Auditory network connectivity in tinnitus patients: a resting-state fMRI study

Objective: Resting-state functional magnetic resonance imaging (fMRI) uncovers correlated activity between spatially distinct functionally related brain regions and offers clues about the integrity of functional brain circuits in people with chronic subjective tinnitus. We chose to investigate auditory network connectivity, adopting and extending previously used analyses methods to provide an independent evaluation of replicability. Design: Independent components analysis (ICA) was used to identify coherent patterns arising from spontaneous brain signals within the resting-state data. The auditory network component was extracted and evaluated. Bivariate and partial correlation analyses were performed on pre-defined regions of bilateral auditory cortex to assess functional connectivity. Study sample: Our design carefully matched participant groups for possible confounds, such as hearing status. Twelve patients (seven male, five female; mean age 66 years) all with chronic constant tinnitus and eleven controls (eight male, three female; mean age 68 years) took part. Results: No significant differences were found in auditory network connectivity between groups after correcting for multiple statistical comparisons in the analysis. This contradicts previous findings reporting reduced auditory network connectivity; albeit at a less stringent statistical threshold. Conclusions: Auditory network connectivity does not appear to be reliably altered by the experience of chronic subjective tinnitus

Stable long-term outcomes after cochlear implantation in subjects with TMPRSS3 associated hearing loss: a retrospective multicentre study

Background The spiral ganglion hypothesis suggests that pathogenic variants in genes preferentially expressed in the spiral ganglion nerves (SGN), may lead to poor cochlear implant (CI) performance. It was long thought that TMPRSS3 was particularly expressed in the SGNs. However, this is not in line with recent reviews evaluating CI performance in subjects with TMPRSS3-associated sensorineural hearing loss (SNHL) reporting overall beneficial outcomes. These outcomes are, however, based on variable follow-up times of, in general, 1 year or less. Therefore, we aimed to 1. evaluate long-term outcomes after CI implantation of speech recognition in quiet in subjects with TMPRSS3-associated SNHL, and 2. test the spiral ganglion hypothesis using the TMPRSS3-group. Methods This retrospective, multicentre study evaluated long-term CI performance in a Dutch population with TMPRSS3-associated SNHL. The phoneme scores at 70 dB with CI in the TMPRSS3-group were compared to a control group of fully genotyped cochlear implant users with post-lingual SNHL without genes affecting the SGN, or severe anatomical inner ear malformations. CI-recipients with a phoneme score <= 70% at least 1-year post-implantation were considered poor performers and were evaluated in more detail. Results The TMPRSS3 group consisted of 29 subjects (N = 33 ears), and the control group of 62 subjects (N = 67 ears). For the TMPRSS3-group, we found an average phoneme score of 89% after 5 years, which remained stable up to 10 years post-implantation. At both 5 and 10-year follow-up, no difference was found in speech recognition in quiet between both groups (p = 0.830 and p = 0.987, respectively). Despite these overall adequate CI outcomes, six CI recipients had a phoneme score of <= 70% and were considered poor performers. The latter was observed in subjects with residual hearing post-implantation or older age at implantation. Conclusion Subjects with TMPRSS3-associated SNHL have adequate and stable long-term outcomes after cochlear implantation, equal to the performance of genotyped patient with affected genes not expressed in the SGN. These findings are not in line with the spiral ganglion hypothesis. However, more recent studies showed that TMPRSS3 is mainly expressed in the hair cells with only limited SGN expression. Therefore, we cannot confirm nor refute the spiral ganglion hypothesis.Otorhinolaryngolog

A RIPOR2 in-frame deletion is a frequent and highly penetrant cause of adult-onset hearing loss

BackgroundHearing loss is one of the most prevalent disabilities worldwide, and has a significant impact on quality of life. The adult-onset type of the condition is highly heritable but the genetic causes are largely unknown, which is in contrast to childhood-onset hearing loss.MethodsFamily and cohort studies included exome sequencing and characterisation of the hearing phenotype. Ex vivo protein expression addressed the functional effect of a DNA variant.ResultsAn in-frame deletion of 12 nucleotides in RIPOR2 was identified as a highly penetrant cause of adult-onset progressive hearing loss that segregated as an autosomal dominant trait in 12 families from the Netherlands. Hearing loss associated with the deletion in 63 subjects displayed variable audiometric characteristics and an average (SD) age of onset of 30.6 (14.9) years (range 0-70 years). A functional effect of the RIPOR2 variant was demonstrated by aberrant localisation of the mutant RIPOR2 in the stereocilia of cochlear hair cells and failure to rescue morphological defects in RIPOR2-deficient hair cells, in contrast to the wild-type protein. Strikingly, the RIPOR2 variant is present in 18 of 22 952 individuals not selected for hearing loss in the Southeast Netherlands.ConclusionCollectively, the presented data demonstrate that an inherited form of adult-onset hearing loss is relatively common, with potentially thousands of individuals at risk in the Netherlands and beyond, which makes it an attractive target for developing a (genetic) therapy.Otorhinolaryngolog

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Op zoek naar stilte: indicatoren van stilte in De Wieden/Weerribben, NP Utrechtse Heuvelrug en de Zak van Zuid-Beveland

In de zomer van 2003 zijn ten behoeve van Stichting Natuur en Milieu, Natuur en Milieu Overijssel, Natuur en Milieufederatie Utrecht en de Zeeuwse Milieufederatie metingen verricht van het geluidniveau in een viertal voor rustige recreatie geschikte natuurgebieden. De vier onderzoeksgebieden maken deel uit van voor rustige recreatie belangrijke streken en vallen deels samen met provinciale stiltegebieden ofwel 'milieu-beschermingsgebieden voor stilte' (in Zeeland: algemeen milieubeschermingsgebied). Het gaat om de aan elkaar grenzende waterrijke en grotendeels open Weerribben en Wieden, het bosrijke en beschutte Nationaal Park Utrechtse Heuvelrug, en de open en grotendeels agrarische Zak van Zuid-Beveland. In elk gebied is enkele keren gemeten: in principe werden op twee werkdagen met tegengestelde windrichting en op een zondag twee rondes in het gebied gemaakt langs een negental, steeds dezelfde meetlocaties. Steeds werd gedurende 10 minuten gemeten en geluisterd. Per minuut werd vastgesteld of in die minuut een motorische bron hoorbaar was: een vliegtuig, auto, motor of brommer, boot, trekker en/of trein. In Zeeland werd ook geluid van bedrijfsactiviteiten gehoord. Door middel van meting zijn van deze bronnen zoveel mogelijk de maximale en gemiddelde geluidniveaus bepaald. Daarnaast is geteld welk deel van de tijd mensen ('niet-gemotoriseerde bronnen') hoorbaar waren. Het onderzoek berust dus zowel op menselijke waarneming (luisteren en noteren) als op instrumentele waarneming (meten en achteraf analyseren).

Genetic Hearing Loss Affects Cochlear Processing

The relationship between speech recognition and hereditary hearing loss is not straightforward. Underlying genetic defects might determine an impaired cochlear processing of sound. We obtained data from nine groups of patients with a specific type of genetic hearing loss. For each group, the affected cochlear site-of-lesion was determined based on previously published animal studies. Retrospectively obtained speech recognition scores in noise were related to several aspects of supra-threshold cochlear processing as assessed by psychophysical measurements. The differences in speech perception in noise between these patient groups could be explained by these factors and partially by the hypothesized affected structure of the cochlea, suggesting that speech recognition in noise was associated with a genetics-related malfunctioning of the cochlea. In particular, regression models indicate that loudness growth and spectral resolution best describe the cochlear distortions and are thus a good biomarker for speech understanding in noise

The Effectiveness of the Interventions to Reduce Sound Levels in the ICU: A Systematic Review.

Excessive noise is ubiquitous in the ICU, and there is growing evidence of the negative impact on work performance of caregivers. This study aims to determine the effectiveness of interventions to reduce noise in the ICU. DATA SOURCES: Databases of PubMed, EMBASE, PsychINFO, CINAHL, and Web of Science were systematically searched from inception to September 14, 2022. STUDY SELECTION: Two independent reviewers assessed titles and abstracts against study eligibility criteria. Noise mitigating ICU studies were included when having at least one quantitative acoustic outcome measure expressed in A-weighted sound pressure level with an experimental, quasi-experimental, or observational design. Discrepancies were resolved by consensus, and a third independent reviewer adjudicated as necessary. DATA EXTRACTION: After title, abstract, and full-text selection, two reviewers independently assessed the quality of each study using the Cochrane's Risk Of Bias In Nonrandomized Studies of Interventions tool. Data were synthesized according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, and interventions were summarized. DATA SYNTHESIS: After screening 12,652 articles, 25 articles were included, comprising either a mixed group of healthcare professionals (n = 17) or only nurses (n = 8) from adult or PICU settings. Overall, the methodological quality of the studies was low. Noise reduction interventions were categorized into education (n = 4), warning devices (n = 3), multicomponent programs (n = 15), and architectural redesign (n = 3). Education, a noise warning device, and an architectural redesign significantly decreased the sound pressure levels. CONCLUSIONS: Staff education and visual alert systems seem promising interventions to reduce noise with a short-term effect. The evidence of the studied multicomponent intervention studies, which may lead to the best results, is still low. Therefore, high-quality studies with a low risk of bias and a long-term follow-up are warranted. Embedding noise shielding within the ICU-redesign is supportive to reduce sound pressure levels

Computational Audiology: New Approaches to Advance Hearing Health Care in the Digital Age

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