodal hearing for any performance measure adopted in this study. Correlation analyses revealed that the bimodal performance and benefits in Mandarin tone, vowel, and syllable recognition could not be predicted by the hearing thresholds in the nonimplanted ear or by the demographic factors of the participants. CONCLUSIONS: Talker variability from trial to trial significantly degraded Mandarin tone and syllable recognition performance in both the CI alone and CI + HA conditions. While bimodal hearing did not reduce the talker variability effects on Mandarin tone and syllable recognition, generally better Mandarin tone and syllable recognition performance with shorter response time (an indicator of less listening effort) was observed when a contralateral HA was used in conjunction with the CI. On the other hand, vowel recognition was not significantly affected by either talker variability or bimodal hearing, because ceiling effects could not be counted out of the vowel recognition results.

Effects of Therapeutic Physical Agents on Achilles Tendon Microcirculation.

STUDY DESIGN: Controlled laboratory study. OBJECTIVES: To measure Achilles tendon microcirculation (total hemoglobin [THb] and oxygen saturation [StO2]) before and after the application of a physical agent in asymptomatic participants, and to compare differences between application location and physical agent dosage. BACKGROUND: Tendon microcirculation can be altered by superficial heating or cryotherapy. METHODS: Fifty-one healthy adults (median age, 22 years; range, 20-34 years) were recruited and randomly assigned into 1 of 4 groups. Participants in each group received an intervention consisting of 1 of the following 4 physical agents: ultrasound (n = 12), interferential current (n = 14), low-level laser (n = 11), or vibration massage (n = 14). In each group, the selected intervention was applied at 2 different doses (ultrasound, 0.8 or 1.2 W/cm(2); laser, 5.4 or 18 J) or target locations (vibration and electrostimulation, calf muscle or Achilles tendon). For each participant, each dose or target location was randomly applied to 1 randomly selected lower leg (each leg receiving only 1 of the 2 options). RESULTS: The StO2 values significantly increased after ultrasound at both doses (P<.008), and the THb value significantly increased for the higher dose only (P<.008). Both THb and StO2 values also significantly increased in response to vibration massage targeting the Achilles tendon (P<.008), and these values were greater than those resulting from the vibration massage applied to the calf muscle (P = .003 and .002, respectively). No significant THb and StO2 differences were found after the application of interferential current or low-level laser. CONCLUSION: Tendon microcirculation increases after ultrasound and vibration massage intervention concentrated on the Achilles tendon. These modalities may be considered for the purpose of temporarily increasing microcirculation in the tendon.

A test protocol for assessing the hearing status of students with special needs.

OBJECTIVES: Individuals with disabilities are often reported to have a high prevalence of undetected hearing disorders/loss, but there is no standardized hearing test protocol for this population. The purposes of this study were (1) to examine the hearing status of students with special needs in Taiwan, and (2) to investigate the use of an on-site hearing test protocol that would adequately detect hearing problems in this population and reduce unnecessary referrals for off-site follow-up services. METHODS: A total of 238 students enrolled in two schools for special education and one habilitation center participated in the study. Most students had intellectual disabilities and some also had additional syndromes or disorders. A hearing screening protocol including otoscopy, tympanometry, and distortion product otoacoustic emissions was administered to examine students' outer, middle, and inner ear functions, respectively. Pure tone tests were then administered as an on-site follow-up for those who failed or could not be tested using the screening protocol. RESULTS: Only 32.4% of students passed. When administered alone, the referral rate of otoscopy, tympanometry, and otoacoustic emissions were 38.7%, 46.0%, and 48.5%, respectively. The integration of these subtests revealed 52.1% of students needed follow-up services, 11.8% could not be tested, 2.5% had documented hearing loss, and 1.3% needed to be monitored because of negative middle ear pressure. The inclusion of pure tone audiometry increased the passing rate by 9.9% and provided information on hearing sensitivity for an additional 8.6% of students. CONCLUSION: Hearing assessments and regular hearing screening should be provided as an integral part of health care services for individuals with special needs because of high occurrences of excessive cerumen, middle ear dysfunction, and sensorineural hearing loss. The training of care-givers and teachers of students with special needs is encouraged so that they can help identify hearing problems and reduce the negative impact of hearing disorders and hearing loss. The screening protocol needs to include subtests that examine the status of different parts of their auditory system. The addition of pure tone audiometry as an on-site follow-up tool reduced the rate of off-site referrals and provided more information on hearing sensitivity.

Perception of speech produced by native and nonnative talkers by listeners with normal hearing and listeners with cochlear implants.

PURPOSE The aim of this study was to evaluate the understanding of English sentences produced by native (English) and nonnative (Spanish) talkers by listeners with normal hearing (NH) and listeners with cochlear implants (CIs). METHOD Sentence recognition in noise was measured in adult subjects with CIs and subjects with NH, all of whom were native talkers of American English. Test sentences were from the Hearing in Noise Test (HINT) database and were produced in English by four native and eight nonnative talkers. Subjects also rated the intelligibility and accent for each talker. RESULTS The speech recognition thresholds in noise of subjects with CIs and subjects with NH were 4.23 dB and 1.32 dB poorer with nonnative talkers than with native talkers, respectively. Performance was significantly correlated with talker intelligibility and accent ratings for subjects with CIs but only correlated with talker intelligibility ratings for subjects with NH. For all subjects, performance with individual nonnative talkers was significantly correlated with talkers' number of years of residence in the United States. CONCLUSION CI users exhibited a larger deficit in speech understanding with nonnative talkers than did subjects with NH, relative to native talkers. Nonnative talkers' experience with native culture contributed strongly to speech understanding in noise, intelligibility ratings, and accent ratings of both listeners with NH and listeners with CIs.

Contribution of bimodal hearing to lexical tone normalization in Mandarin-speaking cochlear implant users.

Native Mandarin normal-hearing (NH) listeners can easily perceive lexical tones even under conditions of great voice pitch variations across speakers by using the pitch contrast between context and target stimuli. It is however unclear whether cochlear implant (CI) users with limited access to pitch cues can make similar use of context pitch cues for tone normalization. In this study, native Mandarin NH listeners and pre-lingually deafened unilaterally implanted CI users were asked to recognize a series of Mandarin tones varying from Tone 1 (high-flat) to Tone 2 (mid-rising) with or without a preceding sentence context. Most of the CI subjects used a hearing aid (HA) in the non-implanted ear (i.e., bimodal users) and were tested both with CI alone and CI + HA. In the test without context, typical S-shaped tone recognition functions were observed for most CI subjects and the function slopes and perceptual boundaries were similar with either CI alone or CI + HA. Compared to NH subjects, CI subjects were less sensitive to the pitch changes in target tones. In the test with context, NH subjects had more (resp. fewer) Tone-2 responses in a context with high (resp. low) fundamental frequencies, known as the contrastive context effect. For CI subjects, a similar contrastive context effect was found statistically significant for tone recognition with CI + HA but not with CI alone. The results suggest that the pitch cues from CIs may not be sufficient to consistently support the pitch contrast processing for tone normalization. The additional pitch cues from aided residual acoustic hearing can however provide CI users with a similar tone normalization capability as NH listeners.

Reversine induces cell cycle arrest, polyploidy, and apoptosis in human breast cancer cells.

BACKGROUND: Reversine, a small synthetic purine analogue, has been reported to be effective in tumor suppression. In the present study, we demonstrated an antitumor activity of reversine that could suppress cellular proliferation and induce cell cycle arrest and apoptosis in human breast cancer cell lines. METHODS: To evaluate whether reversine could suppress cell growth of MCF-7 and MDA-MB-231 cells and induce cell death, the cell viability, cell cycle, and apoptosis were determined in this study. RESULTS: Reversine treatment in human breast cancer cells reduced cell viability in a dose-dependent manner. Cell cycle accumulation at the G2/M phase in reversine-treated cells was also determined. Moreover, polyploidy was also found in reversine-treated cells. Apoptosis in reversine-treated cells was exhibited with PARP cleavage and caspase-3 and caspase-8 activation, but not caspase-9 activation, indicating that caspase-dependent apoptosis mediated by an extrinsic pathway took place in reversine-treated cells. Furthermore, reversine attenuated cell death in cells pretreated with a pan-caspase inhibitor before reversine treatment. CONCLUSIONS: In the present study, we demonstrated that reversine contributes to growth inhibition in human breast cancer cells through cell cycle arrest, polyploidy, and/or apoptosis induction. The apoptosis mediated by reversine was induced by the mitochondria-independent pathway. Therefore, the potential role of reversine as a novel therapeutic agent for the treatment of breast cancer is worthy of further investigation.