Explore the vast range of titles available.

[...]while there are multiple ways of perceiving tinnitus, it is also associated with multiple causal risk factors—hearing loss, temporomandibular joint disorder, and aging being among the most common ones. Within this topic, current knowledge is reviewed and new theories of tinnitus generation are proposed, animal models are used to understand the neural correlates better, audiological, and psychological aspects are explored, neuroimaging techniques investigate the involved brain networks, new questionnaire instruments are developed and others adapted to new languages, genome-wide associations are pioneered, mobile applications are used to explore tinnitus on new time-scales, and, finally, multiple therapeutic approaches are tested. [...]the fifth chapter refers to advances on tinnitus therapies. Age-related hearing loss and tinnitus can go hand in hand and one of the most well-established theories considers tinnitus as the perceptual consequence of neuronal hyperactivity in the central auditory system; emerging after loss of normal input from the ear.

Tinnitus disability is a heterogeneous and complex condition, affecting more than 10% and compromising the quality of life of 2% of the population, with multiple contributors, often unknown, and enigmatic pathophysiology. The available treatment options are unsatisfactory, as they can, at best, reduce tinnitus severity, but not eliminate its perception. Given the spread of tinnitus and the lack of a standardized treatment, it is crucial to understand the economic burden of this condition. We conducted a systematic review of the literature on PubMed/MEDLINE, Embase, the Cochrane Database of Systematic Reviews (CDSR) and Google Scholar, in order to identify all the articles published on the economic burden of tinnitus before 1 April 2021 (PROSPERO—International prospective register of systematic reviews—No: CRD42020180438). Out of 273 articles identified through our search strategy, only five articles from studies conducted in the United States of America (USA), the Netherlands and the United Kingdom (UK) provided data on tinnitus’s economic costs. Three studies provided mean annual estimates per patient ranging between EUR 1544 and EUR 3429 for healthcare costs, between EUR 69 and EUR 115 for patient and family costs and between EUR 2565 and EUR 3702 for indirect costs, including productivity loss. The other two studies reported an annual mean cost of EUR 564 per patient for tinnitus-related clinical visits, and total costs of EUR 1388 and EUR 3725 for patients treated with a sound generator and Neuromonics Tinnitus Treatment, respectively. Our comprehensive review shows a gap in the knowledge about the economic burden of tinnitus on healthcare systems, patients and society. The few available studies show considerable expenses due to healthcare and indirect costs, while out-of-pocket costs appear to be less financially burdensome. Comprehensive health economic evaluations are needed to fill the gaps in current knowledge, using a unified method with reliable and standardized tools.

(2017) and a study from Fioretti et al. in this Research Topic Indeed, analysis of the Perceived Stress Questionnaire (PSQ) revealed that the increased stress-reporting by female patients was related to an increase in worries, tensions and demand, something that was also reflected in the general depression scale, where women scored significantly higher than men. Author Disclaimer CC was supported by the UK National Institute for Health Research (NIHR) Biomedical Research Centre but the views expressed herein are his own and do not represent those of NIHR nor the UK Department of Health and Social Care. Med. 9:3812. doi: 10.3390/jcm9123812 Christopher R. Cederroth1,2,3 and Winfried Schlee4* * 1Section of Experimental Audiology, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden * 2National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom * 3Hearing Sciences, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham, United Kingdom * 4Department of Psychiatry and Psychotherapie, University of Regensburg, Regensburg, Germany

Ototoxicity is one of the major side-effects of platinum-based chemotherapy, in particular cisplatin (cis-diammine dichloroplatinum II). To our knowledge, no systematic review has previously provided a quantitative summary estimate of the impact of genetics upon the risk of developing hearing loss. We searched Embase, Medline, ASSIA, Pubmed, Scopus, and Web of Science, for studies documenting the genetic risk of ototoxicity in patients with cancer treated with cisplatin. Titles/abstracts and full texts were reviewed for inclusion. Meta-analytic estimates of risk (Odds Ratio) from the pooled data were calculated for studies that have been repeated twice or more. The search identified 3891 papers, of which 30 were included. The majority were retrospective (44%), ranging from n = 39 to n = 317, some including only patients younger than 25 years of age (33%), and some on both genders (80%). The most common cancers involved were osteosarcoma (53%), neuroblastoma (37%), prostate (17%) and reproductive (10%). Most studies performed genotyping, though only 5 studies performed genome-wide association studies. Nineteen single-nucleotide polymorphisms (SNPs) from 15 genes were repeated more than twice. Meta-analysis of group data indicated that rs1872328 on ACYP2 , which plays a role in calcium homeostasis, increases the risk of ototoxicity by 4.61 (95% CI: 3.04–7.02; N = 696, p  < 0.0001) as well as LRP2 rs4668123 shows a cumulated Odds Ratio of 3.53 (95% CI: 1.48–8.45; N = 118, p  = 0.0059), which could not be evidenced in individual studies. Despite the evidence of heterogeneity across studies, these meta-analytic results from 30 studies are consistent with a view of a genetic predisposition to platinum-based chemotherapy mediated ototoxicity. These new findings are informative and encourage the genetic screening of cancer patients in order to identify patients with greater vulnerability of developing hearing loss, a condition having a potentially large impact on quality of life. More studies are needed, with larger sample size, in order to identify additional markers of ototoxic risk associated with platinum-based chemotherapy and investigate polygenic risks, where multiple markers may exacerbate the side-effects.

BACKGROUNDThe heterogeneity of tinnitus is thought to underlie the lack of objective diagnostic measures.METHODSLongitudinal 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.RESULTSWe 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.CONCLUSIONSOur 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.FUNDINGThis study was supported by the GENDER-Net Co-Plus Fund (GNP-182), the European Union's Horizon 2020 grants no. 848261 (Unification of Treatments and Interventions for Tinnitus [UNITI]) and no. 722046 (European School for Interdisciplinary Tinnitus Research [ESIT]).

The 3Rs principle of replacing, reducing and refining the use of animals in science has been gaining widespread support in the international research community and appears in transnational legislation such as the European Directive 2010/63/EU, a number of national legislative frameworks like in Switzerland and the UK, and other rules and guidance in place in countries around the world. At the same time, progress in technical and biomedical research, along with the changing status of animals in many societies, challenges the view of the 3Rs principle as a sufficient and effective approach to the moral challenges set by animal use in research. Given this growing awareness of our moral responsibilities to animals, the aim of this paper is to address the question: Can the 3Rs, as a policy instrument for science and research, still guide the morally acceptable use of animals for scientific purposes, and if so, how? The fact that the increased availability of alternatives to animal models has not correlated inversely with a decrease in the number of animals used in research has led to public and political calls for more radical action. However, a focus on the simple measure of total animal numbers distracts from the need for a more nuanced understanding of how the 3Rs principle can have a genuine influence as a guiding instrument in research and testing. Hence, we focus on three core dimensions of the 3Rs in contemporary research: (1) What scientific innovations are needed to advance the goals of the 3Rs? (2) What can be done to facilitate the implementation of existing and new 3R methods? (3) Do the 3Rs still offer an adequate ethical framework given the increasing social awareness of animal needs and human moral responsibilities? By answering these questions, we will identify core perspectives in the debate over the advancement of the 3Rs.

Background: The causes of the current obesity pandemic have not been fully elucidated. Implication of environmental endocrine disruptors such as bisphenol A (BPA) on adipose tissue development has been poorly investigated. Objectives: The aim of the present study was to evaluate the effects of perinatal exposure to BPA on early adipose storage at weaning. Methods: Pregnant Sprague-Dawley rats had access to drinking water containing 1mg/LBPA from day 6 of gestation through the end of lactation. Pups were weaned on postnatal day (PND) 21. At that time, we investigated perigonadal adipose tissue of pups (weight, histology, gene expression). For the remaining animals, we recorded body weight and food intake for animals on either standard chow or a high-fat diet. Results: Gestational exposure to BPA did not alter the sex ratio or litter size at birth. On PND1, the weight of male and female BPA-exposed pups was increased. On PND21, body weight was increased only in females, in which parametrial white adipose tissue (pWAT) weight was increased about 3-fold. This excess of pWAT was associated with adipocyte hypertrophy and overexpression of lipogenic genes such as C/EBP-α (CAAT enhancer binding protein alpha), PPAR-y (peroxisome proliferator-activated receptor gamma), SREBP-1C (sterol regulatory element binding protein-1C), LPL (lipoprotein lipase), FAS (fatty acid synthase), and SCD-1 (stearoyl-CoA desaturase 1). In addition, gene expression of SREBP-1C, FAS, and ACC (acetyl-CoA carboxylase) was also increased in liver from BPA-exposed females at PND21, without a change in circulating lipids and glucose. After weaning, perinatal BPA exposure predisposed to overweight in a sex-and diet-dependent manner. We observed no change in food intake due to perinatal BPA exposure in rats on either standard chow or a high-fat diet. Conclusions: Perinatal exposure to a low dose of BPA increased adipogenesis in females at weaning. Adult body weight may be programmed during early life, leading to changes dependent on the sex and the nutritional status. Although further studies are required to understand the mechanisms of BPA action in early life, these results are particularly important with regard to the increasing prevalence of childhood obesity and the context-dependent action of endocrine disruptors.

Bisphenol-A (BPA) is one of the most widespread endocrine disrupting chemicals (EDC) used as the base compound in the manufacture of polycarbonate plastics. Although evidence points to consider exposure to BPA as a risk factor for insulin resistance, its actions on whole body metabolism and on insulin-sensitive tissues are still unclear. The aim of the present work was to study the effects of low doses of BPA in insulin-sensitive peripheral tissues and whole body metabolism in adult mice. Adult mice were treated with subcutaneous injection of 100 µg/kg BPA or vehicle for 8 days. Whole body energy homeostasis was assessed with in vivo indirect calorimetry. Insulin signaling assays were conducted by western blot analysis. Mice treated with BPA were insulin resistant and had increased glucose-stimulated insulin release. BPA-treated mice had decreased food intake, lower body temperature and locomotor activity compared to control. In skeletal muscle, insulin-stimulated tyrosine phosphorylation of the insulin receptor β subunit was impaired in BPA-treated mice. This impairment was associated with a reduced insulin-stimulated Akt phosphorylation in the Thr(308) residue. Both skeletal muscle and liver displayed an upregulation of IRS-1 protein by BPA. The mitogen-activated protein kinase (MAPK) signaling pathway was also impaired in the skeletal muscle from BPA-treated mice. In the liver, BPA effects were of lesser intensity with decreased insulin-stimulated tyrosine phosphorylation of the insulin receptor β subunit.In conclusion, short-term treatment with low doses of BPA slows down whole body energy metabolism and disrupts insulin signaling in peripheral tissues. Thus, our findings support the notion that BPA can be considered a risk factor for the development of type 2 diabetes.

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. We conducted a cross-sectional study using survey data from the Swedish LifeGene cohort containing information on self-reported tinnitus ( = 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. (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. 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.