Significant Threshold Differences Research Articles

Digit-in-Noise Test as a Hearing Screening Test for Individuals With Intellectual Disability.

Diagnosis of intellectual disability (ID) may overshadow, or co-occur with, hearing impairment, but screening is frequently inaccessible due to various factors that prevent successful test execution. There is a pressing need for easily, locally administered hearing tests. This study aimed to assess the efficacy of the digit-in-noise (DIN) test, as well as three variations of it, as a hearing screening for individuals with mild to moderate ID. Additionally, we explored correlations between participant characteristics and cognitive-linguistic abilities, with DIN test performance. Forty participants with ID aged 21-40 were recruited from two supported employment centres, 31 of whom met full inclusion criteria. Controls were 20 typically developed (TD) participants, aged 21-40. The original DIN test (DIN(3)) was administered, and those unable to recall the three digits were administered a version with two digits (DIN(2)). Participants unable to successfully complete DIN(3) or DIN(2) were administered versions with added visual and verbal performance feedback. A significant difference in speech receptive threshold in noise (SRTn) between DIN(2) and DIN(3) was only present for the ID group. A moderate negative relationship between DIN(2) SRTn and vocabulary and a positive relationship with age was found for the ID group; no correlation was found with digit span or matrices. The DIN(2) SRTn was correlated with the average hearing level of pure tones measured by audiometry. Our findings highlight the DIN(2) as the most effective version, as its signal-to-noise ratio (SRTn) threshold was closest to the typically developed (TD) control group. This study is the first step towards developing a hearing screening test for individuals with ID who are at elevated risk of impairment and who have insufficient evaluation access. Our findings suggest that adults with mild to moderate ID can sufficiently perform the adapted DIN(2) as a hearing screening test.

Clinical Phenotypic Characterization of the SLC26A4 Mutation in Pendred Syndrome/Nonsyndromic Enlarged Vestibular Aqueduct.

To summarize the Solute Carrier Family 26 Member 4 (SLC26A4) mutations and clinical phenotypic characteristics of patients with Pendred syndrome/nonsyndromic enlarged vestibular aqueduct (PS/NSEVA). A retrospective cohort study for the Chinese population was performed to analyze the hearing test results of 406 patients with PS/NSEVA who had a SLC26A4 mutation and the relationship between inner ear imaging and audiology. There was a significant difference in the mean hearing threshold in patients with biallelic mutations (M2), monoallelic mutations (M1), and nonallelic mutations (M0) and between patients with isolated vestibular aqueduct enlargement (IEVA) and patients with IEVA combined with Mondini malformation. There was no significant difference between patients with different gene mutation types or different sexes, or between the width of the vestibular aqueduct (VA) and the mean hearing threshold. The degree of hearing loss was linearly correlated with age. We propose that the presence and absence of SLC26A4 mutation, whether combined with Mondini malformation and patient age, are essential factors affecting the degree of hearing loss in the Chinese population. However, the number and type of mutations, degree of VA expansion, and sex of the patients did not affect the clinical audiological phenotype. 3 Laryngoscope, 2024.

Asymmetric Glaucoma and Corresponding Hearing Impairment.

Background/Objectives: This study aims to explore the potential relationship between unilateral or asymmetric glaucoma and ipsilateral hearing impairment. Methods: In this retrospective study, visual and hearing functions were assessed in patients with unilateral or asymmetric glaucoma. Correlations between retinal nerve fiber layer (RNFL) thickness, visual field mean deviation (MD) values, and pure tone audiometry (PTA) measurements across various frequencies were analyzed to explore potential associations between visual and ipsilateral hearing functions. Differences in PTA values between ears ipsilateral to the more affected glaucomatous eyes and the contralateral ears were studied for statistical significance. Results: Twenty-six patients with unilateral or asymmetric glaucoma were included in the study. Significant differences in hearing thresholds between the ears corresponding to the more severely glaucomatous eyes and the contralateral ears were found at 0.7, 1, 1.5, and 3 kHz (p < 0.05). Additionally, a statistically significant difference was observed in the speech frequencies (0.5, 0.7, 1, 1.5, 2, 3, and 4 kHz) between ears corresponding to glaucomatous or more affected glaucomatous eyes and the contralateral ears (p = 0.016). Furthermore, a moderately positive correlation was found between differences in MD and PTA values at 0.125 kHz (r = 0.50; p = 0.01). Conclusions: This study highlights a potential association between unilateral or asymmetric glaucoma and ipsilateral hearing impairment, particularly at speech-relevant frequencies. These findings underscore the importance of integrated sensory assessment in the management of glaucoma patients, suggesting that early detection and intervention for concurrent hearing loss could enhance overall quality of life.

Evaluating the accuracy of a self-administered smartphone hearing test application in a geriatric population.

As the global population ages, hearing loss becomes increasingly prevalent, and is associated with neurocognitive and psychiatric comorbidities, impacting quality of life. Early screening and timely intervention might prevent or delay cognitive decline, a gap in care that can potentially be addressed by self-administered smartphone hearing tests. This study aims to evaluate the accuracy of Mimi™ (Berlin, Germany), a commercially available self-administered smartphone hearing test compared to pure tone audiogram (PTA) in terms of both hearing levels and hearing thresholds in our local geriatric population > 65 years-old. Fifty-two participants above 65 years of age requiring conventional audiograms were recruited from a National Referral University Hospital Otolaryngology clinic from March to June 2022. All participants were administered the conventional PTA tests in a sound-proof booth conducted by audiology technicians followed by Mimi™ Hearing Test in a quiet clinic room. Comparisons between the hearing levels of both tests were analyzed using Spearman's rank correlation coefficient, Bland-Altman plots and Gwet's Kappa which looked at concordance. Hearing thresholds were then analysed using the Wilcoxon signed rank (SR) test. Mimi™ showed strong to very strong correlation with good agreement compared to readings obtained from formal PTA. Concordance in determining hearing loss also showed substantial to almost perfect agreement at each individual frequency, with values of kappa falling between 0.735-0.857. In terms of thresholds, there were no significant differences in thresholds given by both tests except for 2.0 kHz, HFPTA and 4FPTA (p < 0.05). Mimi™ serves as a good screening tool for detection of moderate hearing loss for early pickup and treatment except at higher frequencies. The smartphone hearing test is also less accurate in determining the extent of hearing loss and formal PTA after hearing loss is detected on screening should still be standard of care.

Comparative Analysis of HPV Detection Efficiency: Evaluating Cobas 8800 Performance in Vaginal Self-Sampling versus Clinician-Collected Samples at a Regional Thai Hospital

Background: This study, conducted at a regional Thai hospital, assesses the comparative efficacy of self-collected versus clinician-collected samples for HPV detection using the Cobas 8800 system among Thai women aged 30–60. Methods: Our methodology involved analyzing 1541 self-collected and 1398 clinician-collected samples. Results: The results show a statistically significant mean difference in cycle threshold (Ct) values favoring clinician-collected samples (1.53; 95% CI: 1.18–1.87, p &lt; 0.0001). This pattern was consistent across various age groups, with the most pronounced differences noted in the oldest cohort (50–59 years), suggesting higher detection efficiency in clinician-collected samples. The study further explored the correlation of Ct values with cytological and histological outcomes, where clinician-collected samples demonstrated superior diagnostic performance, particularly in identifying LSIL and HSIL conditions, evidenced by AUC values of 0.793 and 0.866, respectively. While self-sampling remains a viable method, with sensitivity reaching up to 48.84% for LSIL and 46.15% for HSIL, clinician collection proved more accurate, likely influencing future national screening policies. Conclusions: This work underscores the need for robust sample collection methods and the importance of ongoing enhancements to self-sampling assays and techniques to ensure their efficacy in cervical cancer screening programs.

Pressure algometry in the general adult population: Age and sex differences.

Experimental pain studies have revealed inter-individual variations in pain perception that are influenced by age, sex, and country of origin. This study aimed to explore the age and sex differences in pressure pain thresholds within the Iranian general population. To assess the pressure pain thresholds, a handheld pressure algometer was applied bilaterally to the middle fingers of both hands. The participants also completed the short form of the McGill Pain Questionnaire to provide a clinical pain rating. This cross-sectional study included 1610 adult subjects (54.96% female, mean age 40.13 ± 10.18 years). The findings indicated that females generally exhibited lower pain thresholds than males when assessing pain detection and tolerance parameters (P < .001). Females also demonstrated a significant lower pressure thresholds and clinical pain ratings compared with men (P < .001). Additionally, significant differences were observed between age groups in terms of pain detection and tolerance thresholds (P = .02 and P = .03, respectively). However, the interaction between sex and age was not significant. No significant differences in pain detection thresholds were observed between the right and left hand (P = .11). This study underscores the potential utility of algometry as a valuable tool for objectifying pain in the Iranian population.

The Loop Technique in Cardiac Resynchronization Therapy: A Prospective Cohort Study.

A new approach called the loop technique has been proven safe and effective for repeated intraoperative transvenous left ventricular (LV) lead dislocations during cardiac resynchronization therapy (CRT) in a 3-year follow-up. This study aimed to report on the 5-year safety and effectiveness of the loop technique. This study was a prospective cohort study. Forty-four patients who underwent CRT device implantation at the Cardiology Department of Shaanxi Provincial People's Hospital between January 2013 and June 2019 were included. Data on patient demographics, medical history, laboratory test results, and echocardiography images at admission were collected. The loop technique was performed with repeated intraoperative dislocations of the LV lead. The intraoperative CRT parameters were also recorded. All patients were followed for 5 years. Several auxiliary examinations were performed during follow-up. The 44 patients were divided into the traditional operation group (n=36, 81.8%) and loop technique group (n=8, 18.2%). The baseline patient characteristics were almost balanced. During the 5-year follow-up, 8 (22.2%) patients in the traditional operation group and 2 (25.0%) patients in the loop technique group died. No lead dislocation or other complications related to CRT were observed. There were no significant differences in mortality rate (P=0.87), cardiac function (P=0.56), echocardiographic indices, threshold (P=0.58), or impedance (P=0.22) of the LV lead. There were no significant differences in the threshold and impedance between postoperative, 3-year, and 5-year follow-ups in the loop technique group (P=0.53). The loop technique is an ideal solution for repeated intraoperative LV lead dislocation during CRT implantation.

Differences in self-reported signs related to central sensitization and pressure pain threshold related to knee osteoarthritis and sarcopenia.

Neuroinflammation, which occurs in knee osteoarthritis and sarcopenia, has attracted attention as a mechanism of central sensitization, but the relationship between central sensitization and these conditions has not been widely studied. This study investigates differences in self-reported signs of central sensitization and pressure pain threshold in individuals with knee osteoarthritis and sarcopenia. We examined 340 patients (mean age ± standard deviation: 76 ± 5.9, women were 86.9%) with knee osteoarthritis scheduled to undergo total knee arthroplasty. For comparison, 129 community-dwelling older people (mean age ± standard deviation: 76 ± 5.5, women were 68.9%) individuals without a history of knee osteoarthritis or any other diagnosed illnesses were matched for age and sex. We assessed central sensitization inventory-9, pressure pain threshold, pain-related factors, skeletal muscle mass index, and hand grip strength. ANCOVA using 2 (patients with knee osteoarthritis and community older people without knee osteoarthritis) × 2 (sarcopenia and robust) was performed to assess outcome measurements. The prevalence of sarcopenia among patients with knee osteoarthritis was 50.3%. ANCOVA revealed an interaction effect for the central sensitization inventory-9. For the main effect of knee osteoarthritis, there was a significant difference in central sensitization inventory-9, and for the main effect of sarcopenia, there was a significant difference in pressure pain threshold. Discrepancies in the evaluation of central sensitization were identified between knee osteoarthritis and sarcopenia. Individuals with knee osteoarthritis had elevated score of self-reported indications of central sensitization, whereas sarcopenic patients had reduced pressure pain thresholds.

To determine the value of iMAX, a new electrodiagnostic method, and its application in the evaluation of peripheral motor nerve excitability

Objective: To test the new method of iMAX (the minimum stimulus current that elicits the maximum compound muscle action potential amplitude) electrodiagnosis, verify the feasibility of this method in evaluating the excitability of peripheral motor axons, and preliminarily explore the clinical application value. Methods: This study was a cross-sectional study. A total of 50 healthy subjects were recruited from the outpatient department of Peking University Third Hospital from June 2022 to March 2023, including 25 males and 25 females, aged 25-68 (48±8) years. Eleven patients with Charcot-Marie-Pain-1A (CMT1A), 7 males and 4 females, aged 19-55 (41±13) years and 21 patients with diabetic peripheral neuropathy (DPN), 10 males and 11 females, aged 28-79 (53±16) years were enrolled in this study. iMAX of bilateral median nerves, ulnar nerves and peroneal nerves were detected in all patients. Repeatable motor responses with minimum motor threshold and amplitude of at least 0.1 mV and the minimum stimulus current intensity, at which the maximum compound muscle action potential amplitude is elicited, were measured respectively [1 mA increment is called (iUP) and, 0.1 mA adjustment is called (iMAX)].Comparison of the parameters: the parameters of threshold, iUP and iMAX were compared among different age groups, genders and sides, body mass index(BMI) values and detection time , as well as between CMT1A patients, DPN patients and healthy subjects. Results: In healthy subjects, the threshold, iUP value and iMAX value were (1.8±0.7) mA, (4.4±1.2) mA, and (4.2±1.3) mA respectively; ulnar nerve (3.1±1.6) mA, (6.8±3.2) mA, (6.4±3.2) mA; peroneal nerve (3.7±2.0) mA, (7.8±2.8) mA, (7.4±2.9) mA. There were statistically significant differences in threshold, iUP value and iMAX value among different age groups (all P<0.001).With the increase of age, there was a trend of increasing threshold, iUP, and iMAX values in different nerves, and the differences are statistically significant (all P<0.001). There were no significant differences in gender, side and detection time threshold, iUP value and iMAX value (all P>0.05). The parameters of healthy subjects with high BMI value were higher than those of healthy subjects with low BMI value(all P<0.05). Compared with the healthy subjects, the parameters of 11 CMT1A patients were significantly increased (all P<0.05), and the parameters of 21 DPN patients were slightly increased (P<0.05). Conclusion: The new iMAX method reflects the excitability of motor axons and early axonal dysfunction, which is an important supplement to the traditional nerve conduction, and can be used to monitor motor axon excitability disorders.

EVALUATION OF THE POSTOPERATIVE ANALGESIC EFFECTS OF TUNING ELEMENT RELIEF PATCHES IN DOGS UNDERGOING OVARIOHYSTERECTOMY

Ovariohysterectomy (OHE) is a common surgical procedure in small animals that causes significant postoperative pain. Tuning Element Relief Patches (TERPs) are silicone patches containing titanium salts, believed to relieve pain by resonating pain-related ion channels. In this experiment, 12 dogs undergoing OHE surgery received subcutaneous robenacoxib (group R, [Formula: see text]) injection or two sheets of TERPs (group T, [Formula: see text]) as postoperative analgesia to assess the analgesic effect of TERPs. The results demonstrated no significant differences in physiological parameters, pain scores and mechanical nociceptive thresholds (MNTs) between groups postoperatively, indicating that the TERPs provide comparable results to robenacoxib in managing postoperative pain in dogs undergoing OHE. While this study provides evidence of the pain-relieving effects of TERPs, further studies are required to evaluate their long-term safety and efficacy in various clinical conditions.

The pursuit of gender equality: a substudy of the PACE-CONDUCT trial on gender differences in His bundle pacing implantation

Abstract Background His bundle pacing (HBP) is an effective alternative to traditional right ventricular pacing, providing physiological pacing. The impact of gender on the success of HBP implantation has not been extensively explored. We conducted a substudy of the PACE-CONDUCT registry to investigate gender differences in HBP implantation success. Methods We analyzed successful HBP implantations performed from 2021 to 2023. A total of 61 patients were included, comprising 22 females (36%) and 39 males (64%) . The mean age of the entire cohort was 73 years, with ages ranging from 51 to 86 years. His bundle thresholds were assessed at implantation, the day following implantation, and four weeks post-implantation. All data were analyzed using IBM SPSS Statistics 29.0, and thresholds were converted into volts × milliseconds for statistical analysis. Results The minimal HBP threshold across all measurements was 0.10 volts × milliseconds, equivalent to a standard threshold of 0.25 volts by 0.4 milliseconds, while the maximal threshold was 7.13 volts × milliseconds, corresponding to a standard threshold of 4.75 volts by 1.5 milliseconds. Gender differences were examined, dividing the patient cohort into male and female groups, and an independent-samples t-test was conducted. The results did not reveal any statistically significant differences in HBP threshold between the two groups at the time of implantation, one day post-implantation, or one month post-implantation. Chi square tests were conducted to determine if there could be any gender differences analyzing the complication rates, also finding negative results. Conclusion This substudy of the PACE-CONDUCT trial found no significant gender-based differences in the success of His bundle pacing implantations, taking the threshold at implantation, one day after and four weeks after implantation as a surrogate of goodness of the HBP implantation itself. Although the cohort size was limited, our findings provide initial insights, suggesting that gender is not a decisive factor in HBP threshold outcomes or in complication rates. Further investigations with larger sample sizes are warranted to explore this topic in greater depth.statistics output

Contrast Discrimination and Global Form Perception in Primary Open-Angle Glaucoma and Primary Angle-Closure Glaucoma.

This study explored early (contrast discrimination) and intermediate (global form perception) visual processing in primary subtypes of glaucoma: primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG). We aimed to understand early and intermediate visual processing in POAG and PACG, matched for similar visual field defect severity. Early visual processing was measured using a contrast discrimination task described by Porkorny and Smith (1997), and intermediate processing using a global form perception task using glass pattern coherence thresholds. Thresholds were determined centrally and at a single midperipheral location (12.5°) in a quadrant without visual field defects. Controls were tested in corresponding quadrants to individuals with glaucoma. Sixty participants (20 POAG, 20 PACG, and 20 age-matched controls), aged 50 to 77years, were included. Visual field defects were matched between POAG and PACG, with mean deviation values of -6.53 ± 4.46 (range: -1.5 to -16.85) dB and -6.2 ± 4.24 (range: -1.37 to -16.42) dB, respectively. Two-Way ANOVA revealed significant differences in thresholds between the glaucoma groups and the control group for both contrast discrimination and global form perception tasks, with higher thresholds in the glaucoma groups. Post hoc analyses showed no significant contrast discrimination difference between POAG and PACG, but POAG had significantly higher thresholds than PACG for form perception. In form perception, POAG showed slightly worse performance than PACG, suggesting that individuals with POAG may experience more severe functional damage than PACG of similar visual field severity.

Prediction of Cochlear Implant Fitting by Machine Learning Techniques.

This study aimed to evaluate the differences in electrically evoked compound action potential (ECAP) thresholds and postoperative mapping current (T) levels between electrode types after cochlear implantation, the correlation between ECAP thresholds and T levels, and the performance of machine learning techniques in predicting postoperative T levels. Retrospective case review. Tertiary hospital. We reviewed the charts of 124 ears of children with severe-to-profound hearing loss who had undergone cochlear implantation. We compared ECAP thresholds and T levels from different electrodes, calculated correlations between ECAP thresholds and T levels, and created five prediction models of T levels at switch-on and 6 months after surgery. The accuracy of prediction in postoperative mapping current (T) levels. The ECAP thresholds of the slim modiolar electrodes were significantly lower than those of the straight electrodes on the apical side. However, there was no significant difference in the neural response telemetry thresholds between the two electrodes on the basal side. Lasso regression achieved the most accurate prediction of T levels at switch-on, and the random forest algorithm achieved the most accurate prediction of T levels 6 months after surgery in this dataset. Machine learning techniques could be useful for accurately predicting postoperative T levels after cochlear implantation in children.

Differences in the epidermal pain threshold between different needle puncture sites.

Puncture of the skin by a needle, such as for peripheral nerve block or for intravenous or arterial catheter placement, may cause pain to the patient, so that analgesic method may be required to reduce pain caused by needle puncture. Nevertheless, there is little information as to which puncture sites are more painful than the other. After obtaining an approval of the study by a research ethics committee and written informed consent from all the participants, we studied 30 volunteers to quantify pain threshold at 13 skin sites of the body, using an algometer. Compared with pain threshold at the cubital fossa (which was regarded as the control value), the relative pain threshold was significantly lower (with clinically meaningful difference) at the lateral carpus (median (interquartile range): 0.66 (0.56-0.73)) and the medial carpus (0.80 (0.73-0.94)); and was significantly higher (with clinically meaningful difference) at the olecranon (2.08 (1.93-2.42)), the forehead (1.59 (1.46-1.74)), the upper shoulder (1.52 (1.38-1.79)), and the dorsal shoulder (1.39 (1.18-1.55)). We conclude that there are significant differences in pain threshold between different puncture sites. Analgesic method before needle puncture may be required at the sites where the pain threshold is relatively low.

Thermal damage to the skin from 8.2 and 95 GHz microwave exposures in swine

A study of burn thresholds from superficially penetrating radio-frequency (RF) energy at 8.2 and 95 GHz for swine skin was conducted. The study determined the thresholds for superficial, partial-thickness, and full-thickness burn severities after 5 seconds of exposure at power densities of 4–30 W/cm2 and 2–15 W/cm2 at 8.2 and 95 GHz, respectively. There were significant differences in the burn thresholds at the different severities between the two frequencies due to the large difference in energy penetration depths. Biopsies were collected from each burn site at 1, 24, 72, and 168 hr post exposure. Each sample was assessed by a burn pathologist against 20 histological factors to characterize the damage resulting from these RF overexposures. A one-dimensional, layered digital phantom that utilized realistic values for dielectric and thermal properties was used to explain some observed thresholds. The results of the heating and cooling response of the animal model and histology scores of each exposure are provided to enhance future efforts at simulation of RF overexposures and to establish damage thresholds.

Validity of endoscopic ossiculoplasty immediately after its introduction for ossicular chain disruption

BackgroundTranscanal endoscopic ear surgery (TEES) reportedly requires a long learning curve and may be associated with more complications and longer operative times than microscopic ear surgery (MES). In this study, we aimed to examine the usefulness and validity of TEES for ossicular chain disruption in the early stages of its introduction in our institution.MethodsTEES was performed on 11 ears (10 with congenital ossicular chain discontinuity and 1 with traumatic ossicular chain dislocation), and MES was performed with a retroauricular incision on 18 ears (6 with congenital ossicular chain discontinuity and 12 with traumatic ossicular chain dislocation) in a tertiary referral center. Postoperative hearing results, operative times, and postoperative hospital length of stay were retrospectively reviewed. The Mann–Whitney U test and Fisher’s exact test was performed to compare variables between the TEES and MES groups. Pre- and postoperative air- and bone-conduction thresholds and the air–bone gap of each group were compared using the Wilcoxon signed-rank test. The Mann–Whitney U test and Wilcoxon signed-rank was performed to compare the pre- and postoperative air–bone gaps between the diagnoses.ResultsNo significant differences in the postoperative air-conduction thresholds, bone-conduction thresholds, air–bone gaps, or incidence of air–bone gap ≤ 20 dB were observed between the TEES and MES groups. The air-conduction thresholds and air–bone gaps of the TEES group significantly improved postoperatively. The air-conduction thresholds and air–bone gaps of the MES group also significantly improved postoperatively. No significant difference was observed in the operative times between the groups (TEES group: median, 80 min; MES group: median, 85.5 min). The TEES group had a significantly shorter postoperative hospital stay (median, 2 days) than the MES group (median, 7.5 days).ConclusionsTEES was considered appropriate for the treatment of ossicular chain disruption, even immediately after its introduction at our institution. For expert microscopic ear surgeons, ossicular chain disruption may be considered a suitable indication for the introduction of TEES.

Effect of mecobalamin combined with holographic copper acupuncture and scraping technique on tinnitus symptoms in patients with sudden sensorineural hearing loss

Purpose: To examine the effect of methylcobalamin combined with holistic copper acupuncture and scraping technique in ameliorating tinnitus symptoms in patients with sudden sensorineural hearing loss. Methods: 80 patients with sudden sensorineural hearing loss from Department of Otolaryngology, The Hefei First People’s Hospital, Hefei, China were selected as subjects for this study. They were divided into control and study groups, respectively, with 40 patients in each group, based on the different treatment interventions received by the patients. Conventional interventions included the use of Ginkgo biloba extract, Tianmasu injection, dexamethasone pharmacological treatments. The control group received methylphenidate tablets in addition to the conventional treatment, while the study group received further intervention comprising the combination of holistic copper acupuncture and scraping technique on the ear, in addition to the treatment received by the control group. The evaluated outcomes included efficacy, auditory threshold levels, and Pittsburgh Sleep Quality Index (PSQI) score. Results: The overall efficacy of the treatment in the control group was 77.5 %, whereas, it was significantly higher in the study group at 97.5 % (p &lt; 0.05). Prior to treatment, there were no significant differences in pure tone audiometry thresholds between the two groups (p &gt; 0.05). However, post-treatment, the study group exhibited significantly lower pure tone audiometry thresholds compared to the control group (p &lt; 0.05). Before PSQI scores were similar for the two groups (p &gt; 0.05). However, after treatment, the PSQI scores in the study group were significantly lower than those in the control group (p &lt; 0.05). Conclusion: The combined application of methylcobalamin, holistic copper acupuncture, and scraping technique is effective for the treatment of patients with sudden sensorineural hearing loss. This integrated treatment approach significantly alleviates tinnitus and improves sleep-related symptoms in patients with sudden sensorineural hearing loss. Furthermore, it promotes the recovery of pure tone audiometry thresholds and other related parameters.

The natural history and genotype–phenotype correlations of TMPRSS3 hearing loss: an international, multi-center, cohort analysis

TMPRSS3-related hearing loss presents challenges in correlating genotypic variants with clinical phenotypes due to the small sample sizes of previous studies. We conducted a cross-sectional genomics study coupled with retrospective clinical phenotype analysis on 127 individuals. These individuals were from 16 academic medical centers across 6 countries. Key findings revealed 47 unique TMPRSS3 variants with significant differences in hearing thresholds between those with missense variants versus those with loss-of-function genotypes. The hearing loss progression rate for the DFNB8 subtype was 0.3 dB/year. Post-cochlear implantation, an average word recognition score of 76% was observed. Of the 51 individuals with two missense variants, 10 had DFNB10 with profound hearing loss. These 10 all had at least one of 4 TMPRSS3 variants predicted by computational modeling to be damaging to TMPRSS3 structure and function. To our knowledge, this is the largest study of TMPRSS3 genotype–phenotype correlations. We find significant differences in hearing thresholds, hearing loss progression, and age of presentation, by TMPRSS3 genotype and protein domain affected. Most individuals with TMPRSS3 variants perform well on speech recognition tests after cochlear implant, however increased age at implant is associated with worse outcomes. These findings provide insight for genetic counseling and the on-going design of novel therapeutic approaches.

Mechanism of noise induced hidden hearing loss based on proteomics

Objective: To explore the mechanism of noise-induced hidden hearing loss by proteomics. Methods: In October 2022, 64 SPF male C57BL/6J mice were divided into control group and noise exposure group with 32 mice in each group according to random sampling method. The noise exposure group was exposed to 100 dB sound pressure level, 2000-16000 Hz broadband noise for 2 h, and the mouse hidden hearing loss model was established. Auditory brainstem response (ABR) was used to test the change of hearing threshold of mice on the 7th day after noise exposure, the damage of basal membrane hair cells was observed by immunofluorescence, and the differentially expressed proteins in the inner ear of mice in each group were identified and analyzed by 4D-Label-free quantitative proteomics, and verified by Western blotting. The results were statistically analyzed by ANOVA and t test. Results: On the 7th day after noise exposure, there was no significant difference in hearing threshold between the control group and the noise exposure group at click and 8000 Hz acoustic stimulation (P>0.05) . The hearing threshold in the noise exposure group was significantly higher than that in the control group under 16000 Hz acoustic stimulation (P<0.05) . Confocal immunofluorescence showed that the basal membrane hair cells of cochlear tissue in noise exposure group were arranged neatly, but the relative expression of C-terminal binding protein 2 antibody of presynaptic membrane in middle gyrus and basal gyrus was significantly lower than that in control group (P<0.05) . GO enrichment analysis showed that the functions of differentially expressed proteins were mainly concentrated in membrane potential regulation, ligand-gated channel activity, and ligand-gated ion channel activity. KEGG pathway enrichment analysis showed that differentially expressed proteins were significantly enriched in phosphatidylinositol 3 kinase-protein kinase B (PI3K-Akt) signaling pathway, NOD-like receptor signaling pathway, calcium signaling pathway, etc. Western blotting showed that the expression of inositol 1, 4, 5-trisphosphate receptor 3 (Itpr3) was increased and the expression of solute carrier family 38 member 2 (Slc38a2) was decreased in the noise exposure group (P<0.05) . Conclusion: Through proteomic analysis, screening and verification of the differential expression proteins Itpr3 and Slc38a2 in the constructed mouse noise-induced hidden hearing loss model, the glutaminergic synaptic related pathways represented by Itpr3 and Slc38a2 may be involved in the occurrence of hidden hearing loss.

Abstract 7288: Evaluation of silica spin-column and bead formats for rapid promoter DNA methylation analysis by qMSP in clinical and point-of-care settings

Abstract Late-stage cancers often lack effective management and treatment options, emphasizing the importance of early diagnosis for better prognosis and lower mortality rates. Molecular markers, such as DNA methylation tests, have shown promise in predicting and detecting cancer at its earliest stages. The COVID-19 post-pandemic scenario is providing a one in one-hundred-year opportunity of utilizing the excess installed PCR capacity world-wide to develop novel Quantitative Methylation Specific PCR (qMSP) screening strategies for cervical cancer screening in low-resource settings. This study aimed to compare the use of commercial bisulfite conversion kits in cervical epithelium liquid cytology samples (liquid cytology) from cancer screening clinics in the United States. Commercially available rapid bisulfite conversion protocols using silica spin column and magnetic beads were compared with conventional DNA extraction followed by bisulfite conversion protocols to profile DNA methylation by qMSP in a panel of methylated genes we previously developed to distinguish normal and cervical cancer patient samples. The results revealed that small sample volumes are suitable for methylation studies. Comparisons among four spin-column kits showed no significant differences in β-actin Cycle Threshold (Cts) values between Abcam, Epigentek, QIAGEN and Zymo D5021 kits. Zymo The best performing spin-column kit was compared with manual and automated versions of magnetic bead kits using a 96-well plate format for higher throughput. Methylation profiling of three genes (β-actin ZNF516, and FKBP6) with manual and automated magnetic bead kits revealed that automation increases throughput without a reduction in amplification efficiency in open PCR systems. Cost analysis showed that the direct kits 96-well plate format were more affordable compared to the Gold Standard manual protocol that uses spin-columns. An optimized version of Zymo D5046 magnetic bead kit provides the fastest turnaround time with similar amplification efficiency, when compared to spin-column or other magnetic bead kits. The test cost per sample is $5.41 dollars to process 83 samples in a 96 well-plate format in less than 2 hours. Another significant finding was showing the feasibility of using as low as 12µL of liquid cytology samples for DNA methylation testing, proving that bodily fluids are a liquid biopsy alternative to plasma. Overall, this comprehensive comparison is useful in determining optimal options for efficient and cost-effective cancer DNA methylation diagnostic tests, particularly in low-resource settings. Citation Format: Fernando Zamuner, Ashley Ramos-Lopez, Amanda Garcia-Negron, Ana Purcell-Wiltz, Andrea Cortes-Ortiz, Aniris Roman, Keerthana Gosala, Eli Winkler, David Sidransky, Mariana Brait, Rafael E. Guerrero-Preston. Evaluation of silica spin-column and bead formats for rapid promoter DNA methylation analysis by qMSP in clinical and point-of-care settings [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7288.