A Subcortical Model for Auditory Forward Masking with Efferent Control of Cochlear Gain.

Previous physiological and psychophysical studies have explored whether feedback to the cochlea from the efferent system influences forward masking. The present work proposes that the limited growth-of-masking (GOM) observed in auditory nerve (AN) fibers may have been misunderstood; namely, that this limitation may be due to the influence of anesthesia on the efferent system. Building on the premise that the unanesthetized AN may exhibit GOM similar to more central nuclei, the present computational modeling study demonstrates that feedback from the medial olivocochlear (MOC) efferents may contribute to GOM observed physiologically in onset-type neurons in both the cochlear nucleus and inferior colliculus (IC). Additionally, the computational model of MOC efferents used here generates a decrease in masking with longer masker-signal delays similar to that observed in IC physiology and in psychophysical studies. An advantage of this explanation over alternative physiological explanations (e.g., that forward masking requires inhibition from the superior paraolivary nucleus) is that this theory can explain forward masking observed in the brainstem, early in the ascending pathway. For explaining psychoacoustic results, one strength of this model is that it can account for the lack of elevation in thresholds observed when masker level is randomly varied from interval-to-interval, a result that is difficult to explain using the conventional temporal window model of psychophysical forward masking. Future directions for evaluating the efferent mechanism as a contributing mechanism for psychoacoustic results are discussed.

Inherent envelope fluctuations in forward masking: Effects of age and hearing loss.

Forward masking is generally greater for Gaussian noise (GN) than for low-fluctuation noise maskers, i.e., GN disruption. Because the minimal hearing loss that is associated with older age may affect GN disruption differently than more significant hearing loss, the current study explored the contribution of minimal hearing loss associated with older age to GN disruption. GN disruption was measured using three masker-signal delays (25, 75, and 150 ms) for three adult groups: younger participants with normal hearing (NH), older participants with minimal hearing loss, and older participants with sensorineural hearing loss. The role of underlying mechanisms was tested using a computational model for midbrain neurons. The primary result suggests that older listeners with mild threshold elevations that typically occur with age may be more susceptible to the deleterious effects of masker envelope fluctuations than younger listeners with NH. Results from the computational model indicate that there may be a larger influence of efferent feedback and saturation of inner hair cells on forward masking and GN disruption than previously considered.

Amplitude-modulation forward masking for listeners with and without hearing loss.

Amplitude-modulation (AM) forward masking was measured for listeners with normal hearing and sensorineural hearing loss at 4000 and 1000 Hz, using continuous and noncontinuous masker and signal carriers, respectively. A low-fluctuation noise (LFN) carrier was used for the "continuous carrier" conditions. An unmodulated low-fluctuation noise (U-LFN), an unmodulated Gaussian noise (U-GN), and an amplitude-modulation low-fluctuation noise (AM-LFN) were maskers for the "noncontinuous carrier" conditions. As predicted, U-GN yielded more masking than U-LFN and similar masking to AM-LFN, suggesting that U-GN resulted in AM forward masking. Contrary to predictions, no differences in masked thresholds were observed between listener groups.

Virtual audiology education tools: A survey of faculty, graduate students, and undergraduate students.

Due to global shifts at educational institutions from in-person courses to online formats caused by the COVID-19 pandemic, the current study aimed to estimate whether currently available virtual audiology education tools are helpful for acquiring necessary audiology skills and knowledge from the perspective of both educators and students. Therefore, a remote survey was developed and distributed to faculty and students in undergraduate communication sciences disorders and graduate audiology programs. Although participation was somewhat limited, the trends observed in the survey results suggested that the majority of both educators and students found the subset of virtual tools easy to use, that these tools improved teaching methods and learning outcomes, and that these tools would likely be used again.

Associations between matrix metalloproteinase, tissue inhibitor of metalloproteinase and collagen expression levels in the adjacent rectal tissue of colorectal carcinoma patients.

As the commonest type of cancer in Europe and the third most common type of cancer worldwide, colorectal carcinoma (CRC) poses a challenge for numerous scientific studies. At present, the cause of this disease is remains to be elucidated, but early diagnosis is only one solution to prevent serious health complications. As a structural scaffold, the extracellular matrix (ECM) is in direct contact with tumour cells and significantly interferes with tumour progression. During the process of tumorigenesis, the ECM undergoes structural changes in which collagens serve an important role. Their life cycle is regulated by proteolytic enzymes called matrix metalloproteinases (MMPs), which are controlled by tissue inhibitors of metalloproteinases (TIMPs). The present study analysed the gene expression of MMPs (MMP1-2-8-10-13), TIMPs (TIMP1-2-4) and collagens (COL1A1 and COL3A1) and the correlation with biochemical parameters in the adjacent rectal tissue (ART) of patients with CRC. The patients who underwent standard neoadjuvant pre-therapy showed increased concentrations of collagen in the normal ART. The mRNA levels of COL3A1, TIMP1 and TIMP2 were significantly higher in the ART of CRC patients (with or without pre-therapy) when compared with the control group. This finding suggested that TIMPs served an important role in the regulation of MMPs and in the modification of collagen content in the ECM. Despite the small data set, the present study provided insights into the transcriptomic relationships between the individual genes that are an integral part of the ECM.

Detection of therapeutically relevant and concomitant rare somatic variants in colorectal cancer.

In colorectal cancer (CRC), clinically relevant biomarkers are known for genome-guided therapy that can be detected by both first and next generation methods. The aim of our work was to introduce a robust NGS assay that will be able to detect, in addition to standard predictive single nucleotide-based biomarkers, even rare and concomitant clinically relevant variants. Another aim was to identify truncating mutations in APC and pathogenic variants in TP53 to divide patients into potentially prognostic groups. A multigene panel with hotspots in 50 cancer-critical genes was used. Finally, 86 patients diagnosed with primary or metastatic colorectal cancer were enrolled. In total, there were identified 163 pathogenic variants, among them in the genes most recurrent mutated in CRC such as TP53 (49%), the RAS family genes KRAS and NRAS (47%), APC (43%), and PIK3CA (15%). In 30 samples, two driver mutations were present in one sample, 11 patients were without any mutations covered by this panel. In one patient, a novel variant in BRAF p.D594E was found, not previously seen in CRC, and was concomitant with KRAS p.G12A. In KRAS, a potentially sensitive mutation to anti-EGFR therapy p.A59T was found along with the PIK3CA missense variant p.E545K. It was possible to divide patients into groups based on the occurrence of truncating APC variant alone or concomitant with TP53 or KRAS. Our results demonstrate the potential of small multigene panels that can be used in diagnostics for the detection of rare therapeutically relevant variants. Moreover, the division of patients into groups based on the presence of APC and TP53 mutations enables this panel to be used in retrospective studies on the effectiveness of treatment with anti-EGFR inhibitors.

Mucosa plication reinforced colorectal anastomosis and trans-anal vacuum drainage: a pilot study with preliminary results.

Dehiscence of colorectal anastomosis is a serious complication that is associated with increased mortality, impaired functional and oncological outcomes. The hypothesis was that anastomosis reinforcement and vacuum trans-anal drainage could eliminate some risk factors, such as mechanically stapled anastomosis instability and local infection. Patients with rectal cancer within 10 cm of the anal verge and low anterior resection with double-stapled technique were included consecutively. A stapler anastomosis was supplemented by trans-anal reinforcement and vacuum drainage using a povidone-iodine-soaked sponge. Modified reinforcement using a circular mucosa plication was developed and used. Patients were followed up by postoperative endoscopy and outcomes were acute leak rate, morbidity, and diversion rate. The procedure was successfully completed in 52 from 54 patients during time period January 2019-October 2020. The mean age of patients was 61 years (lower-upper quartiles 54-69 years). There were 38/52 (73%) males and 14/52 (27%) females; the neoadjuvant radiotherapy was indicated in a group of patients in 24/52 (46%). The mean level of anastomosis was 3.8 cm (lower-upper quartiles 3.00-4.88 cm). The overall morbidity was 32.6% (17/52) and Clavien-Dindo complications ≥ 3 grade appeared in 3/52 (5.7%) patients. No loss of anastomosis was recorded and no patient died postoperatively. The symptomatic anastomotic leak was recorded in 2 (3.8%) patients and asymptomatic blind fistula was recorded in one patient 1/52 (1.9%). Diversion ileostomy was created in 1/52 patient (1.9%). Reinforcement of double-stapled anastomosis using a circular mucosa plication with combination of vacuum povidone-iodine-soaked sponge drainage led to a low acute leak and diversion rate. This pilot study requires further investigation.Registered at ClinicalTrials.gov.: Trial registration number is NCT04735107, date of registration February 2, 2021, registered retrospectively.

Inherent envelope fluctuations in forward maskers: Effects of masker-probe delay for listeners with normal and impaired hearing.

Forward-masked thresholds increase as the magnitude of inherent masker envelope fluctuations increase for both normal-hearing (NH) and hearing-impaired (HI) adults for a short masker-probe delay (25 ms). The slope of the recovery from forward masking is shallower for HI than for NH listeners due to reduced cochlear nonlinearities. However, effects of hearing loss on additional masking due to inherent envelope fluctuations across masker-probe delays remain unknown. The current study assessed effects of hearing loss on the slope and amount of recovery from forward maskers that varied in inherent envelope fluctuations. Forward-masked thresholds were measured at 2000 and 4000 Hz, for masker-probe delays of 25, 50, and 75 ms, for NH and HI adults. Four maskers at each center frequency varied in inherent envelope fluctuations: Gaussian noise (GN) or low-fluctuation noise (LFN), with 1 or 1/3 equivalent rectangular bandwidths (ERBs). Results suggested that slopes of recovery from forward masking were shallower for HI than for NH listeners regardless of masker fluctuations. Additional masking due to inherent envelope fluctuations was greater for HI than for NH listeners at longer masker-probe delays, suggesting that inherent envelope fluctuations are more disruptive for HI than for NH listeners for a longer time course.

Effects of inherent envelope fluctuations in forward maskers for listeners with normal and impaired hearing.

Gaussian noise simultaneous maskers yield higher masked thresholds for pure tones than low-fluctuation noise simultaneous maskers for listeners with normal hearing. This increased masking effectiveness is thought to be due to inherent fluctuations in the temporal envelope of Gaussian noise, but effects of fluctuating forward maskers are unknown. Because differences in forward masking due to age and hearing loss are known, the current study assessed effects of masker envelope fluctuations for forward maskers in younger and older adults with normal hearing and older adults with hearing loss. Detection thresholds were measured in these three participant groups for a pure-tone probe in quiet and in Gaussian and low-fluctuation noise forward maskers with either 1 or 1/3 equivalent rectangular bandwidths. Higher masked thresholds were obtained for forward maskers with greater inherent envelope fluctuations for younger adults with normal hearing. This increased effectiveness of highly fluctuating forward maskers was similar for older adults with normal and impaired hearing. Because differences in recovery from forward masking between listeners with normal and impaired hearing may relate to differences in cochlear nonlinearities, these results suggest that mechanisms other than cochlear nonlinearities may be responsible for recovery from rapid masker envelope fluctuations.

Nonadditivity of forward and simultaneous masking.

The current study measured the additional masking obtained for combinations of forward and simultaneous maskers as a function of forward masker bandwidth, signal delay, and simultaneous masker level. The effects of the two individual maskers were equated in all conditions. Additional masking increased with increasing masker level, increasing signal delay, and decreasing masker bandwidth. The portion of the simultaneous masker that made the greater contribution to additional masking was the part that overlapped with the signal, not with the forward masker. The changes in additional masking observed as a function of forward masker bandwidth and the interaction between the effects of forward and simultaneous maskers call into question the use of additional masking as a measure of basilar membrane compression and present problems for the use of simultaneous noise to simulate hearing loss.

Neural coding of formant-exaggerated speech in the infant brain.

Speech scientists have long proposed that formant exaggeration in infant-directed speech plays an important role in language acquisition. This event-related potential (ERP) study investigated neural coding of formant-exaggerated speech in 6-12-month-old infants. Two synthetic /i/ vowels were presented in alternating blocks to test the effects of formant exaggeration. ERP waveform analysis showed significantly enhanced N250 for formant exaggeration, which was more prominent in the right hemisphere than the left. Time-frequency analysis indicated increased neural synchronization for processing formant-exaggerated speech in the delta band at frontal-central-parietal electrode sites as well as in the theta band at frontal-central sites. Minimum norm estimates further revealed a bilateral temporal-parietal-frontal neural network in the infant brain sensitive to formant exaggeration. Collectively, these results provide the first evidence that formant expansion in infant-directed speech enhances neural activities for phonetic encoding and language learning.