Association Analysis of Candidate Gene Polymorphisms and Audiometric Measures of Noise-Induced Hearing Loss in Young Musicians.

INTRODUCTION: This study aimed to investigate the association between candidate genetic variants and audiometric measures of noise-induced hearing loss (NIHL) in young musicians. METHODS: The study analyzed a database by Phillips et al. (Feasibility of a bilateral 4000-6000 Hz notch as a phenotype for genetic association analysis. Int J Audiol 2015;54:645-52.) which included behavioral hearing thresholds, distortion-product otoacoustic emissions (DPOAE), tympanometric, and genetic data of 166 participants meeting the inclusion criteria. Nineteen single nucleotide polymorphisms (SNPs) in 13 cochlear genes previously associated with NIHL in factory workers were included in the present investigation. The average hearing threshold at 3000 and 4000 Hz (AHT) and average DPOAE signal to noise ratio (DPOAE SNR) in both ears were calculated. RESULTS: The regression analyses showed that two SNPs- one in KCNE1 (rs2070358) and the other in CAT (rs12273124) revealed a statistically significant relationship with DPOAE SNR in both ears. Two SNPs in MYH14 and one in GJB4 revealed a significant association with DPOAE SNR in the left ear. Two SNPs in HSP70, one in CDH23 and one in KCNJ10 showed significant association with DPOAE SNR in the right ear. None of the included SNPs showed association with AHT in both ears. CONCLUSIONS: A genetic variant in KCNE1 was associated with the strength of the cochlear amplifier as assessed by DPOAE SNR. Musicians carrying causal genetic variants to NIHL might exhibit changes in their auditory functions early in the lifespan even when most subjects had their hearing thresholds within normal limits. These participants are likely to show the clinical manifestation of NIHL in the future if no preventive measures are applied.

Glutathione and glutamate in schizophrenia: a 7T MRS study.

In schizophrenia, abnormal neural metabolite concentrations may arise from cortical damage following neuroinflammatory processes implicated in acute episodes. Inflammation is associated with increased glutamate, whereas the antioxidant glutathione may protect against inflammation-induced oxidative stress. We hypothesized that patients with stable schizophrenia would exhibit a reduction in glutathione, glutamate, and/or glutamine in the cerebral cortex, consistent with a post-inflammatory response, and that this reduction would be most marked in patients with "residual schizophrenia", in whom an early stage with positive psychotic symptoms has progressed to a late stage characterized by long-term negative symptoms and impairments. We recruited 28 patients with stable schizophrenia and 45 healthy participants matched for age, gender, and parental socio-economic status. We measured glutathione, glutamate and glutamine concentrations in the anterior cingulate cortex (ACC), left insula, and visual cortex using 7T proton magnetic resonance spectroscopy (MRS). Glutathione and glutamate were significantly correlated in all three voxels. Glutamine concentrations across the three voxels were significantly correlated with each other. Principal components analysis (PCA) produced three clear components: an ACC glutathione-glutamate component; an insula-visual glutathione-glutamate component; and a glutamine component. Patients with stable schizophrenia had significantly lower scores on the ACC glutathione-glutamate component, an effect almost entirely leveraged by the sub-group of patients with residual schizophrenia. All three metabolite concentration values in the ACC were significantly reduced in this group. These findings are consistent with the hypothesis that excitotoxicity during the acute phase of illness leads to reduced glutathione and glutamate in the residual phase of the illness.

End-stage renal disease in patients with rheumatoid arthritis.

OBJECTIVES: To determine the frequency of end-stage renal disease (ESRD) in patients with rheumatoid arthritis (RA), the causes of ESRD, and the treatment of RA in the setting of ESRD. METHODS: Cross-sectional study of RA (N = 3754) and non-RA (N = 326,776) patients in the United States Renal Data System (USRDS) during 2011 (N = 330,530). The epidemiology of ESRD in RA was determined and the etiology of ESRD in patients with and without RA was compared. The frequency of patients with RA with at least one filled prescription for prednisone/prednisolone, a DMARD, and/or a biologic in 2011 was determined. RESULTS: The prevalence of RA with ESRD in the USRDS in 2011 was 1.1%. There were significant differences in age, race, sex, and BMI category between the groups (p < 0.01). Diabetes (33.5%) and hypertension (30.6%) were the most common primary causes of ESRD in patients with RA. Amyloidosis, vasculitis, and analgesic nephropathy combined accounted for less than 10% of cases of ESRD. Prednisone was the most commonly filled medication that could be used to treat RA (45.9% of RA patients). Hydroxychloroquine was the most frequently filled DMARD (13.5%); biologics were uncommon (etanercept 2.5%, adalimumab 1.5%; golimumab, infliximab, anakinra, and abatacept <1%). CONCLUSIONS: The co-occurrence of RA with ESRD was 1.1% in the USRDS by 2011. Physicians should be aware of the critical impact of the comorbidities of diabetes and hypertension in causing ESRD in RA patients. Use of DMARDS other than hydroxychloroquine and biologics to treat RA in the setting of ESRD appears to be infrequent. Further prospective studies of treatment strategies for RA in ESRD are needed.

Abnormal visuomotor processing in schizophrenia.

Subtle disturbances of visual and motor function are known features of schizophrenia and can greatly impact quality of life; however, few studies investigate these abnormalities using simple visuomotor stimuli. In healthy people, electrophysiological data show that beta band oscillations in sensorimotor cortex decrease during movement execution (event-related beta desynchronisation (ERBD)), then increase above baseline for a short time after the movement (post-movement beta rebound (PMBR)); whilst in visual cortex, gamma oscillations are increased throughout stimulus presentation. In this study, we used a self-paced visuomotor paradigm and magnetoencephalography (MEG) to contrast these responses in patients with schizophrenia and control volunteers. We found significant reductions in the peak-to-peak change in amplitude from ERBD to PMBR in schizophrenia compared with controls. This effect was strongest in patients who made fewer movements, whereas beta was not modulated by movement in controls. There was no significant difference in the amplitude of visual gamma between patients and controls. These data demonstrate that clear abnormalities in basic sensorimotor processing in schizophrenia can be observed using a very simple MEG paradigm.