Mucormycosis  is a serious but rare fungal infection caused by a group of fungi belonging to the order Mucorales. These molds exist throughout the environment and generally do not cause serious problems in humans. Mucormycosis mainly affects individuals who are immunocompromised. The clinical manifestations of mucormycosis are wide-ranging; they include sinusitis  as well as cutaneous, gastrointestinal, pulmonary, and disseminate infections. Many uncertainties remain regarding how to control these infections despite the recent addition of triazoles to the antifungal arsenal for treating this infection. Currently, lipid formulations of amphotericin B have become the standard treatment for mucormycosis due to their efficiency. Moreover, a growing body of data supports the need for surgical excision of infected and/or necrosed tissue whenever practical. In this mini review, the current status of treatment options for mucormycosis and recent studies of novel therapeutic options will be presented. Mucor spp., Rhizopus spp., Rhizomucor, Lichtheimia spp., and others. These organisms are ubiquitous in the environment, so most individuals are exposed to them on a daily basis . AMB. AMB8]. Triazoles act by inhibiting the ergosterol synthesis pathway . Both poA recent guideline summarizes the usage of posaconazole and isavuconazole to treat mucormycosis . When thA combination therapeutic approach is common for the severely immunocompromised population. This methodology has clinical benefits that include the synergistic effects of the drugs and a broader coverage against pathogens compared to monotherapy . AMB is Other combination drug therapy consists of AMB and triazoles, although the data on this combination are contradictory. In vitro studies have demonstrated a synergistic effect between polyenes and posaconazole, but in murine models, this combination shows no benefit. However, a combination treatment with LAMB and isavuconazole shows a synergistic improvement in a murine mucormycosis model . This diNecrosis and thrombosis during mucormycosis can result in poor delivery of antifungal drugs. Consequently, the elimination of affected tissue may serve as a critical form of care to completely eradicate the infection . It shouTherapeutic options are limited for mucormycosis when compared to other pathogenic infections. Currently, only two drug agents  are used in clinical settings. It is challenging to find a distinctive drug target for Mucorales. Recent sequencing has revealed evidence of whole-genome duplication events, which might explain this pathogen’s resistance to multiple antifungal agents .Rhizopus species [Presently, there are two agents under investigation: oteseconazole (VT-1161) and fosmanogepix (APX001) in clinical trials for other pathogenic fungi. Oteseconazole is an oral tetrazole and an inhibitor of fungal Cyp51; this is the same enzyme as Erg11, which encodes for lanosterol 14-α-demethylase. This enzyme is responsible for the synthesis of sterols. Therefore, the inhibition of Erg11/Cyp51 ultimately results in the cell membrane being depleted of ergosterol. Additionally, in vivo studies showed the administration of oteseconazole prolonged survival when given as a therapeutic or as a prophylaxis . Fosmano species . These rMucor, in which inhibition of or mutations in calcineurin result in the blocking of hyphal growth of the fungus and the exhibition of only yeast-locked growth [Calcineurin is a Ser/Thr phosphatase and regulates virulence factors in many pathogenic fungi. Calcineurin has therefore been considered a promising drug target. The phosphatase plays key roles in controlling the invasive hyphal growth in d growth . Howeverd growth . It is tMucor [bycA genes, and without calcineurin function, the expression of the gene is elevated, resulting in the blocking of hyphal growth. It appears that up-regulation of bycA can recapitulate the calcineurin inhibition phenotype. Thus, any molecules that elevate the expression of bycA may be excellent drug candidate(s) (A recent study demonstrated that an amino acid permease (BycA) is a key downstream factor of calcineurin in Mucor . Calcineidate(s) .Over the years, multiple options for mucormycosis treatments have become available. AMB, isavuconazole, and posaconazole, and the surgical debridement of necrotic tissue when necessary are the most common practices in treating mucormycosis. Existing clinical data on mucormycosis treatment are very limited and thus are not helpful for physicians. Unmet needs related to diagnosis, treatment, and education of mucormycosis lead to a poor prognosis for patients. Increasing our knowledge and understanding of these organisms is highly important in the advancement of treatments for mucormycosis.


Low resting metabolic rate (RMR), as a risk factor for weight gain and obesity, can be influenced by many factors. Empirical research has confirmed the role of appetite and related hormones in obesity and energy intake. This study aimed to investigate the relationship between appetite and related hormones in overweight or obese Iranian women with normal and hypo RMR.. An impedance body analyzer was used to obtain the body composition and an indirect calorimeter was used to assess the RMR. The Flint questionnaire was used to assess appetite, dietary intake, and physical activity were assessed by FFQ and IPAQ questionnaires respectively, and ELISA kits were used to assess leptin, ghrelin, and insulin hormones.This case–control study was conducted on 42 Iranian adult women , aged 18–48 yearsP-value = 0.027) and RMR, and a positive association between insulin hormone level  and RMR. Also, results of the appetite questionnaire showed that, in general, both appetite  and hunger variable  have a positive association with RMR. There was no significant association between leptin levels and RMR.The results of the study demonstrated a negative association between ghrelin hormone level (β = -0.34, 95%CI = -61.70,-3.86, It is evident that appetite and related hormones have a potential role in promoting a normal RMR. Obesity is one of the most important health problems in the last century, and whilst its incidence continues to rise . The etiThe brain regulates energy homeostasis through neuropeptide signals from adipose tissue and the gastrointestinal tract; for this reason, the gastrointestinal tract is one of the main components of the food and appetite control system . Many inThe Insulin and Leptin hormones, balance food intake and energy expenditure. Their circulating levels are associated with body fat content . They afSeveral studies demonstrated the associations between leptin and RMR when adjusting for body composition. Two of these controlled for fat-free mass (FFM), one of them reported a correlation in women but not in men , whereasNonetheless, the relationship between appetite and related hormones with RMR requires further investigation. As studies have yielded conflicting results and did not assess the association in stratified RMR groups. Moreover, they did not evaluate appetite sensation, physical activity, and dietary intakes . Thus, we sought to discern whether appetite and hormones differed in overweight/obese women with normal RMR and hypo RMR. To the best of our knowledge, this is the first study of its kind in this field.1-µ2=2) between the case and control groups in the Type I error α = 0.05 and the power of 1-β = 0.90. According to a study by Marzullo and colleagues [We conducted a case–control study and enrolled 42 women from Tehran (21 cases and 21 controls), matched for age and BMI, who had been referred to a nutritional laboratory from September 2019 to January 2019. The sample size was determined to recognize the difference of 2 ng , and all subjects signed written informed consent prior to participation.In this study, RMR was measured by indirect calorimetry  . VentilaPredicted RMR (Harris-Benedict) = 665 + 9.56 × weight (kg) + 1.84 × height (cm) – 4.67 × age (year).Body composition, including weight, body mass index (BMI), body fat mass (BFM), fat-free mass (FFM), visceral fat level, visceral fat area, skeletal muscle mass, body fat percentage (PBF%), waist to hip ratio (WHR), waist circumference (WC), and soft lean mass were obtained using a body composition analyzer . To measA person's usual dietary intake over the past year was assessed by interview, using a semi-quantitative, 147-item food frequency questionnaire (FFQ). Based on this questionnaire, the subjects were asked to report the frequency of their food consumption for each food item on a daily, weekly, monthly, or yearly basis. The reliability and validity of this questionnaire in Iranian populations have already been confirmed . StandarIn order to assess the physical activity of the participants, the short form of the International Physical Activity Questionnaire (IPAQ), designed by the World Health Organization, was used . The valIn this study, the Flint appetite questionnaire was used to assess mental feelings about appetite . The valFrom all participants, following 12-h overnight fasting, 10 cc of fasting blood was drawn between 7–10 am. After storage for 30 min at room temperature, a blood clot formed and was centrifuged at 3000 g for 20 min. Serums were stored in clean microtubes in a freezer at -80° C until the analysis was performed.All hormones were measured by the enzyme-linked immunosorbent assay (ELISA) method. Leptin levels were assessed with an LDN kit , with a sensitivity of 0.50 ng/ml, total ghrelin levels were assessed, with a sensitivity of 0.01 ng/ml with Crystal Day Christian Day kit, China, and insulin levels were assessed with an IBT kit , with a sensitivity of 0.11 μU / ml.Intra- and inter-assay coefficients of variation (CV) reported by the manufacturer were 3.7– 5% and 5.9–5.8% for leptin, CV < 8%, and CV < 10% for total ghrelin, and 3.7–4.2% and 3.7–4.2% for insulin, respectively.P-values less than 0.05 were, a priori, considered statistically significant. The normality of variable distribution was evaluated using Kolmogorov–Smirnov and Shapiro Wilk tests. Because our data did not show a normal distribution, we used non-parametric tests. The Wilcoxon test was used to determine the difference between quantitative variables between case and control groups. Chi-square test or Fischer exact tests were used to determine the distribution of qualitative variables between case and control groups. Linear regression analysis was used to determine the relationship between appetite and related hormones with RMR, in a crude and adjusted model (adjusted for body fat percentage).All data were analyzed using SPSS software version 25, where The present study was conducted on 42 obese and overweight Iranian women, of which, 59.5% were married, 69% occupied, 92.8% had a college education and 52.3% had good economic status.2, 0.92(0.07), 96.50(14.8) cm, 33.10(12.10) kg, 45.20(7.82) kg. The median age, weight, BMI, WHR, WC, BFM, and FFM were not significantly different among the case and control groups; however, there was a statistically significant difference between the case and control groups in terms of PBF%. Also, the median of measured RMR was significantly higher in controls compared to cases,  .Baseline participant characteristics are presented in Table . The medBased on the test of qualitative variables  between the case and control groups, there was no significant difference between the two groups .In Table P-value = 0.001) were positively related to RMR  and RMR  and RMR, which remained significant after adjusting for the confounding variable. We also investigated the association between RMR and related hormones separately in case and control groups. The results showed that there was a negative relationship between serum ghrelin levels and RMR in the “hypometabolic” group , after adjusting for PBF%, the results remained significant. While, no association was found between serum ghrelin levels and RMR in the “normometabolic” group . However the association between Insulin level and RMR was significant in both “hypometabolic” group  and “normometabolic” group  in humans. The relationship between ghrelin and energy metabolism levels in obese and overweight people evidently needs further investigation [Our results indicated a significant inverse relationship of the ghrelin hormone with RMR in the study population, which is congruent with the results of Pierre et al. . Indeed,tigation .Our analysis conducted separately in stratified RMR groups showed that there is a negative relationship between serum ghrelin levels and RMR only in the “hypometabolic” group. And no association was found between serum ghrelin levels and RMR in the “normometabolic” group. However, Marzullo et al. have shown different results from our research, they suggested that ghrelin secretion is decreased in obesity in cases of impaired energy expenditure . DiscrepOne might hypothesize that ghrelin is expected to intervene endogenously to improve impaired energy metabolism. These hypotheses raise the possibility that the metabolic effects of ghrelin may extend beyond the regulation of satiety, food intake, and substrate oxidation, and may play a role to improve energy efficiency in overweight and obese women.The present study demonstrates that the serum level of insulin hormone is positively associated with RMR in two groups with normal and impaired metabolism, which is concordant with Drabsch et al. and Huang et al. , 78. HomIn fact, the results showed that, the higher the level of insulin hormone, the higher the RMR, which is consistent with Ravussin et al., through the Euglycemic Insulin clamp technique the thermic effect of insulin and glucose injection can be studied in detail . The phy.Considering the strengths of the current study, to our knowledge, this study evaluated the relationship between appetite and related hormones with RMR in obese/overweight women by matching two important confounders, age, and BMI for the first time. Moreover, RMR was measured by indirect calorimetry, which is considered as the gold standard for measuring energy expenditure . Also, aIn conclusion, the results of this study showed that there is a significant positive relationship between insulin levels and appetite sensation with RMR in the study population. No association was found between leptin levels and RMR. And a negative association between ghrelin levels with RMR in the “hypometabolic” group. Although speculative, it seems that serum ghrelin levels may play a role in the regulation of energy homeostasis by intervening endogenously to improve the state of impaired energy balance and increase energy efficiency.


M = 69.5, SD = 8.6; M:F = 13:11) who had used hearing aids in everyday life for >1 month  and the normal-hearing group included 26 listeners . Speech perception in noise was measured under no mask–auditory-only (no-mask–AO), no mask–auditory–visual (no-mask–AV), and mask–AV conditions at five signal-to-noise ratios  using five lists of 25 monosyllabic Korean words. Video clips that included a female speaker’s face and sound or the sound only were presented through a monitor and a loudspeaker located 1 m in front of the listener in a sound-attenuating booth. The degree of deterioration in speech perception caused by the mask (no-mask–AV minus mask–AV) was significantly greater for hearing-impaired vs. normal-hearing participants only at 0 dB SNR (Bonferroni’s corrected p < 0.01). When the effects of a mask on speech perception, with and without hearing aids, were compared in the hearing-impaired group, the degree of deterioration in speech perception caused by the mask was significantly reduced by the hearing aids compared with that without hearing aids at 0 and −4 dB SNR (Bonferroni’s corrected p < 0.01). The improvement conferred by hearing aids (unaided speech perception score minus aided speech perception score) was significantly greater at 0 and −4 dB SNR than at −16 dB SNR in the mask–AV group (Bonferroni’s corrected p < 0.01). These results demonstrate that hearing aids still improve speech perception when the speaker is masked, and that hearing aids partly offset the effect of a mask at relatively low noise levels.Although several previous studies have confirmed that listeners find it difficult to perceive the speech of face-mask-wearing speakers, there has been little research into how masks affect hearing-impaired individuals using hearing aids. Therefore, the aim of this study was to compare the effects of masks on the speech perception in noise of hearing-impaired individuals and normal-hearing individuals. We also investigated the effect of masks on the gain conferred by hearing aids. The hearing-impaired group included 24 listeners (age:  As COVID-19 infections have spread worldwide, mask-wearing is recommended for preventing infection and transmission. However, the widespread use of masks causes inconvenience in everyday conversation. Many previous studies have confirmed that mask-wearing interferes with communication not only in hearing-impaired individuals, but also in individuals with normal hearing . ListeneThe adverse effects of masks on speech perception can be explained by the consequent sound attenuation  and the Hearing-impaired listeners may have greater difficulty perceiving masked speech, because they are more susceptible than normal-hearing individuals to the sound attenuation caused by the mask and depend more strongly on lip reading during conversation. Recent surveys have shown that hearing-impaired listeners were significantly more affected by masked speech than those without hearing impairment . Two behWe hypothesized that the effects of masks on hearing-impaired individuals are greater than those on individuals with normal hearing. Our second hypothesis was that masks reduce the benefit of hearing aids in speech perception, although hearing aids can partially compensate for the deterioration in speech perception caused by masks. To test our hypotheses, we compared the effects of masks on speech perception in hearing-impaired individuals and normal-hearing individuals against relatively intense background noise. We also investigated the effect of masks on speech perception in within-subject comparisons, by comparing the deterioration in speech perception caused by the mask in hearing-impaired individuals with and without hearing aids.M = 69.5, SD = 8.6; M:F = 13:11) who had used hearing aids in everyday life for more than 1 month  and the normal-hearing group included 26 listeners . p > 0.05) but there was a significant difference in age (p < 0.05). The pure-tone averages across 500, 1,000, 2,000, and 3,000 Hz in the normal-hearing group and were 14.7 (SD = 6.8) dB hearing level (HL) on the right side and 14.8 (SD = 6.3) dB HL on the left side. In the hearing-impaired group, pure-tone averages were 53.5 (SD = 21.9) dB HL in the right ear and 53.2 (SD = 22.0) dB HL in the left ear , and the order of the words in the lists was randomly assigned for each of the no-mask–AO, mask–AV, and no-mask–AV conditions. The phonetic balance, equal range of the phonetic composition of speech, words in common usage, and the words’ familiarity was considered when the word lists were developed. The equivalent average difficulty and phoneme composition of the lists were verified. The subjects were asked to repeat the words verbally while ignoring the noise and the number of correct responses was measured for a total of 25 words. The tests were performed in the following order: no-mask–AO, mask–AV, and no-mask–AV conditions. Under each condition, the order was −16, −12, −8, −4, and 0 dB SNR. For the hearing-impaired subjects, the tests were performed first without hearing aids, and then performed again with hearing aids. Speech perception was measured by fixing the monosyllabic words at 65 dB SPL when calibrated at the listeners head position 1 m away from the loudspeaker and changing the speech-shaped noise to five scales of −16, −12, −8, −4, and 0 dB SNR.A female speaker recorded a video clip while reading five lists of 25 monosyllabic Korean words against eight-talker babble noise, using a lapel microphone  and a cellphone camera , once without wearing a mask and again with the Korean filter 94% (KF94) mask. The KF94 mask has been certified by the Korean Food and Drug Administration and is made of four layers of unwoven material with an ultra-electrostatic filter. The dustproof effect is similar to those of filtering facepiece 2 on European standards and N95 on American standards. The recorded video clip was provided The same female speaker who made the video clip recorded standard Korean phrases with similar proportions of consonants and vowels using a lapel microphone  in a soundproof booth. With and without the KF94 mask, and the long-term average speech spectrum of the recorded phrase was analyzed with the Computerized Speech Lab .post-hoc test, the significance levels after Bonferroni’s correction of the p-values were deemed to be 0.003 (0.05/15) or 0.01 (0.05/5) for multiple comparisons. All statistics were performed using IBM SPSS software .A 2 × 3 × 5 mixed repeated-measures analysis of covariance (ANCOVA), controlled for age (covariate), was used to analyze the effects of the hearing status , the experimental conditions , and the noise level  on speech perception in noise. To compare the effects of masks on speech perception when hearing aids were worn in the hearing-impaired group, a 2 × 3 × 5  pure repeated-measures analysis of variance (ANOVA) was used. In the SD = 1.5) dB at ≥2 kHz relative to the no-mask condition. The maximum reduction in sound level was around 6.2 dB at 7 kHz  = 38.85, p < 0.001], the experimental condition , and SNR . The covariate age was significantly related to monosyllabic perception . The planned contrasts revealed that the hearing-impaired group  had significantly worse monosyllabic perception than the normal-hearing group. There was no significant interaction among the three factors , but the interaction between hearing status and SNR tended toward significance (p = 0.051). In the post-hoc test, speech perception was lower under both the no-mask–AO and mask–AV conditions than under the no-mask–AV conditions in both the normal-hearing and hearing-impaired groups (without hearing aids) at all noise level . In both the normal-hearing group and hearing-impaired group (without hearing aids), the mask–AV conditions produced better speech perception than the no-mask–AO conditions at −16 and −12 dB SNR , but there was no difference at −8, −4, or 0 dB SNR. When the degree of deterioration in speech perception caused by the mask (no-mask–AV minus mask–AV) was compared between two groups at each noise level, the difference was only significantly greater in the hearing-impaired group than in the normal-hearing group at 0 dB SNR , the experimental condition , and SNR . There were significant interactions between the condition and SNR  and among the three factors , but no other significant interaction was observed . When the effects of a mask on speech perception with and without hearing aids were compared in the hearing-impaired group, the degree of deterioration in speech perception caused by the mask (no-mask–AV minus mask–AV) was significantly reduced by the hearing aids compared with the degree of deterioration without hearing aids at 0 dB SNR and −4 dB SNR .In the hearing-impaired group, hearing aids significantly improved speech perception relative to that without hearing aids at all noise levels under both the no-mask–AV conditions and mask–AV conditions  was significantly higher than that of the normal-hearing group . However, the effect of this age difference on the outcomes is presumed to be minimal. A previous large survey of 1,700 people showed that the age of the listener did not affect the degree of communication disturbance caused by masks (A limitation of this study was that the mean age of the hearing-impaired group (by masks . MoreoveIn conclusion, the perception of masked speech by hearing-impaired individuals was more adversely affected against relatively low background noise than was that of normal-hearing individuals. Hearing aids still improved speech perception in a mask-wearing environment, and hearing aids partly offset the mask effect at relatively low noise levels.The original contributions presented in this study are included in the article, further inquiries can be directed to the corresponding author.The studies involving human participants were reviewed and approved by the Institutional Review Board of Nowon Eulji Medical Center. The patients/participants provided their written informed consent to participate in this study.HS: conceptualization, funding acquisition, and critical review. HS, Y-HA, and JC: experiment design. HC: experiment performance. JC: data preparation and analysis. HC, DK, and JP: methodology. JC and HS: writing manuscript. All authors have read and agreed to the published version of the manuscript.


Aim: to perform a comparative study, through audiometric tests, in workers exposed to noise only and noise associated with chemical products. Materials and Methods:155 steel workers (18 - 50 years) exposed to noise (group I), and exposed to noise and chemical products (group II) for a period that varies from 3 to 20 years. Results: significant difference in the rate of occupational hearing loss in the right ear between groups I (3.6%) and II (15.5%). A significantly higher rate of occupational hearing loss in group II (18.3%) and I (6%). With respect to the average time of exposure to aggressive agents, group I was exposed by a significantly higher time. Retrospective study. Discussion: The fact that the right ear was more affected in group II is controversial and should be better investigated in the future, since some studies show that the left ear would be more prone to noise-induced hearing loss. Conclusion: group II had proportionally a higher rate of hearing loss when compared with group I, even after having been exposed to aggressive agents for a lower average time.Exposure to ototoxic chemical products in the presence or absence of noise can cause irreversible injury to the hearing of workers for a significantly short period of exposure period.  We will use the term occupation hearing loss in this article, as a reference about the harm against hearing that the work environment can cause, regardless of noise.Among the factors that may results in occupational risk, noise certainly appears as the most frequent; many workers are exposed, especially steelworkers.10There have been few epidemiological studies about the exposure time needed for causing hearing loss. Some researchers have stated that individuals in contact with ototoxic chemical products may start presenting hearing loss after two to three years of exposure to these substances, while individuals exposed to noise would take about four to five years to present similar symptoms. The frequency of compromised individuals increases after five to seven years; the progression of loss decreases until about 15 years, when it tends to stabilize as long as the exposure conditions persist and there are no additional causal factors.6Prolonged exposure to noise and to chemical agents, however, do not make it certain that occupational hearing loss will occur; besides the environmental issues, there are also those pertaining to each individual, such as genetic factors, age, sex, and race, and endogenous factors linked to the causative agent, its form and occurrence, among others.5Exposure to chemical products currently remains undervalued; as a results noise is considered as the only cause of occupational hearing loss. It should be stated that occasionally noisy settings are not the main cause of hearing loss, giving place to places where workers are exposed to ototoxic chemical products.11Certain chemical products, such as solvents, heavy metals, asphyxiants, and more recently, the organophos-phorate pesticides, have been investigated for their potentially ototoxic effect, since these substances are found in a variety of production processes.Organic solvents, especially toluene, xylene, styrene, n-hexane, trichloroethylene and ethanol are the most studied of this class; these are high priority ototoxic substances, but there are other that are less ototoxic such as ethyl acetate and carbon disulphide. All of these may be related to auditory disorders.A study in a printing company in the state of Sao Paulo, based on a multiple logistic regression test, showed a high percentage of audiometric changes that occurred by exposure to ototoxic substances rather than by noise.A longitudinal study that surveyed industry workers exposed to chemical products during 20 years revealed that there was a high percentage of hearing loss, even though these workers had been exposed to low sound pressure levels.Experimental rats exposed to a mixture of styrene and xylene developed hearing loss; exposure to styrene caused permanent and progressive damage to their auditory system. This experiment suggested that these substances are more ototoxic than toluene, possibly due to the fact that they administered jointly, which may have facilitated absorption and increased the toxicity risk.14Another experiment in which rats were exposed to ethanol and styrene clearly demonstrated that the former substance caused no harm to the animal’s auditory system; styrene, on the other hand, permanently altered the threshold and caused further harm to the outer hair cells. Simultaneous exposure to two substances increase the effect on thresholds and the loss of hair cells, being more harmful.Based on research, we may state that simultaneous exposure to noise and ototoxic substances is synergic, where the effect of combined exposure is higher than the sum of the effect of each agent singly.Workers were divided into four groups in a study done at a specific industry. The first group was exposed to a mixture of organic solvents, the second group was exposed to the same mixture and also to noise above 80 dBHL, the third group was exposed to neither (and was used as the control group), and the fourth group was exposed to noise above 80 dBHL only. Compared to the control group, the highest prevalence of hearing loss was found in the first and second groups, particularly at 3 000 to 8 000 Hz. Hearing loss in the fourth group was concentrated at 4 000 Hz. There was a positive correlation among the dose accumulation of organic solvents, noise, and the degree of hearing loss.We thus need to reflect on the tolerance levels to various agents in the working environment; these may be present within acceptable parameters, as established by Brazilian law for each substance singly, but may become unacceptable when combined, which reinforces their effect on the auditory system.21Hearing loss due to ototoxic chemical substances has similar audiometric features compared to hearing loss due to noise. It is always sensorineural and irreversible, and may be unilateral or bilateral.Noise and chemical substances may injure the cochlea;In rats, aromatic solvents - such as styrene - appear to decrease the auditory sensitivity, particularly at middle frequencies. These substances may cause permanent hearing loss by affecting first the outer hair cells, and eventually the spiral ganglia.A few researchers have shown that exposure to toluene, styrene and carbon monoxide may alter the function and morphology of outer hair cells in experimental animals.23Other clinical and epidemiological studies support us in stating that there is an association between various solvents and changes in central auditory pathways; based on audiometric findings, we may also perceive that these substances cause mild to moderate hearing loss.A survey was made of workers of a given industry that were exposed to a mixture of aromatic and aliphatic solvents. The results revealed a low speech recognition rate in voice audiometry compared to pure tone audiometry, and that cortical responses were altered at the frequencies that were tested. The conclusion was that the auditory system might be vulnerable at a cortical level, which was confirmed by speech discrimination tests and cortical responses, two of the most sensitive tests available for detecting cortical central auditory injuries.Annex I of the Regulation Norm 15 defines the tolerance levels for continuous and intermittent noise. However, the specific Brazilian labor laws do not state that periodic audiometric testing should be done in workers exposed to ototoxic chemicals; periodic audiometric testing is required only of workers exposed to noise levels above 85 dBHL 8 hours per day.20In 1998, the North-American army started taking exposure to chemical substances into account in the prevention of hearing loss; this extended to workers exposed to certain substances such as styrene, which were included in hearing conservation programs regardless of their exposure level to noise.Research institutions, such as the NIOSH and the ACGIH, have also recommended audiometric testing of these workers as of 1998.28The Social Security Law 3048 of 6 May 1999 opened the possibility of recognizing certain chemical substances as occupational etiological agents or risk factors for ototoxic hypoacusis; thus, this type of exposure should be taken into account when searching for a cause-effect relation between hearing loss and the work environment.The European Parliament has recently started requiring that employers pay attention to the effects of the interaction among noise, chemical substances and health.Comparing the general features - such as audiometric tracings and the affected site - of hearing loss induced by noise and ototoxic chemical substances raises awareness of the difficulties in making a differential diagnosis and identifying the cause. The diagnosis is based on confirming the exposure and finding signs and symptoms, even though the effects are poorly established.10The purpose of this study was to compare auditory thresholds, by using audiometric tests, of two groups of workers, one exposed only to noise and another exposed to noise and chemical substances.A case-control study was undertaken of 155 workers in a steel company in the state of Rio de Janeiro. All subjects were male; 81 were allocated to group I (exposure to noise), and 71 to group II . The mean age was 31 (+/- 7) years, ranging from 18 to 50 years; the mean general exposure time was 7 (+/- 4) years, ranging from 3 to 20 years.The chemical substances that were assessed were: acetone, styrene, resins, and cobalt, among others of less relevance.The study was done in different sectors of the factory, in which noise ranges from 80.5 dBHL to 99.5 dBHL, and where exposure time is 8 hours per day. Workers used individual protection equipment as required by the Regulation Norm 6,20 Law 3214/78; of relevance to our study is the use of adequate breathing masks and ear protectors, both certified by the Ministry of Labor and Employment. The company is committed to the physical integrity of its employees, and its technical unit effectively inspects the use of safety equipment, with penalties - as defined by law - for non-compliance.Trained professionals employed by the company measured the noise levels with company-owned environmental monitoring equipment. Measurements were done at different sites of the working area on the A-scale, slow-response circuit, as required by the Regulation Norm 15, annex number 1, Law 3214/78.20 A Quest model Q-400 dosimeter, duly calibrated according to the norm IEC 60651, procedure PC-06 - REV 00, October 2005, was used.The results of organic vapor evaluations in the samples were lower than the limits required by the Regulation Norm 15, annex 11, Law 3214/78.20 PVC-filter cassettes were used, and a certified specialized laboratory issued the technical reports.A retrospective study of sequential audiometric tests in 2005, carried out by a trained professional: a speech therapist according to the Federal Medical Board and the Speech Therapy Federal Board and according to the requirements contained in the Law 19 of the Ministry of Labor and Employment (1998).Tests were done in an audiometry test suite wherein the sound pressure was within the maximum limits required by the ISO 8253.1 Norm; the audiometer was a MAICO MA 41 device, which is calibrated electroacoustically once a year.All workers had a 14-hour auditory rest period before testing; all underwent meatoscopy of both ears before testing. Those with abnormal external acoustic meatuses were excluded from the study and referred for healthcare.Audiometric tests were done at 500, 1 000, 2 000, 3 000, 4 000, 6 000 and 8 000 Hz (air conduction), and 500, 1 000, 2 000, 3 000 and 4 000 Hz (bone conduction) if air conduction results were altered. Voice audiometries were also done in all subjects (speech reception threshold and speech recognition score).Occupational hearing loss was considered as present when auditory thresholds were over 25 dBHL at 3 and/or 4 and/or 6 KHz, above other tested frequencies, whether altered or not, in both air and bone conduction, in one or both sides.The Research Ethics Committee approved this study (number 127/06).The statistical analysis consisted of the chi-square χ2) test for comparing occupational hearing loss between both groups, Student’s t test form independent samples (age) for comparing the age (in years) and Mann-Whitney’s test for comparing the duration of exposure (in years). Qualitative data were summarized by frequency (n) and percentages (%).  test forData on Data on 19The fact that the right ear was more affected in group II deserves further discussion, since opinions vary in different studies. Some researchers present data showing that there is a prevalence of occupational hearing loss in one ear when ears are compared. This may occur, for instance, when a machine is located next to a specific side of the worker, or when only one side of the work site in which workers undertake their activities is open; these conditions were not present in the steel mill in question.A few studies have suggested that the left ear is more susceptible to noise injury, although evidence for this statement is scarce. Other equally important studies have shown that male adult hearing is about 4 dB (HL) lower in the left ear compared to the right ear.Audiometric testing is essential for both the prevention and monitoring of occupational hearing loss. Also needed is a hearing conservation program for workers exposed to chemical substances, with or without exposure to noise levels over 85 dB.Group II had a higher prevalence of occupational hearing loss compared to group I, although the latter was exposed to the aggressive agent for a longer period.


The present paper investigates the use of the magnetic hysteresis loop technique to nondestructively evaluate microstructural degradation in heat-resistant martensitic (HRM) steels. The degradation impairs the safe operation of thermal power plants and it is thus essential to periodically assess it using nondestructive evaluation (NDE) techniques. In this contribution, HRM steels are thermally aged up to 16,000 h at 675 °C to simulate the microstructural degradation, then the changes in the magnetic coercivity, hardness, and microstructure are systematically characterized and the relations between them are determined. Both coercivity and hardness decrease with thermal aging duration, which can be interpreted in terms of the microstructure parameters’ evolution based on the pinning of crystal defects on domain walls and dislocations. Coercivity and hardness share the same softening trend with aging time, and good linear relations between coercivity, hardness, and microstructure parameters are found. These results provide a key to understanding the magnetic parameter evolution in HRM steels and suggest the possibility of using magnetic technologies for the NDE of microstructure degradation in thermal power plants. Heat-resistant martensitic (HRM) steels are widely employed in thermal and nuclear power plants, owing to their good creep and oxidation resistance, together with excellent thermal properties and low cost as compared to bainitic steels and austenitic steels ,3,4,5,6.Currently, the microstructural degradation state is directly investigated using surface metallographic replication or inferred from surface hardness; however, these techniques cannot shed light on the interior of steels. Conventional ultrasonic techniques based on backscatter or velocity are only applicable at the last stage, prior to failure. Thus, alternative NDE techniques capable of revealing the microstructural degradation condition of the interior of HRM steels during their whole service life are desired. Specifically, magnetic hysteresis loop (HL) technology attracts great attention because magnetic properties are sensitive to the evolutions of crystal defects, such as dislocations, precipitates, and boundaries ,15,16,17The changing trend of magnetic coercivity in served, aged, or crept HRM steels has been investigated in previous reports. For instance, Liu et al. , KarimiaIn this study, the relationships between coercivity, hardness, and crystal defects are explored. The microstructure parameters, including the spacing of precipitates, dislocation density, and martensitic lath width of the thermally aged P91 steel at different aging durations, are determined based on systematic microscopic analysis. The magnetic and mechanical properties are acquired via HL and hardness measurements, respectively, and their behaviors are interpreted based on the hindrance of crystal defects to the movement of domain walls (DWs) and dislocations. The corresponding relationships between magnetic properties, mechanical properties, and crystal defects are thus investigated based on these analyses.t1 + C)T1 = (lgt2 + C)T2, where t is time in hours, T is temperature in K, and C is LM constant, . The chemical composition of the investigated steel is shown in s = (A/N)0.5, where s is the spacing of precipitates, A is the area of the field of SEM view, and N is the number of precipitates in this field. At least 250 precipitates located at 10 different fields of view were employed to calculate the average size and spacing of precipitates. The lath width of martensite and the recovery of dislocations were determined using transmission electron microscopy (TEM). The lath width is defined as the length of the minor axis of the martensitic lath. At least 10 different locations with an area of 70 μm2 each were chosen to evaluate the lath width of martensite. The specimens used for TEM observation were prepared through a twin jet electro-polisher (Struers TenuPol-5) in a solution of 5% perchloric acid and 95% ethanol (Vol. %) at −25 ℃. The dislocation density was calculated based on the X-ray diffraction (XRD) using the Williamson–Hall method [The effects of the evolution of microstructure on the aspects of precipitation size and spacing, dislocation density, and martensitic lath width for the thermally aged P91 steels at varying durations were systematically observed using electron microscopy. The size and spacing of precipitates were characterized using scanning electron microscopy (SEM). The spacing of precipitates was calculated using −1), with a fine step size of 1 Oe in the regime of −50 and +50 Oe to acquire a more accurate coercivity.Magnetic HLs were measured using a vibrating sample magnetometer (VSM). Specimens with a length of 6 mm, width of 4 mm, and thickness of 0.6 mm were cut out by electrical discharge machining, ground, and further electro-polished to a thickness of 0.2 mm for VSM measurements. The maximum applied magnetic field was 10,000 Oe  and sub-grain boundaries (SGBs) (23C6 precipitates decreases and the corresponding spacing of the precipitates increases (0.81 μm) when aged for 1000 h  a due to r 1000 h b. Additir 1000 h b, which Detailed TEM observation was carried out on the present steels to reveal the evolution of the substructures with respect to the aging duration . The as-14 m−2  [All crystal defects, including precipitates, dislocations, and lath boundaries, can affect the coercivity of HRM steels. The crucial point is to determine the leading factor at different aging stages. The stress field of dislocations can retard the movement of DWs and increase their coercivity. It is reported that coercivity changes linearly with the square root of dislocation density ,33. Unliipitates ,34, wherdegrees) ,35, so i23C6 precipitates of the present P91 steels with aging durations larger than 500 h  mainly ascribe the changes in coercivity to the evolution of precipitates ,37. ThisHV is Vickers hardness, cH is coercivity in Oe, and t is the aging time. The dislocations play the leading role in affecting the hardness and coercivity in the early stage (t < 500 h). In particular, the hardness also varies with the square root of dislocations following Taylor’s law [ρσ is dislocation hardening, M is the Taylor factor, G is the shear modulus, b is Burgers vector, and ρ is dislocation density. Therefore, the relationship between hardness and coercivity is linear. With the increase in aging time beyond 500 h, the precipitates play an important role in governing the hardness and coercivity during prolonged aging larger than 500 h. The coercivity linearly varies with the reciprocal of precipitation spacing . The present two-stage linear relationship between coercivity and hardness is different from the single linear relationship reported on the heat-resistant bainitic steels [The relation between hardness and coercivity is shown in or’s law :(3)σρ=0. spacing b. The stc steels ,40, whic23C6 precipitates, and the growth of martensitic laths. The recovery of dislocations plays a principal role in affecting the coercivity at the early aging stage, and the ripening of M23C6 precipitates exerts an important influence on coercivity at the late aging stage. Coercivity and hardness share the same softening trend with aging time, and a good two-stage linear connection between coercivity and hardness was found. These results provide a key to understanding the magnetic parameter evolution in HRM steels and suggest the possibility of using magnetic technologies for the NDE of microstructure degradation in thermal power plants.In this study, the evolutions of the magnetic properties, mechanical properties, and microstructure parameters of P91 HRM steels after thermal aging were investigated, and the relations between them were determined. The coercivity and hardness decreased with thermal aging duration due to dislocation recovery, the coarsening of M


Average normalized 18FDG uptake of 25% of voxels with highest uptake was calculated for the PAC employing a probabilistic atlas and cerebellar cortex as reference. Differences in glucose metabolism of the PAC were assessed by an asymmetry index (AI-PAC). We tested the correlation between outcome of CI surgery (6 months post implantation), AI-PAC and clinical predictors. Pre-operative AI-PAC showed a positive correlation with speech recognition with CI . With a pre-operative AI-PAC ≥ 4.2%, patients reached good CI outcome in sentence recognition of 59–90% and number recognition of 90–100% and less favorable CI outcome in monosyllabic word recognition of 25–45%. Age at symptom onset was significantly associated with all measures of speech recognition, while deafness duration was only associated with sentence recognition. AI-PAC allows for a reliable and quantitative pre-operative prediction of early improvement in speech recognition after CI. 18FDG PET may be a valuable addition to the objective pre-operative assessment of CI candidates. Further studies in larger cohorts and with longer follow-up times are needed.Patients with asymmetric hearing loss show an asymmetry of glucose metabolism of the primary auditory cortex (PAC). We investigated whether this asymmetry could serve as an objective predictor for speech recognition with CI. Nine patients underwent  A cochlear implant (CI) is the only therapy that can improve binaural hearing and therefore speech recognition in background noise and localization of sound sources in subjects with AHL and SSD12. Patients to receive CI are evaluated by a pre-operative workup consisting of: (1) anamnesis and ENT medical examination, (2) subjective hearing tests (e.g. pure tone and speech audiometry in quiet and noise), (3) objective hearing tests (e.g. brainstem evoked response audiometry), (4) evaluation of hearing-related quality of life, (5) balance tests and (7) imaging techniques (CT and/or MRI)15. Predictions of CI outcome are mostly based on the context of all data collected during pre-operative workup and the duration of deafness16. However, the results of CI recipients with AHL and SSD differ considerably between subjects19. Given the invasiveness and high costs of CI, there is a high need for a valid predictor of CI outcome in subjects with AHL. Although various clinical and audiological parameters are widely available, they have proven to be of only limited value16.Asymmetric hearing loss (AHL) and its extreme form single-sided deafness (SSD) impair speech understanding in background noise20. In addition, the degree of asymmetry of glucose metabolism between ipsi- and contralateral PAC varied between subjects. With longer duration of deafness, the initially reduced activity in the auditory cortex contralateral to the more hearing-impaired ear increased20, so that asymmetry of PAC decreased with time. Thus, we hypothesized that these changes might be due to cross-modal takeover of the PAC by other sensory systems 22. Therefore, the outcome with CI can possibly be predicted before actual implantation. The aim of this study was to examine whether the neuronal activity in the PAC assessed by 18FDG PET predicts speech recognition with CI.In a prior study, we showed that AHL and SSD alter glucose metabolism [as a measure of neuronal activity] of the contralateral colliculus inferior and primary auditory cortex (PAC)18FDG PET for clinical indication . Characteristics of included CI recipients are given in Table Approval by the local ethics committee of the Freiburg University  was granted and all subjects gave written informed consent. The present study was conducted in accordance with the guidelines of the Declaration of Helsinki . We retrospectively included nine right-handed CI recipients with AHL or SSD (mean age 46 ± 20 years) who received a pre-surgical 23, number recognition in the Freiburg intelligibility test23 and the Oldenburg sentence test (OLSA)25 in quiet. All audiometry tests were performed in a sound-proof booth using the Auritec AT 1000 device. Speech material was presented via headphones to the better-hearing ear and via audio cable to the CI.We included hearing tests performed six months after initial fitting of the CI. Audiometry tests of speech recognition at 65 dB SPL (decibel sound pressure level) included monosyllabic word recognition in the Freiburg intelligibility test23 consists of 10 groups of 20 monosyllabic words each and 10 groups of 10 two-digit numbers each. We presented one group of words and one group of numbers at 65 dB SPL. The participants were asked to repeat the words or numbers and guess if unsure. Adults with normal hearing are expected to repeat 100% words and numbers correctly at 65 dB SPL26.The Freiburg intelligibility test26. Higher scores (in % correct) in all three tests indicate better performance.The 5-word-sentences of the OLSA are randomly combined from ten possible words: name—verb—numeral—adjective—object resulting in sentences that are grammatically correct but semantically unpredictable. The participants were asked to repeat the sentences and guess words if unsure. Adults with normal hearing are expected to repeat 100% of sentences correctly at 65 dB SPL20. In brief: Prior to PET, patients fasted for at least 6 h and were intravenously injected with 207 ± 24 MBq 18FDG (euglycaemia). At 50 min after injection under resting conditions , a static 10-min PET scan was acquired. During the first 50 min after injection 4 patients with AHL wore a hearing aid on their better ear to mirror their every-day hearing situation  and an in-house 18FDG PET template. In analogy to Speck et al.20, averaged 18FDG uptake of the 25% of voxels with the highest uptake within the PAC was calculated after proportional scaling of individual PET data to the uptake in cerebellar cortex. The PAC volume of interest (VOI) was taken from Morosan et al.27 and comprised the subregions Te1.0, Te1.1, and Te1.2 . The cerebellar cortex VOI was taken from the SUIT atlas28.All PET scans were performed on a fully digital high-resolution clinical PET/CT system . PET acquisition and processing was performed as previously described18FDG uptake of the PAC were assessed by an asymmetry index . The reference value of AI-PAC was derived from the control population as the upper limit of the 95% confidence interval of the absolute value of AI-PAC. As a control sample, 18FDG PET scans of healthy individuals  with normal hearing acquired under identical conditions with the same PET system were evaluated . Of note, given the recent advent of fully-digital PET/CT system, the currently available control sample showed higher mean age than the patient sample . However, a confirmatory analysis of an age-matched cohort acquired with a different state-of-the-art, conventional PET/CT scanner showed that the AI-PAC is stable across age , 44 ± 9 years, AI-PAC [95% CI] = 3.22 [1.7–4.7]). The AI-PAC was not significantly different between control cohorts (p > 0.1) and there was no significant association with age, neither within nor across cohorts .Individual differences in normalized 27, the course of the auditory pathway30, and the inferior colliculi.All patients received cerebral MRI with special focus on the structures of the inner ear and the auditory pathway. The delay from MRI to PET examinations was on average 78 ± 76 days. All MRI scans were re-evaluated by an experienced radiologist (5 years of experience in neuroimaging). Special attention was paid to the PACDeafness duration and age at symptom onset were evaluated as commonly used predictors of CI outcome. The onset of deafness was defined as the time at which a hearing aid was no longer worn on the poorer-hearing ear because of the lack of benefit. Deafness duration and age at symptom onset were primarily treated as continuous variables. For exploratory reasons, deafness duration was split to short and long duration based on the median of the cohort. Age at symptom onset was additionally dichotomized into ‘perilingual’ vs. ‘postlingual’ SSD and AHL (see Table https://www.R-project.org/).Pearson correlation analyses were performed to estimate the strength of relationship between each of the hearing tests  and non-audiological parameters  as well as among non-audiological parameters. As for clinical decision making it is common to use binary stratifiers, we calculated effect size (Cohen’s d) between binary groups for each predictor. Statistical analyses were performed using R software  PAC and audiological tests, disease duration or age at symptom onset .Pre-operative AI-PAC showed a significant positive correlation with sentence recognition  and number recognition , and trend-level association to monosyllabic word recognition  with CI six months after initial fitting. For patients with AI-PAC ≥ 4.2%, OLSA and numerical recognition with CI were 59–90% and 90–100%, respectively, indicating good to excellent CI outcome  showed very large group difference in OLSA , number recognition  and monosyllabic word recognition , respectively  were observed. Visual and voxel-wise assessments of healthy controls revealed no pathological findings.Pre-operative deafness duration was significantly negatively associated with OLSA with CI . Neither number recognition nor monosyllabic word recognition were associated with deafness duration  showed large to very large differences in OLSA , number recognition  and monosyllabic word recognition , respectively , number recognition  and monosyllabic word recognition , see Fig. Based on perilingual vs. postlingual SSD and AHL , groups showed very large differences in OLSA performance , number recognition  and monosyllabic word recognition , for onset perilingual vs. postlinugal SSD and AHL, respectively.18FDG PET was examined as a possible objective predictor of CI outcome in patients with AHL and SSD. The AI-PAC before CI was associated with performance in the audiological tests six month after initial fitting of CI indicating that better early outcome was associated with higher AI-PAC, i.e., greater neuronal activity of the ipsi- relative to the contralateral PAC. Moreover, for patients with AI-PAC exceeding the asymmetry that was present in a control cohort, 6-month follow-up examinations showed good to excellent performance in sentence and number recognition here, emphasizing the value of the 18FDG PET as a predictor of early CI outcome in patients with AHL. These patients, with a pre-operative AI-PAC ≥ 4.2%, showed better monosyllabic word recognition than those with a lower AI-PAC. Nevertheless, monosyllabic word recognition was poorer than expected for 6-months follow-up examination in both groups33.In the present study, the asymmetry of neuronal activity of the auditory cortex as assessed by 20. Moreover, hypometabolism in the auditory cortex contralateral to the more hearing-impaired ear diminished in patients with longer duration of hearing impairment20, possibly indicating a reorganization at the cortical level. Similar effects were shown by Han et al.34 in 37 patients with bilateral deafness: the hypometabolism in both auditory cortices decreased with longer duration of deafness. Driven by these findings, we hypothesized that the asymmetry of the glucose metabolism will inversely reflect the level of cortical reorganization in the PAC.Previously, our group has shown that asymmetric hearing loss has a significant impact on glucose metabolism of the auditory pathway35 showed a predictive value of the glucose metabolism in prefrontal cortex and superior temporal gyrus on CI outcome in 33 children with congenital bilateral deafness using 18FDG PET. In 2021, Sun et al.36 used preoperative MRI to demonstrate that outcome with CI in subjects with bilateral hearing impairment can be predicted by gray matter volume in the left superior, middle temporal cortex and bilateral thalamus. In contrast, Han et al.34 found that the metabolism of the PAC did not correlate with CI outcome in subjects with bilateral deafness and interpreted the lack of prognostic value as a sign of resistance of the PAC to cross-modal plasticity in patients with postlingual bilateral deafness. In the cohort of patients with AHL and SSD presented in the current study, the metabolism of the PAC contralateral to the more hearing-impaired ear similarly to Han et al.34 did not correlate with CI outcome, while the AI-PAC indeed showed good prognostic value.Our results and conclusions are strengthened by the literature on subjects with bilateral deafness. Lee et al.40. In most studies in subjects with bilateral deafness, the age of deafness onset is set to the time when oral communication becomes impossible even with well-fitted hearing aids. This is, however, not feasible for patients with AHL and SSD, as an oral communication is further possible using the better-hearing ear. The onset of deafness is therefore defined as the time at which a hearing aid is no longer worn on the poorer-hearing ear because of the lack of benefit. Ambiguity in determining the time of the disease onset and the respective deafness duration can among others explain limited association to the post-operative outcome. This underlines the possible advantage of the AI-PAC as an objective predictor that is not dependent on the memory or cooperation of the patient.Duration of deafness in AHL and SSD is ill-defined and in general is a highly subjective measure that relies heavily on individual disease burden and patient’s memory. Nevertheless, it is widely used and has been proven to be a predictive factor of CI outcome in subjects with bilateral deafness42. In this study, the reported age at symptom onset for patients with SSD/AHL onset in childhood heavily relies on informal reports of their parents. Nevertheless, we found a positive correlation between age at deafness onset and speech recognition with CI: patients with later disease onset showed stronger benefit from an implantation. As discussed by Han et al.34, deafness at an older age may lead to less cross-modal plasticity of the auditory cortex. This hypothesis is further promoted by findings of Lee et al.35 in subjects with prelingual bilateral deafness. In support of this theory, two participants with perilingual AHL included in the present study had low AI-PAC. These findings further support a stronger plasticity at younger age. A prompt therapy with CI may therefore be advisable in young patients with AHL or SSD.Similarly, to deafness duration, age at symptom onset is not usually a reliable measure. Especially difficult is the definition of age at symptom onset in childhood for SSD and AHL. Before the obligatory bilateral newborn hearing screening (in Germany since 2009), children with prelingual SSD were usually not diagnosed before they reached school age38, degree of residual hearing38, tinnitus43, surgical technique44 and pre-existing vestibulopathy45. In contrast, the literature of predictive factors in subjects with SSD and AHL is sparse. A meta-analysis by Kitterick and Lucas16  showed a significant negative association between speech recognition in noise with CI and duration of deafness and a significant positive correlation with residual hearing in the implanted ear16. As only two included subjects showed residual hearing in the poorer-hearing ear in the present study, we were not able to examine the impact of residual hearing on CI outcome in the present study.Besides deafness duration and age at symptom onset, various alternative markers have been proposed as predictors of CI outcome in patients with bilateral deafness: age47 and the temporal difference limen47 was assessed to estimate functional intactness of the auditory nerve. Only those perilingual onset patients in whom promontory test indicated functional intactness of the auditory nerve were considered as candidates for CI. Despite the possible limited outcome in patients with longer hearing impairment, possible (SSD) or starting hearing impairment (AHL) of the better-hearing ear was one of the main reasons to decide for an implantation in all included patients. The negative effect of SSD on the hearing capacity of the better-hearing ear as well as a possible protective effect of a CI were previously reported by Arndt et al.48. Nevertheless, perilingually deafened patients are still borderline candidates for a CI and are therefore extensively consulted on a possibly limited outcome of implantation. Additional predictive factors like the one investigated in the present study cortex could further improve the indication and examination in such borderline candidates.Patients with longer durations of deafness are usually considered as borderline candidates for CI. Nevertheless, some perilingual patients with long disease duration reported in this study have been considered for CI implantation based on the following considerations: First, the earliest reported date has been chosen as time of symptom onset and, therefore, the duration of hearing impairment is likely to be overestimated. Second, functional integrity of the auditory nerves in these patients was confirmed by promontory tests. Promontory test was performed by placing an electrode through the local anesthetized eardrum on the promontory to electrically stimulate the auditory nerve. A hearing impression during stimulation, gap detection during hearing impressionWe decided to report hearing measurements six months after initial fitting of the speech processor of the CI to test our hypothesis that pre-operative AI-PAC is correlated to outcome with CI. Still, six months of CI experience is a relatively short time to assess final outcome.49 showed that subjects with pre- and postlingual deafness have a performance peak six months after initial fitting of their CI. Nevertheless, ongoing improvements are still reported twelve months after initial fitting51 and in some tasks  even later12. Thus, the present relatively short follow-up time limits the predictive value of the AI-PAC to early outcome with CI. In particular, this applies to patients with early onset, in whom improvements with CI may require more time49. We are therefore planning to further validate our results in one, two, and five years after initial fitting.Cusumano et al.This study is further limited in number of enrolled patients. Given the heterogeneity of the cohort in terms of etiology, disease onset and duration, the results need to be reproduced in larger studies. Moreover, the potential value of proposed predictor has to be separately addressed in pre- and postlingual patients.Spatial hearing tests and OLSA in noise were not available for all included subjects six months after initial fitting of the CI. Therefore, we did not include these audiometric tests in our study. In future, prospective studies including a higher number of participants’ spatial hearing tests and speech recognition in background noise are planned at 6 months after initial fitting and yearly afterwards.18FDG PET may serve as a potential predictor of early post-operative CI outcome and employed as unbiased objective precision medicine tool in patients with AHL and SSD. Studies with a larger number of subjects and longer follow-up time are necessary to confirm our hypothesis.In conclusion, pre-operative asymmetry of the glucose metabolism in the PAC assessed by


Despite recent evidence that sensory loss may increase risk of dementia, mood disorders, and poor physical health in older adults, nearly all research to-date has been conducted in populations that are predominantly White and from high-income countries. This session will investigate the intersectionality of race with sensory loss with a focus on health equity and inclusion of traditionally underrepresented populations. It will evaluate sensory loss across multiple senses, how patterns vary by race, and whether socioeconomic status can explain these differences. In the US, prevalence of impairment in vision, touch, and smell is lower in Whites compared to Black or Hispanics. Interestingly, hearing loss prevalence is lower in Blacks than Whites, but dementia incidence is higher. This session will describe incident dementia risk associated with hearing loss in Black compared to White Americans. It will also address the relationship between dual (hearing and vision) loss and depressive symptoms in India to explore the generalizability of findings to lower middle-income countries. Sensory impairments may intersect with racial discrimination to exacerbate social and health disparities. This session will also describe racial disparities in food insecurity among Americans with vision loss. Finally, we will present results of a randomized controlled trial of an innovative, community-delivered approach to affordable, accessible hearing care. The study represents the largest U.S.-based trial cohort to date of low-income older adults and older African American adults with hearing loss.


Wulira app is a valid and potentially cost-effective alternative to pure tone audiometry in screening for occupational hearing loss. We aimed to determine the prevalence of occupational hearing loss among workers in a metal industry company in Kampala district.Occupational noise is a common cause of hearing loss in low-income countries. Unfortunately, screening for hearing loss is rarely done due to technical and logistical challenges associated with pure tone audiometry. We recruited 354 participants conveniently from a steel and iron manufacturing industry in Kampala. All eligible participants answered a pretested and validated questionnaire and were assessed for noise induced hearing loss in a quiet office room approximately 500 meters from the heavy machinery area using the Wulira app. Descriptive statistics such as proportions were used to describe the study population while inferential statistics were used to determine associations.Of the 354 participants sampled, 333 (94.1%) were male, and the median age was 27, IQR (25–30). Regarding the risk factors of hearing loss, fourteen (3.9%) had history of smoking and more than half (65.5%) had worked in the industry for more than 2 years. The overall prevalence of hearing loss among industrial workers was 11.3% (40/354). 16.2% and 9% had mild hearing loss in the right and left ear respectively. Bilateral audiometric notch was present where fourteen (4%) of the participants had notch in their right ear while seven (2%) had notch in their left ear. Residing outside Kampala district was associated with hearing loss , p = 0.013).One in 10 workers in a metal manufacturing industry in Kampala had occupational hearing loss. Industrial workers residing outside Kampala were likely to develop hearing loss. Periodic screening should be done for early detection and intervention to prevent progression of hearing loss in this population. The World Health Organisation (WHO) reports that close to half a billion people suffer from disabling hearing loss which is expected to rise to 630 million by 2030 . This isIn Uganda, metal manufacturing industries contribute significantly to the economy of the country through provision of employment and payment of taxes –15. HoweTo reduce the risk of OHL, early detection and prevention is critical in addressing this occupational hazard. To differentiate age related hearing loss from OHL, the use of audiometric notch has been proposed . This caHowever, mobile audiometry, which is hearing loss screening using mobile phones and tablets, could bridge this challenge. One of the available mobile phone -based hearing loss screening tools is the Wulira app which has a specificity of 93.2% and 91.5% for the right and left ear respectively and sensitivity of 91.4% and 88.4% for the right and left ear . This shWe conducted a cross-sectional study among participants from a metal manufacturing industry in Kampala district from January 2021 to April 2021. We approached all the three potential metal manufacturing industries in Kampala who had more than 400 employees. Only one factory granted us permission to recruit their employees and a non-disclosure agreement was signed with the industry.The industry employs over 900 workers of which an estimated 400 individuals work with machines that produce noise. Individuals with hearing loss are excluded from working at the factory during the pre-employment hearing evaluation. We retrieved a list of employees who worked in the noisy sections of the industry from the management and randomly selected 354 participants. There was no measure of ambient noise in the factory sections. Study participants who worked more than 4 hours a day in the highly noisy machine areas were approached to participate in the study. Industrial workers who were 18 years and above and had consented to take part were included into the study. We excluded factory employees who used hearing aids, had current history of bilateral outer, middle, or inner ear infectious pathology based on examination by an audiologist. Those with vertigo were considered to have benign paroxysmal positional vertigo, which minimally affected their participation in the hearing assessments.Using the Kish and Leslie formula for a single proportion , at a deWedemark, Germany https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool,  7 Oct 2022Reviewer #1: It is a very good study, but I have a doubt. The industry had 900 employees, 300 were excluded for not working exposed to noise. That gives me 600 and not 400 employees exposed to noise. Is it a mistake?Response: Thank you for your comment. Yes, this is mistake in the write up. The actual number exposed to noise is 400 as outlined in the study population section of the manuscript. The actual number of employees excluded is 500. The tables have been updated as such.Reviewer #2: There is a difference in the rate of hearing loss between ears. Was this significant? The authors include this fact in the discussion, nevertheless, this an unexpected finding in workers exposed to noise coming from several sources simultaneously. There was a difference between low-frequency and high-frequency hearing loss, the former being more prevalent. This is also an unexpected finding since occupational hearing loss is characterized by high-frequency hearing loss.The last two comments lead me to check the original publication about the Wulira app. The paper previously published by the authors showed that the app had a good sensitivity and specificity to detect subjects with normal hearing. But the sensitivity dropped to approximately 53% when subjects had mild hearing loss, and even below 50% for more severe cases. Maybe the app should be employed as a screening tool for identifying subjects with normal hearing levels, but the use as a diagnostic method of levels of hearing loss is still questionable. This issue could explain the findings of differences between ears and the higher prevalence of low-frequency hearing loss.This is the reason I do not recommend this paper for publicationResponse: Thank you for your comment. Yes, there is a statistically significant difference between the hearing loss between the ears. The P value is less than 0.001. It is true that this is an unexpected finding among workers exposed to noise from different directions/sources simultaneously. Previous research has, however, noted differences in hearing loss by ear side among Finnish individuals exposed to chronic noise (1) while other researchers have demonstrated asymmetry in OHL (2).This has been added to the discussion lines 253—259.Regarding the high prevalence of low frequency noise induced hearing loss, this contrasts with previous studies as we have highlighted in our discussion previously. We also agree that the frequency of “high frequency hearing loss” should be more for noise induced hearing loss than that seen in our study. The other possible explanation for this could be the inherent Wulira app performance as you highlight. This has been added to the discussion, line 270—271. The other underlying diseases/conditions for causing low frequency hearing loss like Meniere’s disease in our population were not ruled and this has been added as a limitation, line 303—304. We have also highlighted throughout the manuscript that the tool should be used as a screening tool.Reviewer #3: The paper study the prevalence of occupational hearing loss among workers of metal manufacturing company located in Kampala, Uganda. The assessment was performed using the Wulira App. It was found that about 10 percent of the workers of this company had occupational hearing loss. The results highlight the importance of hearing loss screening among this populations and the usefulness of the Wulira App as an alternative to pure tone audiometry as a screening tool.The paper is well written and clear. The methodology is sound, and the results are interesting. For these reasons, I recommend accepting the paper after the following issues are addressed:* Major Issues- Show some examples of the audiometry obtained with the Wulira App. For instance, show one audiometry of a subject with occupational hearing loss and one of a subject without it. This will allow the reader to get a better understanding of the kind hearing loss observed in the population studied.Response: Thank you for your comment. These have been addedhttps://en.wikipedia.org/wiki/Pie_chart#Use_and_effectiveness for the rationale about avoiding pie charts. I suggest checking this reference (in particular section 6.1) for some guidelines about appropriately presenting bar graphs: https://clauswilke.com/dataviz .- Use a bar plot for figure 2. See Response: Thank you for your comment. A bar plot has been added- Line 202: Explain why reporting the religion is relevant. And if it is, please also report the other religions of the population.Response: Thank you for your comment. Religion is not important and hence has been removed.- In the paragraph starting at line 239 you compare the prevalence of your results with other studies and suggests some reasons to explain the differences. One factor that you do not consider explaining the difference is the use of the Wulira App. Is it possible that differences in the results are because you use a different tool to get the audiogram? Please comment about this issue in the discussion section.Response: Thank you for your comment. We included a sentence explaining the fact that other studies used PTA as compared to ours that utilized Wulira App. See lines 243—244.* Minor Issues- Line 68: Change "Occupational hearing loss" by "Occupational Hearing Loss."Response: Thank you for your comment. This have been addressed. - Line 91: The sentence "Much as the Constitution ..." is hard to read. Please re-write to facilitate the understanding.Response: Thank you for your comment. This have been addressed.- Line 94: Add a coma before and after of "which is the gold standard for hearing loss screening."Response: Thank you for your comment. This have been addressed.- Line 97: Add a coma before and after "which is hearing loss screening using mobile phones and tablets."Response: Thank you for your comment. This have been addressed.- Line 197: Change "achieved. " by "achieved ."Response: Thank you for your comment. This have been addressed.- Line 225: Change "respectively. (Table 4)" by "respectively (Table 4)."Response: Thank you for your comment. This have been addressed.References.1. Pirilä T, Sorri M, Jounio-Ervasti K, Sipilä P, Karjalainen H. Hearing asymmetry among occupationally noise-exposed men and women under 60 years of age. Scandinavian Audiology. 1991;20(4):217-22.2. Le TN, Straatman LV, Lea J, Westerberg B. Current insights in noise-induced hearing loss: a literature review of the underlying mechanism, pathophysiology, asymmetry, and management options. Journal of Otolaryngology-Head & Neck Surgery. 2017;46(1):1-15.AttachmentResponse to reviewers.docxSubmitted filename: Click here for additional data file. 8 Dec 2022Using mobile audiometry (Wulira app) to assess noise induced hearing loss among industrial workers in Kampala, Uganda: A Cross-sectional studyPONE-D-22-16420R1Dear Dr. Semulimi,We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at onepress@plos.org.If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact Kind regards,Paul Hinckley Delano, Ph.D.Academic EditorPLOS ONEAdditional Editor Comments :Reviewers' comments:Reviewer's Responses to Questions  Comments to the Author  1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.Reviewer #3: All comments have been addressedReviewer #4: All comments have been addressed**********  2. Is the manuscript technically sound, and do the data support the conclusions?  The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #3: YesReviewer #4: Partly**********  3. Has the statistical analysis been performed appropriately and rigorously?   Reviewer #3: YesReviewer #4: Yes**********  4. Have the authors made all data underlying the findings in their manuscript fully available?PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.  The Reviewer #3: YesReviewer #4: Yes**********  5. Is the manuscript presented in an intelligible fashion and written in standard English?  PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.Reviewer #3: YesReviewer #4: Yes**********  6. Review Comments to the Author  Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. Reviewer #3: (No Response)Reviewer #4: The article presented a study of the prevalence of occupational hearing loss among workers in a metal industry company in Kampala district. All recommendations have been addressed by the authors in the current version of the manuscript.**********  7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). 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Compared to normally-hearing employees, those with hearing loss suffer from higher Need For Recovery (NFR) after work. The aims of this study are to assess the NFR of employees with hearing loss before and after aural rehabilitation and to examine to what extent change in the NFR can be explained by changes in subjective listening effort, personal adjustments, communication strategies, auditory work demands, and self-reported hearing ability.t test. Hierarchical multiple analyses were performed.We included patients who received aural rehabilitation in two audiological centers in the Netherlands because of hearing complaints in their work situation. Outcomes were measured by questionnaires at baseline and 3 month follow-up. The NFR before and after the rehabilitation was compared with a M = 45.03) compared to before the aural rehabilitation (M = 51.89), t = −3.43, p < 0.01). Change in NFR could best be explained by the change in personal adjustments .In total, 60 patients  participated in the study, of which 50 completed the follow-up questionnaires. The NFR was significantly lower after the aural rehabilitation (The NFR of employees with hearing loss can be improved by aural rehabilitation, but this study shows that current practices reduce the NFR only in part of the employees. Therefore, improving current practices should be considered and evaluated, for example by applying a different combination of rehabilitation components. Especially, interventions that affect personal adjustments may be promising to further reduce the NFR in employees with hearing loss. Hearing loss is a prevalent health problem and can severely affect the well-being and work functioning of employees  and some factors influence both NFR and LE according to this model. Specifically, NFR and LE are influenced by the feeling that something should change at work and by making personal adjustments, which include self-acceptance, acceptance of loss, and stress and withdrawal. It was found that “feeling that something should change” and a poorer ability to make personal adjustments were associated with higher NFR and higher LE.Differences between the constructs NFR and LE were also reported in that study. According to the model, NFR is influenced by employees’ general health condition, but LE is not. Reporting a moderate or poor health condition, rather than a good health condition, was found to correlate moderately with a higher NFR. Furthermore, it was found that LE is influenced by employees’ hearing status measured with pure-tone audiometry, but NFR is not. Earlier studies report inconsistent results regarding the association between hearing status and NFR  and 3 months follow-up (T1). Between T0 and T1, patients received different components of aural rehabilitation.This prospective study was performed in employees with hearing loss who received aural rehabilitation at two audiological centers in the Netherlands, respectively at one location of the Amsterdam University Medical Center (UMC) and at three locations of Libra Revalidation and Audiology. Outcomes were measured by an extensive online questionnaire at baseline  for this study, for sending a second survey for research purposes after 3 months, and for accessing their patient file to extract their pure-tone audiometry results and the type of intervention that was applied. Patients were excluded if the reason for their referral was an auditory fitness for job assessment, because these patients visit the audiological center to ensure that they can perform their job safely and effectively rather than to reduce their LE and NFR. Patients were also excluded if the first visit at the audiological center was cancelled, if the baseline questionnaire was not filled in or was filled in after the start of the intervention, and if there was no indication for aural rehabilitation , patients who used one hearing aid at T0 and received a second hearing aid , patients who used hearing aids at T0 and received new hearing aids (repeated fitting), and patients who used hearing aids at T0 of which the settings were optimized (fine-tuning HA). Sensory management interventions were provided by or under supervision of an audiologist.Sensory management interventions could include the provision and fitting of hearing aids and other assistive listening devices, such as table microphones. We distinguished the provision and fitting of hearing aids in patients who did not use hearing aids at Perceptual training could involve a speech reading training. This training could be provided individually or the patient could be referred for a group training. Perceptual training was provided by a speech therapist and a social worker.Instruction and counselling were described as one category, because we expected that the subtle difference between instruction and counselling could not be recognized easily based on a patient file. The instruction/counselling could focus on coping—the development of effective listening strategies and coping behavior—or on work adjustments, such as adjusting working hours or environmental changes that improve room acoustics at the workplace. The instruction/counselling could be provided by an audiologist, psychologist, social worker, or an occupational physician.We retrospectively derived the details of the provided aural rehabilitation components  from patient files Table . RegardiT0 and T1, patients received questionnaires by email. The questionnaires at T0 and T1 are the same, except for demographics that were only included at T0 . The questionnaires included questionnaires assessing the NFR, LE, “feeling that something should change”, personal adjustments, communication strategies, auditory work demands, and self-reported hearing ability.At The baseline questionnaires are routinely administered at the two audiological centers. The moment that patients receive these questionnaires slightly differ between the two centers. Patients who visited the Amsterdam UMC received the baseline questionnaire before the intake at the audiological center. Patients who visited Libra Revalidation and Audiology received the baseline questionnaire just after the intake with the audiologist. The follow-up questionnaires are not routinely administered at the audiological centers and were sent for research purposes.All questionnaires were sent via the clinical management program Castor Electronic Data Capture . This program complies with the Good Clinical Practice guidelines.NFR was assessed using the NFR scale that is part of the Questionnaire on the Experience and Evaluation of Work 2.0 (QEEW 2.0)  was used to assess personal adjustments and communication strategies , defined as the mean pure-tone thresholds for air conduction at 1000, 2000, and 4000 Hz with a 5:1 weighting favoring the better ear (American Academy of Otolaryngology (Committee on Hearing 1979).Self-reported hearing ability was assessed with the Speech, Spatial, and Qualities of hearing scale (SSQ) . Every determinant was used separately in a univariate regression model and hierarchical multiple analyses were performed. For the primary and the secondary outcome measures, the first block consisted of the potential confounders age, gender, educational level, and BHI. In the next blocks, the determinants were added one by one. For each block, we calculated the change in amount of variance.Data were analyzed using the Statistical Package for Social Sciences (SPSS) version 26.0 (Armonk New York USA). For all tests, the type I error was set to 0.05 and all tests were two-sided.r = 0.46, p < 0.01), LE , general health condition , and personal adjustments .Table r = 0.46, p < 0.01), auditory work demands , and personal adjustments . A non-significant association was found between LE and the BHI .In accordance with the previous findings, LE was moderately associated with “feeling that something should change” , personal adjustments (p < 0.01), and SSQ quality (p < 0.01). In the hierarchical regression analyses, the amount of variance changed significantly when the determinants subjective listening effort, personal adjustments, and SSQ quality were added to the model , auditory work demands (p = 0.01), SSQ speech (p < 0.01), SSQ spatial (p = 0.03), and SSQ quality (p = 0.03). In the hierarchical regression analyses, the amount of variance changed significantly when the SSQ speech was added to the model  the aural rehabilitation. Also, the study population was too small to run subgroup analyses on patients who received the same intervention. The post hoc power analysis that was based on the effect size of NFR revealed that the 80% power was not achieved. This implies that our study might have been slightly underpowered to detect changes in the NFR. Despite this, we found a significant difference in the NFR.We carefully described the components of aural rehabilitation that were provided using patient files, but we may have missed some aspects of the provided rehabilitation. For example, audiologists of the included audiological centers often give some kind of instruction on how the hearing aids or assistive listening devices function and how they can be properly used. However, this type of instruction was not administered in the patient files, and is therefore not reported in this study. Another study limitation is that the follow-up time of this study was relatively short. Aural rehabilitation was provided within this period in most, but not in all patients, which resulted in the exclusion of a few patients. An advantage of the follow-up time of 3 months is that there is a smaller chance that the NFR has changed due to other reasons than the aural rehabilitation.The NFR and LE of employees with hearing loss can be improved by aural rehabilitation, but this study shows that this is true in only part of the employees. Therefore, improving current practices should be considered and evaluated, for example by applying a different combination of rehabilitation components. Especially, interventions that affect personal adjustments may be promising to further reduce the NFR in employees with hearing loss.