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PRDM (PRDI-BF1 and RIZ homology domain containing) family members are sequence-specific transcriptional regulators involved in cell identity and fate determination, often dysregulated in cancer. The PRDM15 gene is of particular interest, given its low expression in adult tissues and its overexpression in B-cell lymphomas. Despite its well characterized role in stem cell biology and during early development, the role of PRDM15 in cancer remains obscure. Herein, we demonstrate that while PRDM15 is largely dispensable for mouse adult somatic cell homeostasis in vivo, it plays a critical role in B-cell lymphomagenesis. Mechanistically, PRDM15 regulates a transcriptional program that sustains the activity of the PI3K/AKT/mTOR pathway and glycolysis in B-cell lymphomas. Abrogation of PRDM15 induces a metabolic crisis and selective death of lymphoma cells. Collectively, our data demonstrate that PRDM15 fuels the metabolic requirement of B-cell lymphomas and validate it as an attractive and previously unrecognized target in oncology., The transcriptional regulator PRDM15 is expressed at low levels in normal tissues but overexpressed in B-cell lymphomas. Here, the authors show that PRDM15 depletion does not affect adult somatic cell homeostasis but leads to a metabolic crisis which impairs B-cell lymphomagenesis.

Hyperacusis, over-sensitivity to sounds, causes distress and disability and the etiology is not fully understood. The study aims to explore possible associations between health-relevant personality traits and hyperacusis. Hyperacusis was assessed using the Hyperacusis Questionnaire (HQ), and clinical uncomfortable loudness levels (ULL). Personality was measured with the Health-relevant Personality (HP5i) Inventory. The study sample was 348 (140 men and 208 women; age 23-71 years). Moderate correlations were found between the personality trait negative affectivity (NA; a facet of neuroticism) and dimensions of the HQ and weak correlations were found with the ULLs. Hedonic capacity (a facet of extraversion) was significantly correlated with the HQ but not with the ULLs. Impulsivity (a facet of conscientiousness) was correlated with the HQ and the ULLs. A significant difference in mean values was found in all hyperacusis measures and different levels of NA - those with higher levels displayed more severe signs of hyperacusis. A multiple logistic regression analysis showed that higher levels of NA increases the odds of having hyperacusis on average 4.6 times for men and 2.4 times for women. These findings imply that health-relevant personality traits should be considered in the diagnosis and treatment of hyperacusis.

ATRX alterations occur at high frequency in neuroblastoma of adolescents and young adults. Particularly intriguing are the large N-terminal deletions of ATRX (Alpha Thalassemia/Mental Retardation, X-linked) that generate in-frame fusion (IFF) proteins devoid of key chromatin interaction domains, while retaining the SWI/SNF-like helicase region. We demonstrate that ATRX IFF proteins are redistributed from H3K9me3-enriched chromatin to promoters of active genes and identify REST as an ATRX IFF target whose activation promotes silencing of neuronal differentiation genes. We further show that ATRX IFF cells display sensitivity to EZH2 inhibitors, due to derepression of neurogenesis genes, including a subset of REST targets. Taken together, we demonstrate that ATRX structural alterations are not loss-of-function and put forward EZH2 inhibitors as a potential therapy for ATRX IFF neuroblastoma.

While multiple mechanisms of BRAFV600-mutant melanoma resistance to targeted MAPK signaling inhibitors (MAPKi) have been reported, the epigenetic regulation of this process remains undetermined. Here, using a CRISPR–Cas9 screen targeting chromatin regulators, we discover that haploinsufficiency of the histone deacetylase SIRT6 allows melanoma cell persistence in the presence of MAPKi. Haploinsufficiency, but not complete loss of SIRT6 promotes IGFBP2 expression via increased chromatin accessibility, H3K56 acetylation at the IGFBP2 locus, and consequent activation of the IGF-1 receptor (IGF-1R) and downstream AKT signaling. Combining a clinically applicable IGF-1Ri with BRAFi overcomes resistance of SIRT6 haploinsufficient melanoma cells in vitro and in vivo. Using matched melanoma samples derived from patients receiving dabrafenib + trametinib, we identify IGFBP2 as a potential biomarker for MAPKi resistance. Our study has not only identified an epigenetic mechanism of drug resistance, but also provides insights into a combinatorial therapy that may overcome resistance to standard-of-care therapy for BRAFV600-mutant melanoma patients., The epigenetic mechanisms of melanoma drug resistance are poorly understood. Here, the authors develop a CRISPR-Cas9 screen targeting epigenetic regulators and discover that SIRT6 haploinsufficiency induces BRAFV600E melanoma cell resistance to MAPK inhibitors via IGF signalling.

Bromodomain and extraterminal domain inhibitors (BETi) represent promising therapeutic agents for metastatic melanoma, yet their mechanism of action remains unclear. Here we interrogated the transcriptional effects of BETi and identified AMIGO2, a trans-membrane molecule, as a BET target gene essential for melanoma cell survival. AMIGO2 is upregulated in melanoma cells and tissues compared to human melanocytes and nevi, and AMIGO2 silencing in melanoma cells induces G1/S arrest followed by apoptosis. We identified the pseudokinase PTK7 as an AMIGO2 interactor whose function is regulated by AMIGO2. Epigenomic profiling and genome editing revealed that AMIGO2 is regulated by a melanoma-specific BRD2/4-bound promoter and super-enhancer configuration. Upon BETi treatment, BETs are evicted from these regulatory elements, resulting in AMIGO2 silencing and changes in PTK7 proteolytic processing. Collectively, this study uncovers mechanisms underlying the therapeutic effects of BETi in melanoma and reveals the AMIGO2-PTK7 axis as a targetable pathway for metastatic melanoma.

Little is known about personality in relation to assessments of the psychosocial work environment and leadership. Therefore the objective of this study is to explore possible associations and differences in mean values between employee health-relevant personality traits and assessments of the psychosocial work environment and leadership behaviors.754 survey responses from ten organizations were selected from a large-scale intervention study. The Health-relevant Personality 5 inventory was used to assess personality. Five dimensions of the psychosocial work environment were assessed with 38 items from the QPSPositive correlations were found between Hedonic capacity (facet of Extraversion) and perceptions of the psychosocial work environment and leadership behavior. Negative correlations were found for Negative affectivity (facet of Neuroticism), Antagonism (facet of Agreeableness), Impulsivity (facet of Conscientiousness) and Alexithymia (facet of Openness). There were also significant differences in mean values of all work environment indicators between levels of health-relevant personality traits. Those with higher levels of hedonic capacity had higher (better) perceptions compared to those with lower levels. Those with higher levels of negative affectivity had lower (worse) perceptions compared to those with lower levels.The findings show a clear association between employee health-relevant personality traits and assessments of the psychosocial work environment and leadership behavior. Personality can be important to take into consideration for leaders when interpreting survey results and when designing organizational interventions.

Hearing problems are a public health issue with prevalence figures far more common than previously estimated. There are well-established risk factors of hearing problems such as age, sex and noise exposure history. Here, we demonstrate additional risk factors, i.e. socioeconomic status and long-term stress exposure that are found to increase the risk of hearing problems. In order to proactively intervene and prevent hearing problems, these newly recognized risk factors need to be taken into consideration. When taking these new risk factors into account, sex differences become even more apparent than previously found. The aim of this review is to summarize our recent findings about the associations between stress and hearing problems.

To validate the hyperacusis questionnaire (HQ) in different strata of emotional exhaustion (EE).HQ-scores and uncomfortable loudness levels (ULLs) were assessed in 348 individuals (140 men and 208 women) with low, intermediate, and high EE-levels.Four individuals (1.1%) met the critical value for hyperacusis according to the HQ. An exploratory factor analysis extracted three factors from the HQ accounting for 57.6% of the variance. Internal consistency was acceptable for all subscales and for the total score, with Crohnbach's alpha ranging from 0.65 to 0.86. When controlling for hearing loss, significant correlations between the HQ and ULLs were found on both ears in those with intermediate (right: -0.328; left: -0.320) and high EE (right: -0.349; left: -0.393), but not with low EE (right: -0.204; left: -0.196). All correlations were negative, indicating that higher HQ-scores are correlated with lower ULLs. The strongest correlations were found for the social dimension, indicating that social aspects may correspond best to audiological parameters (ULLs) of hyperacusis.The results emphasize the need to take other factors, such as emotional exhaustion (long-term stress), into consideration when assessing hyperacusis with a questionnaire.

Aims With the globally increasing prevalence of diabetes and the knowledge on how to prevent the disease there is a high demand for an effective way of identifying people at risk. The hypothesis behind this investigation was that incorporation of the FINnish Diabetes Risk SCore (FINDRISC) questionnaire in a regular workplace survey would be a feasible way to identify individuals and groups at risk for diabetes that could benefit from preventive interventions. Method The eight FINDRISC questions were slightly modified and incorporated to Webb-QPS, an online work place survey, and distributed by e-mail to 5166 employees at Karolinska University Hospital (KUH). Results The total number of responders to Webb-QPS was 3581 (69%). Of those responding 3029 (84%) replied to the FINDRISC section which comprises 59% of the original population. A group of 1082 high risk individuals could be considered for intervention whereof 298 (9.8%) are expected to develop diabetes the upcoming 10 years if left without intervention. Conclusion It is feasible to incorporate a diabetes risk score such as the FINDRISC in a workplace survey. A group that could be subject to preventive intervention programs was identified.

Endogenous human centromeres form on megabase-sized arrays of tandemly repeated alpha satellite DNA. Human neocentromeres form epigenetically at ectopic sites devoid of alpha satellite DNA and permit analysis of centromeric DNA and chromatin organization. In this study, we present molecular cytogenetic and CENP-A chromatin immunoprecipitation (ChIP) on CHIP analyses of two neocentromeres that have formed in chromosome band 8q21 each with a unique DNA and CENP-A chromatin configuration. The first neocentromere was found on a neodicentric chromosome 8 with an inactivated endogenous centromere, where the centromeric activity and CENP-A domain were repositioned to band 8q21 on a large tandemly repeated DNA. This is the first example of a neocentromere forming on repetitive DNA, as all other mapped neocentromeres have formed on single copy DNA. Quantitative fluorescent in situ hybridization (FISH) analysis showed a 60% reduction in the alpha satellite array size at the inactive centromere compared to the active centromere on the normal chromosome 8. This neodicentric chromosome may provide insight into centromere inactivation and the role of tandem DNA in centromere structure. The second neocentromere was found on a neocentric ring chromosome that contained the 8q21 tandemly repeated DNA, although the neocentromere was localized to a different genomic region. Interestingly, this neocentromere is composed of two distinct CENP-A domains in bands 8q21 and 8q24, which are brought into closer proximity on the ring chromosome. This neocentromere suggests that chromosomal rearrangement and DNA breakage may be involved in neocentromere formation. These novel examples provide insight into the formation and structure of human neocentromeres.

A growing trend among clinical studies is the use of heart rate monitors (HRMs) for assessment of heart rate variability (HRV). These instruments offer a convenient alternative to traditional electrocardiographs (ECGs) for recording and processing of R-R data. Reports on the validity of such systems are, however, conflicting. This study aimed to assess the validity of a commercial HRM on a large study sample, with emphasis on gender and age. Simultaneous recordings of R-R intervals were conducted with the Polar RS800 HRM and a 3-lead ECG on 341 individuals. Data editing was performed with individually designated software for each instrument. Agreement on SDNN, RMSSD, and HF- and LF power was assessed with intraclass correlations (ICCs), standard errors of measurement (SEMs) and Bland and Altman plots. The HRM was not able to identify 18 observations with non-sinus beats. For men, agreement between instruments ranged from good to excellent (ICC ≥ 0.8) on all HRV measures, and SEMs were generally small. For women the results were weaker, with unacceptable agreement between instruments on SDNN. Women over 60 years did not reach a critical ICC value of 0.75 on any of the HRV measures. Bland and Altman plots demonstrated that the RS800 generally overestimated HRV, and that uncertainty increased with higher values. Since the Polar system did not identify errors satisfactorily, or return valid values of HRV for certain groups, it is concluded that, whenever possible, traditional ECGs should be used for both gathering and editing of HRV data.

In web-based health promotion programs, large variations in participant engagement are common. The aim was to investigate determinants of high use of a worksite self-help web-based program for stress management. Two versions of the program were offered to randomly selected departments in IT and media companies. A static version of the program including health screening tool, diary and information about stress was offered to the control group. Additional materials, i.e. interactive, cognitive-based and classical stress management exercises and a chat room, were offered to the intervention group. Baseline data regarding participants' demographics, health (self-ratings and biological measures), lifestyle, work-related factors and group membership were analyzed to study determinants of employees' participation in the program during a period of 12 months. Multiple logistic regression analysis was used and found intervention group membership, being a woman, having at most a secondary education, regular physical exercise habits and having positive expectations of the program were significant predictors of high use. The findings demonstrate that the interactivity of a web-based program is an important factor for determining participation in a web-based worksite stress management program. Implications for those developing and implementing future web-based health promotion activities are discussed.

For nurses, the transition from higher education to working life involves several types of changes and seems to be a major contributing cause of distress and, consequently, ill health on a longer term basis. The aim of this study was to longitudinally monitor the development of self-rated health (SRH) in nurses, starting from the last semester at the university with subsequent follow-ups when the nurses had entered working life. The Longitudinal Analyses of Nurses' Education and working life is an ongoing nationwide longitudinal project focusing on mapping health and career development in nurses in Sweden. SRH is one of the most widely used single-item measures of perceived health status with a well-established predictive ability on future health outcomes, including morbidity and mortality. This study found a small but significant and continuous decline in SRH among nurses during 3 years of follow-ups, starting from their last semester of nursing education and continuing 3 years into their working life. The most pronounced decline in SRH seems to occur in the transition between student life and working life and is most explicit among the youngest nurses. However, the long-term effect on SRH when entering into working life seems to be more pronounced among the older nurses.

Experimental and epidemiological research indicate an association between long-term stress and hearing problems, yet the mechanisms underlying these disorders are not yet fully established. Thus, in order to better understand the pathogenesis of stress-related hearing problems, the present study explored the symptoms and general physiological and psychosocial status of musicians in symphony orchestras. Orchestral musicians are an ideal group to study since physical, psychosocial, work-environmental and acoustic stressors are highly prevalent. The subjects where obtained from two different studies. The first group included 250 participants from 12 orchestras and is entitled "the epidemiological study". The second group, entitled "the longitudinal study", included 47 musicians who were assessed at five occasions (every half year) during two years. Thirty-one of the 47 participants were selected for sampling of physiological variables, i.e. 24-hour ECG to assess heart rate variability to evaluate the synergistic action of the autonomic system as well as saliva cortisol and testosterone levels. The results indicate that self-reported hearing problems are associated with perceived poorer psychosocial environment, as well as mental health symptoms and stress. High-frequency power of heart rate variability (parasympathetic activity) showed a negative relationship to hearing problems, implying a poorer ability to "unwind" from stress. Cortisol levels were not correlated to hearing problems whereas testosterone levels showed a tendency to be lower in subjects with hearing problems than in others. These findings provide evidence for a relationship between long-term stress and self-reported hearing problems and demonstrate a protective role of parasympathetic and anabolic activity on hearing status.

Studies show that first-line nurse managers (F-LNMs) experience high psychological job demands and inadequate managerial guidance. The purpose of this study was to investigate whether F-LNMs have higher stress levels and show more signs of stress-related ill health than registered nurses (RNs).The aim of this study was to examine possible differences in self-rated health between F-LNMs and RNs on various psychosocial factors (e.g. job demand, job control and managerial support).Data were collected at a university hospital in Sweden. Sixty-four F-LNMs and 908 RNs filled in a web-based questionnaire.Both F-LNMs and RNs reported having good health. Approximately 10-15% of the F-LNMs and RNs showed signs of being at risk for stress-related ill health. Statistically significant differences (Mann-Whitney U-test) were found in the distribution between the F-LNMs and the RNs on three indices of job control, job demand and managerial support.Our findings suggest that F-LNMs were able to cope with high-demand job situations because of relatively high control over work.The implication for nursing management shows the needs for a work environment for both F-LNMs and RNs that includes high job control and good managerial support.

BackgroundHearing problems is one of the top ten public health disorders in the general population and there is a well-established relationship between stress and hearing problems. The aim of the present study was to explore if an acute stress will increase auditory sensitivity (hyperacusis) in individuals with high levels of emotional exhaustion (EE).MethodsHyperacusis was assessed using uncomfortable loudness levels (ULL) in 348 individuals (140 men; 208 women; age 23-71 years). Multivariate analyses (ordered logistic regression), were used to calculate odds ratios, including interacting or confounding effects of age, gender, ear wax and hearing loss (PTA). Two-way ANCOVAs were used to assess possible differences in mean ULLs between EE groups pre- and post-acute stress task (a combination of cold pressor, emotional Stroop and Social stress/video recording).ResultsThere were no baseline differences in mean ULLs between the three EE groups (one-way ANOVA). However, after the acute stress exposure there were significant differences in ULL means between the EE-groups in women. Post-hoc analyses showed that the differences in mean ULLs were between those with high vs. low EE (range 5.5-6.5 dB). Similar results were found for frequencies 0.5 and 1 kHz. The results demonstrate that women with high EE-levels display hyperacusis after an acute stress task. The odds of having hyperacusis were 2.5 (2 kHz, right ear; left ns) and 2.2 (4 kHz, right ear; left ns) times higher among those with high EE compared to those with low levels. All these results are adjusted for age, hearing loss and ear wax.ConclusionWomen with high levels of emotional exhaustion become more sensitive to sound after an acute stress task. This novel finding highlights the importance of including emotional exhaustion in the diagnosis and treatment of hearing problems.

Tinnitus, the perception of sound without external source, is a highly prevalent public health problem with about 8% of the population having frequently occurring tinnitus, and about 1-2% experiencing significant distress from it. Population studies, as well as studies on self-selected samples, have reported poor psychological well-being in individuals with tinnitus. However, no study has examined the long-term co-variation between mood and tinnitus prevalence or tinnitus severity. In this study, the relationship between depression and tinnitus prevalence and severity over a 2-year period was examined in a representative sample of the general Swedish working population. Results show that a decrease in depression is associated with a decrease in tinnitus prevalence, and even more markedly with tinnitus severity. Hearing loss was a more potent predictor than depression for tinnitus prevalence, but was a weaker predictor than depression for tinnitus severity. In addition, there were sex differences for tinnitus prevalence, but not for tinnitus severity. This study shows a direct and long-term association between tinnitus severity and depression.

BACKGROUND: Several studies have established impaired sleep is a common problem among nurses. Overworked, fatigued and stressed nurses are at a higher risk of making mistakes that threaten patient safety as well as their own health. The aim of the present study was to longitudinally monitor the development of sleep quality in nurses, starting from the last semester at the university, with three subsequent annual follow-ups once the nurses had entered working life. METHODOLOGY/PRINCIPAL FINDINGS: Nationwide, longitudinal questionnaire study of nursing students and newly qualified nurses in Sweden. The results imply a continuous decline in sleep quality among nurses during the three years of follow-up, starting from their last semester of nursing education and continuing for three years into their working life. The most pronounced short-term decline in sleep quality seems to occur in the transition between student life and working life. CONCLUSION/SIGNIFICANCE: This finding is important since it may affect the quality of care and the health of nurses negatively.

Hearing problems are among the top 10 most common burdens of disease and are projected to be become even more common by the year 2030. The aim of the present study was to give a current assessment of the prevalence of communication difficulties because of hearing loss and tinnitus, in the general Swedish working and non-working populations in relation to sex, age, socioeconomic status (SES) and noise exposure. How prevalence is affected by SES has not been previously established.A total of 18 734 individuals were invited to participate in the study, of which 11 441 (61%) enrolled. Of the participants, 9756 answered the questionnaire for those who work and 1685 answered the version for non-workers.The most important findings are that 31% in the working population and 36% in the non-working population report either hearing loss or tinnitus or both. The prevalence of hearing problems increases with age, is higher among men and persons with low self-rated SES, and covaries with exposure to noise at work. Severe hearing problems are already present in men and women under 40 years of age who are exposed to work-related noise.Prevalence of hearing problems is far more common than previously estimated and is associated with SES and noise exposure history. Hearing problems have a gradual onset that can take years to become recognised. In order to proactively intervene and prevent this deleterious, yet avoidable handicap, statistics need to be regularly updated.

A Swedish web-based service (www.escreen.se) offers self-assessment and self-monitoring of alcohol and drug use via on-line screening with the Alcohol Use Disorders Identification Test (AUDIT) and the Drug Use Disorders Identification Test (DUDIT) as well as in-depth risk assessment using extended versions of both tests (Alcohol-E and DUDIT-E). Users receive individualized feedback concerning their alcohol and drug consumption and can follow their alcohol and drug use over time in personal diagrams and by writing in an electronic diary. This study describes user characteristics, service utilization patterns, and psychometric test properties for 2361 individuals who created a valid account over 20 months starting in February 2007. Problematic alcohol use according to AUDIT criteria was indicated for 67.4%, while 46.0% met DUDIT criteria for problematic drug use. Men and women accessed the service equally, with a mean age of 23 years. Internal consistency reliability figures were 0.90 for 1846 first-time AUDIT users and 0.97 for 1211 first-time DUDIT users; among 213 second-time AUDIT users reliability was 0.93, and 0.96 for 97 second-time DUDIT users. Internet-based alcohol and drug monitoring could function as a self-help tool or as a complement to substance abuse treatment.

To evaluate the influence of a web-based stress management program on neck-shoulder-back pain and perceived pain-relatedness to stress in a prospective and controlled study.Study points were baseline, after 6 months intervention and at 12 months follow-up on 226 news media employees in two study groups and one control group.Between groups no significant differences were found at any study point. Within groups, the study group with less intensive program improved in pain-relatedness to stress at follow-up. Between baseline and after intervention, the group with more intensive program showed decreased low back pain, and the control group showed less pain-relatedness to stress. Within group differences varied according to pain localization and were inconsistent.Present web-based stress management program did not influence neck-shoulder-back pain or perceived pain-relatedness to stress in stress-intensive occupations.

Physiological and psychological mechanisms have been proposed to link stress and musculoskeletal pain (MSP), and a number of stress biomarkers in patients with chronic pain have shown to be associated with stress-related disorders as well as health and recovery. The aim was to study if similar results might be found in a working population, in stress and computer intensive occupations with mild/moderate pain in neck, shoulder and back. The questions were if there are: (1) associations between self rated neck, shoulder and back pain (VAS) on one hand and stress-related (catabolic), recovery related (anabolic) variables, cardiovascular/lifestyle factors and immune markers on the other hand. (2) associations between long term changes in pain and stress marker values (6 month period). (3) predictive values in stress biomarkers for pain (12 month period) A study group with 121 media workers, 67 males (average 45 years) and 53 females (average 43 years), at three news departments of a media company was recruited. Pain occurrence and pain level in neck, shoulder, upper and low back were self-rated at three times with a 6-month interval towards the last month. Stress biomarker sampling was performed, at the same intervals. An additional similar questionnaire with momentary ratings focusing on “at present” i.e. within the same hour as stress biomarker sampling was performed. There were no changes in medicine intake or computer working hours during the 12 month study period. The total pain level and prevalence of pain decreased between baseline and 12 months´ follow-up. The rate of participation was 95%. Cross-sectional analyses on differences in stress biomarkers in groups of “no pain” and “pain” showed less beneficial stress biomarker levels (P

Background The aim of the present study was to assess possible effects on mental and physical well-being and stress-related biological markers of a web-based health promotion tool. Methods A randomized, prospectively controlled study was conducted with before and after measurements, involving 303 employees (187 men and 116 women, age 23–64) from four information technology and two media companies. Half of the participants were offered web-based health promotion and stress management training (intervention) lasting for six months. All other participants constituted the reference group. Different biological markers were measured to detect possible physiological changes. Results After six months the intervention group had improved statistically significantly compared to the reference group on ratings of ability to manage stress, sleep quality, mental energy, concentration ability and social support. The anabolic hormone dehydroepiandosterone sulphate (DHEA-S) decreased significantly in the reference group as compared to unchanged levels in the intervention group. Neuropeptide Y (NPY) increased significantly in the intervention group compared to the reference group. Chromogranin A (CgA) decreased significantly in the intervention group as compared to the reference group. Tumour necrosis factor α (TNFα) decreased significantly in the reference group compared to the intervention group. Logistic regression analysis revealed that group (intervention vs. reference) remained a significant factor in five out of nine predictive models. Conclusion The results indicate that an automatic web-based system might have short-term beneficial physiological and psychological effects and thus might be an opportunity in counteracting some clinically relevant and common stress and health issues of today.

Background Current human and experimental studies are indicating an association between stress and hearing problems; however potential risk factors have not been established. Hearing problems are projected to become among the top ten disabilities according to the WHO in the near future. Therefore a better understanding of the relationships between stress and hearing is warranted. Here we describe the prevalence of two common hearing problems, i.e. hearing complaints and tinnitus, in relation to different work-and health-related stressors. Methods A total of 18,734 individuals were invited to participate in the study, out of which 9,756 (52%) enrolled. Results The results demonstrate a clear and mostly linear relationship between higher prevalence of hearing problems (tinnitus or hearing loss or both) and different stressors, e.g. occupational, poorer self-rated health, long-term illness, poorer sleep quality, and higher burnout scores. Conclusions The present study unambiguously demonstrates associations between hearing problems and various stressors that have not been previously described for the auditory system. These findings will open new avenues for future investigations.