Detrending produced slightly better agreement between the inertial measurement unit and Vicon system on firm surfaces (delta range: −0.05 to 0.06 vs. 0.00 to 0.14 m.s−2), whereas the quaternion method performed better when walking on compliant and uneven walkways (delta range: −0.16 to −0.02 vs. −0.07 to 0.07 m.s−2). The technique used to compensate for gravitational accelerations requires consideration in future research, particularly when walking on compliant and uneven surfaces. These findings demonstrate trunk accelerations can be accurately measured using a wireless inertial measurement unit and are appropriate for research that evaluates healthy populations in complex environments.Although accelerometers are extensively used for assessing gait, limited research has evaluated the concurrent validity of these devices on less predictable walking surfaces or the comparability of different methods used for gravitational acceleration compensation. This study evaluated the concurrent validity of trunk accelerations derived from a tri-axial inertial measurement unit while walking on firm, compliant and uneven surfaces and contrasted two methods used to remove gravitational accelerations; i) subtraction of the best linear fit from the data (detrending); and ii) use of orientation information (quaternions) from the inertial measurement unit. Twelve older and twelve younger adults walked at their preferred speed along firm, compliant and uneven walkways. Accelerations were evaluated for the thoracic spine (T12) using a tri-axial inertial measurement unit and an eleven-camera Vicon system. The findings demonstrated excellent agreement between accelerations derived from the inertial measurement unit and motion analysis system, including while walking on uneven surfaces that better approximate a real-world setting (all differences <0.16 m.s Accelerometry is a reliable and cost-effective alternative for the measurement of gait in various populations. One of the main advantages, compared to conventional optical motion capture systems, is that data can be collected continuously over an extended time period and over long distances Importantly, previous research has examined the accuracy of the measures derived from these devices against a ‘gold standard’ method  to evaluate concurrent validity under both strictly-controlled experimental conditions Although alternating current (AC) coupled accelerometers are known to be insensitive to gravitational accelerations This research aimed to provide a comprehensive assessment of the; 1) concurrent validity of trunk accelerations derived from a three-dimensional IMU for groups of younger and older adults when walking on firm, compliant and uneven surfaces; and 2) effect of using two different methods to correct for gravitational acceleration; namely, detrending and subtraction using orientation information derived from the IMU. Assessment of concurrent validity of trunk accelerations derived from an accelerometer is of particular importance, given this body segment is often used to evaluate walking stability and falls risk in different populations The experimental protocol was approved by the Human Research Ethics Committee at the Queensland University of Technology and conducted in accordance with the Declaration of Helsinki.Twelve healthy older participants aged between 65 and 90 years  and twelve healthy younger adults aged between 20 and 25 years  gave written informed consent to participate in this study . Particith thoracic vertebra to measure trunk accelerations during walking. The IMU was attached to the skin using Tesa 4965 polyester double-sided tape  and firmly reinforced using Micropore tape . A custom-made rigid body that comprised three 14 mm reflective markers was firmly secured around, but not in contact with (at least 3 mm clearance), the IMU using an adjustable Velcro strap. Lateral slippage of the rigid body was minimised by a firm backing that allowed it to sit neatly against the spinous processes of the spine between the trunk extensor muscles  was attached to the skin overlying the spinous process of the 12 muscles . The rigParticipants walked barefoot at a self-selected and preferred pace along 3 surfaces; i) a firm surface ; ii) a compliant surface ; and iii) an uneven surface . The uneven surface comprised a series wooden blocks , which were placed at random locations under a layer of foam and artificial turf. Three-dimensional accelerations were collected wirelessly via Bluetooth from the IMU at 100 Hz and interpolated to an effective sampling rate of 200 Hz using a cubic spline function. The three reflective markers on the rigid body were tracked (200 Hz) within the central 4 m length of the walkways by a calibrated eleven-camera motion analysis system . The accelerometer recordings were synchronised with the three-dimensional motion analysis data by an event signal triggered by the experimenter during each trial. Three trials were performed on each surface and the order in which the walking surfaces were completed was randomised for each individual.Data were analysed using software developed in MATLAB . Accelerations from the IMU were derived in relation to the accelerometer's axis system and low-pass filtered at 10 Hz using a bi-directional fourth order Butterworth filter. Two methods were then used to separate the movement-related accelerations from the gravitational acceleration. The first method, the "detrending" method, assumed the gravitational component was a very low frequency component that offset the movement-related accelerations, and accounted for this offset by removal of the best linear fit from the acceleration signal. The second method, the "quaternion" method, used the orientation information provided by the IMU, expressed in quaternions, which were derived from a statistical combination of the internal 3D magnetometer, gyroscope and accelerometer using a proprietary Kalman filter. The gravity vector (me point .(1)Posit2) test. To compare the mean RMS AP, ML and VT accelerations derived from the Vicon system and the IMU using both the detrended and quaternion methods  on the firm, compliant and uneven surfaces , a repeated measures ANOVA was used. When a statistically significant main effect was identified, the Fisher's least significant difference post-hoc test was used to determine which methods and/or surfaces were significantly different. If one or more of the assumptions of the parametric procedures were violated, the data were analysed using the non-parametric Kruskal-Wallis or Friedman tests.To evaluate differences between the older and younger participant groups, continuous demographic variables were examined using a one-way analysis of variance (ANOVA) and the degree of association between the categorical variables was assessed with the chi-square  and the Vicon motion analysis system during the three walking trials, ICCs were calculated for the repeated measurements taken on each surface , absolute agreement). For this study, ICCs<0.4 were considered to represent poor agreement, values between 0.4 and 0.75 were considered to represent fair to good agreement and values >0.75 represented excellent agreement p<0.05.Given the excellent trial-to-trial reliability observed, the RMS accelerations for the three trials on each walking surface were averaged and the concurrent validity of the IMU and Vicon systems was appraised using a two-way ANOVA with random effects model. The intraclass correlation coefficient , absolute agreement) was calculated as the ratio of the variance between the participants and between the instruments in relation to the relative error −2 & 0.00 to 0.07 m.s−2 for the detrending and quaternion methods, respectively; −2 & 0.11 to 0.14 m.s−2 for the detrending and quaternion methods, respectively). These findings were supported by the Bland-Altman analyses (The average difference between the accelerations derived from the IMU and the Vicon system (delta) showed excellent agreement for ML and VT accelerations on the firm walkway using both methods of gravity correction  and younger participants .The age of the participants did not influence the agreement between the systems, and the IMU provided accurate acceleration patterns along all three axes while walking on the firm, compliant and uneven surfaces for both groups . With thThis study confirms the concurrent validity of accelerations derived from a light-weight IMU positioned on the trunk  of younger and older people while walking on firm, compliant and uneven surfaces. A key observation was that trunk acceleration amplitude could be accurately measured using wireless accelerometer technology, even on surfaces that were less stable and predictable and, thus, representative of a real-world setting. Additionally, the results indicated that compensation for gravitational acceleration using the orientation information provided by the IMU was superior to using detrending methods, when the walking surface was compliant or uneven.Although numerous studies have investigated the accuracy of orientation −2), but this was less evident when gravity was subtracted using the quaternion data (range = −0.07 to 0.07 m.s−2). The main difference between the two methods was the manner in which gravitational acceleration was accounted for. The detrending method assumed that gravity offsets the data in a constant manner and did not account for gravitational acceleration that potentially violated this assumption. For example, the detrending method may not be appropriate when the orientation of an accelerometer changes in relation to gravity more rapidly than a linear fit of the data can predict. As such, correction for the effects of gravity on a sample-by-sample basis using the orientation information (quaternions) provided by the IMU would be expected to provide a more accurate representation of segmental accelerations and this was confirmed by the present results.The amplitude of trunk accelerations for the older and younger participants were comparable with previous data of younger It should be acknowledged that some of the small differences observed between the IMU and Vicon systems in the current study can be explained by the fact that the accelerations were directly measured by the IMU, but were calculated from displacement data for the Vicon system. It is widely recognised that derivation of accelerations from displacement data using the conventional finite difference approach can amplify high-frequency noise present in the displacement data. Although the displacement data collected using the Vicon system were low-pass filtered prior to differentiation, it is important to consider the potential influence on the comparison data. Furthermore, although the findings presented in this study provide support for the validity of gait-related accelerations derived from a trunk-mounted IMU in healthy older and younger adults, additional research is required to determine whether these findings are transferable to other populations.In summary, this study demonstrates that a light-weight three-dimensional IMU can accurately evaluate trunk accelerations for healthy younger and older adults while walking on firm, compliant and uneven surfaces. Although, the detrending method provides slightly better gravity compensation on the firm surface for AP accelerations derived from this IMU, agreement was improved when gravity was subtracted using the quaternion method on the compliant and uneven surfaces. These findings have important implications for the investigation of postural stability and gait on more challenging surfaces that better approximate real-world environments (e.g. within the home). Future research is needed to examine whether accelerometer technology is suitable to evaluate postural stability and gait during more complex tasks, such as turning and changing direction while walking.


This animal study was designed to determine if minocycline ameliorates cochlear damage is caused by intratympanic injection of the ototoxic aminoglycoside antibiotic neomycin. Baseline auditory-evoked brainstem responses were measured in gerbils that received 40 mM intratympanic neomycin either with 0, 1.2, or 1.5 mg/kg intraperitoneal minocycline. Four weeks later auditory-evoked brainstem responses were measured and compared to the baseline measurements. Minocycline treatments of 1.2 mg/kg and 1.5 mg/kg resulted in significantly lower threshold increases compared to 0 mg/kg, indicating protection of hearing loss between 6 kHz and 19 kHz. Cochleae were processed for histology and sectioned to allow quantification of the spiral ganglion neurons and histological evaluation of organ of Corti. Significant reduction of spiral ganglion neuron density was demonstrated in animals that did not receive minocycline, indicating that those receiving minocycline demonstrated enhanced survival of spiral ganglion neurons, enhanced survival of sensory hairs cells and spiral ganglion neurons, and reduced hearing threshold elevation correlates with minocycline treatment demonstrating that neomycin induced hearing loss can be reduced by the simultaneous application of minocycline. Aminoglycoside antibiotics are effective antibacterial agents that generate ototoxic metabolic products. Systemic administration can lead to destruction of vestibular and cochlear hair cells, causing disequilibrium and/or hearing loss –12. MembIdeally their use should be better controlled; however, the addition of an inexpensive agent that ameliorates ototoxicity may be a viable means to prevent unnecessary hearing loss and vestibular disorders. Such an agent would need to suppress the mechanism of ototoxicity. Recent advances have been made in elucidating the mechanism of toxicity to hair cells and have demonstrated substantial apoptosis within twelve hours of exposure to aminoglycoside in guinea pig  and initHair cell apoptosis is believed to be initiated by interference with mitochondrial protein synthesis leading to production of free oxygen radicals and activation of inducible nitric oxide synthetase, producing nitric oxide. Reaction of free oxygen radicals with nitric oxide creates peroxynitrite radicals that initiate the intrinsic or mitochondrial apoptosis pathway , 25. ThePharmacologic agents that inhibit hair cell apoptosis would ideally act as early on as possible in the apoptosis pathway and offer long-term protection to maximize their efficacy. Like all pharmacologic agents they would be subject to meeting the administration, distribution, metabolism, elimination (ADME) and toxicology, drug interaction, and specificity requirements required for approval by pharmaceutical agencies worldwide. Finding a new application for an already approved pharmacologic agent to be used for amelioration of hair cell apoptosis would be ideal . Additio in vitro hair cell death in rat cochlear explants [ in vivo ability to ameliorate hearing loss in gerbils following intratympanic neomycin application.Minocycline is a long-time worldwide approved inexpensive tetracycline derivative that has antibiotic, anti-inflammatory, free radical scavenging and antiapoptotic induction properties –36. Mostexplants . TherefoMeriones unguiculatus) of either sex (60–80 g) were used for this study and were randomly assigned to minocycline treatment groups. Animal numbers represented were n = 6, n = 8, and n = 7 for 0 mg/kg, 1.2 mg/kg, and 1.5 mg/kg minocycline, respectively. The human equivalent dose for 1.2 mg/kg based on the body surface area normalization method would be 1.2 × (4/37) = 0.13 mg/kg or 7.8 mg in a 60 kg human, assuming Km gerbil of 4 and Km human of 37, where Km is the ratio of body mass to surface area defined in [Six-month-old gerbils  injection of minocycline hydrochloride  in normal saline daily, for five days. Day one minocycline injections were given immediately following baseline ABR measurements.Following baseline ABR measurements animals received a single intratympanic injection of 40 mM neomycin  in Ringer's balanced lactate in the left bulla and Ringer's balanced lactate vehicle alone in the right bulla. 40 mM neomycin was chosen based on it producing only partial hearing loss in our pilot experiments, therefore making it more likely for us to see any minocycline effect. The injection volume was approximately 150 Four weeks after treatment, ABR measurements were performed for left and right ears of each animal. Animals were then anesthetized and sacrificed. Bullae were dissected for histological preparation and analysis of the cochleae. Animal procedures were performed in accordance with the guidelines of the National Institutes of Health and were approved by the Northwestern University Animal Care and Use Committee.The method has been described previously . VoltageμV.After the animals were deeply anesthetized, ABRs were obtained by subtracting ipsilateral mastoid potentials from vertex potentials measured relative to a ground electrode, which was placed in the neck. The electrodes were connected to a differential amplifier . The amplifier setting was at 10,000. Further filtering (300 to 3000 Hz) of the signal was obtained through a Frequency Devices filter (IP90). The sampling rate was 200 kHz, and responses to 100 stimulus presentations were averaged. ABR thresholds were defined as sound levels required for a visible wave II in the response to acoustic stimuli. The noise floor in an averaged ABR recording was typically 1 μm longitudinally to obtain midmodiolar sections mounted on glass slides, dewaxed, hydrated, stained with hematoxylin alone, and dehydrated and cover slips were mounted.Bullae were dissected from euthanized gerbils and were fixed for two hours in 4% paraformaldehyde in Phosphate Buffered Saline  at room temperature. Postdissection fixation continued overnight at 4°C. Bullae were washed in PBS (pH 7.4) and the inner ear structures were partially exposed by limited removal of surrounding bone. Tissues were decalcified for 48 hours at 4°C in 4% formic acid and 2% sodium citrate, washed in PBS to remove acid and citrate, dehydrated through graded ethanol, cleared in xylene, and embedded in Paraplast-Xtra paraffin wax . Cochleae were sectioned at 10 Quantification of spiral ganglion neurons (SGN) was performed in left ears to determine if there was a correlation between minocycline treatment and the respective ABR measurements. Right ear ABRs were used as internal controls to ensure that changes in the left ear ABRs were treatment specific and not systemic or due to the intratympanic injection procedure itself.μm and with a nucleolus was counted. The resulting significant cell overcount established by comparison of the stereological count of spiral ganglia sections was corrected for by a factor of 0.71x. The stereologic counting and establishing of the correction factor has been validated and published previously [The counting was conducted as described previously . In brieeviously .μm divisions. Area measurements were obtained by tracing the bony opening of Rosenthal's canal. The total number of pixels within a circumscribed area was calculated and converted into square millimeters.In addition to counting cells, the cross-sectional area of Rosenthal's canal was determined. Measurements were taken using ImageJ . The program's scale was calibrated and the scale setting was changed from pixels to micrometers. This conversion was accomplished by determining the number of pixels between two lines of the image of a standard slide having 10 Hematoxylin stained tissue sections were examined microscopically and digital images captured. The number of observations of hair cells was tallied for the minocycline treatment and corresponding cochlear turns. Ten sections for each cochlear turn were evaluated for each of three animals per minocycline treatment group and no minocycline and no neomycin control group. Cell types scored were inner hair cells (IHC), the three rows of outer hair cells (OHC) 1, 2, and 3 and the three rows of Deiters cells (DC) 1, 2, and 3, and are identified in ABR thresholds were entered into IgorPro 4 (Wavemetrics) software to generate threshold shift values by subtracting baseline thresholds from week 4 thresholds for each treatment. Threshold shift and frequency curves were plotted with standard deviations . For staMean SGN densities were calculated separately for the upper base, middle, and upper middle regions of the cochlear turns for each animal in each treatment group and tested for statistical significance by one-way ANOVA followed by Tukey HSD test using IgorPro 4 (Wavemetrics) software. Qualitative histological examination of the upper base, middle, and upper middle regions of the cochleae was performed on SGN appearance in Rosenthal's canal and the presence or absence of hair cells in the organ of Corti.Left ears were treated with neomycin and animals received either 0, 1.2, or 1.5 mg/kg micocycline IP. At week 4 after neomycin left ear ABR thresholds were elevated from their baseline obtained at week 0 for all minocycline treatment groups . To quanP = 0.028 one sided).As absolute thresholds beyond the speaker output limit could not be determined in most 0 mg/kg minocycline treated animals only measures below 20 kHz were considered in the calculation of the mean threshold shifts, thereby underestimating the threshold shift in the 0 mg/kg cohort. For example, in some animals, no ABR response could be evoked for stimulus frequencies above 19 kHz, indicating a larger threshold shift than the difference between the sound level for the baseline ABR threshold and the maximum sound level of the speaker. They were deaf at those tested frequencies. Two animals in the 0 mg/kg minocycline group had no detectable thresholds above 12 kHz which meant that they had no quantifiable thershold shift, so for statistical purposes we used Fisher's exact test as described in the methods to include these animals . ThreshoP < 0.05).The mean SGN densities in the upper base, middle, and upper middle regions of the left ear cochlear turns are shown in Photomicrographs of organ Corti within left ear cochleae of animals treated with neomycin and those of the corresponding untreated right ear controls demonstrate hair cell toxicity of the neomycin treatment, are shown in  in vivo that minocycline reduces but does not completely eliminate neomycin induced hearing loss. Furthermore, the specific significant reduction of threshold shift only spans a frequency range of 6–19 KHz, which encompasses part of the upper basal turn extending to the middle turn  of hair cell and SGN protection because our end point was directed at determining a late stage functional hearing benefit, which is a preliminary step in determining efficacy and minocycline dosage. Additional studies within hours of neomycin administration would be required to detect potential antiapoptotic and ant-inflammatory effects of minocycline on hair cells. Current evidence suggests that minocycline inhibition of p38 MAP kinase phosphorylation and inhibition of caspases are possible. On balance, we believe that reporting our results without precise mechanism data is consistent with the sentiment of the public request for publication of even negative minocycline efficacy studies, which may have impeded progress in this field .We did, however, find in pilot studies that there was no difference between wild type and Bax knockout noise induced hearing loss and, therefore, hair cell apoptosis. This lack of protection due to noise exposure in Bax knockout mice is consistent with Bak protein perhaps being the dominant of these two proapoptosis proteins in mitochondrial apoptosis in hair cells. In support of this, others have reported that in age-related hearing loss studies that there was no difference between middle age wild type and middle age Bax knockout mice in their ABR thresholds, while Bak knockout mice had lower thresholds and this correlated with greater density of SGNs and number of outer hair cells only in the Bak knockout mice . Further in vitro, 0.1 μM minocycline has been shown to inhibit the apoptosis promoting enzyme activity of poly (ADP-ribose) polymerase 1 (PARP-1) and confer 85% increased survival of neurons in culture, and 5 mg/kg intraperitoneal minocycline delayed cell death and inhibited caspase-1 and caspase-3 expression in the brains of a mouse model of Huntington's disease [Clinically, the use of minocycline for hearing preservation would be limited by its partial efficacy, likely a reflection of redundant apoptosis pathways in hair cells and potential species differences. Several other agents that may partially protect hearing are being examined in animal models of chemical ototoxicity and noise mediated deafness . For exa disease . In huma disease . It shou disease , may not disease .Often traumatic brain injury is associated with sound overpressure damage to the cochlea, such as munitions explosions, which can lead to permanent hearing threshold elevation. Such noise induced hearing loss is primarily by apoptosis, and the medical use of minocycline to ameliorate hearing loss could be tested, based on our demonstration of minocycline amelioration of neomycin induced hearing loss. In addition, combination use of minocycline with aminoglycoside antibiotics for bacterial infection could also be evaluated as a means of ameliorating ototoxic hearing loss.


SD = 0.5). For both indices, context use decreased with increasing hearing loss once the average hearing loss exceeded 55 dB HL. In right-handed patients, significantly greater context influence was observed for words presented in the right ears than for words presented in the left, especially in patients with many years of education. The correlations between raw word scores (and context influence indices) and word occurrence frequencies showed a significant age-dependent effect, with a stronger correlation between perception scores and word occurrence frequencies when the occurrence frequencies were based on the years corresponding to the patients' youth, showing a “historic” word frequency effect. This effect was still observed for patients with few years of formal education, but recent occurrence frequencies based on current word exposure had a stronger influence for those patients, especially for younger ones.Top-down contextual influences play a major part in speech understanding, especially in hearing-impaired patients with deteriorated auditory input. Those influences are most obvious in difficult listening situations, such as listening to sentences in noise but can also be observed at the word level under more favorable conditions, as in one of the most commonly used tasks in audiology, i.e., repeating isolated words in silence. This study aimed to explore the role of top-down contextual influences and their dependence on lexical factors and patient-specific factors using standard clinical linguistic material. Spondaic word perception was tested in 160 hearing-impaired patients aged 23–88 years with a four-frequency average pure-tone threshold ranging from 21 to 88 dB HL. Sixty spondaic words were randomly presented at a level adjusted to correspond to a speech perception score ranging between 40 and 70% of the performance intensity function obtained using monosyllabic words. Phoneme and whole-word recognition scores were used to calculate two context-influence indices (the j factor and the ratio of word scores to phonemic scores) and were correlated with linguistic factors, such as the phonological neighborhood density and several indices of word occurrence frequencies. Contextual influence was greater for spondaic words than in similar studies using monosyllabic words, with an overall j factor of 2.07 ( Speech perception in hearing-impaired patients involves not only the audibility of the speech material but also the entire process of reconstructing meaningful words from partial or deteriorated acoustic input resulting from hearing damage  and patient characteristics such as age, ear tested (left vs. right), years of education and hearing loss were examined.n = 72), moderate  or severe , according to the International Bureau for Audiophonology guidelinesOne hundred sixty patients  who were native French speakers and who presented for routine clinical ENT examinations were involved in this study. The patients underwent routine clinical examinations, including otoscopy, tympanometry, pure-tone audiometry at octave intervals from 250 to 8000 Hz and speech audiometry. The patients' number of years of education (YE) ranged from 7 to 17 (mean = 10.6 years) and was obtained from the highest diploma/degree reported by the patients. All of the patients experienced hearing loss after language acquisition, and none presented articulation problems or neurological problems. Most of the patients had noise-induced hearing loss and/or presbycusis (62%), 21% of them presented mixed conductive and sensorineural hearing loss, and 18% presented with sensorineural hearing loss of other origins. Hearing impairments were classified as mild .After a clinical otoscopy examination, the patients underwent pure-tone audiometry using an Interacoustics° AC 40 clinical audiometer in a soundproof booth. Air and bone conduction hearing thresholds, in decibel hearing levels (dB HL), were obtained at octave intervals from 250 to 8000 Hz. For each ear, a four-frequency  average pure-tone threshold (PTA) was obtained. Tympanometric measurements were taken using an air pressure from −600 to +300 daPa (Interacoustics° AA222).Triphonemic monosyllabic word lists currently used in French ENT practices Lafon,  were preSD = 7.6) greater than the patient's average PTA. The pre-recorded words were presented monaurally to the subjects, who were seated in a soundproof booth, and sound levels were monitored using an Interacoustics AC40 audiometer. One ear (left or right) was chosen at random for each patient. The examinees responded verbally after each word presentation, and an experienced audiologist identified the patients' correct and incorrect responses.At this stimulus level, which was kept constant, 60 spondees taken from the Fournier disyllabic word corpus  to fall as scores approach 100%, both word and phoneme scores were first converted into rau scores:Because W/Pho did not follow a Gaussian distribution, an arcsine transformation was used to meet the Gaussian distribution requirement for statistical analysis. W/Pho increases (up to 100%) as contextual influence increases: indeed, the more we rely on contextual information, the more we tend to complete patchy sensory information and to increase the number of whole words repeated rather than constituent parts alone .d statistic, η2 for ANOVAs , to avoid the inflated type II error rate resulting from more classical multicomparison adjustments such as the Bonferroni correction. For the correlational analysis involving hundreds of correlations, random permutation tests . Several types of patient subgroups were defined within the total population according to hearing loss and/or age and/or years of education (YE) and/or ear tested (right or left) and/or gender. Due to the evolution of education possibilities within the last 80 years in the country, the number of YE showed a decrease as age increased, especially as the same diploma requires more years of education nowadays than 60 years ago. Hence, YE was treated as a dichotomous variable, with a high YE group and a low YE group. There was no interaction between YE group and Ear tested, or PTA, or gender. No statistically significant interactions were detected between Age groups, PTA groups, gender or ear tested  > 370, p < 0.0001, with the highest scores for disyllabic phonemic scores (mean = 79 rau) and the lowest scores for monosyllabic phonemic scores (mean = 57 rau).As expected, the ANOVA-R and pairwise comparisons between the different scores  showed significant differences: SD = 0.5), and the mean W/Pho = 77.6% (SD = 8.9), with a significant correlation between the two . No statistically significant correlations were obtained between j (or W/Pho) and the patients' ages or PTA.The mean j factor was 2.07 . However, in our population, no significant relationship was observed between word scores and age, and only a weak relationship was obtained between age and PTA .Disyllabic word scores decreased significantly with increasing PTA  in the high-YE group, with a significant difference compared to the low-YE group . For all of the word scores and for W/Pho, there was a significant main effect of PTA and a significant interaction between YE and PTA groups. W/Pho was significantly greater in low-YE patients with mild hearing loss and significantly lower for patients with severe hearing loss  = 2.7, p = 0.10].When the population was divided into two groups according to YE, W/Pho decreased significantly as PTA increased  = 0.8, p = ns] or for PTA or age. However, there was a statistically significant interaction between YE and the ear tested, with several context indices: F = 7.74  for the j factor and F = 5.0  for W/Pho, with a significantly greater contextual influence for right ears than for left ears in the high-YE group  and a greater contextual influence for the high-YE group than for the low-YE group for the right ears  = 10.7, p = 0.002, η2 = 0.14 for the j factor and F = 6.8, p = 0.01, η2 = 0.09 for W/Pho. No significant differences based on the YE or PTA group were obtained for word scores.When only right ears were selected, a significant difference was obtained between the high-YE and low-YE groups, with the high-YE group having greater contextual influence indices than the low-YE group: one-way ANOVA: z = 2.4, p < 0.02), regardless of the occurrence frequency used.The percentage score, for each word, calculated across the 160 patients, varied from 17.5 to 92% (word score) and between 49.8 and 95% (phonemic score). Correlations between the word scores and several linguistic factors, such as occurrence frequency , phonological neighborhood density, and number of high-frequency phonological neighbors, indicated that occurrence frequency was a major influence and that no other linguistic factors had significant correlations . Correlations between word scores and occurrence frequencies obtained from the Google Books N_gram French database, calculated in 5-year units from 1900 to 2005, showed the strongest correlations for occurrence frequencies from 1950 (Table The correlations between word scores and occurrence frequency tended to be stronger (but not significantly so) for cumulative oral frequencies than for the maximum occurrence frequency of the phonological form, or the written frequency (r of 0.10 (SE = 0.04). This value is significantly (p < 0.0001) below the average r observed in the data (0.34) and lower than the number of significant correlations observed (60), showing that the pattern of correlations observed here cannot be attributed to chance.Significant correlations were obtained between word scores and word amplitude, calculated in RMS per octave, with the strongest correlations for 0.5 and 1 kHz and with significantly stronger correlations for phonemic scores than for word scores Table . No signStepwise regression analysis starting with five potential explanatory variables representing acoustic factors (0.5 and 1 kHz amplitude in dB) and linguistic factors  yielded statistically significant models that could explain 40% of the variance of word scores and 54% of the variance of phonemic scores Table  using onr = 0.53, p < 0.0005) than for all groups older than 60 years of age  = 4.3, p < 0.006, F = 2.4, p = 0.07]. For the youngest and low-YE patients, the “older words” scores were significantly lower than (1) the scores of the older patients and high-YE patients and (2) the “newer words” scores , with a decreasing difference as age increased that was mostly related to an increase in the “older words” score as age increased. This could explain why the younger patients, especially those with low YE values, were more sensitive to the current spoken word occurrence frequencies from the Lexique° database. Both the age and YE effects disappeared when the 1950s occurrence frequencies were used  and by Boothroyd and Nittrouer  across our population showed greater contextual influence than the data reported by Olsen et al.  , which underlines the importance of YE to spoken word recognition scores in an elderly, hearing-impaired population in an audiological clinic. YE can be considered a very crude reflection of lexical knowledge and cognitive ability. Indeed, in a meta-analysis, Verhaeghen  reportedThe lack of an age effect on contextual influence indices that was observed in this study appears to contrast with the results of Krull et al. , who obsThe present results suggest that the degree of compensation from sublexical influence was not only educational level-specific, hearing loss-dependent and, to some degree, age-dependent (in terms of occurrence frequency), it is also ear-dependent and has a significant interaction with YE; there was a significantly stronger contextual influence for words presented in the right ears than in left ears in the high-YE patient group among the subgroup of 150 right-handers, with no significant differences in hearing loss, age or word scores between the right and left ears. Moreover, when only the right ears were considered, the high-YE group exhibited significantly greater contextual influence than the low-YE group on the two context influence indices. The so-called right ear advantage linked to hemispheric functional asymmetry for language processing is usually observed behaviorally when both ears are competing, i.e., words presented in a subject's right ear are more likely to be repeated than words presented concomitantly in the left ear at a comfortable loudness level , and the population tested here  differs from the typical university student cohorts used in psycholinguistics studies. Indeed, even for isolated words presented in silence, contextual influences can add substantial variability to speech scores. Top-down lexical compensation (or the lack thereof) for partial phonological information can greatly increase inter-subject variability depending on the patient's YE, age, hearing loss and ear tested. The influence of the ear tested was only visible for contextual influence indices and not for raw scores; thus, it is probably negligible in practice compared with other factors. The historical word occurrence frequency effect, which was of variable importance depending on the patients' age and number of years of education, suggests a strong interaction between linguistic factors and patient-specific factors. This interaction emphasizes the need to consider linguistic factors carefully (including the “history” of these factors) when developing speech recognition material (and to avoid focusing only on acoustic factors) , and years of formal education. These patient-specific factors interact differently with linguistic material-specific factors, such as the occurrence frequency and phonological similarities of words. This phenomenon is illustrated by the historical occurrence frequency effect observed here, in which spondaic word recognition scores showed a stronger correlation with the word occurrence frequencies corresponding to the patient's youth than with current word occurrence frequencies; the older hearing-impaired patients were more likely to repeat a word that is rarely heard now but was common in their youth than a word that occurs frequently in daily communications  but was rare in their youth. This finding was especially true for patients with more years of education. Even at the isolated word level, when words are presented in silence, lexical influence can partially compensate for bottom-up loss of phonological information in mild to moderate hearing loss and can improve spondaic recognition scores, but it depends strongly on general and linguistic knowledge.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.


MLH3 in human cell lines. Monitoring these cell lines during the cell cycle using live cell imaging combined with confocal microscopy, we detected accumulation of MLH3 at the centrosomes. Fluorescence recovery after photobleaching (FRAP) revealed high mobility and fast exchange rates at the centrosomes as it has been reported for other DNA repair proteins. MLH3 may have a role in combination with other repair proteins in the control of centrosome numbers.Mutations in human DNA mismatch repair (MMR) genes are commonly associated with hereditary nonpolyposis colorectal cancer (HNPCC). MLH1 protein heterodimerizes with PMS2, PMS1, and MLH3 to form MutLα, MutLβ, and MutLγ, respectively. We reported recently stable expression of GFP-linked  MLH3 expression is hardly detectable in human cells since being expressed up to 60 times lower than other MMR proteins [MLH3 in human cell line [Mutations in human DNA mismatch repair (MMR) genes are commonly associated with hereditary nonpolyposis colorectal cancer (Lynch syndrome). To form the MMR protein complexes, MSH2 heterodimerizes with MSH3 and MSH6, while MLH1 heterodimerizes with PMS2, PMS1, and MLH3 to form MutSα, MutSβ, MutLα, MutLβ, and MutLγ, respectively. While MutLβ is the key player in MMR, reports on the function of MutLγ concentrate on observations in meiotic recombination events. Knockout-mice revealed a crucial role of MutLγ in crossing-over during meiosis , but invproteins  and stabproteins ,6. Recenell line . Using mWe detected accumulation of GFP-MLH3 forming two distinct fluorescent foci per cell. The position of the two foci on each side of the aequatorial plane during the different phases of the cell cycle suggested that these might resemble accumulation of MLH3 at the centrosomes a. ImmunoTo investigate the nature of these accumulation foci, fluorescence recovery after photobleaching (FRAP) technique was applied. After photobleaching of one of two foci (compare “before” to “0 s”-picture), every 4 s an image was taken. Recovery of signal relative to the other centrosomal foci is achieved within 28 s. Fluorescence recovery to 100% was observed in eight independent measurements . This hiBy taking advantage of the capacity of confocal microscopy to eliminate any reflected light from out of the focus, we were able to detect structures within the cell, that are invisible in epifluorescence microscopes. Of course, recombinant expression always harbours the danger of producing artefacts by vast over-expression. In our hands, we achieved a remarkably low expression level applying a multicistronic expression system , which tMsh2−/− mice showed an increased number of centrosomes in every third cell as well as modifications at the telomers. The localization of MSH2 at the centrosomes was reported subsequently by Narine et al., 2010 [However, a potential function of MLH3 at the centrosomes may lie in the control of centrosome numbers. If not under proper control, a multipolar spindle apparatus, due to supernumerary centrosomes, leads to a defective mitosis and is described for a number of different cancer types . Regulatl., 2010 . Furtherl., 2010 ,16. Sincl., 2010 , this mi2. Subculturing was achieved by splitting confluent cultures about 1:5 every 3 days by detaching cells by tapping the culture flasks. Stable expressing cell lines were generated as described before [MLH3 was amplified by RT-PCR from primary human MRC-5 lung cells. cDNAs were fused N-terminally and in frame to GFP and C-terminally to an internal ribosomal entry site (IRES), while latter one was fused to the selectable marker gene puromycin-N-acetyltransferase to be expressed in a bi- or tricistronic manner. Cells were transfected with plasmid DNA using SuperFect Transfection Reagent according the manufacturer’s guideline . Forty-eight hours after transfection, selective pressure was applied by 0.7 μg/mL puromycin. After 14 to 20 days clones were isolated, expanded and analysed for fluorescence and exclusive nuclear localization.Human embryonal kidney cell line 293  was grown in 90% Dulbecco’s MEM supplemented with 10% fetal bovine serum, 100 U/mL penicillin, 100 μg/mL streptomycin and Glutamax-I  at 37 °C with 10% COCells were grown in chamberslides  upon semi-conluency and were fixed subsequently using 4% formaldehyde/PBS for 15 min at 37 °C. After permeabilization over night in 0.1 M Tris–HCl/50 mM EDTA/0.5% TritonX-100 blocking was performed for 2 h with 3% bovine serum albumin/0.1% Tween20. Antibodies were applied in PBS/1% fetal bovine serum/0.1% Tween20 for 2 h each. Mouse monoclonal anti-γ-tubulin antibody  was applied 1:50, followed by goat-anti-mouse-tetramethylrhodamine  1:200.2-content. Furthermore, an objective heater (Zeiss) excluded any undesired cooling by the objective itself.Microscopy was performed on a Zeiss LSM 510 Meta  using the 488 nm laser line to excite GFP and a Plan-NeoFluar 40×/1.3 oil immersion objective. The pinhole was set to 1–2 mm. Live cell imaging experiments were performed at physiological conditions in chamberslides, using a heating stage in combination with an incubation unit and an active gas mixer  to achieve 37 °C temperature and physiologic COIrel = (T0 × It)/(Tt × I0), where T is the total cellular intensity at the time points 0 and t and I the average intensity of the bleached region at the time points 0 and t.FRAP was carried out by bleaching a defined area inside the nucleus with 25% laser power, 100% transition and 20 iterations. Several images were taken before bleaching, followed by one image directly after the bleach and consecutive images every 2 s with 5% transition. Fluorescence intensity was measured at each time point. Background was subtracted before fluorescence loss due to monitor bleaching was normalized, to calculate relative intensity MLH3 accumulates with fast exchange rates at the centrosomes.MMR protein


In evaluating hearing disability in medicolegal work, the apportionment of age- and gender-related sensorineural hearing loss should be considered as a prior factor, especially for the elderly. However, in the literature written in the English language no studies have reported on the age- and gender-related mean hearing threshold for the South Korean population.This study aimed to identify the mean hearing thresholds in the South Korean population to establish reference data and to identify the age- and gender-related characteristics.This study is based on the Korea National Health and Nutrition Examination Survey (KNHANES) 2010–2012, which was conducted by the Korean government, the data of which was disclosed to the public. A total of 15,606 participants (unweighted) representing 33,011,778 Koreans (weighted) with normal tympanic membrane and no history of regular or occupational noise exposure were selected and analyzed in this study. The relationship between the hearing threshold level and frequency, age, and gender was investigated and analyzed in a highly-screened population by considering the sample weights of a complex survey design.A gender ratio difference was found between the unweighted and the weighted designs: male:female, 41.0%: 59.0%  vs. 47.2%:52.8% . As age increased, the hearing threshold increased for all frequencies. Hearing thresholds of 3 kHz, 4 kHz, and 6 kHz showed a statistical difference between both genders for people older than 30, with the 4 kHz frequency showing the largest difference. This paper presents details about the mean hearing threshold based on age and gender.The data from KNHANES 2010–2012 showed gender differences at hearing thresholds of 3 kHz, 4 kHz, and 6 kHz in a highly-screened population. The most significant gender difference in relation to hearing threshold was observed at 4 kHz. The hearing thresholds at all of the tested frequencies worsened with increasing age. The mean hearing thresholds suggested in this study will be useful for the formulation of healthcare-related hearing policies and used as reference data for disability ratings for hearing loss due to various causes. When court-ordered hearing examination is requested due to car accidents or work-related injuries, the age and gender of the patient are very important when determining the allocation of causation among the multiple factors that caused or significantly contributed to the injury or disease, and the resulting impairment. If a victim has no record of having undergone a hearing test prior to the car accident or work-related injury, the hearing threshold should be estimated. For example, in medicolegal cases, it might be difficult to consider if the pre-accident hearing threshold of a 70-year-old man is similar to that of a 20-year-old woman. Only a few reports have provided reference data for age- and gender-related hearing threshold levels for Koreans, and the studies that did had limitations in that their study population was uncertain  or the sThe KNHANES 2010–2012 was a complex, stratified, multistage, probability-cluster survey of a representative sample of the non-institutionalized civilian population in South Korea. Therefore, it provides reliable audiological data for stratified samples representing the entire Korean population. This present study aims to extract and objectively analyze the hearing data and to show the age- and gender-related authentic mean hearing threshold.The KNHANES is an ongoing cross-sectional survey of the civilian non-institutionalized population of South Korea. Many field survey teams performed interviews and physical and laboratory examinations. Those teams included otolaryngologists, ophthalmologists, and nurse examiners with mobile examination units.The KNHANES participants were not randomly sampled. Since the survey was designed using a complex, stratified, multistage probability-sampling model based on the National Census Data, individual participants were not equally representative of the Korean population. The KNHANES website provides survey datasets that include information regarding the survey location, strata by age, sex, and various other factors, and the sample weight for each participant. In all of the analyses, survey sample weights were used, which were calculated by taking the sampling rate, response rate, and age/sex proportions of the reference population into account in order to provide representative estimates of the Korean civilian population. Previous articles have described the KNHANES methodology in detail , 8–11.A total of 23,621 individuals , representing 47,761,044 individuals  in South Korea participated in the survey from July 2010 to December 2012. Among them, pure tone audiometry data were acquired from 8,147 male participants representing 19,826,055 Korean men and 10,435 female participants representing 19,689,497 women, whose ages ranged from 12 to 85.Table 1shows the detailed exclusion procedures; 83.5% (weighted) of the representative population were included in this study.To determine the mean hearing thresholds of the Korean population not affected by factors that are hazardous to hearing, including middle ear disease or noise exposure, better ears were selected and then the following exclusion criteria were established: participants with abnormal tympanic membrane on otoscopy or a history of regular or occupational noise exposure were excluded. To determine which ear (right or left) was better in individual participants, six-tone average thresholds , four-tone averages , and thresholds at 1 kHz, 2 kHz, 0.5 kHz, 3 kHz, 4 kHz, and 6 kHz, in both ears, were compared one-by-one. For example, if the six-tone average for the right ear is smaller than the left ear, the right ear is the better ear regardless of all the other thresholds. If the six-tone averages for both ears are the same, the four-tone averages for both ears are compared. Pure-tone audiometric testing was performed with a GSI SA-203 audiometer . Testing was conducted in a sound-treated booth inside the mobile examination center reserved for KNHANES. Otolaryngologists, who had been trained to operate the audiometer, provided instructions to participants and obtained the recordings. All audiometric testing was done under the supervision of an otologist. Only air conduction thresholds were measured. Supra-auricular headphones were used in the sound-treated booth. The otolaryngologist provided basic instructions to the participant regarding the automated hearing test. Automated testing was programmed according to a modified Hughson-Westlake procedure with appropriate masking. The lowest level at which the subject responded to 50% of the pure tone was set as the threshold. The automated hearing test involving air-conducted pure-tone stimuli showed good test-retest reliability and validity comparable to the manual pure-tone audio test , 13. ParThe KNHANES obtained a written informed consent from each participant prior to conducting the survey, and the Institutional Review Board of Ewha Womans University Mokdong Hospital approved this present research study (IRB No. ECT-201509-033).http://www.R-project.org). The statistical values, including mean hearing thresholds and frequency averages, were calculated with the 'survey' package from the R repository sites. The package was developed for analyses of complex survey samples and this made it possible to provide statistics taking sample weights and strata into consideration. Cross-tabulations, the calculations of means, and t-tests were performed using the 'svytables', 'svymean', and 'svyttest' functions, respectively , according to gender and age. P values<0.05 were considered statistically significant.Statistical analyses and graphing were performed using R software . Mean hearing thresholds by age and gender according to frequency were calculated. Plots were made to discover the relationship between hearing threshold level and frequency, age, and gender .To find the distribution difference of the unweighted sample number and the representative population number by age and gender, a plot was made with triple Y axes . A mean pure tone audiogram based on age group is shown in Fig 4.To compare the mean hearing threshold of both genders for each age group  at the six tested frequencies and the four-tone averages, multiple t-tests, adjusted by Bonferroni correction and based on the complex survey design, were performed. Plots were made to verify the gender difference of the four-tone averages (Table 2). The age of the participants ranged from 12 to 85. The mean age was 45.8±19.0 (unweighted) and 40.9±17.8 (weighted). Differences in the gender ratio were found between the unweighted and weighted designs: M:F, 41.0%: 59.0%  vs. 47.2%:52.8%  . In comparing the proportion of the unweighted and weighted groups by age  in males, the unweighted groups were found to be under-sampled in contrast to the representative population. The unweighted groups by age  in males were over-sampled in contrast to the weighted groups by the representative population.In the KNHANES 2010–2012 data, the number of highly-screened participants who underwent audiometric testing was 15,606, representing 33,011,778 Koreans  averages are shown in Fig 4shows the mean audiograms for the Korean population as a function of gender, frequency, and age. As the age of the male or female participants increased, the hearing thresholds at all frequencies increased. The higher the frequencies, the greater the hearing loss.This study used three years of pooled data: 2010, 2011, and 2012. The KNHANES 2010–2012 sampling weights ranged from 75.66 to 45,812.38 persons, and the median and mean values were 4,792.564 and 6470.565, respectively. The number of participants in 2010, 2011, and 2012 were 6,532, 6,302, and 5,817, respectively. The total Korean non-institutionalized population in 2010, 2011, and 2012 was 39,514,595, 40,324,566, and 38,978,241, respectively. The KNHANES guideline for data processing suggests that, in order to adjust sampling weights, the sample weights should be divided by 3; that is, the number of years of data pooled. Thus, the adjusted and pooled number representing the total Korean non-institutionalized population 2010–2012 was 39,605,801.While several papers addressing hearing thresholds for the Korean population have been published, they have only focused on certain groups, including visitors at health screening centers, adolescents, male firefighters, the elderly, and residents of specific regions –4, 15. KIt is difficult to directly compare their results with the results from our study, as they supplied median hearing thresholds. Bahng and Lee reported the hearing thresholds of 263 people whose ages ranged from 60 to 84 . They foKim et al. reported gender differences with hearing thresholds for 1,116 visitors at a health screening center that were otologically normal, and they reported no occupational or non-occupational noise exposure . They foHoffman et al. reported hearing results from the US National Health and Nutrition Examination Survey (NHANES), 1999–2004 . Their aFig 2E). Fig 2D and 2F shows that there is less of a gender difference for the mean threshold at 3 kHz and 6 kHz than at 4 kHz. The exclusion of subjects exposed to regular or occupational noise exposure was the minimum criteria used to eliminate the effect of noise on hearing thresholds. The real amount of exposure an individual has to noise cannot be investigated. It is assumed that the most remarkable reason for the gender difference at the 4 kHz threshold is due to socio-environmental factors, not biological differences; men are exposed to more noise than women. This hypothesis is supported by the tendency that gender difference for hearing thresholds decreased in retired people (>70 years).There have been controversies about gender differences in relation to hearing thresholds in the literature. Some studies have reported that there was no difference in hearing thresholds between males and females . In contFig 4shows the mean pure-tone audiogram results by age and gender. As age increased, the mean threshold at each frequency increased in spite of gender. We thought that this pattern resulted from the aging effect. The hearing threshold for males was worse than it was for females. However, increased hearing thresholds at 6 kHz were noted, irrespective of age and gender, as compared to the other frequencies. This outcome might be due to the known calibration problem in the TDH-39 earphone of the GSI SA-203 audiometer, which could give rise to a roughly 5 dB increase at 6 kHz compared to the average thresholds for most other audiometric frequencies [quencies , 23.Table 3and Fig 4, can be used as reference data to estimate the pre-accidental hearing threshold based on age and gender.The information from this present study, provided in Gender difference in mean hearing threshold was observed at the frequencies of 3 kHz, 4 kHz, and 6 kHz from the data obtained from the KNHANES 2010–2012. The most significant gender-related hearing threshold difference was observed at 4 kHz. Our results will be useful for formulating healthcare-related hearing policies, and they can be used as basic reference data for disability ratings for hearing loss due to various causes.S1 Table(CSV)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S3 Table(XLSX)Click here for additional data file.


Triclosan (TCS) is a broad-spectrum antimicrobial agent that is frequently used in pharmaceuticals and personal care products. Reports have shown that TCS is a potential endocrine disruptor; however, the potential effects of TCS on placental endocrine function are unclear. The aim of this study was to investigate the endocrine disrupting effects of TCS on the placenta in pregnant rats. Pregnant rats from gestational day (GD) 6 to GD 20 were treated with 0, 30, 100, 300 and 600 mg/kg/d TCS followed by analysis of various biochemical parameters. Of the seven tissues examined, the greatest bioaccumulation of TCS was observed in the placenta. Reduction of gravid uterine weight and the occurrence of abortion were observed in the 600 mg/kg/d TCS-exposed group. Moreover, hormone detection demonstrated that the serum levels of progesterone (P), estradiol (E2), testosterone (T), human chorionic gonadotropin (hCG) and prolactin (PRL) were decreased in groups exposed to higher doses of TCS. Real-time quantitative reverse transcriptase-polymerase chain reaction (Q-RT-PCR) analysis revealed a significant increase in mRNA levels for placental steroid metabolism enzymes, including UDP-glucuronosyltransferase 1A1 (UGT1A1), estrogen sulfotransferase 1E1 (SULT1E1), steroid 5α-reductase 1 (SRD5A1) and steroid 5α-reductase 2 (SRD5A2). Furthermore, the transcriptional expression levels of progesterone receptor (PR), estrogen receptor (ERα) and androgen receptor (AR) were up-regulated. Taken together, these data demonstrated that the placenta was a target tissue of TCS and that TCS induced inhibition of circulating steroid hormone production might be related to the altered expression of hormone metabolism enzyme genes in the placenta. This hormone disruption might subsequently affect fetal development and growth. Triclosan (TCS) is a broad-spectrum antimicrobial agent that is used in clinical settings and in various personal care and consumer products, including soaps, hair products, toothpaste, medical devices, plastics, textiles, children toys, and others . CurrentIn vitro studies, TCS exhibited estrogenic and androgenic activity in both ER- and AR-mediated bioassays [In vivo studies, TCS is also reported to have estrogenic activity as it can increase uterine weight in female rats [in vitro study reported that TCS exhibited anti-estrogenic activity in breast cells (MCF-7), inhibiting estradiol (E2)-induced cell growth [Analysis of the chemical structure of TCS implies that it may have chemical properties related to many toxic compounds, such as polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), bisphenol A (BPA) and dioxins, due to the similar halogenated biphenyl ether . Data frioassays . In vivoale rats , resultiale rats , and canale rats . Treatmeale rats . Conversl growth . In malel growth . In addil growth  and affel growth ,23. In hl growth .in vivo have not been studied. The aims of this study were to investigate the endocrine disrupting effects of TCS on the placenta in pregnant rats and to evaluate the mechanism of these effects by exploring the possible involvement of genes associated with hormone biosynthesis and decomposition.The placenta is an important endocrine organ that connects the developing fetus to the maternal uterus. The placenta can synthesize a number of hormones, such as hCG, P and estrogen, which play important roles in implantation, pregnancy maintenance and embryo development ,26. StudThis study was carried out in strict accordance with the Guidelines for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocol was approved by the Animal Care and Use Committee of Hubei Province .ad libitum. All rats were acclimatized for 1 week before experiments were begun. Pairing for mating was 2 females:1 male. The females were examined each morning, and mating was confirmed by the presence of a sperm-positive vaginal smear; this day considered GD 0. Pregnant rats were housed one per cage and were randomly assigned to the control group or treatment groups (ten pregnant rats per group) in a manner that provided for comparable body weight, means and distribution across groups.Sprague–Dawley (SD) rats aged 8–9 weeks  were obtained from the Hubei Center for Disease Control and Prevention, Wuhan, China. Animals were maintained in a mass air displacement room with a 12 h light–dark cycle at 20–26°C and with a relative humidity of 30–70%. The animals had access to food and water TCS  was purchased from Sigma Aldrich . To achieve different doses, TCS was dissolved in corn oil vehicle, which was prepared fresh each day. TCS was administered orally via gavage to rats in the treatment group for GD 6 to GD 20 at doses of 30, 100, 300 and 600 mg/kg body weight/day in a volume of 5 mL/kg of body weight. Control rats were treated similarly with the vehicle alone. Each experimental day, the rats were weighed to administer the dose per kilogram of body weight. The chosen doses were based on a study in which the acute oral 50% lethal dose (LD50) in SD rats was between 3,700 and > 5,000 mg/kg . At GD 212 (Item No. CLM-6779-MT-1.2) purchased from Cambridge Isotope Laboratories  was added as internal standard solution. Then, the mixtures were extracted by 8 mL methanol for 20 min at 4°C and centrifuged at 3,000 × g for 10 min. The supernatants (800 μL) were diluted to 1 mL with pure water, and the concentrations of TCS were analyzed using an Acquity ultra performance liquid chromatography (UPLC) system coupled to a Xevo triple quadrupole mass spectrometer  [The concentration of TCS in placenta was analyzed in 0, 30, 100 and 300 mg/kg/d TCS-exposed groups . In addition, in order to compare the cumulative amount of TCS in different tissues , the samples of 30 mg/kg/d group were used. Tissue samples were homogenized in liquid nitrogen and hydrolyzed in lysis solution, including 2 mL acetic acid-sodium acetate (pH = 5.2) and 50 μL β–glucuronidase/arylsulfatase for 24 h at 37°C. Then, the samples were cooled to room temperature. In total, 40.0 ng TCS-13CMA, USA) ,30.Concentrations of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), hCG, prolactin (PRL), P, E2 and T were detected according to the manufacturers’ protocols by radioimmunoassay (RIA) using commercial kits from Beijing North Institute . The sensitivities of the assays were 1.0 mIU/mL, 1.0 mIU/mL, 10 mIU/mL, 40 μIU/mL, 0.2 ng/mL, 2 pg/mL and 0.02 ng/mL for LH, FSH, hCG, PRL, P, E2 and T, respectively. The standard curve ranges for the assays were 5–200 mIU/mL, 2.5–100 mIU/mL, 50–1600 mIU/mL, 125–2000 μIU/mL, 0.2–100 ng/mL, 5–4000 pg/mL and 0.1–20 ng/mL for LH, FSH, hCG, PRL, P, E2 and T, respectively. The intra-assay and inter-assay coefficients of variation were less than 10% and 15%, respectively, for all the kits. Samples were analyzed and standard curves were generated simultaneously in all of the plates. Standards, controls and samples were analyzed in duplicate, and the average was calculated for each sample.Three placentas (select randomly) from each pregnant rat were pooled, producing six pools of placenta for each group. Total RNA was isolated from the pools using an RNeasy Mini Kit  according to the manufacturer’s instructions. Placental RNA in the 600 mg/kg/d TCS-exposed group was absent due to the occurrence of abortion. The total RNA was digested by DNase I  to remove genomic DNA contamination. The purified total RNA was measured at 260 and 280 nm using a Bio-Rad SmartSpec 3000 spectrophotometer . The 260:280 nm ratios and a 1% agarose-formaldehyde gel stained with ethidium bromide were used to verify the quality of the RNA in each sample. The first-strand cDNA was synthesized from 1 μg total RNA mixed with random 6-mers using a PrimeScript II 1st Strand cDNA Synthesis Kit . The expression levels of target genes were detected by real-time quantitative PCR, with the housekeeping gene β-actin used as an internal control. SYBR Green PCR Master Mix reagent kits  were used according to the manufacturer’s instructions for quantification of gene expression with a 7300 real-time PCR system . PCR primers  were desp value < 0.05 was considered statistically significant.All data analysis was performed with SPSS 13.0. The results are presented as the means ± SD (n = 6). Statistical analyses of hormone production and gene transcription profiles between control and exposed cells were evaluated by one-way analysis of variance (ANOVA) followed by post hoc LSD tests. A p < 0.05). Additionally, compared with the control group, significant differences in gravid uterine weight were observed in the 600 mg/kg/d TCS-exposed group (p < 0.05), whereas no significant differences were observed in the other three TCS treatment groups.The net body weight gain and gravid uterine weight of pregnant rats exposed to TCS from GD 6 to GD 21 are shown in Litters were delivered by cesarean section on day 21 of pregnancy, and the number of living fetuses was calculated . In the The concentrations of TCS in the different tissues of the 30 mg/kg/d TCS-exposed group are shown in The concentrations of TCS in the placenta are shown in p > 0.05). However, the levels of hCG in serum exhibited significant inhibition in the TCS exposure groups compared with the control group: the levels of hCG were dramatically reduced by 43.0%, 34.4%, 37.4% and 42.6% in the 30, 100, 300 and 600 mg/kg/d TCS-exposed groups, respectively (p < 0.05). In rats receiving 100 and 600 mg/kg/d TCS, the levels of PRL in serum were dramatically decreased by 18.9% and 53.9%, respectively (p < 0.05), and no significant differences were observed between the control and other exposure groups (p > 0.05). In addition, the levels of P were significantly reduced by 34.3%, 31.4% and 63.3% and 58.3% in the 30, 100, 300 and 600 mg/kg/d TCS-exposed groups, respectively (p < 0.05). Similarly, in rats receiving 100, 300 and 600 mg/kg/d TCS, the levels of E2 in serum were dramatically decreased by 35.0%, 31.4% and 55.6%, respectively (p < 0.05). Additionally, the oral administration of 300 and 600 mg TCS resulted in 46.7% and 70.0% decreases in serum levels of T, respectively (p < 0.05).The effects of TCS on hormone secretion by the pituitary and placenta of pregnant rats are shown in p < 0.05); no significant differences were observed in other TCS treatment groups compared with the control group. The expression levels of 3β-HSD1, CYP17A1, and CYP19A1 were not altered after TCS exposure, while expression of 17β-HSD3 was down-regulated in the 100 mg/kg/d TCS-exposed group (p < 0.05).We studied the transcriptional levels of genes responsible for hormone  biosynthesis and metabolism in the 0, 30, 100 and 300 mg/kg/d TCS-exposed placenta . As showp < 0.05). However, the steroid 5α-reductase 3 (SRD5A3) gene was sharply down-regulated in all the TCS exposure groups (p < 0.05). Moreover, the genes related to E2 metabolism were investigated as shown in p < 0.05).The genes involved in P and T metabolism are shown in p < 0.05). Similarly, the AR expression level was also increased in the highest dose group compared to that of the control group (p < 0.05).Hormones can trigger a number of events through binding to their receptors. In the present study, we further analyzed the expression levels of hormone receptor genes, including P receptor (PR), androgen receptor (AR) and estrogen receptor (ERα) . The up-in vitro study demonstrated that TCS exposure could disturb hormone secretion by and cell viability of human choriocarcinoma-derived placental cells [in vivo are limited, the aims of this study were to investigate the endocrine disrupting effects of TCS on placenta and to further evaluate the potential mechanisms of these effects.Studies in mammals have shown that TCS is an endocrine-disrupting chemical  that hasal cells . In addiin vivo. The results showed that TCS treatment resulted in a reduction in body weight gain in the 300 and 600 mg/kg/d TCS-exposed groups and in a decrease in the number of living fetuses as well as miscarriage in the 600 mg/kg/d TCS-exposed group, which suggested that these doses of TCS might have general toxicity. Notably, the placenta displayed the greatest bioaccumulation of TCS among the seven examined tissues, and the cumulative amount of TCS in the placenta increased in a dose-dependent manner, suggesting that the placenta might be one of the target organs of TCS. Therefore, the potential hazards of TCS to human reproductive health, especially for pregnant women, require further examination.To the best of our knowledge, the present study is the first to examine the effects of TCS on the development and endocrine function of the placenta during rat pregnancy Unlike the human placenta, which plays an important role in producing P and estrogen, the rat placenta does not produce estrogen, as rats do not express aromatase, and only secretes small amounts of P . Indeed Placental PRL hormone is important to fetal growth and pregnancy maintenance . GestatiHormone receptors play important roles in the process of hormones exerting their biological effects. In pregnant women, increased PR and ER expression levels were observed in the endometrium and decidua after terminating early pregnancy by mifepristone application . SimilarIn conclusion, the placenta might be a target tissue of TCS in pregnant rats. From GD 6-GD 20 in pregnant rats, TCS exposure decreased the circulating PRL, hCG, P, T and E2 levels in serum, which is a complex phenomenon. Based on the present results, we speculated that hormone metabolism enzymes, rather than biosynthesis enzymes, might contribute to the inhibition of P, T and E2 production after TCS exposure during pregnancy. Furthermore, we proposed that the increased expression of hormone receptors  in the placenta might be a protective mechanism to counteract the adverse effects that low hormone levels could have on the placenta and fetus.


Hearing loss and tinnitus are global public health concerns. There have been some studies suggesting a relationship between hearing loss and tinnitus and impaired health-related quality of life (HRQoL), but there have been no large cross-sectional epidemiologic studies of a representative sample of the entire country population investigating this possible association.The aim of this study was to investigate the relationship between hearing loss and tinnitus and HRQoL in South Korea using data from the Korea National Health and Nutrition Examination Surveys during 2010–2012.Cross-sectional data of 11,266 adults who completed the Korea National Health and Nutrition Examination Surveys were analyzed. Subjects were divided into four groups as follows: normal hearing without tinnitus, normal hearing with tinnitus, hearing loss without tinnitus, and hearing loss with tinnitus.Among the population that was ≥19 years of age, the prevalence of unilateral hearing loss was 9.69% and that of tinnitus in the prior 12 months was 32.76%. The hearing loss with tinnitus group had the highest percentage of subjects who responded “some or extreme problems” in all five dimensions  of HRQoL. After adjustment for age, gender, body mass index, smoking status, alcohol intake, regular exercise, house income, education level, diabetes, hypertension, and stress level, the HRQoL odds ratios (OR) were 1.47  for mobility, 1.59  for usual activity, and 1.84  for anxiety/depression in the hearing loss with tinnitus group, compared with the normal hearing without tinnitus group. The ORs for the normal hearing with tinnitus group compared with the hearing loss without tinnitus group was increased in all five dimensions of HRQoL after adjustment for confounders.Hearing loss with tinnitus has a considerable impact on HRQoL in the Korean population. In our study, the hearing loss without tinnitus group showed better a HRQoL than the normal hearing with tinnitus group. Hearing loss and tinnitus continue to be bothersome and challenging clinical problems. Hearing loss can interfere with the ability to understand speech sounds, leading to difficulties in communication and learning, reduced work productivity, increased depression and anxiety, and social isolation . Age-relThe Korean National Health and Nutrition Examination Surveys (KNHANES), which is a government-driven survey by the Korea Center for Disease Control and Prevention, has been conducted since 1998. The Korean Society of Otorhinolaryngology—Head and Neck Surgery participated in this project, and interviews and examinations were performed by trained ear, nose, and throat residents. KNHANES (2010) was the first population-based study to use a questionnaire for determining hearing loss and tinnitus as well as HRQoL such as people’s level of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression in the noninstitutionalized civilian population of South Korea. Although people with hearing loss and tinnitus are at an increased risk of experiencing HRQoL problems, population-based studies for hearing loss and tinnitus are lacking. The aim of this study was to analyze the prevalence of hearing loss and tinnitus and its potential risk factors, including lifestyle habits and anthropometric measurements, using KNHANES data. In addition, the association of hearing loss with HRQoL was also evaluated based on the questionnaire in South Korea.The study protocol was approved by the Institutional Review Board of the Catholic Medical Center.This study was based on data collected during the 2010–2012 KNHANES. Conducted by the Division of Chronic Disease Surveillance under the Korea Centers for Disease Control and Prevention since 1998, the KNHANES is a nationwide survey designed to accurately assess national health and nutrition levels. A field survey team that included an otolaryngologist, an ophthalmologist, and nurse examiners for health assessments moved with a mobile examination unit and performed interviews and physical examinations. The survey consists of a health interview, a nutritional survey, and a health examination survey. The survey amasses data via household interviews and by direct standardized physical examinations conducted in specially equipped mobile examination centers. The KNHANES methodology has been described in detail previously /severely annoying and causes sleep problem). The participants were grouped as having annoying tinnitus if the severity of tinnitus was annoying or severely annoying.Pure-tone audiometric testing was conducted using an SA 203 audiometer . Testing was conducted in a soundproof booth inside the mobile unit reserved for the KNHANES. Otolaryngologists, who had been trained to operate the audiometer, provided instructions to participants and obtained the recordings. All audiometric testing was performed under the supervision of an otolaryngologist. Only air conduction thresholds were measured. Supra-auricular headphones were used in the soundproof booth. The otolaryngologist provided basic instructions to the participant regarding the automated hearing test. Automated testing was programmed according to a modified Hughson-Westlake procedure; it used a single, pure tone of 1–2 seconds. The lowest level at which the subject responded to 50% of the pure tone was set as the threshold. The automated hearing test involving air-conducted pure-tone stimuli showed good test—retest reliability and validity comparable to the manual pure-tone audio test ,12. PartHRQoL was evaluated using the EuroQol, which consists of two parts: the health-status descriptive system  and the EQ visual analog scale. The EQ-5D records the level of self-reported problems according to five dimensions  ,14. Each2).Medical history and lifestyle habits information were collected using self-reported questionnaires. Smoking history was categorized into three groups: current smoker, ex-smoker, or nonsmoker. Based on the amount of alcohol consumed per day during the 1-month period before the interview, the subjects were classified into three groups: nondrinkers, mild to moderate drinkers (<15 g/day), or heavy drinkers (≥15 g/day). Regular exercise was defined as strenuous physical activity performed for at least 20 minutes at a time at least three times a week. Weight and height were measured by well-trained medical professionals. Standing height was measured when the subject faced directly ahead with shoes off, feet together, arms by the sides, and heels, buttocks, and upper back in contact with the wall. The unit of height was measured in centimeters with one decimal point using the SECA 225 . Body mass index was calculated as weight (kg)/height  to reflect the complex sampling design and sampling weights of the KNHANES and provide nationally representative prevalence estimates. The procedures included unequal probabilities of selection, oversampling, and nonresponse so that inferences could be made about the Korean adolescent participants.The prevalence and 95% confidence intervals (CIs) for tinnitus were calculated. In the univariate analysis, the Rao-Scott chi-square test (using PROC SURVEYFREQ in SAS) and logistic regression analysis (using PROC SURVEYLOGISTIC in SAS) were used to test the association between hearing, tinnitus, and HRQoL in a complex sampling design. Participants’ characteristics were described using means and standard errors for continuous variables and numbers and percentages for categorical variables. We first adjusted for age and gender (model 1) and then adjusted for the variables in model 1 plus smoking status, alcohol intake, physical activity, body mass index (model 2), and then for model 2 plus income, education level diabetes, hypertension, and stress level (model 3).Among the 11,266 participants ≥19 years of age, the prevalence of unilateral hearing loss was 9.69% and that of tinnitus in the prior 12 months was 32.76%. In both the presence of tinnitus and the absence of tinnitus groups, subjects with hearing loss were older and less likely to exercise regularly, more likely to have a low income, and more likely to have chronic disease such as diabetes or hypertension compared with subjects with normal hearing . In bothSubjects were divided into four groups according to the hearing status and the presence of tinnitus: normal hearing without tinnitus, normal hearing with tinnitus, hearing loss without tinnitus, and hearing loss with tinnitus. The hearing loss with tinnitus group had the highest percentage of subjects who responded “some or extreme problems” in all five dimensions of EQ-5D. In the hearing loss with tinnitus group, the overall EQ-5D levels were as follows: 39.4% for mobility, 13.3% for self-care, 27.1% for usual activities, 39.2% for pain/discomfort, and 22.4% for anxiety/depression . The heaWe analyzed the distribution of those four categories according to age groups. The proportion of subjects with normal hearing without tinnitus decreased significantly from 81% in the younger age group (41–50 years) to 50% in the older age group (≥71 years) (P for trend <0.0001; This study of a population-based sample of adults in Korea aged 19 years or older found an association between hearing loss and tinnitus and disability with HRQoL. Our results from a large cross-sectional study of a representative sample of the Korean population support those from previous smaller trials that have demonstrated the association between hearing loss and tinnitus and HRQoL. HRQoL is used as an outcome measurement that encompasses physical, emotional, and social dimensions in different populations. In patient populations, it is used to assess the relative burden a chronic disease has on HRQoL or the effect of a new treatment .Several studies have found associations between hearing loss or tinnitus with worse subjective and objective measures of physical and psychological HRQoL. Chia et al. reported an association between hearing impairment and decreased physical and mental health scores of HRQoL . SindhusWe demonstrated that HRQoL in the hearing loss with tinnitus group was significantly impaired compared with the normal hearing without tinnitus group after adjusting for sociodemographic factors and comorbidities. In the subgroup analyses, a significant deterioration of HRQoL was observed in the tinnitus group. When adjusted for age and gender in model 1, the normal hearing with tinnitus group had a greater OR in all five dimensions of HRQoL than the hearing loss without tinnitus group. Furthermore, there was no significant effect of hearing loss without tinnitus on all five dimensions of HRQoL after adjusting for sociodemographic factors and comorbidities. Our data indicate that HRQoL has a closer relationship with tinnitus than hearing loss. Many authors reported that hearing impairment increased burden of communication and poorer HRQoL –18. ThisThis study has several limitations. First, we do not know the relative severity or grade of tinnitus in the absence of objective testing and more detailed questions. Second, the present study was cross-sectional. Although the causal relationship of risk factors with hearing loss or tinnitus is inconclusive, the results may be reliable because this is a population-based study from all parts of Korea. Third, there may be some response bias when reporting some parameters such as lifestyle habits and psychological stress because the KNHANES was conducted by using self-administered questionnaires.In conclusion, subjects with hearing loss with tinnitus appear to have a greater risk of deterioration of HRQoL than those patients who simply have hearing loss or tinnitus. Tinnitus compared with hearing loss has a strong association with a psychological health of HRQoL.


It appeared that higher capacity could be used in the sense of a compensatory mechanism with respect to the adverse effects of hearing loss, especially with low context speech.Everyday communication frequently comprises situations with more than one talker speaking at a time. These situations are challenging since they pose high attentional and memory demands placing cognitive load on the listener. Hearing impairment additionally exacerbates communication problems under these circumstances. We examined the effects of hearing loss and attention tasks on speech recognition with competing talkers in older adults with and without hearing impairment. We hypothesized that hearing loss would affect word identification, talker separation and word recall and that the difficulties experienced by the hearing impaired listeners would be especially pronounced in a task with high attentional and memory demands. Two listener groups closely matched for their age and neuropsychological profile but differing in hearing acuity were examined regarding their speech recognition with competing talkers in two different tasks. One task required repeating back words from one target talker (1TT) while ignoring the competing talker whereas the other required repeating back words from both talkers (2TT). The competing talkers differed with respect to their voice characteristics. Moreover, sentences either with low or high context were used in order to consider linguistic properties. Compared to their normal hearing peers, listeners with hearing loss revealed limited speech recognition in both tasks. Their difficulties were especially pronounced in the more demanding 2TT task. In order to shed light on the underlying mechanisms, different error sources, namely having misunderstood, confused, or omitted words were investigated. Misunderstanding and omitting words were more frequently observed in the hearing impaired than in the normal hearing listeners. In line with common speech perception models, it is suggested that these effects are related to impaired object formation and taxed working memory capacity (WMC). In a  Age-related hearing loss is a common chronic condition in older persons . The GOESA presents high context speech and includes everyday sentences with three- to seven-word lengths and with a high word predictability of j = 2.5  and formant frequencies using “praat”  of 0 dB across all sentence pairs. In order to consider not only acoustic characteristics of different talkers, but also linguistic properties, the superimposed sentences were either drawn from the low context speech material of the OLSA stimulus type  or from both low context (OLSA) and high context sentences of the GOESA (denoted as LC/HC). In the latter case, both sentence sets were used as a target as well as a masker, depending on the given voice characteristics . The number of OLSA and GOESA targets was balanced. Stimuli were presented at an average level of 70 dB SPL via a free-field loudspeaker placed in front of the participant's head at a distance of 1.2 m in a sound-treated booth.Procedures based on methods described by Humes et al.  and MeisPrior to the measurements, the participants were intensively familiarized with the stimulus materials and the procedures. Stimuli presented during familiarization were discarded for the measurements.Fourteen older adults aged 58–79 years (mean 68.3 years) with good hearing  listeners in the following) and 14 older adults with typical age related hearing loss (denoted as hearing impaired (HI) listeners) aged 60–85 years (mean 69.6 years) participated in the study. Hearing loss was predominantly symmetrical, with between-ear differences typically less than 15 dB HL. None of the listeners was provided with hearing aids. Mean pure-tone thresholds are given in Table post-hoc grouping criterion  of the listeners. With the VLMT lists of 15 words were visually presented and the participants were requested to recall back as many words as possible. This procedure was repeated five times and the mean across the repetitions was calculated as the outcome value. Thus, a value of 10 corresponds to 10/15 words recalled per list in average. The test primarily addresses verbal short-term memory and learning abilities, but also captures the individual WMC of the participant .Both groups underwent cognitive screening using the DemTect inventory , and used as a further between-subject variable. Log-transforms were applied since not all data were normally distributed. All statistical analyses were performed using IBM SPSS Statistics 22.Mixed design ANOVAs for the number of words repeated back and the number of different errors were conducted, with task  and stimulus type  as within-subject variables, and listener group  as the between-subject variable. Moreover, for a overall number of words repeated back, irrespective of substitution or confusion errors. The outcome is given as the average across the three tests lists (14 sentence pairs each) presented for each condition . In general, the 2TT task obviously yielded more words repeated back than the 1TT task and the NH listeners repeated back more words than the HI listeners. Subjecting the data to a mixed design ANOVA revealed significant main effects of task  and group . Moreover, a significant interaction task × group  could be observed. This significant interaction was evaluated further. Post-hoc independent samples t-tests revealed that the difference between the 1TT and the 2TT task was significantly greater in the NH listeners than in the HI listeners . No other main effects or interactions were significant.Figure F = 38.24, p < 0.001] and group . Moreover, a significant interaction stimulus type × task  could be observed. Post-hoc independent samples t-tests revealed that the 1TT and the 2TT tasks revealed similar outcome in the LC/LC condition but that in the LC/HC condition more target words were repeated back correctly in the 2TT than in the 1TT task . No other main effects or interactions were significant.Figure F = 202.75, p < 0.001] and a significant interaction error type × group . Post-hoc t-tests showed that omissions occurred more frequently than substitutions and confusions , and that the listener two groups showed a significant difference for substitutions , a strong trend toward significance for omissions  but no significant differences in confusions (p < 0.05). No other main effects or interactions were significant.Three different error types, namely substitutions, confusions and omissions were documented. Subjecting the number of errors to a mixed model ANOVA with error type as the within- and group as the between-subjects variable revealed a significant main effect of error type , stimulus type , and group . Moreover, a significant interaction task × group  could be observed. Post-hoc independent samples t-tests revealed that the group-difference in substitutions was only significant in the 1TT condition . No other main effects or interactions were significant.Figure F = 71.49, p < 0.001] and stimulus type . Furthermore, a significant interaction of task × stimulus type  was found. Post-hoc paired comparison t-tests confirmed that the difference in confusions between the 1TT and the 2TT task was significantly larger for the LC/LC condition compared to the LC/HC condition . No other main effects or interactions were significant.The number of confusions  for the different conditions is shown in Figure F = 871.57, p < 0.001], and group . Furthermore, a significant interaction task × group could be observed . Post-hoc t-tests revealed that the difference between the 1TT and the 2TT task was significantly larger in the HI than the NH listeners . No other main effects or interactions were significant.Figure post-hoc analysis. Figure F = 44.63, p < 0.001], group , and VLMT score . The significant main effects of stimulus type and group reflect the outcome already presented in Figure F = 9.68, p = 0.05]. Additionally, a significant stimulus type × group × VLMT interaction  could be observed, suggesting greater differences in target word recognition between the two VLMT-groups in the HI listeners than in the NH listeners, especially for low context speech. Post-hoc t-tests revealed that only the VLMT-group difference in the HI listeners with the LC/LC condition was significant . No other main effects or interactions were significant.Following the significant group difference for omissions and the model assumptions regarding the importance of WMC for speech recognition in adverse conditions, the participants were further characterized with respect to their VLMT scores in a gure F1, 4 = 44.63gure F1, 4 = 44.63Several studies have addressed speech recognition with competing talkers and mainly focused on differences between younger and elderly listeners. These examinations demonstrated that older listeners performed worse than younger listeners even when group differences in hearing loss were taken into account  seemed to be beneficial for auditory stream segregation, and these cues largely remained useful for the participants with age-related hearing loss. There is evidence that sensorineural hearing loss is associated with worsened processing of temporal fine structure cues that might deteriorate F0 discrimination (Moore and Glasberg, per se, since speech recognition was near perfect when the sentences were presented at 70 dB SPL without competing masker. Thus, it is unlikely that HL rendered single words completely unintelligible. It might be speculated that the increased amount of omissions in the HI group additionally reflects increased cognitive load due to the sensory impairment and the corresponding mechanisms proposed by the ELU model: The hearing loss of the participants might have disrupted the rapid and automatic matching of the entries in the episodic buffer and representations in LTM. As a consequence of the implicit process disruption, a compensatory mechanism taxing WMC might be invoked—labeled “explicit processing” by Rönnberg (The most frequently observed error type was omissions, and there were significant main effects of task and group. Predictably, more omissions occurred with the more demanding 2TT task that required to repeat back words from two target talkers instead of only one target talker. Furthermore, the hearing-impaired participants revealed consistently more omissions than the normal-hearing listeners though the groups were carefully matched with regard to their WMC. It should be noted that this observation also seems not to be due to the slight-moderate hearing loss Rönnberg  and RönnRönnberg , 2013. TRönnberg , this mipost-hoc group splitting with respect to WMC was performed. Though this additional separation resulted in a relatively low number of observations, a further significant main effect of VLMT score as well as a further significant interaction of VLMT score, listener group, and stimulus type could be shown for target word recognition. The main effect of VLMT score revealed that participants with higher WMC repeated back more target words than those with lower WMC. It could be argued that this simply reflects similarities between the VLMT paradigm and the speech recognition tests as both require to repeat back words. However, the significant interaction of VLMT score, listener group, and stimulus type revealed that the effect of group-split regarding the VLMT score held only for the HI listeners in the LC/LC condition. This suggests that WMC was especially important for the HI listeners when they could not rely on context information. In the LC/LC condition the HI listeners with better WMC approached the results of the NH listeners. This might be interpreted in the sense of a compensatory effect of cognitive function on the detrimental impact of hearing loss. However, due to the small group size in the post-hoc analysis this finding should be treated with caution and requires a more comprehensive examination. Nevertheless, it seems in line with Wingfield and Stine-Morrow (Following the results discussed above a e-Morrow  and Winge-Morrow  who showTaken together, the results suggest an interplay of hearing loss and cognitive load regarding speech recognition with competing talkers. We anticipated that the hearing impaired listeners would experience difficulties on different stages of speech processing. This held true for word object formation and word recall, but not for stream segregation. We also hypothesized that difficulties for the HI listeners would be pronounced in the more demanding 2TT compared to the 1TT attention task. The results suggest extra difficulties with higher cognitive load for the HI compared to the NH listeners as they were especially limited in repeating back words in the 2TT task, though both groups showed near perfect speech recognition in quiet and showed similar outcome in their neuropsychological profile. When the groups were further separated with respect to their WMC it appeared that the HI listeners could use working memory in the sense of a compensatory mechanism with regard to the detrimental effects of hearing loss—especially when no supporting context cues were available. However, due to the relatively small number of participants this has to be examined further. Apart from these differences found between the groups the results revealed that context could be used by the normal hearing listeners and the listeners with typical age-related hearing loss in a similar manner.HM designed the work, analyzed the data and wrote the manuscript, SS acquired the data and revised the manuscript critically, MO, SR, and MW revised the manuscript critically.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.