The circadian clock at the intercept of sleep and pain

Peer reviewe

Glucose utilization in the auditory system: Cochlear dysfunctions and species differences

1. 1. Deoxyglucose uptake in peripheral auditory tissues and inferior colliculus of the young CBA or C57BL/6J mouse increases with intensity of an acoustic stimulus from 25 to 85 dBA and decreases from 85 to 115dBA.2. 2. In 36-month-old CBA and 9-month-old C57BL with sensorineural hearing loss the metabolic response to stimulation is attenuated 50% or more.3. 3. Metabolic responses to stimuli are qualitatively and quantitatively different in the gerbil and in the guinea-pig.4. 4. It is concluded that cochlear dysfunctions are characterized by abnormal evoked metabolism; and that the stimulus-response pattern varies with species.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24949/1/0000376.pd

Circadian vulnerability of cisplatin?induced ototoxicity in the cochlea

The chemotherapeutic agent cisplatin is renowned for its ototoxic effects. While hair cells in the cochlea are established targets of cisplatin, less is known regarding the afferent synapse, which is an essential component in the faithful temporal transmission of sound. The glutamate aspartate transporter (GLAST) shields the auditory synapse from excessive glutamate release, and its loss of function increases the vulnerability to noise, salicylate, and aminoglycosides. Until now, the involvement of GLAST in cisplatin?mediated ototoxicity remains unknown. Here, we test in mice lacking GLAST the effects of a low?dose cisplatin known not to cause any detectable change in hearing thresholds. When administered at nighttime, a mild hearing loss in GLAST KO mice was found but not at daytime, revealing a potential circadian regulation of the vulnerability to cisplatin?mediated ototoxicity. We show that the auditory synapse of GLAST KO mice is more vulnerable to cisplatin administration during the active phase (nighttime) when compared to WT mice and treatment during the inactive phase (daytime). This effect was not related to the abundance of platinum compounds in the cochlea, rather cisplatin had a dose?dependent impact on cochlear clock rhythms only after treatment at nighttime suggesting that cisplatin can modulate the molecular clock. Our findings suggest that the current protocols of cisplatin administration in humans during daytime may cause a yet undetectable damage to the auditory synapse, more so in already damaged ears, and severely impact auditory sensitivity in cancer survivors

Pure tone overstimulation changes the micromechanical properties of the inner hair cell stereocilia

The effect of permanent noise-induced hearing loss on the auditory brainstem response (ABR) and the micromechanical properties of cochlear hair cell stereocilia in guinea pigs was investigated. The threshold of movement of the stereocilia was measured by applying force from a fluid filled pipette. After exposure to a 1.0 kHz pure tone signal at 105 dB(A) for 72 h the threshold of the ABR was broadly elevated by approximately 50 dB. Inner hair cell stereocilia showed a decrease in threshold while the outer hair cell stereocilia bundles remained unaltered. This effect was localized to the 13-15 mm distance from the stapes corresponding to the region of maximal stimulation. The effect was recorded within 1 h of exposure and remained constant with exposures up to 7 days. Following a one month recovery period from sound exposure, normal threshold values of stereocilia movement were observed, indicating recovery. At this time, swelling of the afferent dendrites beneath the inner hair cells was observed throughout the cochlea together with approximately 30% scattered loss of outer hair cells in the 13 to 15 mm region. The ABR showed some recovery (approximately 20 dB), yet a threshold shift remained.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26868/1/0000433.pd

Gender-Specific Risk Factors and Comorbidities of Bothersome Tinnitus

Objective This study aims to identify gender-specific risk factors associated with the presence of bothersome tinnitus (compared with non-bothersome tinnitus), including sociodemographic and lifestyle factors, tinnitus-associated phenomena (hearing loss, traumatic experiences, sleep disturbances), and physical as well as mental comorbidities. Methods We conducted a cross-sectional study using survey data from the Swedish LifeGene cohort containing information on self-reported tinnitus (N = 7615). We (1) analyzed risk factor and comorbidity frequencies, (2) computed multivariate logistic regression models to identify predictors of bothersome tinnitus within both genders, and (3) moderated logistic regression models to compare effects between genders. Results (1) The majority of factors that differed in frequencies between bothersome and non-bothersome tinnitus were equal for both genders. Women with bothersome tinnitus specifically reported higher rates of cardiovascular disease, thyroid disease, epilepsy, fibromyalgia, and burnout, and men with bothersome tinnitus reported higher rates of alcohol consumption, Ménière's disease, anxiety syndrome, and panic (compared with non-bothersome tinnitus, respectively). (2) Across both genders, multivariate logistic regression analyses revealed significant associations between bothersome tinnitus and age, reduced hearing ability, hearing-related difficulties in social situations, and reduced sleep quality. In women, bothersome tinnitus was specifically associated with cardiovascular disease and epilepsy; in men, with lower education levels and anxiety syndrome. (3) Moderated logistic regression analyses revealed that the effects of low education and anxiety syndrome were present in men, but not in women, whereas the effects of age, reduced hearing ability and related difficulties, cardiovascular disease, epilepsy, and burnout were not gender specific. Conclusion Irrespective of gender, bothersome tinnitus is associated with higher age, reduced hearing ability, hearing-related difficulties, cardiovascular disease, epilepsy, and burnout. Gender-specific effects comprise low levels of education and the presence of anxiety syndrome for men. These findings need to be interpreted with caution, yet they suggest the presence of gender-specific biopsychosocial influences in the emergence or maintenance of bothersome tinnitus. Future studies ought to investigate the underlying mechanisms of the observed relationships

The search for noise-induced cochlear synaptopathy in humans:Mission impossible?

Animal studies demonstrate that noise exposure can permanently damage the synapses between inner hair cells and auditory nerve fibers, even when outer hair cells are intact and there is no clinically relevant permanent threshold shift. Synaptopathy disrupts the afferent connection between the cochlea and the central auditory system and is predicted to impair speech understanding in noisy environments and potentially result in tinnitus and/or hyperacusis. While cochlear synaptopathy has been demonstrated in numerous experimental animal models, synaptopathy can only be confirmed through post-mortem temporal bone analysis, making it difficult to study in living humans. A variety of non-invasive measures have been used to determine whether noise-induced synaptopathy occurs in humans, but the results are conflicting. The overall objective of this article is to synthesize the existing data on the functional impact of noise-induced synaptopathy in the human auditory system. The first section of the article summarizes the studies that provide evidence for and against noise-induced synaptopathy in humans. The second section offers potential explanations for the differing results between studies. The final section outlines suggested methodologies for diagnosing synaptopathy in humans with the aim of improving consistency across studies

Alterations in auditory brain stem response distinguish occasional and constant tinnitus

BACKGROUND. The heterogeneity of tinnitus is thought to underlie the lack of objective diagnostic measures. METHODS. Longitudinal data from 20,349 participants of the Swedish Longitudinal Occupational Survey of Health (SLOSH) cohort from 2008 to 2018 were used to understand the dynamics of transition between occasional and constant tinnitus. The second part of the study included electrophysiological data from 405 participants of the Swedish Tinnitus Outreach Project (STOP) cohort. RESULTS. We determined that with increasing frequency of the occasional perception of self-reported tinnitus, the odds of reporting constant tinnitus after 2 years increases from 5.62 (95% CI, 4.83–6.55) for previous tinnitus (sometimes) to 29.74 (4.82–6.55) for previous tinnitus (often). When previous tinnitus was reported to be constant, the odds of reporting it as constant after 2 years rose to 603.02 (524.74–692.98), suggesting that once transitioned to constant tinnitus, the likelihood of tinnitus to persist was much greater. Auditory brain stem responses (ABRs) from subjects reporting nontinnitus (controls), occasional tinnitus, and constant tinnitus show that wave V latency increased in constant tinnitus when compared with occasional tinnitus or nontinnitus. The ABR from occasional tinnitus was indistinguishable from that of the nontinnitus controls. CONCLUSIONS. Our results support the hypothesis that the transition from occasional to constant tinnitus is accompanied by neuronal changes in the midbrain leading to a persisting tinnitus, which is then less likely to remit.publishedVersio

Методика використання фізичних задач в курсі охорона праці

(uk) У статті розкривається важливість розв’язання фізичних задач в курсі охорона праці. Використання фізичних задач забезпечить повноцінне засвоєння навчального матеріалу з курсу.(en) In the article importance of of physicaltasks opens up in a course labour protection. The use of physical tasks will provide the valuable mastering of educational material from a course

Relationship between headaches and tinnitus in a Swedish study

The heterogeneity of tinnitus is likely accounting for the lack of effective treatment approaches. Headaches have been related to tinnitus, yet little is known on how headaches impact tinnitus. We use cross-sectional data from the Swedish Tinnitus Outreach Project to i) evaluate the association between headaches and tinnitus (n = 1,984 cases and 1,661 controls) and ii) investigate the phenotypic characteristics of tinnitus subjects with tinnitus (n = 660) or without (n = 1,879) headaches. In a multivariable logistic regression model, headache was significantly associated with any tinnitus (odds ratio, OR = 2.61) and more so with tinnitus as a big problem (as measured by the tinnitus functional index, TFI ≥ 48; OR = 5.63) or severe tinnitus (using the tinnitus handicap inventory, THI ≥ 58; OR = 4.99). When focusing on subjects with tinnitus, the prevalence of headaches was 26% and reached 40% in subjects with severe tinnitus. A large number of socioeconomic, phenotypic and psychological characteristics differed between headache and non-headache subjects with any tinnitus. With increasing tinnitus severity, fewer differences were found, the major ones being vertigo, neck pain and other pain syndromes, as well as stress and anxiety. Our study suggests that headaches could contribute to tinnitus distress and potentially its severity.publishedVersio

Association between Hyperacusis and Tinnitus

The following are available online at http://www.mdpi.com/2077-0383/9/8/2412/ s1We gratefully acknowledge the support and generosity of Nancy Pedersen, head of LifeGene.Many individuals with tinnitus report experiencing hyperacusis (enhanced sensitivity to sounds). However, estimates of the association between hyperacusis and tinnitus is lacking. Here, we investigate this relationship in a Swedish study. A total of 3645 participants (1984 with tinnitus and 1661 without tinnitus) were enrolled via LifeGene, a study from the general Swedish population, aged 18–90 years, and provided information on socio-demographic characteristics, as well as presence of hyperacusis and its severity. Tinnitus presence and severity were self-reported or assessed using the Tinnitus Handicap Inventory (THI). Phenotypes of tinnitus with (n = 1388) or without (n = 1044) hyperacusis were also compared. Of 1661 participants without tinnitus, 1098 (66.1%) were women and 563 were men (33.9%), and the mean (SD) age was 45.1 (12.9). Of 1984 participants with tinnitus, 1034 (52.1%) were women and 950 (47.9%) were men, and the mean (SD) age was 47.7 (14.0) years. Hyperacusis was associated with any tinnitus [Odds ratio (OR) 3.51, 95% confidence interval (CI) 2.99–4.13], self-reported severe tinnitus (OR 7.43, 95% CI 5.06–10.9), and THI ≥ 58 (OR 12.1, 95% CI 7.06–20.6). The association with THI ≥ 58 was greater with increasing severity of hyperacusis, the ORs being 8.15 (95% CI 4.68–14.2) for moderate and 77.4 (95% CI 35.0–171.3) for severe hyperacusis. No difference between sexes was observed in the association between hyperacusis and tinnitus. The occurrence of hyperacusis in severe tinnitus is as high as 80%, showing a very tight relationship. Discriminating the pathophysiological mechanisms between the two conditions in cases of severe tinnitus will be challenging, and optimized study designs are necessary to better understand the mechanisms behind the strong relationship between hyperacusis and tinnitus.GENDER-NET Co-Plus Fund GNP-182Decibel Therapeutics, Inc.Svenska Lakaresallskapet SLS-779681Tysta SkolanHorselforskningsfonden 503European Union (EU) 72204655 848261NIHR Nottingham Biomedical Research CentreSwedish Medical Research Council (SMRC) K2014-99X-22478-01-3Karolinska InstitutetNational Institute for Health Research (NIHR