Association between the atherogenic index of plasma and hearing loss based on a nationwide cross-sectional study.

BACKGROUND: Hearing loss (HL) is a worldwide public health issue for which the role of dyslipidemia has not been fully elucidated. This study aimed to use the atherogenic index of plasma (AIP), a well-established serum lipid marker, to investigate the association of dyslipidemia with HL among the general population. METHODS: Participants (n = 3267) from the National Health and Nutrition Examination Survey database (2005-2012, 2015-2018) were included in the present study. The AIP was calculated based on the following formula: log10 (triglycerides/high-density lipoprotein cholesterol). HL was defined as a pure-tone average of at least 20 dBHL in the better ear. Weighted multivariable logistic regression, subgroup analysis, generalized additive model, and threshold analysis were adopted to reveal the association between the AIP and HL. RESULTS: In this study of US adults, a positive association was found between the AIP and high-frequency HL. However, the association between the AIP and low-frequency HL was not as strong. In addition, a reverse L-shaped curve with an inflection point located at -0.27 was detected between the AIP and high-frequency HL, followed by a significant positive association after the inflection point. CONCLUSIONS: The potential of the AIP as a bioindicator for high-frequency HL is noteworthy, and maintaining an AIP value below a certain threshold might provide beneficial outcomes in the management of high-frequency HL.

Prestin and otolin-1 proteins in the hearing loss of adults chronically exposed to lead.

BACKGROUND: Some studies in animal models and humans suggest that exposure to lead is associated with hearing loss. Lead can reach the inner ear through the blood circulation; evidence suggests that lead could accumulate in the inner ear, causing inner ear damage. AIM: To evaluate prestin and otolin-1 protein levels and their relationship with an increased hearing threshold in participants exposed to lead. METHODS: We conducted a cross-sectional study with 315 participants from Tlaxcala, Mexico. Blood lead levels (BPb) were evaluated by graphite furnace atomic absorption spectrometry. Serum prestin and otolin-1 were quantified using ELISA. Auditory function at frequencies of 0.125 to 8 kHz was evaluated in a soundproof chamber. RESULTS: Participants were classified according to BPb: group I (<10 µg/dL) had a median BPb of 6 µg/dL and prestin levels of 11.06 ng/mL. While participants in group II (≥10 µg/dL) had a median of BPb 20.7 µg/dL (p < 0.05) and prestin levels of 0.15 ng/mL (p < 0.001). Participants in both groups showed a normal hearing. Otolin-1 levels were higher for participants with normal hearing and lower for participants with hearing loss in both groups, p > 0.05. Multiple linear regression models predict an average decrease of 0.17 to 0.26 ng/mL in prestin levels per decibel increase for the frequencies evaluated. CONCLUSIONS: Participants with high BPb showed an increase in hearing threshold, and prestin levels decreased proportionally to the hearing threshold increase. This is the first study to evaluate prestin as a potential biomarker for hearing damage, evaluated by audiometry, in participants with lead exposure.

'Cochlear-type' hearing loss as part of aquaporin-4 neuromyelitis optica spectrum disorder.

Neuromyelitis optica spectrum disorder is an inflammatory autoimmune central nervous system condition caused in the majority of cases by aquaporin-4 IgG antibodies. Aquaporin-4 is expressed in the cochlear and vestibular nuclei regions in the brainstem and a handful of cases of retro-cochlear type hearing loss have been documented in the literature. Aquaporin-4 has also been reported within the organ of Corti and the cristae and maculae of the vestibular apparatus. We present a case where there is evidence of peripheral (labyrinthine) rather than central pathology and propose this is due to autoimmune inflammation as part of neuromyelitis optica spectrum disorder. This is the first case in the literature suggesting a 'cochlear-type' hearing loss occurring as part of neuromyelitis optica spectrum disorder. It raises the possibility of peripheral relapses of neuromyelitis optica spectrum disorder going unnoticed, resulting in patient morbidity, and highlights the importance of research within this area.

The Role of Anti-Endothelial Cell Autoantibodies and Immune Response in Acute Low-Tone Hearing Loss.

OBJECTIVE: Immunity is associated with acute low tone hearing loss. However, the exact pathophysiology of immunity-mediated acute low tone hearing loss remains unknown. In this study, we evaluated the presence, therapeutic effectiveness, and immunopathological mechanisms of anti-endothelial cell autoantibodies (AECEs) in patients with acute low-frequency hearing loss. MATERIAL AND METHODS: Forty-nine patients who were treated as inpatients having acute low-frequency hearing loss and additional symptoms, such as ear fullness, tinnitus, dizziness, or hyperacusis, were enrolled in this study. Serum samples from these patients were collected for laboratory serum autoimmunity detection, including AECAs, antinuclear antibodies, immunoglobulin, and circular immune complex. Therapeutic responses to combination therapy in short-term outcome and serum cytokine levels were compared between AECA-positive and AECA-negative patients. RESULTS: Anti-endothelial cell autoantibodies-positive patients tended to show significantly less response to standard therapy compared with AECAs controls (P < .05). Moreover, some serum cytokine levels elevated in both AECAs- and AECAs+ groups. Positive ratio of interleukin-8 and concentrations of macrophage inflammatory protein-1α were found higher in AECAs+ groups (P < .05). CONCLUSION: The results supported that AECAs might wield influence on the short-term outcome of acute low-tone hearing loss (ALHL) treatment. Furthermore, AECA-mediated acute low-frequency hearing loss possibly involved dysregulation of inflammation process and release of cytokines.

Analysis of miRNA-mRNA Interaction Network Reveals Gap Junction Beta 2 as a Potential Candidate Gene Involved in Psoriatic Hearing Loss Pathogenesis.

BACKGROUND: Recent studies have shown that patients with psoriasis, a chronic inflammatory skin disorder that may accompany the serious systemic disease, are at risk of developing sudden sensorineural hearing loss. The pathogenesis remains unclear, and the mechanisms of this disorder are difficult to explore in the clinical setting due to psoriasis hearing loss's infrequent incidence. Here, we aimed to identify key candidate genes that may be involved in the pathogenesis of psoriatic hearing loss. METHODS: In the present study, through online databases and literature review, we utilized microRNA-mRNA network analysis and gene ontology annotation analysis, coupled with experimental data from clinical samples, to investigate the relationship between psoriasis and hearing loss. RESULTS: We identified nine miRNAs implicated in both psoriasis and the auditory system. By using bioinformatics techniques, 12 target genes were identified. Finally, the gap junction beta-2 protein (GJB2) was found to be relevant to both psoriasis and hearing loss. Also, the expression of connexin 26 (Cx26), encoded by GJB2, was significantly downregulated in psoriatic patients' plasma (p < 0.0001) and was negatively correlated with psoriasis area and severity index (PASI) clinical score (r, -0.286; p = 0.036). CONCLUSION: GJB2 is a potential candidate gene for hearing loss in psoriasis.

Hearing Loss in Alzheimer's Disease Is Associated with Altered Serum Lipidomic Biomarker Profiles.

Recent data have found that aging-related hearing loss (ARHL) is associated with the development of Alzheimer's Disease (AD). However, the nature of the relationship between these two disorders is not clear. There are multiple potential factors that link ARHL and AD, and previous investigators have speculated that shared metabolic dysregulation may underlie the propensity to develop both disorders. Here, we investigate the distribution of serum lipidomic biomarkers in AD subjects with or without hearing loss in a publicly available dataset. Serum levels of 349 known lipids from 16 lipid classes were measured in 185 AD patients. Using previously defined co-regulated sets of lipids, both age- and sex-adjusted, we found that lipid sets enriched in phosphatidylcholine and phosphatidylethanolamine showed a strong inverse association with hearing loss. Examination of biochemical classes confirmed these relationships and revealed that serum phosphatidylcholine levels were significantly lower in AD subjects with hearing loss. A similar relationship was not found in normal subjects. These data suggest that a synergistic relationship may exist between AD, hearing loss and metabolic biomarkers, such that in the context of a pathological state such as AD, alterations in serum metabolic profiles are associated with hearing loss. These data also point to a potential role for phosphatidylcholine, a molecule with antioxidant properties, in the underlying pathophysiology of ARHL in the context of AD, which has implications for our understanding and potential treatment of both disorders.

Environmental exposure to lead and cadmium and hearing loss in Chinese adults: A case-control study.

Hearing loss is the second most common nonfatal problem affecting the Chinese population. Historical studies have suggested an association between exposure to heavy metals, such as cadmium and lead, and hearing loss. Few studies have investigated this relationship in the general population in China. We conducted a case-control study with 1008 pairs of participants from a cross-sectional epidemiological survey conducted in Zhejiang Province. A self-designed questionnaire was adopted to collect information on demographics, chronic diseases, lifestyles and environmental noise. Pure-tone averages of hearing thresholds at frequencies of 0.5, 1, 2, and 4 kHz were computed. Blood lead and cadmium levels were analyzed with an atomic absorption spectrometer. After adjusting for all other potential confounding factors, compared with the lowest blood cadmium quartile (0.00-0.53 µg/L), blood cadmium quartile 2 (0.54-0.92 µg/L), quartile 3 (0.93-1.62 µg/L) and quartile 4 (1.63-57.81 µg/L) exhibited significantly elevated risks for hearing loss, with odds ratios of 1.932 (95% CI: 1.356-2.751), 2.036 (95% CI: 1.423-2.914) and 1.495 (95% CI: 1.048-2.133), respectively (P-trend<0.001). However, an association of lead with hearing loss was not found. Young age (less than 60 years), male sex and current smoking were associated with increased blood cadmium concentration. Additionally, a positive association between blood cadmium and lead concentrations was found. Therefore, we conclude that exposure to environmental cadmium may be a risk factor for hearing loss among the general population in China.

Exploring the association of Bone Alkaline Phosphatases And Hearing Loss.

Hearing loss becomes increasingly common with age and affects quality of life. Recently, scientists have published articles about the relationship between metabolic disease and hearing loss. Metabolic disease was previously found to be highly related to an increase in alkaline phosphatase. Thus, there may be an indirect relationship between alkaline phosphatase (ALP) and hearing loss. In this paper, we will demonstrate the relationship between ALP and hearing loss. We included 3877 National Health and Nutrition Examination Survey (NHANES) participants, who represent the noninstitutionalized civilian population in the United States from age 20 to age 69, and examined the association between ALP and frequency distributions of pure-tone air-condition (PTAC) thresholds. After adjusting for pertinent variables, the subjects who belonged to the higher quartiles of ALP tended to have worse hearing thresholds (pure tone average at high and low frequencies) than the first quartile of ALP (p < 0.001). The results showed a positive correlation between ALP and hearing loss, in both males and females (p < 0.001) and in subjects whose body mass indices (BMI) were less than 30 (p < 0.001). In conclusion, ALP may play a role in detecting hearing loss.

Type 1 diabetes and hearing loss: Audiometric assessment and measurement of circulating levels of soluble receptor for advanced glycation end products.

BACKGROUND: We examined the hearing function in adults with and without type 1 diabetes (T1D) to investigate whether an association exists between hearing loss and duration of diabetes, haemoglobin A1C level, diabetes complications and levels of select serum and urinary biomarkers. METHODS: We measured pure tone audiometry (PTA) thresholds; serum levels of C-reactive protein (CRP), vascular endothelial growth factor (VEGF), soluble receptors for advanced glycation end-product (sRAGE); and urinary isoprostane in 30 adults with T1D (age 43.8 ± 11.4 years). We also measured PTA thresholds in 11 adults without diabetes (age 53 ± 5.5 years). RESULTS: 63.3% of adults with T1D had high-frequency hearing loss. Among adults with T1D, those with hearing loss were older (48.2 vs 36.2 years old, P < .01), had a longer duration of diabetes (30.7 vs 21.2 years, P = .02), a greater prevalence of peripheral neuropathy (57.9 vs 9.1%, P = .02) and significantly lower median levels of sRAGE (1054.27 vs 1306.83 pg/mL, P = .03) compared to those with normal hearing. Adults with T1D between the ages of 40 and 60 years old, who had diabetes for ≥35 years, had significantly higher PTA thresholds at both 500and 8000 Hz than age-matched adults without diabetes. CONCLUSIONS: A significant proportion of adults with T1D have high-frequency hearing loss before age of 60 that is positively associated with age, duration of diabetes and presence of peripheral neuropathy. Our results are in support of previous studies suggesting a potential protective role of sRAGE against AGE toxicity and diabetes complications.

Four-point impedance as a biomarker for bleeding during cochlear implantation.

Cochlear implantation has successfully restored the perception of hearing for nearly 200 thousand profoundly deaf adults and children. More recently, implant candidature has expanded to include those with considerable natural hearing which, when preserved, provides an improved hearing experience in noisy environments. But more than half of these patients lose this natural hearing soon after implantation. To reduce this burden, biosensing technologies are emerging that provide feedback on the quality of surgery. Here we report clinical findings on a new intra-operative measurement of electrical impedance (4-point impedance) which, when elevated, is associated with high rates of post-operative hearing loss and vestibular dysfunction. In vivo and in vitro data presented suggest that elevated 4-point impedance is likely due to the presence of blood within the cochlea rather than its geometry. Four-point impedance is a new marker for the detection of cochlear injury causing bleeding, that may be incorporated into intraoperative monitoring protocols during CI surgery.

Cadmium, obesity, and education, and the 10-year incidence of hearing impairment: The beaver dam offspring study.

OBJECTIVES/HYPOTHESIS: To determine the 10-year incidence of hearing impairment (HI) and associated risk factors in the Beaver Dam Offspring Study (BOSS; 2004-present), a large middle-aged cohort followed for 10 years. STUDY DESIGN: Prospective cohort study. METHODS: Hearing thresholds were measured at baseline (2005-2008) and 5- (2010-2013) and 10-year (2015-2017) follow-up examinations. HI was defined as a pure-tone average >25 dB HL in either ear. BOSS participants free of HI at baseline with at least one follow-up examination (N = 2,065) were included. Potential risk factors evaluated included cardiovascular measures, health history, lifestyle factors, inflammatory markers, vitamins D and B12, lead, and cadmium. RESULTS: Participants were 21 to 79 years (mean age = 47.9 years) at baseline. The 10-year cumulative HI incidence was 17.4% (95% confidence interval [CI]: 15.7-19.2) and was twice as likely in men (24.4%, 95% CI: 21.5-27.7) than in women (12.2%, 95% CI: 10.3-14.3). In a multivariable adjusted model, age (hazard ratio [HR] = 1.48, 95% CI: 1.38-1.59, per 5 years), male sex (HR = 2.47, 95% CI: 1.91-3.18), less than a college education (HR = 1.35, 95% CI: 1.02-1.79), body mass index (HR = 1.03, 95% CI: 1.01-1.05, per kg/m2 ), and higher cadmium levels (HR = 1.42, 95% CI: 1.05-1.92, quintile 5 vs. quintiles 1-4) were associated with the 10-year cumulative incidence of HI. There was no association between high lead levels, vitamins D or B12, and 10-year incidence of HI. CONCLUSIONS: In addition to age and sex, obesity, education, and blood cadmium levels were associated with increased incidence of HI. These prospective results add to evidence that age-related HI is a multifactorial preventable disorder. LEVEL OF EVIDENCE: 2b Laryngoscope, 130:1396-1401, 2020.

Higher serum magnesium concentration is associated with lower hearing thresholds and risk of hearing loss among a Chinese population.

BACKGROUND AND OBJECTIVES: Hearing loss is a sensory impairment caused by genetic and environmental factors. Previous epidemiological studies of magnesium intake and hearing loss have yielded conflicting results. METHODS AND STUDY DESIGN: We investigated the association between serum magnesium concentrations and hearing loss in a population from the Zhejiang region of China. A cross-sectional study of 3,267 participants aged 18 years and older from five hospitals was conducted from October 2016 to May 2018. An audiometric examination was conducted, and hearing thresholds were computed as pure-tone averages (PTAs) at speech (0.5, 1, 2, and 4 kHz) and high frequencies (3, 4, and 6 kHz). Magnesium concentrations were measured using an inductively coupled plasma mass spectrometer. RESULTS: A linear regression analysis revealed a negative association between magnesium levels and hearing losses from lower to high PTAs. After the adjustment of potential confounders, participants in the highest magnesium quartile had a lower PTA (quartile 4: -1.89%; 95% confidence interval (CI: -3.07 to -0.701); p=0.022) and high PTA (quartile 4: -3.05%; 95% CI: -4.64 to -1.46; p=0.005) than those in the lowest quartile. A logistic regression analysis showed a dose-dependent reduction in the odds of high frequency hearing loss across magnesium quartiles. In model 3, after adjusting for all potential confounders, participants with the highest magnesium quartiles had a 54.0% (OR: 0.460; 95% CI: 0.339-0.587) reduction in the odds of high-frequency hearing loss. CONCLUSIONS: Higher whole blood levels of magnesium in this population were associated with lower hearing thresholds and risk of hearing loss.

The Effect of Antioxidant Supplementation in Patients with Tinnitus and Normal Hearing or Hearing Loss: A Randomized, Double-Blind, Placebo Controlled Trial.

Tinnitus is the perception of sound in the absence of any external stimulus. Oxidative stress is possibly involved in its pathogenesis and a variety of antioxidant compounds have been studied as potential treatment approaches. The objective of the present study was to assess the effects of antioxidant supplementation in tinnitus patients. This is a randomized, double-blind, placebo-controlled clinical trial. Patients (N = 70) were randomly allocated to antioxidant supplementation (N = 35) or to placebo (N = 35) for a total of 3 months. Demographic, anthropometric, clinical, and nutritional data were collected. Serum total antioxidant capacity (TAC), oxidized LDL (oxLDL), and superoxide dismutase (SOD), tinnitus loudness, frequency, and minimum masking level (MML), and scores in Tinnitus Handicap Inventory questionnaire (THI), Tinnitus Functional Index (TFI), and Visual Analogue Scale (VAS) were evaluated at baseline and follow-up. Tinnitus loudness and MML significantly decreased from baseline to post measure (p < 0.001) only in the antioxidant group, the overall change being significantly different between the two groups post-intervention (p < 0.001). THI and VAS decreased only in the antioxidant group. Differences in changes in serum TAC, SOD, and oxLDL post-intervention were insignificant. In conclusion, antioxidant therapy seems to reduce the subjective discomfort and tinnitus intensity in tinnitus patients.

The relationship of high-frequency distortion product otoacoustic emission (DPOAE) values with hematological parameters in tinnitus patients.

PURPOSE: In this study, we aimed to investigate whether there is any positive or negative correlation between high-frequency distortion product otoacoustic emission (DPOAE) values and mean platelet volume (MPV) and neutrophil/lymphocyte ratio (NLR) in tinnitus patients. METHODS: The study was performed with 52 volunteers (27 females, 25 males) aged between 35 and 50 years who presented with tinnitus to the otolaryngology outpatient clinic of a tertiary care center. Pure voice audiometric examination, DPOAE measurement, complete blood count values of the study participants were examined. RESULTS: In both ears, a significant and negative correlation was observed between 4000 and 8000 Hz airway and 4000 Hz bone conduction pathways with NLR rates (p < 0.05). A statistically significant relationship was found between the bone conduction pathway PTA and discrimination values for both ears and NLR s (p < 0.05). A positive correlation was detected between NLRs and DPOAE measurements recorded at 4444 Hz, 5000 Hz, 8000 Hz, 8889 Hz, 10,000 Hz and 11,429 Hz frequencies in the right and 4444 Hz, 5000 Hz, 6154 Hz, 8000 Hz, 10,000 Hz and 11,429 Hz frequencies in the left ears, respectively (p < 0.05). CONCLUSIONS: We concluded that there is a significant correlation between high-frequency pure tone audiometry measurements and high frequency DPOAE measurements and NLR. Further studies are needed to determine the utility of NLR as a marker for the recognition and follow-up of hearing loss in patients with tinnitus.

Hearing impairment as an early sign of alpha-mannosidosis in children with a mild phenotype: Report of seven new cases.

Alpha-mannosidosis (AM) is a very rare (prevalence: 1/500000 births) autosomal recessive lysosomal storage disorder. It is characterized by multi-systemic involvement associated with progressive intellectual disability, hearing loss, skeletal anomalies, and coarse facial features. The spectrum is wide, from very severe and lethal to a milder phenotype that usually progresses slowly. AM is caused by a deficiency of lysosomal alpha-mannosidase. A diagnosis can be established by measuring the activity of lysosomal alpha-mannosidase in leucocytes and screening for abnormal urinary excretion of mannose-rich oligosaccharides. Genetic confirmation is obtained with the identification of MAN2B1 mutations. Enzyme replacement therapy (LAMZEDER ) was approved for use in Europe in August 2018. Here, we describe seven individuals from four families, diagnosed at 3-23 years of age, and who were referred to a clinical geneticist for etiologic exploration of syndromic hearing loss, associated with moderate learning disabilities. Exome sequencing had been used to establish the molecular diagnosis in five cases, including a two-sibling pair. In the remaining two patients, the diagnosis was obtained with screening of urinary oligosaccharides excretion and the association of deafness and hypotonia. These observations emphasize that the clinical diagnosis of AM can be challenging, and that it is likely an underdiagnosed rare cause of syndromic hearing loss. Exome sequencing can contribute significantly to the early diagnosis of these nonspecific mild phenotypes, with advantages for treatment and management.

Screening of mitochondrial tRNA mutations in 300 infants with hearing loss.

Mitochondrial DNA (MtDNA) mutations are the important causes for hearing loss. To see the contribution of mtDNA to deafness, we screened for mutations in mt-tRNA genes from 300 deaf infants and 200 healthy subjects. Moreover, we analyzed the mtDNA copy number and ROS levels in patients carrying the mt-tRNA mutations. Consequently, 3 mt-tRNA mutations: tRNALeu(UUR) A3243G; tRNAAla T5655C and tRNAGlu A14692G were identified, however, these mutations were not detected in controls. Of these, the A3243G mutation created a novel base-pairing (13G-23A) in the D-stem of tRNALeu(UUR); while the T5655C mutation occurred at the very conserved acceptor arm of tRNAAla; in addition, the A14692G mutation was located at position 55 in the TΨC loop of tRNAGlu. Molecular analysis showed that patients harbouring the A3243G, T5655C and A14692G mutations had a lower level of mtDNA copy number, while ROS level increased significantly when compared with controls. Through the application of the pathogenicity scoring system, we noticed that the A3243G, T5655C and A14692G should be regarded as 'definitely pathogenic' mutations associated with deafness. Thus, our study provided novel insight into the pathophysiology, early detection of mitochondrial deafness.

An Epidemiologic Study of the Association between Free Recall Dichotic Digits Test Performance and Vascular Health.

BACKGROUND: Associations between vascular health-related factors and hearing loss defined using audiometric pure-tone thresholds have been found. Studies have not focused on a potential relationship between vascular health-related factors and central auditory processing. PURPOSE: The aim of this study was to evaluate, on a population level, the relationship of vascular health-related factors with central auditory function. RESEARCH DESIGN: A cross-sectional, population study. STUDY SAMPLE: Subjects were participants in the Epidemiology of Hearing Loss Study (EHLS) or the Beaver Dam Offspring Study (BOSS)-prospective studies of aging and sensory loss. BOSS participants were the adult offspring of participants in the EHLS. Participants who completed the Dichotic Digits Test (DDT) during the fourth examination period of the EHLS (2008-2010) or the second examination period of the BOSS (2010-2013) were included (n = 3,655, mean age = 61.1 years). DATA COLLECTION AND ANALYSIS: The DDT-free recall test was conducted using 25 sets of triple-digit pairs at a 70 dB HL presentation level. The total number of correctly repeated digits from the right and left ears was converted to a percentage correct and used as an outcome. The percentage correct in the left ear was subtracted from the percentage correct in the right ear and used as an outcome. Vascular health-related measures obtained during the examination included blood pressure, mean carotid intima-media thickness, femoral pulse wave velocity (PWV), hemoglobin A1C, and non-high-density lipoprotein (HDL) cholesterol, and, in the EHLS participants, C-reactive protein and interleukin-6. Information on vascular health-related history and behaviors was self-reported. General linear modeling produced estimates of the age- and sex-adjusted least squares means for each vascular factor, and multiple linear regression was used for multivariable modeling of each outcome. RESULTS: After multivariable adjustment, participants with diabetes had a significantly lower (worse) mean DDT-free recall total score (-2.08 percentage points, p < 0.001) than those without diabetes. Participants who exercised at least once per week had a significantly higher (better) mean DDT-free recall total score (+1.07 percentage points, p < 0.01) than those who did not exercise at least once per week. Alcohol consumption was associated with a higher DDT-free recall total score (+0.15 percentage points per +25 g ethanol, p < 0.01). In multivariable modeling of the right-left ear difference in DDT-free recall scores, participants with a history of cardiovascular disease (CVD) or higher PWV demonstrated significantly larger differences (CVD: +3.11 percentage points, p = 0.02; PWV: +0.36 percentage points per 1 m/sec, p < 0.01). Higher levels of non-HDL cholesterol were associated with smaller right-left ear differences (-0.22 percentage points per 10 mg/dL, p = 0.01). Adjustment for handedness did not affect the results. CONCLUSIONS: Vascular health-related factors may play a role in central auditory function.

A Wars2 Mutant Mouse Model Displays OXPHOS Deficiencies and Activation of Tissue-Specific Stress Response Pathways.

Mutations in genes essential for mitochondrial function have pleiotropic effects. The mechanisms underlying these traits yield insights into metabolic homeostasis and potential therapies. Here we report the characterization of a mouse model harboring a mutation in the tryptophanyl-tRNA synthetase 2 (Wars2) gene, encoding the mitochondrial-localized WARS2 protein. This hypomorphic allele causes progressive tissue-specific pathologies, including hearing loss, reduced adiposity, adipose tissue dysfunction, and hypertrophic cardiomyopathy. We demonstrate the tissue heterogeneity arises as a result of variable activation of the integrated stress response (ISR) pathway and the ability of certain tissues to respond to impaired mitochondrial translation. Many of the systemic metabolic effects are likely mediated through elevated fibroblast growth factor 21 (FGF21) following activation of the ISR in certain tissues. These findings demonstrate the potential pleiotropy associated with Wars2 mutations in patients.

Auditory function and quality of life in patients receiving cisplatin chemotherapy in head and neck cancer: A case series follow-up study.

BACKGROUND: Cisplatin is one of the anticancer drugs used for head and neck cancers. Although some studies have shown that cisplatin can cause ototoxicity, periodic audiometric assessments have not been extensively studied in the Indian rural population. Hence, this study has been undertaken to evaluate the effects of cisplatin on hearing. MATERIALS AND METHODS: Fifty-nine patients with squamous cell carcinomas of head and neck, who received cisplatin chemotherapy, were recruited. Serum creatinine, blood urea, serum proteins, and audiometry were assessed before and after the first, second, and third chemotherapy cycle. The cochleotoxic effect of cisplatin was assessed by pure tone audiometry. Hearing loss was graded accordingly. All patients were administered a quality of life questionnaire at baseline and at the end of the third cycle. RESULTS: Hearing loss was observed in 12 patients at speech frequencies and those at higher frequencies were 12 (4000 Hz), 18 (6000 Hz), and 28 (8000 Hz). The hearing loss was symmetrical, sensorineural, and showed a strong correlation with the low serum albumin levels at the end of the third cycle. Dizziness was seen in eight patients, at the end of the study. The commonly observed adverse effects were nausea, vomiting, hair loss, fatigue, and tinnitus. CONCLUSION: The studies have shown hearing loss in higher frequencies, but in our study, we have observed hearing loss at speech frequency in 22.2% of patients receiving cisplatin, who also had low serum albumin levels. Periodic audiometric monitoring and serum albumin level may be helpful to provide timely intervention to prevent further hearing loss and deterioration in the quality of life.

Haemoglobin A1c and hearing impairment: longitudinal analysis using a large occupational health check-up data of Japan.

OBJECTIVES: The aim of this study was to determine whether haemoglobin A1c (HbA1c) level is associated with the incidence of hearing impairment accounting for smoking status and diabetic condition at baseline. METHODS: Participants were 131 689 men and 71 286 women aged 30-65 years and free of hearing impairment at baseline (2008) who attended Japanese occupational annual health check-ups from 2008 to 2015. We defined low-frequency hearing impairment at a hearing threshold >30 dB at 1 kHz and high frequency at >40 dB at 4 kHz in the better ear in pure-tone audiometric tests. HbA1c was categorised into seven categories. The association between HbA1c and hearing impairment was assessed using the Cox proportional hazards model. RESULTS: On 5 years mean follow-up, high HbA1c was associated with high-frequency hearing impairment. In non-smokers, HbA1c≥8.0% was associated with high-frequency hearing impairment, with a multivariable HR (95% CI) compared with HbA1c 5.0%-5.4% of 1.46 (1.10 to 1.94) in men and 2.15 (1.13 to 4.10) in women. There was no significant association between HbA1c and hearing impairment in smokers. A J-shaped association between HbA1c and high-frequency hearing impairment was observed for participants with diabetes at baseline. HbA1c was not associated with low-frequency hearing impairment among any participants. CONCLUSIONS: HbA1c ≥8.0% of non-smokers and ≥7.3% of participants with diabetes was associated with high-frequency hearing impairment. These findings indicate that appropriate glycaemic control may prevent diabetic-related hearing impairment.