The Effects of Iron Deficiency on the Gut Microbiota in Women of Childbearing Age.

Iron deficiency anemia (IDA) is the most prevalent and common nutritional deficiency worldwide and is a global health problem with significant risk, particularly among women of reproductive age. Oral iron supplementation is the most widely used and cost-effective treatment for iron deficiency and IDA. However, there are limitations regarding side effects such as enteritis, treatment compliance, and bioavailability. Intestinal microbiome characteristic research has been recently conducted to overcome these issues, but more is needed. Against this background, a metagenomics study on the 16S gene in the feces of young women vulnerable to IDA was conducted. As a result of analyzing 16 normal subjects and 15 IDA patients, significant differences in bacterial community distribution were identified. In particular, a significant decrease in Faecalibacterium was characteristic in IDA patients compared with normal subjects. Furthermore, in the case of patients who recovered from IDA following iron supplementation treatment, it was confirmed that Faecalibacterium significantly recovered to normal levels. However, no significance in beta diversity was seen compared with before treatment. There were also no differences in the beta diversity results between the recovered and normal subjects. Therefore, intestinal dysbiosis during the disease state was considered to be restored as IDA improved. Although the results were derived from a limited number of subjects and additional research is needed, the results of this study are expected to be the basis for developing treatment and prevention strategies based on host-microbiome crosstalk in IDA.

Relationship between spectrotemporal modulation detection and music perception in normal-hearing, hearing-impaired, and cochlear implant listeners.

The objective of this study was to examine the relationship between spectrotemporal modulation (STM) sensitivity and the ability to perceive music. Ten normal-nearing (NH) listeners, ten hearing aid (HA) users with moderate hearing loss, and ten cochlear Implant (CI) users participated in this study. Three different types of psychoacoustic tests including spectral modulation detection (SMD), temporal modulation detection (TMD), and STM were administered. Performances on these psychoacoustic tests were compared to music perception abilities. In addition, psychoacoustic mechanisms involved in the improvement of music perception through HA were evaluated. Music perception abilities in unaided and aided conditions were measured for HA users. After that, HA benefit for music perception was correlated with aided psychoacoustic performance. STM detection study showed that a combination of spectral and temporal modulation cues were more strongly correlated with music perception abilities than spectral or temporal modulation cues measured separately. No correlation was found between music perception performance and SMD threshold or TMD threshold in each group. Also, HA benefits for melody and timbre identification were significantly correlated with a combination of spectral and temporal envelope cues though HA.

Improved prognostic stratification using NCCN- and GELTAMO-international prognostic index in patients with diffuse large B-cell lymphoma.

The National Comprehensive Cancer Network (NCCN)-International Prognostic Index (IPI) and GELTAMO (Grupo Español de Linfomas/Trasplante Autólogo de Médula Ósea)-IPI were developed to enable better risk prediction of patients with diffuse large B-cell lymphoma (DLBCL). The present study compared the effectiveness of risk prediction between IPI, NCCN-IPI, and GELTAMO-IPI in patients with DLBCL particularly in terms of determining high-risk patients. Among 439 patients who were enrolled to a prospective DLBCL cohort treated with R-CHOP immunochemotherapy, risk groups were classified according to the three IPIs and the prognostic significance of individual IPI factors and IPI models were analyzed and compared. All three IPI effectively separated the analyzed patients into four risk groups according to overall survival (OS). Estimated 5-year OS of patients classified as high-risk according to the IPI was 45.7%, suggesting that the IPI is limited in the selection of patients who are expected to have a poor outcome. In contrast, the 5-year OS of patients stratified as high-risk according to NCCN- and GELTAMO-IPI was 31.4% and 21.9%, respectively. The results indicate that NCCN- and GELTAMO-IPI are better than the IPI in predicting patients with poor prognosis, suggesting the superiority of enhanced, next-generation IPIs for DLBCL.

Effects of age and hearing mechanism on spectral resolution in normal hearing and cochlear-implanted listeners.

Spectral resolution limits speech perception with a cochlear implant (CI) in post-lingually deaf adults. However, the development of spectral resolution in pre-lingually deaf implanted children is not well understood. Acoustic spectral resolution was measured as a function of age (school-age versus adult) in CI and normal-hearing (NH) participants using spectral ripple discrimination (SRD). A 3-alternative forced-choice task was used to obtain SRD thresholds at five ripple depths. Effects of age and hearing method on SRD and spectral modulation transfer function (SMTF) slope (reflecting frequency resolution) and x-intercept (reflecting across-channel intensity resolution) were examined. Correlations between SRD, SMTF parameters, age, and speech perception in noise were studied. Better SRD in NH than CI participants was observed at all depths. SRD thresholds and SMTF slope correlated with speech perception in CI users. When adjusted for floor performance, x-intercept did not correlate with SMTF slope or speech perception. Age and x-intercept correlations were positive and significant in NH but not CI children suggesting that across-channel intensity resolution matures during school-age in NH children. No evidence for maturation of spectral resolution beyond early school-age in pre-lingually deaf implanted CI users was found in the present study.

Highly elevated serum lactate dehydrogenase is associated with central nervous system relapse in patients with diffuse large B-cell lymphoma: Results of a multicenter prospective cohort study.

Central nervous system involvement remains a challenging issue in the treatment of patients with diffuse large B-cell lymphoma. We conducted a prospective cohort study with newly diagnosed diffuse large B-cell lymphoma patients receiving rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone to identify incidence and risk factors for central nervous system involvement. Among 595 patients, 279 patients received pre-treatment central nervous system evaluation, and 14 patients had central nervous system involvement at diagnosis (2.3% out of entire patients and 5.0% out of the 279 patients). For those patients, median follow-up duration was 38.2 months and some of them achieved long-term survival. Out of 581 patients who did not have central nervous system involvement at diagnosis, 26 patients underwent secondary central nervous system relapse with a median follow-up of 35 months, and the median time to central nervous system involvement was 10.4 months (range: 3.4-29.2). Serum lactate dehydrogenase > ×3 upper limit of normal range, the Eastern Cooperative Oncology Group performance status ≥ 2, and involvement of sinonasal tract or testis, were independent risk factors for central nervous system relapse in multivariate analysis. Our study suggests that enhanced stratification of serum lactate dehydrogenase according to the National Comprehensive Cancer Network-International Prognostic Index may contribute to better prediction for central nervous system relapse in patients with diffuse large B-cell lymphoma. This trial was registered at clinicaltrials.gov identifier: 01202448.

Influence of Tinnitus on Auditory Spectral and Temporal Resolution and Speech Perception in Tinnitus Patients.

Although cochlear damage is believed to trigger the perception of tinnitus in the central auditory system, its pathophysiological mechanism is still unclear. We aimed to investigate the pathophysiology of tinnitus using psychoacoustic assessments of auditory spectral and temporal resolution and speech perception in noise. Human subjects with tinnitus and symmetric hearing thresholds were divided into three groups: nine unilateral tinnitus subjects with normal hearing thresholds (Group 1), 12 unilateral tinnitus subjects with hearing loss (HL; Group 2), and nine bilateral tinnitus subjects with HL. Fifteen normal-hearing subjects without tinnitus were also tested as a control group. Four different tests were administered: (1) the spectral-ripple discrimination (SRD) test, (2) the temporal modulation detection (TMD) test, (3) the Schroeder-phase discrimination (SPD) test, and (4) the speech recognition threshold (SRT) in noise test. There were no significant differences in SRD, TMD, and SPD between the tinnitus-affected ears (TEs) and non-tinnitus ears (NTEs) in Groups 1 and 2 (p > 0.05). In contrast, the TEs showed poorer SRTs than the NTEs in these two subject groups (p = 0.022 and 0.049). No inferiority of spectral/temporal resolution in TEs compared with NTEs suggests that there may be no more outer hair cell (OHC) damage on the tinnitus side given that damaged OHCs are associated with broadening the auditory filters. The decoupling of the SRT results from the spectral/temporal resolution data could imply that the occurrence of tinnitus does not depend upon the degree of damage to the OHCs, but rather upon different plastic changes in the central auditory system after cochlear damage. SIGNIFICANCE STATEMENT: We can easily find unilateral tinnitus patients who have symmetric hearing thresholds. Our research question was what kind of difference would be responsible for the tinnitus in the tinnitus-affected ears but not in the non-tinnitus ears of subjects with symmetric hearing thresholds. The answer to this fundamental question could help us to understand the pathophysiology of tinnitus. We evaluated the potential influence of tinnitus upon the subjects' auditory spectral and temporal resolution and speech perception in noise by comparing these psychoacoustic performances between tinnitus-affected ears and non-tinnitus ears in the same subjects.

Relationship between channel interaction and spectral-ripple discrimination in cochlear implant users.

Cochlear implant (CI) users can achieve remarkable speech understanding, but there is great variability in outcomes that is only partially accounted for by age, residual hearing, and duration of deafness. Results might be improved with the use of psychophysical tests to predict which sound processing strategies offer the best potential outcomes. In particular, the spectral-ripple discrimination test offers a time-efficient, nonlinguistic measure that is correlated with perception of both speech and music by CI users. Features that make this "one-point" test time-efficient, and thus potentially clinically useful, are also connected to controversy within the CI field about what the test measures. The current work examined the relationship between thresholds in the one-point spectral-ripple test, in which stimuli are presented acoustically, and interaction indices measured under the controlled conditions afforded by direct stimulation with a research processor. Results of these studies include the following: (1) within individual subjects there were large variations in the interaction index along the electrode array, (2) interaction indices generally decreased with increasing electrode separation, and (3) spectral-ripple discrimination improved with decreasing mean interaction index at electrode separations of one, three, and five electrodes. These results indicate that spectral-ripple discrimination thresholds can provide a useful metric of the spectral resolution of CI users.

Detection of acoustic temporal fine structure by cochlear implant listeners: behavioral results and computational modeling.

A test of within-channel detection of acoustic temporal fine structure (aTFS) cues is presented. Eight cochlear implant listeners (CI) were asked to discriminate between two Schroeder-phase (SP) complexes using a two-alternative, forced-choice task. Because differences between the acoustic stimuli are primarily constrained to their aTFS, successful discrimination reflects a combination of the subjects' perception of and the strategy's ability to deliver aTFS cues. Subjects were mapped with single-channel Continuous Interleaved Sampling (CIS) and Simultaneous Analog Stimulation (SAS) strategies. To compare within- and across- channel delivery of aTFS cues, a 16-channel clinical HiRes strategy was also fitted. Throughout testing, SAS consistently outperformed the CIS strategy (p ≤ 0.002). For SP stimuli with F0 = 50 Hz, the highest discrimination scores were achieved with the HiRes encoding, followed by scores with the SAS and the CIS strategies, respectively. At 200 Hz, single-channel SAS performed better than HiRes (p = 0.022), demonstrating that under a more challenging testing condition, discrimination performance with a single-channel analog encoding can exceed that of a 16-channel pulsatile strategy. To better understand the intermediate steps of discrimination, a biophysical model was used to examine the neural discharges evoked by the SP stimuli. Discrimination estimates calculated from simulated neural responses successfully tracked the behavioral performance trends of single-channel CI listeners.

Maximizing the spectral and temporal benefits of two clinically used sound processing strategies for cochlear implants.

Previous work showed that the Fidelity120 processing strategy provides better spectral sensitivity, while the HiResolution processing strategy can deliver more detailed temporal information for Advanced Bionics cochlear implant users. The goal of this study was to develop a new sound processing strategy by maximizing the spectral benefit of Fidelity120 and the temporal benefit of HiResolution to improve both aspects of hearing. Using acoustic simulations of Fidelity120 and HiResolution strategies, a dual-processing strategy was created by combining Fidelity120 in the low frequency channels and HiResolution in the high frequency channels. Compared to Fidelity120, the dual processing provided an improvement in performance for Schroeder-phase discrimination at 200 Hz and temporal modulation detection at 200 Hz with the cost of a slightly decreased performance for spectral-ripple discrimination relative to Fidelity120. Spectral-ripple discrimination was better with the dual processing than with HiResolution. However, no benefit for speech perception in noise was found for the dual-processing strategy over Fidelity 120 or HiResolution in our preliminary tests. Some other more optimal combination of Fidelity120 and HiResolution may be required to maximize the spectral and temporal benefits to yield improved speech perception.

Improved perception of speech in noise and Mandarin tones with acoustic simulations of harmonic coding for cochlear implants.

Harmonic and temporal fine structure (TFS) information are important cues for speech perception in noise and music perception. However, due to the inherently coarse spectral and temporal resolution in electric hearing, the question of how to deliver harmonic and TFS information to cochlear implant (CI) users remains unresolved. A harmonic-single-sideband-encoder [(HSSE); Nie et al. (2008). Proceedings of IEEE International Conference on Acoustics, Speech, and Signal Processing; Lie et al., (2010). Proceedings of IEEE International Conference on Acoustics, Speech, and Signal Processing] strategy has been proposed that explicitly tracks the harmonics in speech and transforms them into modulators conveying both amplitude modulation and fundamental frequency information. For unvoiced speech, HSSE transforms the TFS into a slowly varying yet still noise-like signal. To investigate its potential, four- and eight-channel vocoder simulations of HSSE and the continuous-interleaved-sampling (CIS) strategy were implemented, respectively. Using these vocoders, five normal-hearing subjects' speech recognition performance was evaluated under different masking conditions; another five normal-hearing subjects' Mandarin tone identification performance was also evaluated. Additionally, the neural discharge patterns evoked by HSSE- and CIS-encoded Mandarin tone stimuli were simulated using an auditory nerve model. All subjects scored significantly higher with HSSE than with CIS vocoders. The modeling analysis demonstrated that HSSE can convey temporal pitch cues better than CIS. Overall, the results suggest that HSSE is a promising strategy to enhance speech perception with CIs.

The ability of cochlear implant users to use temporal envelope cues recovered from speech frequency modulation.

Previous studies have demonstrated that normal-hearing listeners can understand speech using the recovered "temporal envelopes," i.e., amplitude modulation (AM) cues from frequency modulation (FM). This study evaluated this mechanism in cochlear implant (CI) users for consonant identification. Stimuli containing only FM cues were created using 1, 2, 4, and 8-band FM-vocoders to determine if consonant identification performance would improve as the recovered AM cues become more available. A consistent improvement was observed as the band number decreased from 8 to 1, supporting the hypothesis that (1) the CI sound processor generates recovered AM cues from broadband FM, and (2) CI users can use the recovered AM cues to recognize speech. The correlation between the intact and the recovered AM components at the output of the sound processor was also generally higher when the band number was low, supporting the consonant identification results. Moreover, CI subjects who were better at using recovered AM cues from broadband FM cues showed better identification performance with intact (unprocessed) speech stimuli. This suggests that speech perception performance variability in CI users may be partly caused by differences in their ability to use AM cues recovered from FM speech cues.

Psychoacoustic performance and music and speech perception in prelingually deafened children with cochlear implants.

The number of pediatric cochlear implant (CI) recipients has increased substantially over the past 10 years, and it has become more important to understand the underlying mechanisms of the variable outcomes in this population. In this study, psychoacoustic measures of spectral-ripple and Schroeder-phase discrimination, the Clinical Assessment of Music Perception, and consonant-nucleus-consonant (CNC) word recognition in quiet and spondee reception threshold (SRT) in noise tests have been presented to 11 prelingually deafened CI users, aged 8-16 years with at least 5 years of CI experience. The children's performance was compared to the previously reported results of postlingually deafened adult CI users. The average spectral-ripple threshold (n = 10) was 2.08 ripples/octave. The average Schroeder-phase discrimination was 67.3% for 50 Hz and 56.5% for 200 Hz (n = 9). The Clinical Assessment of Music Perception test showed that the average complex pitch direction discrimination was 2.98 semitones. The mean melody score was at a chance level, and the mean timbre score was 34.1% correct. The mean CNC word recognition score was 68.6%, and the mean SRT in steady noise was -8.5 dB SNR. The children's spectral-ripple resolution, CNC word recognition, and SRT in noise performances were, within statistical bounds, the same as in a population of postlingually deafened adult CI users. However, Schroeder-phase discrimination and music perception were generally poorer than in the adults. It is possible then that this poorer performance seen in the children might be partly accounted for by the delayed maturation in their temporal processing ability, and because of this, the children's performance may have been driven more by their spectral sensitivity.

Evidence of across-channel processing for spectral-ripple discrimination in cochlear implant listeners.

Spectral-ripple discrimination has been used widely for psychoacoustical studies in normal-hearing, hearing-impaired, and cochlear implant listeners. The present study investigated the perceptual mechanism for spectral-ripple discrimination in cochlear implant listeners. The main goal of this study was to determine whether cochlear implant listeners use a local intensity cue or global spectral shape for spectral-ripple discrimination. The effect of electrode separation on spectral-ripple discrimination was also evaluated. Results showed that it is highly unlikely that cochlear implant listeners depend on a local intensity cue for spectral-ripple discrimination. A phenomenological model of spectral-ripple discrimination, as an "ideal observer," showed that a perceptual mechanism based on discrimination of a single intensity difference cannot account for performance of cochlear implant listeners. Spectral modulation depth and electrode separation were found to significantly affect spectral-ripple discrimination. The evidence supports the hypothesis that spectral-ripple discrimination involves integrating information from multiple channels.

Biomarker responses in pelagic and benthic fish over 1 year following the Hebei Spirit oil spill (Taean, Korea).

After the Hebei Spirit oil spill incident (7th December, 2007) in the west coast of Korea, contamination of biliary PAH metabolite and hepatic biomarkers in a pelagic and a benthic fish was monitored for 1 year. Concentrations of 16 PAHs and alkylated PAHs in fish muscle were highest (22.0 ng/g d.w. for 16 PAHs and 284 ng/g d.w. for alkylated PAHs) at 5 days after the spill and then decreased rapidly to background levels at 11 months after the spill. Fish from the oiled site had elevated biliary PAH metabolite concentrations immediately after the spill; these declined steadily in both species, but were still above reference site concentrations 2 months after the spill. Oiled-site fish showed hepatic CYP 1A induction whose trend closely followed those of biliary PAH metabolite concentrations, implying continuous exposure to PAHs. Brain acetylcholinesterase activity was not related to oil exposure.

Stage IV marginal zone B-cell lymphoma--prognostic factors and the role of rituximab: Consortium for Improving Survival of Lymphoma (CISL) study.

Stage IV marginal zone B-cell lymphomas (MZL) are detected in more than 25% of lymphoma patients. In this study, we conducted retrospective analyses of specific cases of stage IV MZL in order to assess their clinical features, as well as the treatments and prognoses of these cases. A total of 94 patients with histological diagnosis of stage IV-MZL from 17 different institutions in Korea were included. Multiple-mucosa-associated lymphoid tissue (MALT)-organs-involved MZL (M-MZL) was detected in 34 patients (36.2%). Bone-marrow-involved stage IV MZL (BM-MZL) was detected in 33 patients (35.1%). Median time to progression (TTP) was 2.4years (95% CI, 1.9-2.9). Five- and 10-year overall survival rates were 84.5% and 79.8%, respectively. Patients with lymph node involvement in stage IV MZL appeared to have worse prognoses in TTP (P=0.015). Thirty-one patients were treated with a regimen including rituximab (CTx-R[+]), and 31 with a regimen that did not include rituximab (CTx-R[-]). The CTx-R(+) group showed better responses than the CTx-R(-) group (83.9%versus 54.8%, P=0.026). However, no differences in TTP duration were detected (P=0.113). Stage IV MZL tend to follow an indolent disease course. Therefore, lymph node involvement is a more valuable prognostic factor for TTP. Rituximab appears to contribute to better responses, but not in cases of TTP.

Psychoacoustic abilities associated with music perception in cochlear implant users.

OBJECTIVES: This study was designed to determine what acoustic elements are associated with musical perception ability in cochlear implant (CI) users and to understand how acoustic elements, which are important to good speech perception, contribute to music perception in CI users. It was hypothesized that the variability in the performance of music and speech perception may be related to differences in the sensitivity to specific acoustic features such as spectral changes or temporal modulations, or both. DESIGN: A battery of hearing tasks was administered to 42 CI listeners. The Clinical Assessment of Music Perception was used, which evaluates complex-tone pitch-direction discrimination, melody recognition, and timbre recognition. To investigate spectral and temporal processing, spectral-ripple discrimination and Schroeder-phase discrimination abilities were evaluated. Speech perception ability in quiet and noise was also evaluated. Relationships between Clinical Assessment of Music Perception subtest scores, spectral-ripple discrimination thresholds, Schroeder-phase discrimination scores, and speech recognition scores were assessed. RESULTS: Spectral-ripple discrimination was shown to correlate with all three aspects of music perception studied. Schroeder-phase discrimination was generally not predictive of music perception outcomes. Music perception ability was significantly correlated with speech perception ability. Nearly half of the variance in melody and timbre recognition was predicted jointly by spectral-ripple and pitch-direction discrimination thresholds. Similar results were observed on speech recognition as well. CONCLUSIONS: This study suggests that spectral-ripple discrimination is significantly associated with music perception in CI users. A previous report showed that spectral-ripple discrimination is significantly correlated with speech recognition in quiet and in noise. This study also showed that speech recognition and music perception are also related to one another. Spectral-ripple discrimination ability seems to reflect a wide range of hearing abilities in CI users. The results suggest that materially improving spectral resolution could provide significant benefits in music and speech perception outcomes in CI users.

Pulmonary marginal zone B-cell lymphoma of MALT type--what is a prognostic factor and which is the optimal treatment, operation, or chemotherapy?: Consortium for Improving Survival of Lymphoma (CISL) study.

Pulmonary marginal zone B-cell lymphoma of the MALT type (P-MZL) is a relatively rare form of lymphoma. We conducted a retrospective analysis of the clinical features and treatment outcomes of P-MZL for the evaluation of prognostic factors, and to collect information about the optimal treatment modality for this condition. From 1991 to 2008, a total of 61 patients with biopsy-confirmed P-MZL were retrospectively analyzed. The median age of our subjects was 60 (range, 34-79) years. Twenty-five of the patients (41%) were initially diagnosed without any symptoms. Video-assisted thoracic surgery was utilized for diagnosis in 19 patients (31%). Thirty-eight patients' conditions (62%) involved a single lobe. Lung lesions were bilateral in 15 patients (25%). Eleven patients evidenced synchronous involvement of extra-pulmonary site MZL. Overall, 56 of 61 patients were treated with surgery (n = 22), chemotherapy (n = 28), or radiotherapy (n = 6). Among them, 46 patients achieved complete or partial remission. The median time to progression (TTP) was 5.6 (95% CI, 2.6-8.6) years. Five patients died during follow-up. Extra-pulmonary MZL and LN involvement were shown to be poor prognostic factors for TTP. We noted no differences between the operation group and chemotherapy group in terms of TTP. P-MZL tends to be an indolent disease-characterized by prolonged survival with frequent relapses. This is similar to what is observed with other cases of MALT-type site MZL. In order to conserve lung function and reduce the risks of operation, chemotherapy should be considered as a first-line option for the treatment of P-MZL.