FTO locus. We conducted bi-directional MR for the ‘forward’ (from body constitution to hearing) and ‘reverse’ directions. We applied the random effects inverse variance-weighted method as the main MR method, with additional sensitivity analyses. Colocalisation analysis suggested that BMI and ARHI shared a causal variant at the FTO gene. We did not find robust evidence for causal associations from body constitution to hearing loss and suggested that some associations may be driven by FTO variants. In the reverse analyses, ARHI was negatively associated with BMI [effect size – 0.22 (95% CI – 0.44 to – 0.01)] and BFP [effect size – 0.23 (95% CI – 0.45 to 0.00)], supporting the notion that ARHI may diminish body constitution. Finally, our data suggest that there is no strong evidence that hearing explains the association between noise exposure and body constitution.Hearing loss and hearing disorders represent possible mediating pathways in the associations between noise exposures and non-auditory health outcomes. In this context, we assessed whether the noise-obesity associations should consider hearing functions as possible mediators and applied Mendelian randomisation (MR) to investigate causal relationships between body constitution and hearing impairments. We obtained genetic associations from publicly available summary statistics from genome-wide association studies in European ancestry adult populations  for (i) body constitution: body mass index (BMI), waist circumference (WC) and body fat percentage (BFP), and (ii) hearing loss: sensorineural hearing loss, noise-induced hearing loss, and age-related hearing impairment (ARHI). We employed colocalisation analysis to investigate the genetic associations for BMI and ARHI liability within an  However, the WHO environmental noise guidelines recently rated the research quality on environmental noise exposure and obesity low and emphasised the importance of studying hearing-related outcomes associated with noise exposure2. Hearing loss is indeed a growing health concern that may mediate or confound the association between noise exposure and its attributed non-auditory health outcomes3.There is evidence from observational studies that long-term exposure to traffic noise is associated with an increasing risk of obesity4 and its related cardiometabolic comorbidities, such as cardiovascular disease6 and diabetes mellitus7. The association is biologically plausible since people with these metabolic diseases have a high probability for poor micro-vascular circulation that reduces blood supply to the cochlea, resulting in damage to the hair cells and, eventually, sensorineural hearing loss. Additional studies show consistent results that elevated body mass index (BMI) is positively associated with hearing loss10. A recent meta-analysis systematically reviewed the 14 published observational studies and found a positive association between hearing loss and BMI and waist circumference (WC)11.More frequently studied, hearing loss has been shown to be positively associated with excess weight10. Amid this uncertainty, some studies found that low BMI was also positively associated with hearing loss12. This association was further supported by a recent large-scale Korean population study, which reported that lower BMI (< 18.5 kg/m2) was associated with an increased risk of hearing loss13. The associations were stronger in men and old people than in women and young generations. Furthermore, an earlier study suggested that malnutrition and being underweight are positively associated with sensorineural hearing loss14, which could be partly a result of degeneration and demyelination of the eight cranial nerve and mitochondrial impairment-affecting neurons.However, the association between body constitution and hearing loss remain inconclusive, as other studies found no, or even a negative association between both conditionsIn the previous literature, the mechanism of the associations was mostly discussed from body constitution to hearing loss and the direction of inference of the two phenotypes lacks investigation from hearing loss to body constitution. The previous studies were observational and cannot rule out the questions of reverse causation, selection bias, survival bias and residual confounding. Conversely, the Mendelian randomisation (MR) approach is more robust to unmeasured confounding and reverse causation which hamper accurate causal inference in conventional epidemiological research.To address these objectives, we set up a genetically informed study (MR) to infer the potential causality and its direction between body constitution and hearing loss. It is plausible that both the forward (from body constitution to hearing loss) and the reverse (from hearing loss to body constitution) association can exist and therefore we hypothesised a bi-directional causation.15, we sought GWAS with non-overlapping samples whenever possible. This was not possible for the analyses between age-related hearing impairment (ARHI) and body fat percentage (BFP), where we used the GWAS of UK Biobank with a maximum 70% participant overlap for these two phenotypes. Since the genetic associations of both BMI and ARHI have a strong signal within the FTO gene region, we conducted colocalisation analysis before the MR analysis to examine whether this signal is driven by a shared causal variant, or whether the association is due to confounding by linkage disequilibrium (LD).We conducted a two-sample, bi-directional MR. Genetic associations for all traits were obtained from publicly available summary statistics of genome-wide association studies (GWAS) Table . The dat2), WC (cm) and BFP (%). For BMI and WC, we used sex-combined joint GWAS and Metabochip meta-analysis from the Genetic Investigation of ANthropometric Traits (GIANT) involving 114 studies and 322,154 participants  reported by Locke16, and 101 studies and 210,088 participants  reported by Shungin17, respectively. Both GWAS were used in the MR analyses with ARHI from UK Biobank.The adult body constitution was measured by BMI  and rank normalised. The descriptions of BMI, WC and BFP from UK Biobank  were presented on its webpage .Apart from GIANT, the data on BMI  and WC  were additionally obtained from UK Biobank19 based on a self-reported hearing difficulty (HDiff) phenotype in the UK Biobank. The details of the questionnaires and case-control assignments for the HDiff phenotype can be found in their published supplement material.Hearing loss traits included sensorineural hearing loss (SNHL), noise-induced hearing loss (NIHL) and ARHI. GWAS on risk of ARHI  was from Wells et al.20 release 6 including 271,341 participants. The phenotypes were collected from nationwide hospital discharge and cause of death registers using the International Classification of Diseases (ICD) codes for SNHL: H90.3, H90.4, H90.5 (ICD-10) and 3891 (ICD-9) and NIHL: H83.3 (ICD-10) and 3881 (ICD-9) (Table Summary-level genetic data for risk of SNHL and NIHL were obtained from the FinnGen−8) single-nucleotide polymorphisms (SNPs) that are associated with the corresponding phenotypes in the aforementioned GWAS. This included 12 SNPs for SNHL and none for NIHL. Therefore, to enable a sufficient number of IVs for MR sensitivity analyses, we included SNPs with P-value <5×10−5 as instruments for these traits21.Whenever possible, the instrumental variables (IVs) for the exposures were composed of genome-wide significant >0.4 and imputation info score<0.9. We selected independent SNPs (LD) R2≤0.001 within a 10000 kb window using the ‘ld_clump’ function on the mrcieu/ieugwasr package. If a variant was unavailable in the outcome GWAS summary statistics, then proxy SNPs with a minimum LD R2=0.9 were searched for.We harmonised the effect alleles in the exposure and outcome datasets based on the guidelines provided by Hartwig2 statistics were calculated for the individual IVs to quantify instrument strength using the method described by Burgess et al.15. The statistical power for continuous exposures was evaluated by calculating the approximate minimum detectable odds ratio (OR) for each exposure at a power of 80%, given the sample size of the exposure, the total variance explained by the instruments and the type 1 error rate of 0.05.F and RFTO locus were associated with BMI and ARHI but it was unclear whether both phenotypes share the same causal variant. We conducted colocalisation analysis to examine it with the method ‘coloc’ developed by Giambartolomei et al.23, assuming a maximum of one causal variant per genomic locus. The method outputs posterior probabilities (PP) for five models of (H0) no causal variants, (H1) causal variant for exposure, (H2) causal variant for outcome, (H3) distinct causal variants for exposure and outcome, and (H4) shared causal variant for exposure and outcome. A PP>0.8 for model H4 was considered evidence of colocalization23. We examined the variants within the FTO gene locus  and used the default prior probabilities of a variant associated with BMI only (P1) and ARHI only (P2) at 10−4, and a variant associated with both traits (P12) at 10–5.Variants at the 24. The random effects model was chosen to account for potential heterogeneity, evaluated by Cochran's Q 25. Evidence of heterogeneity was defined with a P-value < 0.05 in the Cochran's Q. We used R version 4.2.026 and TwosampleMR package27 for all analyses.We used the inverse variance weighted (IVW) method as the primary analysis in both forward and reverse MR to calculate the IVW estimator by meta-analysing the SNP-specific Wald estimates using a multiplicative random effects model. The Wald estimate for each SNP was calculated as a ratio between the coefficients for the SNP-to-outcome and the SNP-to-exposure regressions presented in the summary statistics28. We adopted complementary MR methods that make different assumptions about horizontal pleiotropy to assess the robustness of the main MR findings: MR-Egger29, weighted median30, weighted mode31 and MR-PRESSO . MR-PRESSO was also used to detect outliers that may indicate pleiotropic effects28. The following additional analyses were conducted: single SNP analysis and leave-one-out analysis to provide visualisation and interpretation of two-sample MR32.There are three assumptions to consider before validating MR Wald ratios as a robust inference of causation: the IVs (i) are associated with the exposure, (ii) are independent of the confounders and (iii) have no effects on outcome other than via the exposure. In particular, horizontal pleiotropy, in which the IVs have an effect on other traits outside of the pathway of the exposure of interest and have an impact on the outcome of interest, or when the IVs have a direct effect on the outcome of interest, violates the third assumptionThe present research used publicly available summary data and did not contact participants, where no extra ethical approval is required.Table 4 of 0.92, supporting a shared causal variant (rs1558902) for BMI and ARHI at the FTO locus. The allele A for variant rs1558902 was positively associated with BMI and negatively associated with ARHI and the MR estimate of BMI on ARHI using only this variant was 0.91 . The variant was in perfect LD with FTO variant rs1421085 adopted in the forward MR analysis (LD R2 = 1). Therefore, based on the known effect of the FTO gene on BMI33, the FTO variant rs7193144 was excluded from the IVs of ARHI in reverse MR to avoid potential exposure misspecification.The results of the colocalisation analysis between BMI and ARHI were shown in Fig. The results of the analyses were shown in Fig. The results of the analyses were presented in Fig. 2 = 48.7%). The funnel plot of individual SNP showed a relatively symmetrical distribution of SNP effects around the effect estimates, suggesting balanced pleiotropy  and directional pleiotropy from the MR-Egger .The directions of estimates from sensitivity analyses were consistent with the IVW in the analysis between ARHI liability and BMI Fig. . We saw The present study investigated the causal association between body constitution traits and hearing loss, employing a range of two-sample Mendelian randomisation analyses and complementary sensitivity analyses. Our findings suggest that the commonly positive association between body constitution and hearing loss in observational studies may not correspond to a causal risk-increasing effect. We found evidence that ARHI is negatively associated with BMI and BFP in the reverse MR analyses.FTO locus. Based on the well-documented association between FTO variants and BMI33, one may favour a scenario in which BMI could influence ARHI. However, there exists a similar probability for the scenarios where ARHI influences BMI or for horizontal pleiotropy in which BMI and AHRI shared a causal variant , we relaxed the p-value threshold from them to increase the number of available IVs. However, the prevalence of NIHL was much higher in the US general population, around 18% of adults aged 20–69 years40. It is however consistent with observations from a recent large study conducted in a cohort from the Republic of Korea (2009–2016) reporting a negative association between hearing loss and BMI13. There are unfortunately some important ethnic differences between our source data (European ancestors) use in the reverse MR and the aforementioned observation to corroborate evidence.Our analysis, suggesting genetic evidence that liability to ARHI could be linked with lower BMI and BFP, was supported by the MR sensitivity analyses. This differs from our original hypothesis that hearing loss-related traits would increase body constitution pertaining to a GWAS study made in European participantsi.e., sarcopenia). In a two-sample MR setting, when the true effect of an exposure on an outcome is null or >0, the association become nominally negative due to population selection on higher ages and bias to instrumental variable estimators36. Figure 36 and Alzheimer’s disease (AD) as a potential confounder, accounting for the potential spurious negative association. Two MR studies38 suggested ARHI and weight loss were early manifestations of AD, supporting the notion that the association between ARHI and BMI could be confounded by AD liability. However, there is no data-driven approach conducted to provide evidence to support the notion. ARHI and BMI are in complex and dynamic causal pathways, and further work is needed to understand these mechanisms using MR with mediation analysis.Furthermore, we cannot rule out a small chance of selection and survival bias as ARHI is indeed age-related. This pertains to a population that must age. On the other hand, ageing can be associated with lowering of BMI through two mechanisms: (i) people with low BMI or BFP live older and (ii) ageing after a certain age is associated with natural lowering of BMI and fat mass .FTO variant is a common cause of high BMI and low risk of ARHI. In the reverse MR, we found evidence for a causal association between ARHI and lower BMI and BFP. Our results therefore suggest that the mediation of hearing functions is not especially strong for the association between noise exposure and body constitution outcomes.In conclusion, we found no evidence to support a causal effect of body constitution on hearing loss in our forward MR analyses. Instead, the colocalisation analysis suggested that the Supplementary Information 1.Supplementary Information 2.


Clostridioides difficile infection (FCDI) is associated with high rates of mortality and morbidity; however, risk factors for FCDI are poorly understood. The objective of this study was to identify clinical and microbiological factors predictive of FCDI.Fulminant This was a multicenter cohort study involving adult hospitalized patients diagnosed with an incident case of CDI (2015-22). Leftover stool samples were collected for ribotyping and determination of binary toxin presence . Disease severity was defined according to IDSA-SHEA CDI severity classification utilizing laboratory values obtained within 24 hrs of a positive CDI diagnostic test. FCDI was defined as CDI with hypotension (systolic blood pressure ≤ 90 mmHg), shock, ileus, or megacolon. Risk factors predictive of FCDI were assessed through multivariable logistic analysis.Overall, 440 patients aged 62±18.2 years were identified . In univariate analysis, hypoalbuminemia  and infection with a CDT-producing strain  were associated with FCDI, and presence of both variables was associated with the highest odds of FCDI . Using backwards stepwise logistic regression, CDI due to a CDT-producing strain and concomitant hypoalbuminemia was an independent predictor of FCDI  after controlling for Charlson Comorbidity Index score >5  and admission from a healthcare facility .Both clinical and microbiological factors were associated with increased odds of FCDI. Early identification of patients at high-risk for FCDI allows for more timely interventions to help mitigate the risk of disease progression. Future studies incorporating host microbiome features and novel biomarkers into CDI severity predictive models are needed.Kevin W. Garey, MS;PharmD, Paratek Pharmaceuticals: Grant/Research Support Anne J. Gonzales-Luna, PharmD, BCIDP, Cidara Therapeutics: Grant/Research Support|Ferring Pharmaceuticals: Personal Fees|Paratek Pharmaceuticals: Grant/Research Support|Seres Therapeutics: Grant/Research Support


Profound sensorineural hearing loss (SNHL) can be successfully treated with a cochlear implant (CI), and treatment is usually accompanied by increased quality of life (QoL). Therefore, the aim of this study was to investigate generic and health-related QoL, as well as the level of audiological outcomes, of CI users, in addition to whether Qol can be restored to the extent of those with normal hearing. Furthermore, different implantation timepoints were compared (early vs. late), and a possible correlation between health and generic QoL questionnaires was investigated. The outcomes from 93 pediatric CI users from Romania were analyzed in the study. Two QoL questionnaires , as well as the HSM sentence test and Soundfield measurements, were assessed. The outcomes revealed that the CI users were able to achieve the same QoL as their age- and-gender matched peers with normal hearing, and hearing was restored with good speech comprehension. No significant difference between early- and late-implanted children was detected, although a tendency of a better Word Recognition Score (+10%) in the early-implanted group was discovered. A moderate and significant correlation between the generic and health-related Qol questionnaire was observed. Audiological examinations are still the standard practice by which to measure the benefit of any hearing intervention; nonetheless, generic and health-related QoL should be assessed in order to provide a full picture of a successful and patient-satisfactory cochlear implant procedure. Hearing loss (HL) is the most common sensory impairment, and, as of today, the only one which can be replaced with an implant . AccordiDepending on the type and severity of hearing impairment, several treatment options are possible, from conventional hearing aids to medical interventions utilizing passive middle ear prostheses, active middle ear or bone conduction implants, and cochlear implants (CI). Cochlear implantation often requires personalized rehabilitation to not only hear sounds, but to enhance speech perception, speech production, and language development ,4. With The progress and benefit of a cochlear implant can be measured via objective measures such as pure tone audiometry, which is measured at certain frequencies and sound levels . Also, sQuality of life questionnaires validate individuals’ subjective perception of different dimensions of life, such as mobility, mental health, sight, hearing, etc. One can distinguish between generic and disease-specific QoL questionnaires and their respective impacts on quality of life . The evaA systematic review of the current literature regarding the QoL of CI users was conducted to obtain an overview of the generic QoL questionnaires utilized in the literature, and to see which questionnaires were employed for pediatric CI users.The generic QoL of the Romanian CI user study cohort was assessed, and they were compared with age- and gender-matched peers with normal hearing.Data from the study cohort were collected to assess the level of speech comprehension and hearing ability of pediatric CI users in Romania using the translated and recorded HSM sentence test and pure tone audiometry.Possible influencing factors, such as early-implanted (≤3 years) CI users versus late-implanted (>3 years) children, were investigated.Finally, possible correlations between the generic and health-related quality of life questionnaires were assessed.Therefore, the aim of this study was to conduct a systematic literature review on the generic QoL of CI users, as well as to provide additional audiological data and QoL scores from a pediatric study cohort of CI users from Romania. Therefore, the following points were the focus of this paper:The methods can be divided into two main areas, with one area describing the methods section for the systematic review. The second main item contains the data collection methods for the Romanian study group of pediatric CI users.The systematic review was conducted according to the PRISMA guidelines . The stuThe Oxford level of evidence guidelines were considered in order to evaluate the quality of the included papers . The fivFor this study, 93 participants, with a mean age of 10.9 ± 5.0 years, were included. The study cohort consisted of 35 female and 58 male children and adolescents from Romania who were suffering from sensorineural hearing loss accompanied with a hearing threshold higher than 70 dB. Every participant was fitted unilaterally with a cochlear implant  and an audio processor  from MED-EL . Adolescents and adults up to 20 years of age were included if the implantation had been carried out in childhood. For this reason, the age range extended from 2 to 20 years.Data were collected during clinical routine measurements at the clinic of Timisoara , as well as from a CI self-help group camp in Eforie. The relevant patient outcomes gathered by responsive clinical personnel were provided in a pseudonymized form. The parents or legal representatives provided their consent for the collection of their children’s data.The QoL questionnaires were completed by the participants themselves, using either the online form or the printed version. If the study participants were too young, the questionnaires were completed with the help of their parents or legal representatives.To measure the generic QoL, the AQoL-6D total utility score, along with the individual utility scores of the six dimensions, were assessed. These dimensions were as follows: Independent Living, Mental Health, Coping, Relationships, Pain, and Senses . The AQoThe SSQ12 consists of twelve questions separated into three main dimensions and an overall outcome . Each quSound field measurements are frequently performed in routine audiological examinations to determine the hearing thresholds over several frequencies . CalibraThe Hochmaier–Schulz–Moser (HSM) sentence test was the assessment of choice for this study where recited sentences must be repeated by the attendant . It was The primary AQoL-6D analysis was conducted with the evaluation tool provided by the AQoL Homepage  for the The pure tone averages (PTAs) for hearing thresholds with frequencies of 0.5, 1, 2, and 4 kHz were calculated ,21 for fAll data sets were tested for normal distribution by applying the Shapiro–Wilk test with a confidence level of 95%, resulting in no normal distribution. Nonparametric statistical tests like the Mann–Whitney U-test, the Spearman rank correlation test, and the Dunn’s multiple comparison were also used. A significance level with an alpha value of 0.05 was set for all tests.There are two primary sections in the results section. The first describes the systematic review’s outcomes. The results of the Romanian study group of pediatric CI users are included in the second main part. Furthermore, unless otherwise specified, all results and numerical values are presented as the mean and standard deviation (SD).The presented outcomes of this systematic review include the results of the screening process; the investigation of the quality of life questionnaires for adults and children that are represented in the current literature; and, finally, the evaluation of the extracted studies.n = 157) are outlined in The process and outcomes of the systematic literature search can be seen in the flow chart in An additional search, specifically for the AQoL with the search terms (cochlear implant *) AND (aqol), was conducted on 28.7.2022/9:00. Two publications were identified, but only one  met the The extracted data of the generic QoL scores for adult CI users are presented in In general, it can be seen in To evaluate the quality of the included papers, the Oxford level of evidence was used, which ranges from level I to V, with the best rating corresponding to level I. Most papers indicated only level IV or IV–V, because they were case series or case–control studies, which can be seen in p = > 0.999) nor those from Maxwell et al. [p = 0.559) were able to demonstrate a significant difference (p < 0.05) between the total utility score of CI users and children with normal hearing.The total utility score of the AQoL-6D of this study was 0.79 (0.17) for the children and adolescents who had been treated with a cochlear implant, which can be seen in the blue bar in the left bar chart of l et al.   Figure. The heaThe HSM sentence test was conducted at a self-help camp in Romania, and 41 children and adolescents with cochlear implants successfully completed the test which can be seen in The study cohort was split into early (≤3 years) and late (>3 years) implantation groups. The assessed quality of life (AQoL-6D and SSQ12) and audiological (PTA and HSM sentence test) parameters were compared with each other. No significant differences between the early and late implantation groups were found for any of the four comparative parameters .A moderate and significant correlation between the generic (AQoL-6D) and the health-specific (SSQ12) questionnaires was found, with a Spearman coefficient of 0.4370 . Additiop < 0.05). Although the absolute numerical norm values achieved by Hawthorne et al. [From the generic QoL results, it can be concluded that CI users can achieve the same level of quality of life as their healthy, normal-hearing peers. After comparing the normative values from two different publication populations ,44, no se et al.  .However, the overall positive outcomes are probably the result of an increase in self-confidence bolstered by the ability to communicate . As no sA total of 79 participants achieved a mean overall score of 6.05(1.63) for the health/hearing-related QoL, assessed by the Speech Spatial Qualities of Hearing Scale (SSQ12), which appears to be rather low in comparison to other publications ,50,51,52A moderate and significant correlation between the outcomes of the generic and health/hearing-specific QoL was detected . UnsurprEven though the literature on AQoL assessments in the population with hearing loss is sparse, the questionnaire was used as the assessment of choice for utilization in the clinical process. The reasons were as follows: first, access was free of charge; second, the statistical software SPSS and STATA provided easy and, therefore, bias-free evaluation tools; and third, the availability of validated population norms enabled statistical comparisons. The provided data calculation syntax for STATA and SPSS ensures correct data analysis and, therefore, better comparability. Thus, no random deviations or obvious calculation errors occurred, as was found in the published outcomes of several HUI 3 questionnaire studies. The HUI was often evaluated incorrectly, which unfortunately made the results unusable for our systematic review and comparisons, especially since a license fee was required to for this questionnaire.During the review process of the different QoL studies, it became evident that a consensus on the application of QoL instruments would be advisable.Unfortunately, not enough comparable data were available to perform a meta-analysis  1,15,16,42,54,55In conclusion, the systematic literature review clearly showed improved QoL after implantation, comparable to that of healthy, normal-hearing children, but also showed some clear limitations: first, a clear classification of health-related and generic QoL questionnaires is necessary. Second, uniform and correct assessments are needed in order for comparisons to be made. Third, more day-to-day evidence is required, which points towards the necessity to implement QoL questionnaires into clinical routines. More data on the QoL of the pediatric population are especially required.The 41 tested CI users achieved impressive speech comprehension, with an overall score of 71.6% (23.8%) on the HSM sentence test . The ratThe tested CI users showed an improvement of around 40 dB with the use of a cochlear implant, as the mean aided hearing threshold was between 24.4 dB (2.62 dB) and 27.3 dB (1.52 dB).The literature repeatedly points out the importance of early implantation to ensure the optimal developmental effects ,58,59. OIn conclusion, both age groups achieved generally good results for all measurements which were undertaken. These great results are probably related to the support of the families and their social environments. This assumption is based on the fact that all examinations, as well as rehabilitation and training , were voluntary, and the parents went above and beyond to provide their children with all the opportunities necessary to further improve their hearing. Obviously, they were doing everything right.Studies investigating the effect of a CI on different aspects of QOL and audiologic performance are important in order to provide realistic expectations to our patients, especially when children are involved. This study has proven that cochlear implant users can achieve the same generic quality of life as their normal-hearing peers. The audiological examinations showed a clear benefit after cochlear implantation. Since speech comprehension is challenging, the good outcomes achieved on the HSM sentence test by the CI users in Romania were impressive. Even though no significant difference was found between late and early implantation, for the QoL and audiological parameters examined, the early implantation group exhibited roughly 10% greater speech understanding compared to the later implantation cohort. No significant correlation between the generic and health-related quality of life questionnaires was found. Thus, both should be administered to obtain a better understanding of children and adolescents treated with cochlear implants and their hearing/health, as well as their general satisfaction in life.


Fusobacterium nucleatum (Fn) has been frequently detected in colorectal cancer. A high load of Fn has been associated with subtypes of colorectal cancers, located in the proximal colon, exhibiting microsatellite instability-high (MSI-H), MLH1 promoter hypermethylation, the CpG island hypermethylation phenotype-high, or BRAF mutation in some studies. Although these features characterize the sessile serrated pathway (SSP) of colon cancers, other studies have shown that Fn infection is associated with KRAS mutations mainly characteristic of non-serrated neoplasia. It is also not clear at what point the association of Fn infection with these genomic alterations is established during colorectal carcinogenesis. Here we show that MSI-H, MLH1 hypermethylation, BRAF mutation or KRAS mutations were independently associated with Fn infection in colorectal cancer. On the other hand, increasing Fn copy number in tissues was associated with increased probability to exhibit MSI-H, MLH1 hypermethylation or BRAF mutations but not KRAS mutations in colorectal cancer. We also show that Fn load was significantly less than that of colorectal cancer and no association was detected between BRAF/KRAS mutations or MLH1 hypermethylation and Fn infection in adenomas. Our combined data suggest that increasing loads of Fn during and/or after adenomacarcinoma transition might promote SSP but not KRAS-driven colorectal carcinogenesis. Alternatively, Fn preferentially colonizes colorectal cancers with SSP and KRAS mutations but can expand more in colorectal cancers with SSP.Fn is enriched in colorectal cancers exhibiting the SSP phenotype, and in colorectal cancers carrying KRAS mutations. Fn infection should be considered as a candidate risk factor specific to colorectal cancers with the SSP phenotype and with KRAS mutations.The authors demonstrated that  Colorectal cancer is the third most common cancer in incidence and is the second cause of cancer death worldwide. In 2020, it was estimated that 1.9 million new cases would be diagnosed, and 935,000 persons would experience death (Fusobacterium nucleatum (Fn) in colorectal cancers in 2012, evidence that the makeup of the gut microbiome contributes as a risk factor for colorectal cancer and influences the initiation and progression of colorectal cancer has been accumulating , and colibactin-producing Escherichia coli are associated with colorectal cancer in epidemiologic studies, found to be enriched in colorectal cancer tissues, and facilitate colorectal tumors in preclinical models -high, and exhibit high levels of microsatellite instability  1 and 3. While the data reported by Ternes and colleagues agree with previous results where Fn infection was associated with MSI-H colorectal cancer that consists of 74% of CMS1 colorectal cancer in TCGA cohort, the association of Fn infection with CMS3 colorectal cancer has not been reported previously  and elevated microsatellite alterations in selected tetranucleotide repeats  tissues using the QIAamp DNA FFPE Tissue Kit (QIAGEN). The MSI/EMAST assay was carried out as described previously . BrieflyFn DNA in colorectal cancer has been described before  and genomic DNA from the human colon cancer cell line, DLD1. We also used the TaqMan-based standard curve method for detection and quantification of Fn DNA in adenoma/polyp tissues. The PCR primer and FAM probe sequences were as follows: Fn forward primer, 5′-GCTTGAAATGGAAGCTACAAGAG; Fn reverse primer, 5′-GGATCA GAACCAACTCCTACAA; Fn-FAM probe: 5′-AGTAGACCCTCGTGTATG. PCR conditions were 95°C for 10 minutes, followed by 45 cycles of 95°C for 15 seconds and 54°C for 1 minute. The reaction mixture consisted of TaqMan Universal Master Mix (Applied Biosystems), 300 nmol/L forward, 900 nmol/L reverse primers, 250 nmol/L Fn-FAM probe and approximately 50 ng of template DNA. For quantifying tumor DNA in adenoma samples, we used the SYBER green–based standard curve method as used for colorectal cancer samples.The method for detection and quantification of d before . Brieflyne of Fn  and the d before . SpecifiFn DNA was examined as follows: We generated a standard curve using the same amount of template Fn genomic DNA  isolated from the Fn strain VPI4355 (ATCC) for each assay  in TaqMan PCR reaction compared with colorectal cancer DNA (5 ng) in SYBER green assay. Fn DNA content in each sample was determined by the following formula: absolute Fn DNA in picogram/absolute tumor genomic DNA in nanograms. On the basis of the fact that the total Fn genome contains 2,170 kilobase pairs  in a 96-well thermal cycler (Applied Biosystems). The primers used were: KRAS forward primer: 5′-GGTACTGGTGGAGTATTTGATAGTG-3′, KRAS reverse primer: 5′-ACCTCTATTGTTGGATCATATTCGT-3′, BRAF forward primer: 5′-TGCTTGCTCTGATAGGAAAATG-3′, and BRAF-reverse primer: 5′-AGTAACTCAGCAGCATCTCAGG-3′.Mutational hot spots on The PCR products were purified by ExoSap-IT (Applied Biosystems) and sent to an outsource vender (Eurofins) for cycling sequencing.hMLH1 locus , the tissues were treated overnight at 4°C with anti-human MLH1 mouse antibody , followed by visualization of the MLH1 signal with ImmPRESS Universal PLUS Polymer Kit The DNA isolated from tumor tissues or cell lines (∼500 ng) was modified with sodium bisulfite using EZ DNA Methylation-Gold Kits . Methylation-specific PCR (MSP) was used for detecting promoter methylation of the H1 locus . The seqH1 locus , except Fn infection and each genomic variable, and other variables, including sex, age, tumor location and stage, in colorectal cancer cohort was tested using a logistic regression model with Firth bias correction. The association between Fn infection and various variables in adenoma/polyp cohort was tested using Fisher exact test. The Mann–Whitney test and Kruskal–Wallis test were used to determine the difference in the amounts of Fn DNA present in different groups of colorectal cancers. The Kaplan–Meier test was used to determine whether Fn infection affected patients’ 5-year overall survival (OS) rate. When P values were less than 0.05, the difference or association was determined significant.All statistical analyses were carried out using the software XLSTAT (Addinsoft). The association between The data generated in this study are available upon request from the corresponding author.Fn infection and molecular subtypes of colorectal cancer including MSI-H, L/E, and MSS  of colorectal cancer. A total of 101 of 304 cases (33.2%) showed mutations at KRAS G12/G13 (Twenty-five of 304 cases (8.2%) exhibited  G12/G13 . Further G12/G13 .Fn was detected in 109 cases  per one nanogram of tumor DNA and the maximum amounts were 291 pg  per one nanogram of tumor DNA, respectively  by univariate logistic regression analysis  or L/E-CRC  of colorectal cancer with BRAF V660E mutation (BRAFV600E-CRC) were infected with Fn whereas significantly fewer of the colorectal cancers with wild-type BRAF  were infected with Fn  lost MLH1 expression, whereas the eight colorectal cancer cases with unmethylated MLH1 (non-MLH1 hypermethylated-CRC) expressed MLH1 (MLH1 hypermethylation determined by our MSP assay accurately reflects silencing of the MLH1 expression. Sixty percent of cases with MLH1 hypermethylation (15/25) were infected with Fn while a significantly lower percentage  of colorectal cancer with unmethylated MLH1 were infected with Fn  of colorectal cancer with KRAS mutations (KRAS mutated-CRC) were infected with Fn. Compared with colorectal cancer without KRAS mutations (non-KRAS mutated-CRC), a significantly higher percentage of cases were infected with Fn  was infected with sed MLH1 , indicatnfection .Fn infection using multivariate logistic regression modeling ; we constructed four independent models where these three variables did not overlap. In Model 1, MSI-H was associated with Fn infection compared with MSS  and with L/E . KRAS mutations  and regional/advanced stage  were also associated with Fn infection, when compared with non-KRAS mutation and local stage, respectively , MLH1 hypermethylation  or BRAF mutation  associated with modeling . Variablectively . Importanfection . FinallyFn loads among subgroups of colorectal cancers, we compared the copy number of Fn among colorectal cancers with L/E, MSS, MSI-H, non-MSI-H, MLH1 hypermethylation, non-MLH1 hypermethylation, BRAFV600E, non-BRAFV600E, KRAS mutation, and non-KRAS mutations using the Kruskal–Wallis test  and MSS-CRC (P < 0.0001), and L/E-CRC had higher Fn loads than MSS-CRC (P < 0.0001). Here, MSI-H-CRC, MLH1 hypermutated-CRC, BRAFV600E-CRC and KRAS mutated-CRC had higher Fn loads compared with non-MSI-H-CRC (P < 0.0001), non-MLH1 hypermutated-CRC (P = 0.001), non-BRAFV600E-CRC (P = 0.022) and non-KRAS mutated-CRC (P = 0.037), respectively (Fn loads between MLH1 hypermethylated-CRC and KRAS mutated-CRC (P = 0.042) and between MSI-H-CRC and KRAS mutated-CRC (P = 0.029) was significant.To see any difference in lis test . The numeviously , MSI-H-Cectively . Also, tFn loads only in Fn-infected colorectal cancers from each group. As shown in Fn among MSI-H, L/E, and MSS-CRC. There was also no difference in the copy number of Fn between (i) MSI-H-CRC and non-MSI-H-CRC (P = 0.088); (ii) BRAFV600E-CRC and non-BRAFV600E-CRC (P = 0.655); and (iii) KRAS mutated-CRC and non-KRAS mutated-CRC (P = 0.692). In contrast, Fn-infected MLH1 hypermethylated-CRC contained more Fn DNA compared with Fn-infected non-MLH1 hypermutated-CRC  and copy number of Fn (explanatory variable) using logistic regression analysis. As shown in Fn is associated with a higher probability of colorectal cancer with MLH1 hypermethylation , MSI-H , and BRAFV600E , but not with KRAS mutations  in univariate logistic regression analysis. After adjusting for tumor site and stage, and patients’ age, sex, and race, a higher copy number of Fn is independently associated with MLH1 hypermethylation , MSI-H , slightly with BRAFV600E  but not with KRAS mutations  or from MSS  and was also accompanied by an increased probability of being L/E from MSS , with MLH1 hypermethylation (P = 0.74), with BRAF mutations (P = 0.41) and with KRAS mutation  by the Mann–Whitney test. Four of 10 SSA (40%) and 10 of 22 TA/TVA (45%) were positive for Fn infection. There was no association between Fn infection and adenoma types and histologic dysplasia , number of cases examined, and difference in comparison (Fn-high vs. Fn-low/negative or Fn-positive versus Fn-negative) may have influenced the outcome of each study.In previous studies, there have been conflicting results regarding the effect of es refs.  and on ter refs. . To compFn probe may deserve further investigation for reproducibility. In contrast, the other 11 studies in Group B used various regimens to detect and quantify Fn loads  of patients with colorectal cancer  were not examined for BRAF and KRAS mutations  of the cohort . MLH1 promoter hypermethylation was detected in one BRAF-mutated adenoma in our cohort , leading to silencing of the expression of the TSGs. It has been shown that BRAF or KRAS mutations in initiated cells co-operate with silenced TSGs by promoter hypermethylation to progress toward carcinoma formation  limited the statistical power of this work. Further study analyzing a cohort with a larger sample size is necessary. Another limitation of this study is that FFPE tissues were used to determine the effect of Fn infection on colorectal cancer patients’ OS rate. By comparing ours with other studies, we conclude that the ability to detect and quantify Fn in FFPE samples by PCR is limited. Therefore, our results showing a lack of association between Fn infection and patients’ OS rate needs to be reevaluated through future study.Although a small preliminary study, this is the first report showing that there is no association between Fn infection is associated with a shorter RFS rate; some studies showed that Fn infection in tumor tissues is associated with shorter RFS of colorectal cancer patients’ postchemotherapy  reotherapy ; and/or otherapy  by Fn inSupplementary Table S1Table S1 lists data for 306 cases of colorectal cancersClick here for additional data file.Supplementary Table S2Table S2 lists data for 32 cases of adenomasClick here for additional data file.Supplementary Table S3Table S3 shows relationship between Fn copy number and genetic pathway in colorectal cancersClick here for additional data file.Supplementary Table S4Table S4 summarizes 22 studies and relationship of Fn infection and colorectal cancerClick here for additional data file.Supplementary Fig S1Fig S1 compares TaqMan and SYBER Green assays for detecting Fn in tissuesClick here for additional data file.Supplementary Fig S2Fig S2 shows the distribution of Fn infection in colorectal cancersClick here for additional data file.Supplementary Fig S3Fig S3 shows Kaplan-Meier curves for overall survival in colorectal cancer patientsClick here for additional data file.


To achieve effective integration of virtual care into family-centered audiology practices, participatory research methods, including parents as vital participants in the delivery of pediatric audiology care, should be considered. A better understanding of the barriers and facilitators influencing the adoption of virtual care for families is warranted.This study aimed to develop a conceptual framework of the factors perceived to influence the adoption of remote pediatric hearing aid support among the parents of children with hearing loss.A total of 12 parents of children who wear hearing aids, between the ages of 0-17 years, were recruited to participate in group or individual interviews as part of the 6-step participatory-based concept mapping (CM) process. Data collection was specific to parents in a Canadian context. Analyses included multidimensional scaling and hierarchical cluster analysis.The CM process resulted in 6 main themes, displayed in a cluster map according to their order of importance. These themes include access to timely, consistent care; technology considerations; convenience; child engagement; cost; and partnership considerations. Key underlying statements and subthemes are highlighted per theme.Findings from this study demonstrate the use of CM in participatory research with parents and as part of a family-centered care model. Future research should aim to investigate the factors that influence the uptake of remote hearing aid support in different contexts, for example, in low- to middle-income countries versus those in high-income countries. Clinical interactions occurring remotely have been slowly increasing in audiology practice over the past few decades, with a rapid increase observed since the onset of the COVID-19 pandemic to improve access to audiological services . Remote For young children, early intervention for hearing loss significantly improves speech and language development trajectories, helping to ensure that children are ready for school entry . LimitedCentral to the development of listening and spoken language is the use of hearing aid technology to support child development. Within virtual environments, barriers still exist when it comes to the effective integration of hearing technology, calling for a better understanding of the implications for parents and families and the range of support required to facilitate virtual care . From thEngaging families and community partners in the research process have been identified as a feasible and effective tool for obtaining a broad range of input to identify priorities in intervention approaches . ConceptTo date, there have been few studies conducted with parents that examine their perspective of virtual audiology services as well as a knowledge gap specific to remote hearing aid support. This study aims to fill this knowledge gap to help guide family-centered virtual hearing aid care, an integral part of early hearing detection and intervention programs, by examining the factors that influence Canadian parents’ use of remote hearing aid support. This work is timely as virtual hearing aid services are continuing to expand globally, and it is incumbent that we understand how to achieve effective delivery in family-centered care models.In this study, CM methodology was used to develop a conceptual framework of the factors that influence adoption of virtual audiology practices by parents of children with hearing loss and the provision of follow-up hearing aid support. The participant recruitment process was guided by selecting appropriate study participants based on the research goals ,25. ConvThis study was part of a sister project also exploring the factors that influence the uptake of remote hearing aid follow-up support by clinicians . Both stParticipants completed web-based tasks, including sorting and rating, using the Concept Systems Global Max software . The ConAll participants were asked to complete a short demographic survey that was delivered in person for face-to-face session attendees and over the phone for telephone interviews. Focus prompt development was consistent with that of the sister project, using expert opinion in the development .Each face-to-face session began with a brief orientation presentation on the topic of remote support in audiology, sample applications, the use case of interest (follow-up hearing aid support), as well as a summarization of the study methods. Before telephone sessions, the orientation step was delivered using a short, animated 4-minute video created in VideoScribe. The video was accessed by the participants through an emailed weblink. During all sessions, participants were asked to develop as many statements as possible to complete the CM focus prompt: “One thing that may influence my use of teleaudiology for remote follow-up hearing aid support is…” A synthesis step was used by the investigators to combine the final statements into 1 large data set and eliminate redundancies. The decisions made during the synthesis step were manually recorded by the investigators, resulting in a list of key statement synthesis decisions. The face-to-face sessions and phone interviews were also audio-recorded.The researchers compiled all the statement sets into 1 large set that was then edited and synthesized by the research team to eliminate redundancies and refine statements to ensure clarity and comprehension. Statements that were unrelated to the prompt were removed; statements were also merged or split to ensure that each statement had 1 clear meaning . The staParticipants were contacted twice through email to complete web-based follow-up tasks. Overall, 8 participants completed the web-based sorting task and 9 completed the importance ranking task. A web link to the Global Max software was sent in the first follow-up email. Instructions were given within the software to facilitate the sorting of the final set of statements into piles and the ranking of the statements based on perceived importance. The importance-ranking instructions provided to the participants were as follows: “Please rate each statement on a scale of 1 to 5 where; 1=relatively unimportant; 2=somewhat important; 3=moderately important; 4=very important; 5=extremely important. To complete each rating, type a number next to each statement.”Following analyses, the research team conducted a final review of the statements, clusters (which are resultant categories of similar ideas generated in the brainstorming phase), and corresponding names of each cluster, with the end goal of achieving group consensus on acceptable labels for each cluster and number of clusters. This final step was mainly driven by the research team due to the outbreak of the global COVID-19 pandemic, which limited contact with the participants.The representation of results was enabled using the Global Max software and used 2 types of analyses: multidimensional scaling and hierarchical cluster analysis. Details regarding the production of the final concept map are described in the representation section. Multidimensional scaling was used to locate each parent statement in a 2D space to display on a point map, following a 2-step process from Kane and Trochim : (1) A sHierarchical cluster analyses, using input from multidimensional scaling, mathematically grouped each statement into adjustable cluster configurations, based on how parents rated and sorted the data. Each cluster represents a unique theme on the resulting map . The selFinal cluster labels reflect the general theme for each cluster of statements. The layers per cluster indicate the level of importance rating provided by the parents for their statements per cluster. A greater number of layers represents greater importance for the group of statements included within the cluster, as judged by individual parents. For example, access to timely, consistent care was rated by the parents as more important when compared to partnership considerations.A list of the main themes, subthemes, and example statements were generated using single cluster go-zone plots, allowing for visualization of the relationship between participant ratings with respect to the concept map . The exaThis study demonstrates how CM was used to develop a conceptual framework in collaboration with parents of children wearing hearing aids to explore factors that may influence the adoption of remote follow-up hearing aid support services delivered through teleaudiology. A total of 12 parents of children who have hearing loss and reside in Ontario, Canada, were recruited to participate in this study. Overall, 6 themes were developed to form the final conceptual framework of the perceived factors that influence the uptake of remote hearing aid support by parents of children with hearing loss. These 6 themes, in order of overall level of importance, were (1) access to timely, consistent care; (2) technology considerations; (3) convenience; (4) child engagement; (5) cost; and (6) partnership considerations.Access to timely, consistent audiological care was rated by the parents as the most important factor in delivering remote hearing aid support to their children. Subthemes in this cluster highlighted that parents value the ability to access hearing aid support remotely in times of hearing aid emergencies or during extracurricular activities where listening demands are different. Virtual audiological consultations with parents and families of children who have hearing loss have shown benefits in terms of flexibility and timely access to support ,11. FurtTechnology considerations were ranked as the second most important factor in the uptake of pediatric remote hearing support. Technological barriers (such as consistent internet connection and availability of training and support) have been cited in the literature as one of the main reasons why remote hearing aid support is not readily adopted worldwide . The topPatient- and family-centered factors pertaining to service accessibility were also deemed important by parents. These include convenience , cost (related to traveling and equipment needed for remote support), and child engagement (addressing the ’child’s need for frequent follow-up appointments following a new hearing aid fitting). Teleaudiology has been reported as a cost-effective manner of service provision . In addiThe final cluster pertained to participation and the collaboration between the professional, the parents, and their family members. Audiologists play a vital role in partnering with parents and families to provide the support needed for the effective day-to-day management of their child’s hearing aids . BuildinThe use step in a CM framework is an ongoing process related to the study objectives and involves working with the stakeholder team to determine the best ways to use the maps and reports produced as part of the CM procedures . A totalStudy limitations include the use of nonrandom sampling, which results in a sampling bias; a small sample size, which limits generalizability; the labor-intensive process of creating a CM framework; and the personal attributes of the participants, which likely shaped the resulting themes in the framework of this study . FurtherResults of this study demonstrate the benefit of CM methodology in facilitating parent engagement in research. Through the inclusion of parent participants, greater value is added when considering family-centeredness in the context of virtual audiology care. Future research could use a similar approach to investigate factors that influence parental uptake of remote hearing aid support in different contexts and across different languages, for example, in low- to middle-income countries versus high-income countries, as well as in populations for whom English is not the predominant language.


The objective of the online survey was to determine worker attitudes towards, perceptions on hearing loss, and management of workplace noise; and to identify barriers within current strategies that prevent effective management of hearing health in Australian mines.This cross-sectional study utilized a modified survey design, initially designed for use by Safe Work Australia for a broader study published in 2010.The survey questionnaire was made available online to volunteer participants, recruited with the assistance of State and National Health and Safety, and mining organizations. Volunteer participants were required to be proficient in English, be employed by an Australian underground or open cut mine, including coal processing plants; or work as a contractor on one of the specified mine sites. All mining employees, regardless of occupation, job title, and occupational hearing loss classification or status, were invited to complete the questionnaire.Almost 60% of respondents indicated that they had high noise exposure for than 10 yr or more, and have some trouble hearing, mostly associated with infrequent tinnitus. Nearly 71% of these workers believe that the noise control strategies in their workplaces are effective, but this mostly refers to the use of hearing protection devices.The results indicate that general knowledge on the cause and effect of noise exposure in the workplace is well understood. However, due to the long latency associated with the development of noise-induced hearing loss (NIHL), there is an issue urgency in terms of risk management. It is surprising that most of the respondents recommended more inspections and administrative controls, especially since most respondents were health, safety, and environment (HSE) professionals. HSE professionals should be advocating for higher order, more permanent solutions, and not purely administrative controls and personal protective equipment. These findings raise the question of whether there is a multifaceted working-culture issue that needs to be addressed, in combination with higher order control implementation. Australian mining industry workers and health, safety, and environment (HSE) professionals surveyed in this study believe noise exposures are well controlled, but hearing protection devices were the primary control strategy used. HSE professionals identified audits, inspections and legislation as the way to solve occupational noise exposure and hearing loss. Given that hearing loss persists in this industry, this study identified the need to increase utilization of engineering control strategies to prevent noise-induced hearing loss.Global research provides evidence that advocates for the multifaceted benefits of preventing disease, particularly the development of occupational hearing loss (OHL). Preventing hearing loss from progressing reduces the economic burden on industry, society, and the government, and increases worker productivity and wellbeing . Despitesufficient hearing loss to interfere with the safe performance of their work, all reasonably practicable steps should be taken to modify the work environment”  legislation across all Australian States require workplaces to manage and control exposure to excessive noise (>85 dB(A)), following a risk-based approach. Each workplace develops site-specific strategies for meeting these legal obligations, which should be consistent with the anticipated risk of harm to workers. Legislative requirements may involve noise exposure assessment and management and audiometric testing of workers as part of the hearing conservation strategies  , usuallRequirements for noise control and audiometric testing has been in place since the late 1970s . CurrentNevertheless, there is limited research available on site-specific management strategies and how workers with current OHL are identified and accommodated in the workplace. Particularly, how their risk of further hearing loss is mitigated. This research aimed to investigate the strategies implemented for managing and preventing OHL in Australian mining, to enable comparison with the The objective of the survey was to determine worker attitudes towards, and perceptions on hearing loss and management of workplace noise (regardless of their hearing status); and to identify barriers within current strategies that prevent efficient and effective management of hearing health in Australian mines.An online survey of workers in the Australian mining industry was undertaken to determine the barriers and beliefs held towards noise control and hearing loss. The objective was to determine the type of noise controls used in mining, and whether HPDs were provided and used at work, including reasons for not wearing HPDs, if there were indications that it is not being used. The survey will also assist the researchers to understand attitudes towards hearing loss and workplace noise.Workers aged 18 yr and older were asked to complete a 15-min online survey. The survey was available to respondents over 12 mo between 30 January 2022 and 1 February 2023. Ethics approval for this project was obtained from the University of Newcastle Human Ethics Research Committee (H-2022-0047) and Edith Cowan Human Research Ethics Committee (2023-04237-Liebenberg).This cross-sectional study utilized a validated survey, initially designed for use by Safe Work Australia for a broader study published in 2010 . ApprovaThe recruitment of workers was facilitated by Coal Services (NSW), Resources Safety & Health (QLD), Chamber of Minerals and Energy, Australian Institute of Occupational Hygienists, Australian Institute of Health and Safety, and the national Construction, Forestry, Mining and Energy Union. These organizations were asked to distribute the invitations to participate, including the survey link, in their periodical newsletters to the mining industry. Additionally, online platforms such as LinkedIn, Facebook, and Twitter were utilized to post the invitation for workers to participate in an attempt to recruit more workers from a range of the Australian mining industries. Before workers completed the anonymous survey, they were asked to read the Participant Information Statement, acceptance of which implied consent. Participants were asked to provide their contact details, if they were interested in receiving feedback, however these details were not linked to their survey responses in any way.n = 55,000,  were lower than the number required for 95% confidence level in the validity of the results, however, this does meet the minimum number of respondents for a 90% confidence level in the results (n = 68). Due to the low confidence level of the results, these results cannot be generalized across the Australian mining population. The data does, however, provide a valuable insight into the perceptions and beliefs of these workers regarding noise control in the mining sector.The survey was accessed a total of 946 times, 72 workers responded to the questionnaire, at least in part, and 48 (66.7%) completed the entire survey. As not all workers completed all the questions, the response rate for each question is indicated for each of the result categories. The number of respondents (Workers employed at underground (30%) and open cut mines (36%), or a combination of these (25%) were the primary respondents to the survey . It is ln = 6), and their current workplace did not typically produce loud noise (n = 2).Eight of the respondents indicated that they were not exposed to loud noise in the 2 wk prior to completing the survey due to not being exposed to loud noise in their current role (n = 16) of the perceived noise exposure profile, followed by loudspeakers, radios, or music (6%).The respondents indicated that most of the noise (54%) was generated using various mining machinery. Continuous running machinery and iron and ore crushers (28%), tools such as power tools, air tools, compressors (38%), and air conditioning and exhaust fans (18%) are considered the main contributors to overall noise exposure profiles. The second largest noise contributor was believed to be vehicles and transport (33%), which was stratified into categories as follows heavy mobile equipment (41%), light vehicles (29%), reversing alarms (28%), and aircraft (2%). Specific activities such as blasting and welding or steel cutting contributed to 7% (Forty-two percent of respondents believed they have good hearing (42%), whereas 48% indicated they have some trouble hearing, and 7% reported a lot of trouble hearing. Three percent of respondents were unsure how to describe their hearing when not wearing HPDs. Most respondents (31%) indicated they were worried about their hearing while working in loud noise, whereas 26% indicated that working in loud noise makes them feel irritated, 16% indicated that they were less enthusiastic about work or tired (11%), due to the noise levels, while 13% of respondents indicated that working in loud noise did not bother them.A quarter of respondents indicated that they had not considered the prospect of losing their hearing, while 67% had thought about hearing loss. When asked if they have experienced tinnitus, or a ringing in their ears, 23% of the respondents indicated that they experience tinnitus constantly, while 48% experience tinnitus sometimes, and 23% had never experienced it. Fifty-nine percent of respondents indicated they believe they are more careful than most of their work mates in protecting their hearing, and 31% indicated that they were similar to their colleagues regarding hearing loss and management. The remaining 10% indicated that they do not believe they are as careful as their work mates.When assessing the worker beliefs regarding hearing loss (HL), all respondents believe that loud noise can cause HL and tinnitus . Most woThe results of the survey indicate that workers believe noise sources are well controlled in their workplace; however, ~90% of all controls reported were limited to the provision of HPDs. Additionally, most of the participants in the study indicated that management of noise was not viewed as a significant health concern in their workplace and was largely ignored, similar to the findings of Safe Work Australia more than a decade ago .Total elimination of noise generation in mining is unlikely due to the nature of the industry which involves crushing of rock and ore, thus preventing the total elimination of noise as a primary control. The controls used throughout the Australian mining industry, as identified through the survey are summarized in n = 60) indicated that their workplaces provide HPDs, and 85% of these workers always wear their HPD as required. The primary reasons for not wearing HPD in loud noise is that having a conversation is hard (46%), and that they do not feel that they are exposed to the loud noise for long enough to warrant wearing HPD (30%). Other reasons include discomfort whilst wearing HPDs (11%), not being able to hear warning signals (5%), the belief that HPD causes ear infections (5%), and that they are unsure how to obtain a good fit or seal when using HPDs (33%).Respondents (Respondents indicated the cost of equipment maintenance (38%), and insurance premiums (36%) were considered particularly important when considering noise control in the workplace, with engineering control costs (55%) and equipment cost (48%) considered somewhat important. Surprisingly, the cost of HPDs were not considered important (33%) with regard to noise control .Half of the respondents (50%) indicated that noise is somewhat controlled in their workplace but also felt that some health and safety rules are not practical and that accidents are likely to occur regardless of prevention strategies implemented. With relation to noise control, the respondents believe that the added benefits of effective noise control include improved worker morale (39%), resulted in fewer compensation claims (34%), and increased productivity (17%). Very few (5%) believe that effective noise control reduces accidents in the workplace.The priorities of noise control and beliefs highlighted by the respondents include that hearing loss in mining is an important issue (11%) for which more education and awareness training is required (11%) and they believe that it is an issue not taken seriously (9%). The respondents also indicated that they believe individuals need to take responsibility (9%) to protect their own hearing.Furthermore, these workers believe that noise cannot be eliminated from industry and that management needs to do more to protect their workers. There is a belief that some workplaces are negligent, and that workers have suffered hearing loss as a direct result of workplace noise. Workers also believe that changes are needed, such as more and tighter regulations, introducing legislating HPD fit testing. There is also a need to focus on higher order controls regarding noise control.The objective of this study was to investigate the perceptions and beliefs of Australian mine workers regarding noise exposure and hearing loss management. A telephone study undertaken by Safe Work Australia (SWA) in 2010 aimed to establish the barriers and enablers to effective noise control and prevention of OHL. The The current research found that general knowledge on the cause and effect of noise exposure in the workplace is well understood, but due to the long latency of noise-induced hearing loss (NIHL), lacked urgency in terms of risk management. Most workers believe that loud noise cause HL and is also the cause of tinnitus. Whilst this is true for HL, the development of tinnitus is idiopathic. Research indicates that the onset of tinnitus is associated with sensorineural HL, ear injuries, or circulatory issues ; howeverThe Almost 60% of respondents indicated that they had high noise exposure for more than 10 yr. This is typically where one would observe workers starting to present with noticeable signs of early onset NIHL. Consequently, it is expected that two of the major aspects highlighted by the worker responses were irritability and concern for their hearing when working in loud noise environments .The main sources of noise were believed to be heavy mobile equipment (HME), light vehicles, power tools, air tools and compressors; and mining machinery including crushers and the ventilation systems. These findings align with noise exposure assessments undertaken in the mining industry globally. Studies by The current research found that besides lower noise levels, higher worker morale and fewer compensation claims are the benefits of improved noise control benefits that most respondents considered important regarding noise control. Previously, the risk of workers’ compensation for OHL was found not to be an enabler for noise control . IncreasOnly 9% of respondents in this study indicated higher order controls such as isolation and substitution solutions are considered for implementation in mining, with most respondents not aware of any intentional investment by their companies towards noise control. These responses are mirrored by a scoping review completed Liebenberg et al. (in press) that investigated the interventions and controls available to workers with OHL.Nearly 71% of workers believe that the noise control strategies in their workplaces are effective, but this mostly refers to the use of HPDs. Over reliance on HPDs appears to be as common now as it was more than a decade ago . Twenty-One common issue reported with wearing HPDs is the perceived inability to communicate well. This is usually an indication that the correct type of HPDs have not been selected or are incorrectly used, for the noise levels generated in the areas of exposure. Many workplaces purchase a standard class of HPD, usually class 5, to accommodate for “worst case” scenarios. However, noise generated from mining equipment has been measured to range between 80–120 dB(A), which requires that the correct classes of HPDs are selected, used, and maintained, for different tasks and exposure profiles. This would not only aid in the prevention of noise-induced hearing loss, but it would also allow for effective communication to occur when used appropriately.When asked about controls employed at their workplace, other than HPDs, the respondents indicated administrative controls (55%) such as audiometric testing and awareness training, audits and inspections, signage, policies, and procedures were common. Hearing loss is believed to be a principal issue, and more education and awareness training is required in addition to undertaking more compliance inspections. The fact that most respondents recommend more inspections and administrative controls is surprising, specifically as most of the respondents self-reported as HSE professionals. Noise control is a complex issue and there are no easy, “one-size fits all” solutions. It should also be noted that complete elimination of noise in the mining sector is unlikely due to the nature of the operations (crushing of rock and ore). Nevertheless, HSE professionals should be advocating for higher order, more permanent solutions rather than lower order, administrative, and personal protective equipment controls. Overall, the respondents reported positive attitudes towards noise control to help prevent hearing loss. However, the results of this survey indicate that the respondents do not engage in frequent and appropriate use of HPDs.Research indicates that although workers might feel positive towards a certain outcome, they do not always follow this belief with appropriate behaviour and action. This finding raises the question whether there is a deeper working-culture issue that needs to be addressed, instead of undertaking more noise assessments, training, and enforcing legislative requirements. Particularly as most of the respondents believe that some Health and Safety rules and regulations are not practicable (63%), and that regardless of control implementation, accidents are still likely to occur in their workplace (50%).Future research is needed to determine the psychosocial aspects behind the fatalistic acceptance of noise exposure at work and the development of NIHL and raise the profile of this topic in industry. Secondly, it is recommended that training and awareness campaigns such as Dangerous Decibels  for younn = 72) was lower than that required (n = 96) to achieve a 95% confidence level in the validity of the results (10% margin of error). The results of the study indicate an over-representation of females (41%) compared to the industry average and are likely to be biased towards workers with an interest in the topic. The results of this study can thus not be generalized across the whole Australian Mining population. The results of the survey still provide valuable insights into the perceptions and beliefs of these workers regarding noise control in the mining sector. Furthermore, many of the respondents (36%) were HSE professionals, which increases self-selection bias of the survey results.The number of respondents (The results of the current research indicate that although the industry sector is different compared to the original sectors included in the


Endocochlear, retrocochlear and/or central origin hearing damage may be related to the absence of appropriate levels of thyroid hormone during morphogenesis and/or auditory system development. Hearing disorders related to the thyroid are not well studied, despite speculation on the pathophysiological mechanisms. The objective of this review was to characterize the main pathophysiological mechanisms of congenital hypothyroidism and to evaluate the relationship with central and peripheral hearing disorders. We conducted a literature review using the databases MedLine, LILACS, Cochrane Library, SciELO, Institute for Scientific Information (ISI), Embase, and Science Direct between July and September on 2016. We identified the studies that address hearing disorder mechanisms on the congenital hypothyroidism. Congenital hypothyroidism may have clinical and subclinical manifestations that affect the auditory system and may be a potential risk factor for hearing impairment. Hearing impairment can severely impact quality-of-life, which emphasizes the importance of monitoring and evaluating hearing during the clinical routine of these patients. The development of the auditory system depends on the presence of proper levels of thyroid hormone (TH) . SeveralThe THs play an important role in the morphogenesis, development and maturation of the auditory pathway. Thus, congenital hypothyroidism (CH) can be a potential risk factor for hearing impairment (HI)  if the hWhile the HI incidence in CH individuals is currently unknown, studies suggest it may affect 20% of carriers -7. The rAlthough the CH auditory aspects have been investigated in different experimental models involving both in humans and animals, the pathophysiological mechanisms have not been well explored and are not fully elucidated. This lack of information makes it difficult to comprehend all the processes involved in the possible hearing disorders that this disease may cause.The aim of this literature review was to evaluate the relationships between CH and both peripheral and central hearing disorders. We focused on the pathophysiological mechanisms involved with these disorders.The literature search was conducted using the following electronic databases: MedLine, LILACS, Cochrane Library, SciELO, Institute for Scientific Information (ISI), Embase, and Science Direct. The databases were consulted between July and September 2016. The databases were mined for literature that specifically focused on pathophysiological processes of congenital hypothyroidism and hearing in human and animal models. The following keywords and descriptors were used during the search and were combined in a number of sequences in English, Portuguese and Spanish languages: hypothyroidism, congenital hypothyroidism, thyroid hormone, thyroid gland, thyroid ontogeny versus auditory hearing maturation, cochlear function, middle olivocochlear system, central auditory processing, hearing loss, and hearing test. The selected studies were chosen based on their title and abstract description. The desired outcomes were structural, physiological, and/or biochemical disorders of the auditory system due to impaired function of the thyroid gland. Papers were excluded from the analysis if they addressed hearing disorders in syndromic cases associated with hypothyroidism or other hypothyroidism conditions that were not caused by abnormalities due to the formation or function of the thyroid gland.CH is related to defective TH action due to decreased or absent hormones. CH is the most common metabolic dysfunction in newborn infants. CH affects 1:3000 to 1:4000 births worldwide  and 1:25NKX2.1, FOXE1, PAX8, and TSHR) and display a complex pathogeny  or transitory 10-20%) (-20% (10)athogeny ,19.Untreated CH can result in a profound impairment of the somatic growth and central nervous system functional differentiation because THs are essential for metabolic development, growth, and homeostasis.4) plays an important role in the development of embryonic inner ear. In CH cases with maturation of the sensory epithelium, the inner ear is injured, which suggests there are periods of sensitivity to THs in the developing cochlea , is mediated by the thyroid hormone receptor (TR). TR is a binding transcription factor that changes target gene expression  and β (THRB)  . The expβ (THRB) ,24,25.A delay of THs supply before hearing function development starts results in permanent defects on the cochlea. The deficits of THs can also lead to permanent decreases of the β-tectorin protein levels in the tectorial membrane, which is associated with tectorial membrane structural abnormalities and cochlear function .The outer hair cells (OHC) are highly sensitive to THs serum levels . In caseSLC26A4 gene expression. This gene encodes the prestin protein that functions as the motor of the OHC and regulates the cochlear amplification process  affect the development of cochlear micromechanics  and damaThere are also descriptions of abnormalities in numerous afferent dendrites and growth delays of the efferent terminals under the OHCs . These fPrevious studies conducted in animal models focused on central nervous system (CNS) development and how the decrease or absence of THs leads to clinical signs suggesting stagnation of normal CNS maturation in CH cases . These fPrior studies of the superior auditory pathway have shown reduced levels of the metabolic activity marker deoxyglucose in the following regions: the cochlear nucleus, superior olivary complex, lateral lemniscus nucleus, inferior colliculus, medial geniculate body, and auditory cortex. These data suggest the entire auditory pathway is sensitive to insufficient TH serum levels .4 into T3 hormone in individuals affected by hypothyroidism and reduce the amount of T3 for the auditory centres , responsible for high frequency sensibility and selectivity show varied results. Therefore, it is possible to see an expressive abnormality of the OAE , signal The tests used to accurately investigate the neurophysiology of the auditory pathway in CH include the brainstem auditory evoked potentials (BAEP) analysis. The test results show diverse findings, such as prolongation of absolute latency of the I ,49, III In considering the reviewed content, it has been shown that hypothyroidism, especially in its congenital form, is a potential risk factor for hearing impairment. It can affect hearing from the peripheral structures to central areas that may also lead to inappropriate auditory development. These defects can affect the comprehension and acquisition of acoustic information. Inappropriate auditory development can lead to scholarly, cognitive, language, behavioural and/or social emotional problems. Therefore, it is critical to monitorand evaluate hearing as part of the clinical routine of these patients.