To investigate the contribution of duration and temporal dispersion (TD) of the distal compound muscle action potential (CMAP) in discriminating chronic inflammatory demyelinating polyneuropathy (CIDP) from diabetic sensorimotor polyneuropathy (DSP) and from CIDP+DSP.We performed a retrospective review of patients diagnosed with CIDP, DSP and CIDP+DSP (responsive to immunotherapy) and examined differences in CMAP duration and TD at baseline.We included 59 subjects: 17 CIDP, 21 DSP and 21 CIDP+DSP. Of these, 16 (94.1%) CIDP, 18 (85.7%) CIDP+DSP and 1 (4.7%) DSP fulfilled the 2010 EFNS/PNS criteria for definite CIDP. There was no difference in CMAP duration or TD in all nerves (compound outcome) or in individual motor nerves. Patients with CIDP/CIDP+DSP had more conduction blocks, slower conduction velocities and more prolonged F wave latencies than those with DSP.Measures of CMAP duration and TD were not helpful in distinguishing CIDP, DSP or CIDP+DSP patients; however, parameters such as F-wave latencies, conduction blocks or the number of demyelinating parameters were useful in this separation.There are no definite nerve conduction criteria to distinguish patients with CIDP+DSP from DSP alone. Further studies focusing on measures of demyelination may provide stronger evidence to guide treatment decisions in CIDP + DSP patients. Diabetic neuropathy is the most frequent complication of diabetes mellitus (DM), however the diagnosis is not always straightforward, as up to 50% of the patients can be asymptomatic . ClinicaDSP usually affects the peripheral nervous system in a length-dependent fashion, where distal segments are predominantly involved, sensory nerves are damaged prior to motor nerves and rarely results in major weakness , 4. ChanThe accurate diagnosis of CIDP in the context of DM should be a matter of utmost importance as CIDP is the most frequent treatable inflammatory neuropathy , 15–17. The European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) clinical and electrodiagnostic criteria for CIDP have been established as the most useful criteria in discriminating demyelinating neuropathies from other processes, demonstrating a very good balance between sensitivity and specificity . Among tThe diagnosis and treatment of CIDP+DM is challenging and can be delayed, as symptoms might be erroneously attributed to DSP or other causes, which can lead to lack of treatment . Our priWe performed a retrospective review of patient charts previously coded as CIDP, DSP and CIDP+DSP from August 2007 - December 2020 according to expert opinion (VB) and included adult patients (aged 18 years and older) with a final diagnosis of DSP, CIDP and CIDP+DSP who responded to immunotherapy . To be included as a CIDP case, only typical variants were considered, defined as: (1) chronic, progressive, stepwise or recurrent, proximal and distal weakness/sensory dysfunction developing over at least 2 months and (2) reduced or absent reflexes in the upper and/or lower limbs. Patients with confirmed hereditary neuropathies, paraproteinemia, other autoimmune diseases, thyroid diseases and suspected paraneoplastic diseases were excluded. Patients had to be free of DM by the time of the first assessment.DM diagnosis was confirmed according to the American Association of Diabetes criteria and was based on the following abnormalities: hemoglobin A1c, fasting plasma glucose, random elevated glucose with symptoms or abnormal 2-h oral glucose tolerance test . To be iWe extracted demographic data, physical examination, measures of disability, laboratory results and electrophysiologic data. Disability was measured by the RODS  in patients with CIDP and the ONLS  in all patients , 34. TheNCS were performed using the Sierra Wave instrument . Age and height-adjusted reference values were used, according to the standards of the TGH (UHN) electrophysiology laboratory. Limb temperature was measured and maintained at ≥32.0°C in the hands and ≥31.0°C in the feet. Motor nerve CMAP amplitudes were measured as peak to trough with a sweep speed of 5 ms/div and a gain of 5 mv/div and the filters were 10-10k for all nerves. The F-wave latency was determined by both the minimum and maximum reproducible latency obtained after 10 supramaximal stimuli and using a sweep speed of 10 ms/div (and adjusted accordingly) and a gain of 500 v/div. Latencies, amplitudes and duration were measured for each nerve at each stimulus site and conduction velocity (CV) between stimulus sites. All motor tracings for the median, ulnar, fibular and tibial nerves were reviewed for quality assessment by two independent technicians (MN and JDC) and posteriorly EFNS/PNS guidelines were applied to classify each case . We considered segments in the forearm and foreleg to determine the presence of demyelinating parameters. Conduction blocks were measured in the median, ulnar and fibular nerves. All NCS included in this study were done at baseline, prior to immunosuppressive/immunomodulating therapy in both CIDP and CIDP+DSP patients.Our main outcome was the difference in duration and TD of the distal CMAP duration between patients with CIDP, DSP and CIDP+DSP. CMAP duration was defined as the interval between onset of the first negative peak and return to baseline of the last negative peak for the following nerves as defined: median ≥ 6.6 ms, ulnar ≥ 6.7 ms, peroneal ≥ 7.6 ms and tibial ≥ 8.8 ms, according to EFNS/PNS guidelines , 28. Thit-tests/Mann-Whitney; analysis of variance (ANOVA) or the Kruskal–Wallis test. Homogeneity of variances were assessed with Bartlett's test. Spearman's correlation coefficient was used to assess correlation between continuous variables. Results were adjusted for multiplicity with the Bonferroni correction and p-values < 0.05 were considered significant. In an exploratory analysis logistic regression was used to model the predicted probability of attaining definite or probable categories in the EFNS/PNS criteria according to the total number of demyelinating parameters. All analyses were performed in Stata version 16.1 .The data was assessed by plots and/or the Shapiro-Wilk test to verify any deviation from normal distributions. Demographic data were expressed as means/standard deviation (SD) for normally distributed data, or median and interquartile range (IQR) for the remainder. Differences in categorical variables were assessed using Fisher or Chi-squared tests, while differences in continuous variables (electrophysiologic parameters) were assessed by We included 59 subjects: 17 with CIDP, 21 with DSP and 21 with CIDP+DSP. There was no difference in age, gender or the duration of the neuropathy in the groups or in the duration of DM in DSP and CIDP+DSP groups. Patients with CIDP/CIDP+DSP had greater disability when compared to patients with DSP . On the other hand, there were no differences in the level of disability between CIDP and CIDP+DSP patients (ONLS and RODS). There were no correlations between the level of disability with age or duration of neuropathy in all groups . The sumSixteen CIDP patients (94.1%), 18 with CIDP+DSP (85.7%) and 1 with DSP (4.7%) fulfilled the EFNS/PNS electrodiagnosis criteria of definite disease before therapy . Five paTwelve CIDP patients (70.6%) and 13 CIDP+DSP patients (62%) had at least one nerve with CB. Three DSP patients (14.3%) had one nerve with CB and these nerves showed only ≥30% CMAP amplitude reduction. The criteria for ≥50% CMAP amplitude reduction was only fulfilled by CIDP patients (6 nerves) and CIDP +DSP (13 nerves). Patients with CIDP+DSP had significantly reduced amplitudes and prolonged F-waves when compared to other groups .Overall, the number of demyelinating parameters  was higher in both CIDP and CIDP+DSP patients . The preThere are multiple diagnostic challenges in differentiating CIDP from other neuropathies and one of the most important is the absence of a clear biomarker, which directly impacts treatment decisions. We have applied EFNS/PNS criteria in a systematic manner and while focusing on measures of distal CMAP duration and dispersion, we could not find any difference between the groups of CIDP, DSP or CIDP+DSP patients in our sample.While unique parameters to distinguish demyelinating features in diseases that are predominantly axonal could provide invaluable support for the diagnosis of CIDP in the context of DM, this has been a matter of debate over the years and no consensus has been reached , 6, 8, 9From a practical standpoint, the treatment response might be affected by the degree of demyelination. Some studies have provided evidence that fulfilling a higher number of electrophysiological criteria in CIDP patients, with and without DM, can be associated with better treatment responses , 23. FurInterestingly, we could also demonstrate that patients with DSP presented with less CB and their nerves showed CB only if defined as a ≥30% CMAP amplitude reduction, which would add only to “probable” category according to EFNS/PNS electrophysiologic criteria and would not be helpful in distinguishing categories. Furthermore, patients with CIDP and CIDP+DSP showed significantly reduced CV and patients with CIDP showed significantly prolonged F-wave latencies. Although this is also a matter of speculation, these findings suggest that as CV can be similarly reduced in both CIDP and CIDP+DSP patients, parameters such as CB and F-wave latencies might better differentiate CIDP patients from DSP. Additionally, F-waves were found to be more significantly prolonged only in CIDP patients, which could suggest a more diffuse demyelinating process, including more proximal segments, as compared to other groups. Whether the CB demonstrated in DSP patients could represent excess segmental demyelination in diabetic polyneuropathy and a superimposed process, is still a matter of debate and should be interpreted with caution.The current study has several limitations. First, although only statistically significant and adjusted results were considered, our sample is small. Furthermore, misclassification and selection bias could be present, as there is no definitive biomarker to diagnose CIDP, either clinical or electrophysiologic.In summary, measures of duration and dispersion of the distal CMAP were not helpful in distinguishing CIDP, DSP or CIDP+DSP patients in our sample. Our findings suggest that these parameters might be less useful than other variables (such as F-wave latencies or CB) to differentiate patients that could respond to therapy. Further studies focusing on other measures of demyelination might provide stronger evidence to guide treatment decisions in CIDP+DSP patients.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by University Health Network Research Ethics Board. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.MA contributed to data collection, statistical analysis, and first draft and review. MN and JC contributed to data collection and quality assessments. CB-T, HK, and VB contributed to design, analysis, and critical review. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


One in four older adults experience social isolation. Sensory impairment is a potentially modifiable risk factor for social isolation. Little is known about the long-term impact of sensory impairment on social well-being. This study quantifies the longitudinal associations between hearing, vision, and concurrent hearing and vision impairment  and social isolation over 8 years among older adults. Data were from the National Health and Aging Trends Study (NHATS), a nationally representative longitudinal study (2011- 2019) of U.S. Medicare beneficiaries. Social isolation was measured by a composite that incorporated four domains: living arrangement, core discussion network size, religious services attendance, and social participation. Baseline hearing and vision were measured by self-report. Associations between sensory impairments and odds of overall social isolation over 8 years were assessed using multivariate generalized logistic mixed models adjusted for demographic and health characteristics. Among 5,552 participants, 18.9% reported hearing impairment, 4.8% reported vision impairment, and 2.3% reported dual sensory impairment. Over 8 years, hearing impairment was associated with 28% greater odds of social isolation. Specifically, participants with hearing impairment were more likely to live alone and limit engagement in social activities. A similar pattern of association was observed for dual sensory impairment; however, estimates did not reach statistical significance. No association was observed between vision impairment and social isolation. Older adults with hearing impairment may be a clinically important subgroup to monitor for social isolation. Interventions for increasing social support and social participation may be especially valuable for older adults with hearing impairment.


Mucormycosis is a type of fatal infectious disease, rarely involved in the oromaxillofacial region. This study aimed to describe a series of 7 cases with oromaxillofacial mucormycosis and to discuss the epidemiology, clinical features, and treatment algorithm thereof.Seven patients in the author’s affiliation have been treated. They were assessed and presented as per their diagnostic criteria, surgical approach, and mortality rates. Reported cases of mucormycosis originally happened in craniomaxillofacial region were synthesized through a systematic review so as to better discuss its pathogenesis, epidemiology, and management.Six patients had a primary metabolic disorder, and one immunocompromised patient had a history of aplastic anemia. The criteria for a positive diagnosis of invasive mucormycosis were based on clinical presentation of signs and symptoms, and a biopsy for microbiological culture and histopathologic analysis. Each patient used antifungal drugs and five of them also underwent surgical resection at the same time. Four patients died due to the unregulated spread of mucormycosis, and one patient died owing to her main disease.Although uncommon in clinical practice setting, mucormycosis should be of great concern in oral and maxillofacial surgery, due to the life-threatening possibility of this disease. The knowledge of early diagnosis and prompt treatment is of utmost importance for saving lives.The online version contains supplementary material available at 10.1186/s12903-023-02823-4. Mucoromycotina [Absidia, Mucor, Rhizomucor, and Rhizopus are responsible for its aetiology, although Apophysomyces, Cunninghamella, and Saksenaea can also be associated pathogenic species [Mucormycosis is a saprophytic opportunistic, but a highly aggressive fungal infection caused by the class Zygomycetes, belonging to members of Mucorales order, subphylum mycotina . Mainly, species , 3. It i species , 5. Due According to the published literature, the prevalence of mucormycosis is the highest in India that stands approximately at 14 per 100,000 populations, whereas it varies between 0.01 and 0.2 for each 100,000 population in European countries and the United States , 7. FollThe diagnosis and treatment of oromaxillofacial mucormycosis is difficult because of its scarcity. Grasping the magnitude of this formidable challenge would help advance our understanding of oromaxillofacial mucormycosis. Our study, therefore, sought to investigate the diagnostic criteria and treatment approach in the Department of Oromaxillofacial Oncology and Surgery, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, China between 2013 and 2021, through 7 rare cases that demonstrate oromaxillofacial mucormycosis; as well as update and collate the review of literature regarding mucormycosis, exploring the epidemiological characteristics, course of infection, treatment regimens, and clinical outcomes.The present study was approved by the Ethics Committee of the First Affiliated Hospital of Xinjiang Medical University .On the whole, 7 cases admitted to our department from 2013 to 2021 were enrolled in this study. For the objective of guiding internal medication, all patients were assigned to consult a clinical pharmacist group as well. Clinical presentation of signs and symptoms, blood routine examination, blood biochemistry indexes, liver/kidney function tests, radiographic imaging, treatment procedure, post-operative histopathological findings, pathogenic microbes’ culture and antimicrobial susceptibility test, and survival and prognosis were retrospectively analyzed and reported. The study protocol was approved by the Ethics Committee, the First Affiliated Hospital of Xinjiang Medical University and followed the principles outlined in the Declaration of Helsinki. Written informed consent to participate in this study was provided by the participants or legal guardian/next of kin. All data generated or analyzed during this study are included in this published article.In this case series, female patients were affected less frequently than the males with a ratio of 2:5. The median age of patients was 45.0 year-old, ranging from 27 to 63. All seven patients were moderately built and moderately nourished, of which six were known as a history of poorly controlled diabetes mellitus without regular treatment ; and one patient was diagnosed with severe aplastic anemia Table . Three oPrior to surgical operation, 6 of our patients underwent endocrine therapy to treat their primary illness; for the remaining aplastic anemia case, we planned to transfuse platelets during surgery, in cases where platelet count did not reach the minimum level . Antifungal pharmacologic  and comprehensive surgical  treatment were given to five patients Table . And theMucoromycotina”, “fungal infections”, “head and neck region”, “maxillofacial” and “oral cavity”, in combination with Boolean Operators ‘OR’ and ‘AND’. We excluded studies lacking the necessary data and cases with other concomitant suppurative infection lesions resulted from bacteria, such as Staphylococcus aureus, Streptococcus, and Escherichia coli. The resulting publications were searched, and the references of all articles were verified to decrease the possibility of omitting relevant publications. The initial search and review of references retrieved 329 related articles, 183 of which were rejected because of information deficit after screening the titles and abstracts. Two experienced investigators (C. Li and Z. Gong) independently extracted the following characteristics from each eligible study: name of the first author, year of publication, geographical location, demographic information, scope of involvement, clinical manifestation, care given, follow-up period, and outcome  CRD42022382257). We searched for relevant articles within several databanks  published from database inception until June 2022. Search strings used were “mucormycosis”, “Zygomycetes”, “Mucorales”, “022382257Mn = 54, Fn = 34)  Fig. .Fig. 4ChAbsidia, Mucor, Rhizomucor, Rhizopus genera can be the most frequently isolated strain from infecting patients) [Mucormycosis, as a rare and fatal deep fungal infection, is given rise to the family Mucoraceae  , 59. Theatients) . Changesatients) , 62.Due to its scarcity, this is always being a formidable challenge for maxillofacial clinicians to work on the diagnosis of mucormycosis, which is also the key crux to the entire therapeutic schedule. Based on the microbiological characteristics of mucormycosis, the experience of our clinical practice as well as the information of our critical review, we reckon that some points deserve attention as the following sections.Disease site. Generally, mucormycosis can be seen in pulmonary, cutaneous, rhino-orbito-cerebral, and even gastrointestinal infections [Rhizopus [(1) fections –66. AmonRhizopus . MaxillaRhizopus , makes aTypical clinical appearance. Grey-black discoloration is observed when the involved tissues undergo necrosis resulting from thrombosed blood vessels. In particular, when the embolization of maxillary, facial or ophthalmic artery forms, massive necrotic area that donated by them can be seen through physical examination. Accordingly, CT angiography may be considered as a necessary imaging examination for maxillofacial mucormycosis  sis Fig. . ProptosPredisposing illness or risk factors. Organ systems as well as microorganisms involved in the location of contamination associate closely with the clinical manifestations of mucormycosis. Maxillofacial mucormycosis is typically caused by direct infection of non-healing/incurable wound or inhalation/swallow of fungal spores. By reviewing the literature, we found mucormycosis affecting maxillofacial region predominantly appeared in immunocompromised patients , embracing diabetes mellitus, hematological disorders, malignant tumor, etc. In our case series presenting maxillofacial mucormycosis, primarily diabetics  had been identified likewise. On the other side, mucormycosis is capable to afflict healthy individuals owing to the role of local factors in the pathogenesis of this disease as described by Mignogna et al. [(3) a et al.  Local ria et al.  . For this life-threatening infection that is considered to be a medical emergency, prompt and aggressive intervention with a combination of ablative surgery, intravenous antifungal treatment as well as hyperbaric oxygen therapy, along with simultaneous appropriate elimination of underlying causes of immunosuppression and risk factors should be recommended.Additional file 1: Table S1. Overview of laboratory methods available for the diagnosis of oromaxillofacial invasive mucormycosis.Additional file 2: Fig. S1. Risk factors for invasive oromaxillofacial mucormycosis.


Studies have shown that elderly people with cognitive impairments benefit more from hearing aids with slower recovery times.To study participation constraints and speech recognition in noise of elderly subjects equipped with hearing aids of different recovery times according to cognitive impairment status.Fifty subjects aged between 60 and 80 years were followed for four months. They were divided at first in groups of individuals without  and with  cognitive impairment based on results of the Alzheimer's Disease Assessment Scale - Cognitive Sub-scale test. Half the members of each group received hearing aids with faster recovery times and half got slower recovery aids, thus forming four groups: two without cognitive impairment  and two suspected for cognitive impairment . All subjects were interviewed, submitted to basic audiological assessment, asked to answer the Hearing Handicap Inventory for the Elderly questionnaire, and tested for speech recognition in noise. ANOVA, McNemar's test, and the Chi-square test were applied. The significance level was set at 5%.There was significant improvement in participation constraint and speech recognition in noise with hearing aids alone. Sub-group G2F needed more favorable signal-to-noise ratios to recognize 50% of the speech in noise.Participation constraint and speech recognition in noise were improved regardless of recovery times or cognitive impairment status. One of the most prevalent disorders among the aging population is presbycusis. Auditory function deterioration is one of the most severe impairments correlated to this processElderly subjects with presbycusis have reduced auditory sensitivity and compromised speech intelligibility. The ensuing involvement of verbal communication skills may worsen overall quality of lifeAnother alteration frequently associated with aging is the impairment of cognitive processes such as memory, attention, perception, comprehension, problem solving, language, and others. Research indicates the existence of a significant correlation between hearing loss and cognitive performance in the elderlyA studyThese explanations motivated the development of research in an attempt to establish the link between hearing and cognition. Considering that perceptual decline and poor perceptual input may result in reduced cognitive performance, the author suggested audiological rehabilitation as a possible intervention.Researchers from the Berlin Study Group on Aging concluded that the interaction between auditory and cognitive processing in elderly subjects with hearing loss results in increased effort to hear, thus limiting the use of the available mental processes for comprehension and recalling what was heardThe authorIn regards to hearing aid fitting, there is a known correlation between cognitive status and the benefit yielded by the hearing aids to various dynamic traits of comprehension. Release times are conventionally categorized as fast  - in which the purpose is to maintain phoneme audibility - and slow  - in which the total volume of the signal is projected at a level comfortable for the hearing aid userRecent studies have tested elderly individuals wearing syllabic and AVC hearing aids for speech recognition in noise. Subjects with better cognitive processing benefitted from fast release devices, whereas individuals with poorer cognitive skills did better with slow release hearing aids. Since then, device makers began to incorporate the outcomes of research into speech processing algorithmsIt is recommended that elderly subjects with presbycusis be referred to hearing aid fitting, once hearing loss is correlated to cognitive impairment and rehabilitation may be associated with overall cognitive improvementBased on what has been stated, this study aimed to assess and compare the self-perceptions related to auditory constraints and performance at speech recognition in noise of elderly individuals before and after they were fitted with nonlinear hearing aids with different release times based on cognitive status.The study was carried out in 2010 and 2011 after permit 0984/10 was issued by the institution's Research Ethics Committee. This longitudinal trial assessed and compared the performance of 50 elderly first-time users of nonlinear hearing aids aged between 60 and 80 years.All enrolled individuals agreed to join the study and signed informed consent terms.The following inclusion criteria were adopted in selecting the study sample: age equal to or greater than 60 and under 80 years; mild to moderately severe bilateral sensorineural hearing loss Participants were selected and placed in two groups, one featuring subjects without cognitive impairment (G1) and another comprised by individuals with cognitive impairment (G2). The Alzheimer's Disease Assessment Scale - Cognitive Sub-scale (ADAS-Cog) was used to form the groups. This scale has been translated and adapted into Brazilian PortugueseFifty subjects - 23 (46%) males and 27 (56%) females - were assigned to their respective groups, as follows: 24 individuals without cognitive impairment to group one (G1) and 26 with cognitive impairment to group two (G2).The groups were further divided into two sub-groups: one with subjects fitted with nonlinear hearing aids with fast release time (320 ms) and the other with individuals fitted with slow release time devices (1280 ms). Participants were fitted with hearing aids of the same model and make.The release time of the device was randomly assigned to the first patient on the group and repeated for every other subject in the list. Thus, four sub-groups were formed: G1F - 12 subjects without cognitive impairment fitted with fast release devices; G1S - 12 subjects without cognitive impairment fitted with slow release aids; G2F - 13 subjects with cognitive impairment fitted with fast release devices; G2S - 13 subjects with cognitive impairment fitted with slow release devices.Listas de Sentenças em Português - LSP (Brazilian Portuguese Sentence List) speech recognition test.The subjects were advised and followed up for four months after having the devices fitted, and were then reassessed. All enrolled group members were first submitted to an interview and basic audiological evaluation, followed by a research protocol that included the Hearing Handicap Inventory for the Elderly (HHIE) self-assessment tool and the The HHIEThe LSPThe evaluations were carried out in a soundproof room, with the subjects wearing hearing aids fitted in accordance with the data taken from their individual audiometric tests and positioned one meter away from the sound source placed on 0° azimuth, i.e., in front of the subjects. In order to obtain free field sound pressure levels, measurements were made as per the procedure described in previous studiesThe application of this tool was based on the ascending-descending strategyHHIE scores and signal-to-noise ratios were analyzed using descriptive statistics. Analysis of va-rianceSignificant differences were observed in the HHIE scores before and after nonlinear hearing aid fitting in all sub-groups four months into wearing the devices. No significant differences were seen between groups.The benefit analysis done using HHIE in the four groups was carried out through one-way ANOVA. Results are shown on Significant differences were seen between stages, but not between groups or interaction. The differences between groups were nearly significant (p ranging between 0.05 and 0.10). The possible differences were searched through multiple post-hoc comparisons shown on Significant difference was seen between stages for all sub-groups as subject scores in the LSP were lower into four months of wearing nonlinear hearing aids.Group G2F (cognitive impairment and fast release devices) had higher scores than the other groups.Hearing loss introduces auditory and non-auditory impacts, such as isolation from society and family.The purpose of hearing aids is to improve subject audibility and include users in society. It is important to look into the auditory constraints imposed by hearing loss before and after subjects are fitted with hearing aids, as this analysis captures relevant clinical information that would otherwise be missed in objective assessments. The HHIE is frequently used to that end.p < 0.001. These results were consistent with the perceived existence of severe participation constraints before the subjects of both groups were fitted with hearing aids, the elimination of such perception after the hearing aids were fitted in G1 subjects, and the still remaining mild perception of limitation reported by individuals in G2.The mean HHIE scores attained before and after hearing aid fitting were 59.6% and 15.9% for G1 subjects (without cognitive impairment) and 70.5% and 25.8% for G2 members (suspected cognitive impairment) respectively, with a statistically significantWhen the four groups were considered it was noted that the individuals suspected for cognitive disorders had higher scores than the subjects on the group without impairment before and after undergoing treatment with a speech and hearing therapist. Differently from other groups, they failed to reach scores consistent with absence of perceived participation constraints after being fitted with hearing aids. This situation revealed that these patients experienced more limitations in participating in activities of daily living. When the benefit of hearing aids was considered, it was found that all groups had a reduction of 42% to 45% in participation constraints.According to the literature, a reduction of 19% in perceived participation constraints after the fitting of hearing aids amounts to a significant improvement when the HHIE scale is applied in the form of an interview. When the HHIE is answered by the patients without the aid of an interviewer, reductions of 36% or more amount to significant improvementOther authorsIn order to communicate well in situations of conversation, individuals must decode and identify the incoming message by integrating auditory and language processing. However, if the decoding function is compromised by poor performance of the peripheral auditory system, other cognitive resources have to be mustered so that good communication can occurStudies have shown that the auditory stimulation provided by the amplification of sounds leads to the reorganization of the auditory pathways, and possibly to improvements in the reception and organization of sound stimuli. Consequently, one's speech recognition skills improve graduallyThe findings in this study were also in agreement with the research of other authorsThis study also noted the importance of using hearing aids to improve the cognitive functions (memory and attention) of elderly individuals with hearing loss, regardless of hearing aid release time.The ADAS-Cog test was used in this study with the purpose of dividing subjects in two groups - without cognitive impairment (G1) and suspected for cognitive impairment (G2) - and to analyze the impact of hearing loss upon cognitive function. After the subjects were given hearing aids, improvements in auditory perception, communication, socialization, and cognition (memory and attention) were reported by individuals from both groups. Therefore, the use of hearing aids by elderly subjects may prevent the occurrence of cognitive alterations associated with auditory perception and attention, and consequently improve the overall quality of life of the elderly. Release times did not affect the results attained by the groups.The reasons for the significant correlation found between cognitive status and fast release devices are yet to be clarified. Temporal auditory processing or some other factor such as cerebral plasticity may mediate this correlationSituations of everyday life are normally associated with the presence of competing noise. Individuals with normal hearing experience difficulties hearing and recognizing speech in these conditions. Thus, it is important to assess the elderly in communication situations that resemble reality with tests to assess speech recognition in noise. The test chosen in this study was the LSPThis study showed a reduction on the group scores after hearing aid fitting, a finding correlated with better performance in situations of speech in noise.Speech recognition is one of the biggest challenges for elderly subjects with hearing loss, particularly when competing noises are present. The signal-to-noise ratio is calculated as the difference between the intensity of one signal (speech) and the competing noise presented simultaneously. Higher S/N ratios indicate more difficulty understanding speech in noise, both for people with normal hearing and subjects with hearing loss, the elderly in particular.Other authorsThe minimum values seen in this study for S/N ratio varied by 1.1 dB on Group 1 (no cognitive impairment) and 1.6 dB on Group 2 (suspected cognitive impairment). Studies have shown that a 1 dB change in the S/N ratio may lead to variations in speech recognition of up to 18%The minimum values seen in this study for S/N ratio before and after the fitting of hearing aids  are in agreement with other studiesPatients in the G2F group had a higher S/N ratio to recognize 50% of the sentences before and after intervention by a speech and hearing therapist only by being fitted with hearing aids. Other factors must be analyzed to justify these findings, such as time of sensory deprivation.The findings in this study indicated reduced participation constraints four months after the subjects started using nonlinear hearing aids. The same was seen for speech recognition in noise.Patients using hearing aids for four months improved from participation constraints and performed better in speech recognition in noise tests regardless of their cognitive status and the release time setting of their hearing aids.


AIRE and heterozygous pathogenic variants in FAM111B, respectively. The clinical diagnosis of APECED and POIKTMP rely on the development of two or more characteristic disease manifestations that define the corresponding syndromes. We discuss the shared and distinct clinical, radiographic, and histological features between APECED and POIKTMP presented in our patient case and describe his treatment response to azathioprine for POIKTMP-associated hepatitis, myositis, and pneumonitis.Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) and poikiloderma in association with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP) are rare inherited syndromes resulting from biallelic pathogenic variants in Through informed consent and enrollment onto IRB-approved protocols  the patient underwent a comprehensive clinical evaluation at the NIH Clinical Center alongside exome sequencing, copy number variation analysis, autoantibody surveys, peripheral blood immunophenotyping, and salivary cytokine analyses.de novo c.1292T>C heterozygous pathogenic variant in FAM111B but no deleterious single nucleotide variants or copy number variants in AIRE.We report the presentation and evaluation of a 9-year-old boy who was referred to the NIH Clinical Center with an APECED-like clinical phenotype that included the classic APECED dyad of CMC and hypoparathyroidism. He was found to meet clinical diagnostic criteria for POIKTMP featuring poikiloderma, tendon contractures, myopathy, and pneumonitis, and exome sequencing revealed a This report expands upon the available genetic, clinical, autoantibody, immunological, and treatment response information on POIKTMP. FAM111B variants  and discuss the phenotypic overlap and differences between these two monogenic syndromes.Early-onset poikiloderma in association with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP) is a rare, autosomal-dominant syndrome caused by variants . Autoimmvariants , 5. The variants , 7. AlthCandida cheilitis that responded to antifungal therapy, dry mouth and eyes, dysphagia, recurrent aphthous stomatitis, gum abscesses, decalcified enamel with several dental caries, hyperkeratosis and xerosis of bilateral palms and soles, anhidrotic ectodermal dysplasia with impaired thermoregulation, kyphosis, arthritis of the hips and ankles, bipedal edema, iron deficiency anemia, and vitamin K-dependent coagulopathy. He also displayed cognitive and speech developmental delays in early childhood.A 9-year-old Ukrainian male presented at the NIH for clinical and genetic evaluation of potential APECED , which was recently found to be enriched in patients with an APECED-like phenotype suffering from autoimmunity . He was euthyroid  while receiving levothyroxine. An ACTH stimulation test revealed intact adrenal function and 21-hydroxylase autoantibodies were negative. Aspartate aminotransferase  and alanine aminotransferase  were elevated while classical autoimmune hepatitis autoantibodies  were negative, a pattern that can be observed in APECED-associated hepatitis . Given hStaphylococcus aureus and Streptococcus pyogenes for which he received amoxicillin/clavulanate. CT chest revealed bilateral pulmonary infiltrates in the apices and right lower lobe with scattered small nodules  NM_198947], which was confirmed by Sanger sequencing  identified a novel, heterozygous missense variant  in APECED-associated hepatitis and pneumonitis respond to azathioprine (AZA)-based treatment , 11. He de novo as in our patient  the variant is absent in healthy controls at gnomAD (https://gnomad.broadinstitute.org), and 3) the variant is within one codon of another pathogenic FAM111B variant, p.Gln430Pro, which was previously reported in a patient suffering from POIKTMP  in association with tendon contractures, progressive muscle weakness, and pulmonary fibrosis. However, 26 other clinical features have been described among the reported 36 patients  indicatiThe classic diagnostic dyad of CMC and hypoparathyroidism had initially raised suspicion for APECED . His othAlthough APECED and POIKTMP share some clinical features , 21. APEMyopathy and poikiloderma are well-described in POIKTMP. Fatty infiltration of the muscle is apparent on MRI with a myogenic pattern on EMG and elevated creatine kinase , 25. HisThere is scarce published information on the management of POIKTMP. Among the reported 36 patients, one had resolution of poikiloderma and hepatitis with corticosteroids and AZA. Another patient with lymphocytic pneumonitis was treated with corticosteroids with little effect and succumbed to his disease . In our via identifying a de novo FAM111B variant. Phip-Seq-based autoantibody profiling of additional POIKTMP patients is needed to discern whether the identified autoantigen targets in our patient are private or broadly shared, and further immunophenotyping of T lymphocytes, including of regulatory T cells, will be needed to better characterize the immunopathogenesis of POIKTMP. The absence of Th17 cytokine-targeted autoantibodies and the normal circulating Th17 cells and salivary S100A9 in our patient indicate that CMC in POIKTMP may occur in the setting of intact type-17 responses. The increased salivary CXCL9 in our patient suggests that enhanced mucosal type-1 responses may contribute to CMC in POIKTMP, which will require investigation in mice and additional patients with POIKTMP. Moving forward, systematic genetic and clinical evaluation and longitudinal follow-up of several POIKTMP patients will be needed to define the full spectrum of the disease phenotype and to further characterize the safety and efficacy of AZA-based treatment.Our patient expands the clinical spectrum of POIKTMP to include CMC, enamel hypoplasia, hypoparathyroidism, and Sjogren’s-like syndrome and highlights the overlap of several disease manifestations with APECED, including the aforementioned diseases, and hypothyroidism, exocrine pancreatic insufficiency, hepatitis, and pneumonitis, which may be ameliorated by lymphocyte-directed immunomodulation. This case additionally highlights the clinical and diagnostic challenges in patients presenting with APECED-like clinical features who do not carry pathogenic AIRE mutations, many of whom remain undiagnosed. Here, ES was critical in establishing a genetic diagnosis The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by National Institute of Allergy and Infectious Diseases IRB board. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin. Written informed consent was obtained from the minor(s)’ legal guardian/next of kin for the publication of any potentially identifiable images or data included in this article.EF, YY, MW, and ML contributed to the conception and design of the study. EF, ML AH, MA, TH, and AS took care of the patient during the course of the study. C-CL performed immunohistochemical analysis of patient tissues. VO, LR, PB, SV and MA performed experiments with patient’s sera and PBMCs. EF wrote the first draft of the manuscript. SH and ML provided supervision over the project. All authors contributed to the article and approved the submitted version.


Several methods are used for hearing loss screening; however, their benefits are uncertain. In this study, we aimed to determine the predictive factors of acute sensorineural hearing loss for clinical application by primary care doctors.This retrospective, cross-sectional study included 365 patients with acute sensorineural hearing loss without prior therapy. The patients’ clinical data, demographic information, and medical histories were obtained, and they were asked about comorbidities. In addition, we assessed lifestyle factors such as stress level, alcohol consumption, marital status, and socioeconomic level. Logistic regression analysis was performed to investigate the diagnostic predictive ability of the selected factors associated with acute sensorineural hearing loss. The hearing levels of all patients were evaluated using pure tone audiometry.We identified significant predictive factors for acute sensorineural hearing loss. The absence of hyperacusis was a predictive factor for sudden sensorineural hearing loss. Younger age, female sex, and marital status were predictive factors for acute low-tone hearing loss. High body mass index, high socioeconomic level, low alcohol consumption, high stress level, hyperacusis, and vertigo/dizziness were predictive factors for Ménière’s disease. High body mass index and ear fullness were predictive factors for perilymph fistula. Low stress level was a predictive factor for acoustic tumours.Our findings can be used to distinguish between the types of acute sensorineural hearing loss. Symptoms, physical status, and lifestyle factors identified during this study are useful markers for predicting acute sensorineural hearing loss occurrence.The online version contains supplementary material available at 10.1186/s12875-022-01830-8. More than 30 million adults in the United States (approximately 15% of the population) experience hearing loss . Acute sASHL includes the following types: sudden sensorineural hearing loss (SSNHL), acute low-tone hearing loss (ALHL), Ménière’s disease (MD), perilymph fistula, and retrocochlear disorders such as acoustic tumour –3. PreciPrevious studies have reported risk factors for ASHL –17. HoweTherefore, this study aimed to determine the predictive factors of different types of ASHL to ensure accurate diagnosis and optimal treatment, with a focus on comparisons among ASHL patients. We did not assess the differences between ASHL patient and healthy individual groups.The Institutional Review Board of Kitano Hospital approved this study  and waived the requirement for written informed consent because of the retrospective nature of the study. Moreover, the study was conducted in accordance with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.This retrospective cross-sectional study included patients diagnosed with ASHL who visited our hospital between January 2014 and January 2019. The inclusion criteria were age ranging from 10 to 100 years and a diagnosis of unilateral ASHL. Patients who could not be adequately interviewed because of communication disorders and those with hearing loss attributable to other causes, such as brain damage, were excluded.All patients underwent detailed clinical interviews conducted by physicians. Patient clinical data, demographic information, and medical history were obtained. The patients were asked about comorbidities, including hypertension  and mental illness (ICD10: F00-99). Lifestyle factors, such as stress, alcohol consumption, marital status, and socioeconomic level, were assessed. All the participants underwent routine general physical examination, general otorhinolaryngological examination, and routine audiological and laboratory tests.The hearing levels of all patients were evaluated using pure tone audiometry. Air conduction was assessed at frequencies of 125 Hz, 250 Hz, 500 Hz, 1 kHz, 2 kHz, 4 kHz, and 8 kHz. In patients with out-of-scale types of hearing loss, 5 dB was considered as a hearing level of 105 dB. For SSNHL, the average hearing level (average of five frequencies: 250–4000 Hz) was used according to the Japan Audiological Society guidelines . For ALHHaematological tests were performed in all patients to assess haemoglobin A1c (HbA1c) levels.Multivariable logistic regression analysis was performed using the incidence of each disease as the dependent variable to investigate the diagnostic predictive ability of selected factors associated with ASHL. The explanatory variables included objective symptoms, age, sex, body mass index (BMI), hypertension, HbA1c, mental illness, stress, Brinkman index score, alcohol consumption, insurance level (socioeconomic level), marital status, family history of hearing loss, subjective symptoms of tinnitus, ear fullness, hyperacusis, and vertigo/dizziness.P<0.05 (two-tailed). The evaluation results were considered not applicable if the calculated sample size after data collection was insufficient for statistical analysis.A model was created after confirming the variance inflation factor. Missing values were imputed using the random Forest method. There were no outliers during the analysis of primary or secondary outcomes. Interactions between parameters were evaluated for each disease. Statistical significance was set at All statistical analyses were performed using EZR , which is a graphical user interface for R . Specifically, it is a modified version of the R commander designed to add statistical functions frequently used for biostatistics.In total, 564 patients were assessed. Among them, 12 patients who did not meet the diagnostic criteria for SSNHL, ALHL, MD, perilymph fistula, or acoustic tumour were excluded. We classified the patients into SSNHL, ALHL, MD, perilymph fistula, and acoustic tumour groups based on the type of ASHL diagnosed via hearing levels . Among tFinally, we included 365 patients in this study (176 men and 189 women). The average patient age was 55.2 years . Other patient demographic characteristics are shown in Supplementary Table 1 [see Additional file P=0.002) (Table P=0.004), marital status , and female sex  were predictive factors for ALHL (Table P=0.02), BMI , hyperacusis , socioeconomic level , stress level , and vertigo/dizziness  were factors associated with MD  and ear fullness   . Primary doctors may not examine the external canals. Further study is needed to clarify.Our diagnostic prediction analysis identified various predictors for each type of ASHL. Some comorbidities that were previously reported to be factors associated with ASHL were not found to be predictive factors in this study. Our findings can help primary care doctors distinguish between different types of ASHL without using an audiometer.Additional file 1: Supplementary Table 1. Demographics of patients with acute sensorineural hearing loss (N=365). Supplementary Table 2. Factors associated with perilymph fistula (N=365). Supplementary Table 3. Factors associated with acoustic tumour (N=365). Supplementary Table 4.P value for interaction between parameters for sudden sensorineural hearing loss. Supplementary Table 5.P value for interaction between parameters for acute low-tone sensorineural hearing loss. Supplementary Table 6.P value for interaction between parameters for Ménière’s disease. Supplementary Table 7.P value for interaction between parameters for perilymph fistula. Supplementary Table 8.P value for interaction between parameters for acoustic tumour.


The electrical cochlear implant (eCI) partially restores hearing in individuals affected by profound hearing impairment (HI) or deafness. However, the limited resolution of sound frequency coding with eCIs limits hearing in daily situations such as group conversations. Current research promises future improvements in hearing restoration which may involve gene therapy and optical stimulation of the auditory nerve, using optogenetics. Prior to the potential clinical translation of these technologies, it is critical that patients are engaged in order to align future research agendas and technological advancements with their needs.Here, we performed a survey study with hearing impaired, using an eCI as a means of hearing rehabilitation. We distributed a questionnaire to 180 adult patients from the University Medical Center Göttingen’s Department of Otolaryngology who were actively using an eCI for 6 months or more during the time of the survey period. Questions revolved around patients needs, and willingness to accept hypothetical risks or drawbacks associated with an optical CI (oCI).Eighty-one participants responded to the questionnaire; 68% were greater than 60 years of age and 26% had bilateral eCIs. Participants expressed a need for improving the performance beyond that experienced with their current eCI. Primarily, they desired improved speech comprehension in background noise, greater ability to appreciate music, and more natural sound impression. They expressed a willingness for engaging with new technologies for improved hearing restoration. Notably, participants were least concerned about hypothetically receiving a gene therapy necessary for the oCI implant; but expressed greater reluctance to hypothetically receiving an implant that had yet to be evaluated in a human clinical trial.This work provides a preliminary step in engaging patients in the development of a new technology that has the potential to address the limitations of electrical hearing rehabilitation. Hearing impairment (HI) is the most prevalent sensory deficit worldwide and is associated with significant socio-economic burden. Disabling HI   affects Causal treatments options for disabling HI–such as gene replacement or supplementation therapy, are currently being explored; yet none have achieved approval for clinical application. For mild to moderate hearing loss, reduced cochlear sensitivity can be compensated by conventional hearing aids which primarily amplify sounds. However, hearing aids do not sufficiently help in more severe cases in which sensory inner hair cells are missing or dysfunctional. In the majority of such cases, the current treatment of choice is an electrical cochlear implant (eCI) which directly stimulates the spiral ganglion neurons (SGNs). Arguably the most successful neuroprothesis, the eCI partially restores hearing and enables speech perception in the majority of the more than one million users. Despite its success, users do not experience full hearing restoration and report significant limitations in their daily lives. Specifically, users typically have difficulty understanding speech in group conversations and/or noisy and reverberating background, with complex acoustic sounds such as music, and with perception use of tonality and voice inflection .Currently, several innovations of hearing restoration are in preclinical development. One of them is the optical cochlear implant (oCI) . Making It is well-documented that the translation from preclinical experiments to clinical investigation is wrought with high rates of failure, significant costs, and large timelines; which presents a contentious issue in the scientific community . AlthougThe aim of the study was to uncover patients’ preferences, expectations, and needs regarding an improved CI. From May 2020 to November 2020, questionnaires were distributed to patients of the Department of Otolaryngology of University Medical Center Göttingen  that were currently using a CI.This study was approved through the Ethik-Kommission der Universitätsmedizin Göttingen (Protocol # 23/11/19An). The study has been reported according to the Consolidated Criteria for Reporting Qualitative Research COREQ;  Tong et.We recruited patients from the University Medical Center Göttingen’s Department of Otolaryngology who were actively using a CI for 6 months or more during the time of the survey period. Purposeful sampling was used to recruit participants from an internal list of patients within the Ear Clinic. Adolescent and adult patients with either unilateral or bilateral implantation were eligible for participation. Children under the age of 16 were excluded. Questionnaires were distributed and collected by post or during routine check-ups. Participation was voluntary and patients were informed that returned questionnaires implied consent. Along with the informed consent form, patients were provided with accessible information regarding the oCI; and were engaged by the research team through in-person outreach events aimed to provide them with more information regarding the oCI. Of the 81 eCI users who completed the custom questionnaire, 68% were older than 60 years.The custom-made questionnaire consisting of five parts and a total of 19 questions was informed by and aligned with the questionnaire items of the SSQ-12  , as wellCollected questionnaires were de-identified and assigned an identification number; responses were then entered into a Microsoft Excel spreadsheet . FrequenWritten responses were inductively analyzed using thematic analysis , where aThe survey was distributed to 180 patients in the Ear Clinic of Göttingen’s Department of Otolaryngology from May to November 2020 (approximately 6 months), and 81 participants returned a completed questionnaire (response rate of 45%). Sixty-eight percent of participants were over the age of 60 years; and 58 (72%) were unilaterally fitted with a CI (59% with left ear implanted). Of participants that had an implant in one ear, 72% wore a hearing aid in the contralateral ear and eight (14%) could hear normally in the other ear. Participant demographics and characteristics of their CI can be found in Participants were asked to rate hypothetical improvements in a new CI on a scale of importance from 0 to 10 . The five improvements with a new CI [compared to what their experience(d) with their current CI] were: having faster rehabilitation after implantation, having greater enjoyment of music, having improved phone calls, having better understanding of speech in noisy environments, and more natural sound impression . OverallParticipants were asked about potential risks and drawbacks that could be associated with the novel type of CI. They were presented with five risks/drawbacks and were asked to indicate if they would accept them or not by responding with yes or no . For twoParticipants were asked about their hypothetical intentions of having a surgery for receiving a new type of CI. They were provided with three possible responses see . Most paParticipants were asked what features they would want in a new CI, providing their responses as an open-text format. Fifty-four (67%) participants completed this section of the questionnaire. Responses regarding their preferences were categorized into 14 individual codes, and the codes sorted into four global themes: addressing intrinsic electrical hearing limitations; new technological features; improving practical features; and enhancing life as a CI user . The mosOf the 14 codes, 5 were areas of improvement that were already explored and surveyed in the first section of the questionnaire regarding the hypothetical improvements to a new CI . Thus, we uncovered nine new features that patients would desire in a new CI Better speech understanding in general, not only in direct conversation , but also from a distance (can protrude faster). Related to this is telephoning. For sound–more balance between high and low tones. For music—the CI highlights the voice very well, but the instrumental is not yet satisfying because it does not sound so “smooth” and “fluid”… (Participant 43)The environmental noise or background noise should not be so loud… It is so exhausting when you hear the air conditioning in the supermarket loudly, or the chirping of the birds… to understanding in the noise. The noise is amplified so much that you have to endure a high volume to understand [speech] as every healthy hearing person. (Participant 4)In this study, we identified CI users’ perspectives and experiences with artificial hearing as well as their preferences and willingness to try a newly developed CI. We found that with current hearing rehabilitation technologies, patients’ needs are not fully being addressed. Taken together, this work provides valuable information for the design and planning of a future early-phase clinical trial for a new CI in development—such as the optical CI.In vivo and in silico preclinical studies confirmed the expectation that the oCI achieves near physiological  spectral selectivity  preclinical estimates of energy of pulse requirements of oCI currently exceed those of eCI and (ii) costs of oCI need to accommodate the medical device and gene therapy. Multiple participants brought up battery-life of their current eCI as an issue they would like to improve. This suggests that despite its importance to them, CI users would be more accepting of short battery time if the oCI would be an improvement in the hearing quality they experience. Fewer participants were acceptant to there being no documented human experience with the new CI yet, as clinical trials have yet to be performed. This is not surprising, since the eCI is an ambitious benchmark to surpass . If therResponses from the open-text section of the questionnaire provides us with valuable insight into what features CI users desire in a new CI, outside of the improvements to the well-documented limitations of artificial hearing. Notably, patients also reported practical considerations  that are of interest for improving current and new CIs–some of which are currently being considered and partially implemented in ongoing CI development ventures .The most notable limitation of this study is the small sampling frame, as we only included participants within a single clinic at one site. This reduces the generalizability of our study’s findings and thus, we suggest that our results should not be generalized to a larger population of individuals with HI. Moreover, the majority of the participants were over the age of 60 (68%); and have progressive hearing loss, thus, have experienced normal hearing previously in their life (data not collected in questionnaire). Therefore, is likely that the experiences and views uncovered in this study may not be applicable to younger adults and adolescents; and individuals who have prelingual hearing loss . The large age range also adds heterogeneity to the sample population, reducing the inferential strength. Another limitation is that we included participants who had been fitted with an eCI ranging from 6 months to several years. Across our sample population, this adds large heterogeneity regarding the stage of hearing rehabilitation, thus reducing the inferential strength of our findings. Furthermore, we included participants that were fitted unilaterally and bilaterally, but did not separate these two groups in our surveying or analysis.In addition, our results may not be reflective of non-responders to our recruitment strategy. It should also be noted that the participants in this survey have developed close patient-to-clinician relationships with some of the researchers conducting this investigation, which could bias the responses of the participants and influence the conclusions drawn from the data. Although there is low generalizability, our intention was to understand the perspectives of patients within this clinic, as this site would be the first to recruit patients for the new oCI. Building on the information elicited from the present study, a future larger survey of hearing-impaired individuals across a more diverse demographic range could confirm findings and/or identify additional views and preferences.The eCI provides a vital means for hearing rehabilitation in individuals affected by HI, however, the sensory experience of its users remains sub-optimal. Through a survey with current eCI users, we explored their experiences with artificial hearing restoration, and uncovered their preferences and opinions for a new CI. From our results, we found that in our survey population there remains an unmet clinical need in CI users’ hearing experience; and that there is openness for receiving and willingness to collaborate in the development of an oCI. Toward the development of the oCI, we will continue adopt strategies that engages patients in a meaningful way to align their preferences and needs to future research endeavors.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Ethik-Kommission der Universitätsmedizin Göttingen. The patients/participants provided their written informed consent to participate in this study.NS and TM: supervision and resources. RK, NS, DK, and TM: conceptualization. RK, NS, VH, and TM: methodology. RK, NS, and TM: investigation. RK and VH: analysis. VH and BW: writing—original draft. All authors: writing—review and editing and approved the submitted version.


To estimate the association between congenital syphilis and neonatal hearing screening failure in the state of Santa Catarina between 2017 and 2019.This is a cross-sectional, retrospective, analytical study with secondary data of neonates from the state of Santa Catarina born between January 2017 and December 2019. We used logistic regression analysis to estimate the association between the main exposure  and the study outcome .The study included 21,434 newborns evaluated in a Brazilian hearing health care service. A total of 351 (1.6%) newborns failed the Neonatal Hearing Screening, and 364 (1.7%) had congenital syphilis. In the adjusted analysis, newborns with congenital syphilis were 3.25 times as likely to fail the Neonatal Hearing Screening as neonates without this disease . As for maternal age, the sample had a higher prevalence (53.5%) of mothers aged 20–29 years.There was an association between congenital syphilis and failure in Universal Neonatal Hearing Screening in the sample studied. There is a need for investments in public policies to value and strengthen the hearing screening program in the state to provide early diagnosis and intervention.5 Hearing is one of the key senses for humans’ overall development,Hearing loss, which is a decrease in the ability to detect speech and environmental sounds, may be attenuated if detected early.This program helps establish the necessary health care actions to ensure the newborn's hearing ability, encompassing the phases of identification, confirmation, diagnosis, and early rehabilitation of hearing loss.Treponema pallidum, which reaches the fetus through the placenta.The Joint Committee on Infant Hearing (JCIH)According to the World Health Organization (WHO), about 1 million pregnant women had active syphilis infection in 2016.12Nonetheless, there is a lack of research in both national and international literature investigating the association between congenital syphilis and failure in UNHS.Congenital syphilis is an easily detectable, treated and curable disease – for that is a turning point that makes it unacceptable that so many neonates have to suffer the potentially catastrophic consequences of this disease in Brazil.This is a cross-sectional, retrospective, analytical study that surveyed and analyzed secondary data provided by a hearing health care service in southern Brazil. The subjects were newborns submitted to the Universal Neonatal Hearing Screening (UNHS) Program at two maternity hospitals in the state of Santa Catarina, between January 2017 and December 2019.The newborns were submitted to the UNHS in their first days of life, while they were in the rooming-in environment or intermediate care unit. In the procedure, the transient evoked otoacoustic emissions (TEOAE) were tested and recorded in both ears separately, as well as the automated auditory brainstem response (ABR) when necessary – i.e., when the newborns already had risk factors for hearing loss. If the ABR response was unsatisfactory, the newborn was referred for auditory monitoring, following the protocol of the state of Santa Catarina.We used the “pass” and “fail” results in the Neonatal Hearing Screening as a variable. Neonates who failed TEOAE and/or ABR either in one or both ears were classified as “fail”.Congenital syphilis was the main research variable (no/yes). The covariables were the year of birth , maternal age , small for gestational age (no/yes), and intensive care Unit (ICU) stay of more than 5 days (no/yes). These variables were included as adjustments, as they could interact with the outcome and exposure analyzed in this study. As suggested by Weinstein and Durante (2011),p-value. We included the variables simultaneously in the adjusted analysis. The associations were considered statistically significant only when their probability was equal to or lower than 0.05, that is, p ≤ 5%.We organized the data in Microsoft Excel spreadsheets and later exported and analyzed them with StataMP v.14.0 software . We presented them in absolute and relative frequencies, with 95% Confidence Intervals (95% CI), to describe the sample’s categorical variables. The prevalence of UNHS failures was estimated according to research, comparing the proportions with the Pearson chi-square test. We used the Odds Ratio (OR), estimated with logistic regression analysis, as an association measure for both crude (bivariate) and adjusted analyses. The main exposure variable was adjusted for all study variables , regardless of the This study was approved by the Research Ethics Committee of the Plataforma Brasil (humanos). CAAE: 85345518.2.0000.0121. All individuals involved (or their parents/guardians) signed the informed consent form.The study included 21,434 newborns evaluated in a Brazilian hearing health care service. The prevalence of test failure in the UNHS was of 1.6% , and 1.7%  of the neonates had congenital syphilis.As for maternal age, the sample had a higher prevalence (53.5%) of mothers 20–29 years old , followed by mothers over 30 years old (32.7%). Regarding the year of birth, there was a similar distribution with approximately 30.0% in each of the three. Concerning other risk indicators, 3.0%  were small for gestational age, and 3.5%  had stayed in the ICU for 5 days or more .Table 1Sp < 0.001). There was also a higher proportion of failure in newborns with congenital syphilis (6.0%) than in those without the disease (1.6%) (p < 0.001)  when compared with other categories, with a statistically significant difference (< 0.001) . Table 3We found significant prevalences of both congenital syphilis and test failure in newborns screened with the UNHS. There was a higher prevalence of UNHS failure in neonates whose mothers were younger. Newborns with congenital syphilis were 3.25 times as likely to fail in the UNHS as the ones without this disease.Congenital syphilis is a preventable disease, whose early diagnosis is essential to an effective treatment. Hence, adequate prenatal care is one of the factors that help reduce the number of cases,The data on UNHS failure in this study is in line with the quality indicators for screening established by the JCIH,A higher proportion of UNHS failure was also reported in neonates of younger mothers (≤19 years). This finding contrasts with the study by Kemp et al. (2015),p-value they had found in the study.Hearing impairment is recurrently found in newborns without RIHL, but with a lower prevalence than in neonates who have these indicators.Even when asymptomatic, congenital syphilis may cause both early and late sensorineural hearing loss in neonates.There is an increasing numberWe must consider some elements when interpreting the results of this study. The cross-sectional design of this research measures the event and the outcome at the same time, so it is not possible to infer about the changes that occurred over time and ensure the causality of associations.Future studies should include a greater number of socioeconomic variables in the analyses, as well as diagnostic tests to assess both the peripheral and central auditory systems. Regarding the potential, this study involves unprecedented results in a large sample of newborns, which had never been studied before. The results support important actions on this topic. Lastly, there was an association between congenital syphilis and UNHS failure in the sample of this study – which indicates the need for investment in public policies to value and strengthen the UNHS in the state to provide early diagnosis and intervention, in addition to raising the mothers' awareness of adequate monitoring during pregnancy.Our study results indicate that congenital syphilis in neonates was associated with UNHS Program failure, we highlight that the population involved in this study is very representative, with data analysis of 21,434 newborns evaluated in a Brazilian reference hearing health service of the UNHS Program.Brazil should prioritize investments in public health, especially to improve prenatal care and policies, valuing and strengthening the hearing screening program to provide early diagnosis and intervention. The results sugges an association that needs to be confirmed in further studies with a different methodology.The authors declare no conflicts of interest.


Age-related hearing loss is one of the leading causes of disability in older adults. This cross-sectional study investigated the association between untreated hearing loss, social  and emotional loneliness , social isolation , social support  and psychological discomfort  in older adults.Cross-sectional study design.M = 63.2 ± 12.0 years) and 87 were males (M = 68.2 ± 8.9 years). All participants completed a hearing assessment, social interaction and support questionnaire and a social and emotional loneliness questionnaire.A total of 202 community derived sample of volunteers, age range 40–89 years, mean age (M) = 65.3 ± 11.0 years were recruited. Of these 115 were females : 0.01 (0.99–1.02)] and intense levels  of emotional loneliness. Depression was significantly associated with satisfaction with social support , and moderate  and intense  levels of emotional loneliness and intense levels of social loneliness .Hearing loss significantly contributed to both moderate [Untreated hearing loss significantly increases the odds of being emotionally lonely. Depression significantly contributes to social and emotional loneliness, satisfaction with social support and social loneliness. Given the higher prevalence of loneliness and psychological discomfort and their associations with untreated hearing loss, hearing-impaired older adults are at significant risk of developing loneliness and psychological discomfort. Therefore, hearing health professionals should be aware of the psychosocial burden that may accompany hearing loss, in order to provide appropriate advice and support. In 2019, 1 billion of the total world population was 60 years or older, which will increase to 2.1 billion by 2050 . As the Social isolation and loneliness are descriptive terms that are often used interchangeably, although they refer to two distinct concepts. Social isolation is an objective and quantifiable measure, while loneliness is a subjective emotional experience . Social Even though the terms’ “social isolation” (negative) and “social support” (positive) are used interchangeably, they do not refer to diametrical concepts . While sLoneliness is associated with depressive symptoms , reducedAge-related hearing loss (ARHL) is prevalent in later life and has an increasing trend across ages; 10.9–17.6% in 60–69 years, 41.9–51.2% in 80–89 years, and 52.9–64.9% in 90 years and above . ARHL isCommunication refers to the “bidirectional transfer of information, meaning, and intent between two or more individuals” . CommuniHence, it is important to investigate the impact of untreated hearing loss on social and emotional loneliness, social isolation, perceived social support, and psychological discomfort .This was a cross-sectional study of a community-derived sample of volunteers and adults in contact with the clinical services of the Ear Science Institute of Australia in Perth, Western Australia. Participants were either native or fluent English speakers older than 40 years, did not use any hearing aids or hearing implants, had bilateral symmetrical pure tone audiometric thresholds of hearing sensitivity and did not have any morbidities or disabilities that prevented them from completing the assessments.The assessment materials consisted of measures of hearing, mental health, social support and interaction, and social and emotional loneliness. The Human Research Ethics Committee of the University of Western Australia approved the study protocol (RA/4/1/7368), and all participants provided written informed consent.This included an otoscopic examination  and a pure-tone audiometric assessment . Following an otoscopic examination, bilateral air conduction thresholds between 0.5 and 8 kHz and bone conduction thresholds between 0.5 and 4 kHz were obtained through standard audiometric assessment protocols conducted by a qualified audiologist in a standard sound-attenuated booth. These data were used to stratify participants into the following groups by their better ear four frequency pure-tone average thresholds at 0.5, 1, 2, and 4 kHz (BE4PTA): normal hearing (NH: 0–25 dB), mild to moderate sensorineural hearing loss (MMH: > 25–55 dB), moderately severe to profound sensorineural hearing loss (MSPH: 56+ dB).The Duke Social Support Index (DSSI-10) was used to measure the social interaction and satisfaction with social support received . The DSSThe social interaction subscale measures the size and structure of the social network and contains questions regarding the number of social interactions a person had within the past week with low social interaction subscale scores indicating greater social isolation . The socThe de Jong-Gierveld loneliness scale  measuredThe Depression Anxiety Stress Scales: DASS-21  was usedParticipants self-reported their sex  and age (in years), years of formal education, physical exercises undertaken, smoking (current and past), alcohol consumption, and current living status . We used the National Adult Reading Test-Revised (NART-R) to assess participants’ premorbid intellectual function scores . All parP-value of less than 0.05 was considered to indicate statistical significance.The statistical analyses were carried out in SPSS Statistics for Windows version 25.0  and R version 3.5.1 . UnivariAll authors accessed the study data and reviewed and approved the final manuscript. We used the STROBE statement to check the completeness of our study report .M = 65.32 ± 11.07 years) took part in the study (M = 63.16 ± 12.05 years of age) and 87 (43%) were female (M = 68.17 ± 8.91 years of age). Detailed information on participant demographics is presented in Two hundred and two volunteers, aged between 40 and 88 years (he study . Of the P = 0.07). Poor satisfaction with social support scores was observed in individuals who live alone (P = 0.003), and experience more stress (P < 0.001), anxiety (P = 0.001), and depression (P < 0.001) or vice versa  and age (P < 0.001). After multivariate analysis for confounders, aging (P = 0.01) and depression (P = 0.01) continued to be statistically significant. These results suggest that higher depression scores and older age contributes to increased social isolation. A statistically significant interaction between age and hearing was observed (P = 0.04). Poorer SI scores are seen for people who are not only older but with poorer hearing. Results are summarized in Two variables have a significant effect on SI in the univariate analyses: depression (P = 0.01) significantly contributed to the intense levels of emotional loneliness. Age (P = 0.02) and (P = 0.02), depression (P < 0.001) and (P < 0.001), anxiety (P < 0.001) and (P < 0.001), stress (P < 0.001) and (P < 0.001), BE 4PTA (P < 0.001) and (P < 0.001) significantly contributed to both moderate and intense levels of EL, respectively . The living alone variables in the equation above are indicators that take the value 1 for participants that live alone. The exponentiated effect estimates are shown above in the equation. The corresponding p-values and 95% CI are BE4PTA , Age , Living alone , and Depression . Interpreting this model suggests that a participant living alone increases their odds of transitioning to the next higher EL level by 54.6%. For each unit of BE4PTA, a participant’s odds of transitioning to the next higher EL level increased by 0.6%. For example, if a person whose hearing deteriorates from no hearing loss to mild to moderate hearing loss, where the BE4PTA increases from 25 to 50 dB, they will have 1.00625 = 1.16 or a 16% increase in their odds of transitioning to the next higher EL level.where βP = 0.01), depression (P = 0.01), and stress (P = 0.01) had a significant impact on intense levels of SL. Results are summarized in Multinominal analysis revealed that age, gender, premorbid IQ (NART-R), anxiety, BE4PTA, smoking, and alcohol ≥ 14 drinks per week had no effect on SL. Three of the variables exhibited a statistically significant association with the SL response. Living alone  compared to older adults who live with someone else and experience emotional loneliness  and perceived social support . Those who had higher depression scores showed increased social isolation scores and poor social support. Previous studies have shown that social support and depression share a bidirectional relationship . AccordiWe failed to observe any significant association between untreated hearing loss and social isolation or perceived social support. The underlying reasons for these results are unclear. DSSI-10 measures both structural  and functional aspects  of social relationships ; howeverOn the other hand, we found that interaction between aging and hearing loss significantly contributed to social interaction/isolation. Aging reduces the number of social contacts and brings a decline in social activity . EpidemiIn summary, we observed a significant relationship between untreated hearing loss and emotional loneliness. Depression was a common factor that contributed to loneliness, social isolation, and poor social support. The following steps can be taken to increase the social support and help reduce the burden of loneliness and isolation: (i) encourage the use of engaged coping strategies such as managing the hearing loss using hearables/hearing aids or hearing implants or using communication strategies ; (ii) prThis is a cross-sectional study; therefore, results must be interpreted cautiously. A study with more power and a longitudinal design could provide more insight into the causal relationship between untreated hearing loss, loneliness, social isolation, and social support.A follow-up manuscript will investigate the effect of hearing loss treatment using hearing aids/hearing implants that could help alleviate loneliness, social isolation, and depression. Future research is required to investigate whether social support could buffer the association between hearing loss and emotional loneliness.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Human Research Ethics Committee of the University of Western Australia approved the study protocol (RA/4/1/7368). The patients/participants provided their written informed consent to participate in this study.TM, JY, and JG-S contributed to the data collection. DJ, OA, and RE contributed to the study design, interpretation of results, and manuscript writing. JW and IS contributed to the analysis, interpretation of data, and drafting the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Fusarium verticillioides is a major concern worldwide. While key genes involved in fumonisin biosynthesis are known, the location within the fungal cell where this process occurs has yet to be fully characterized. In this study, three key enzymes, i.e., Fum1, Fum8, and Fum6, associated with early steps of fumonisin biosynthesis pathway, were tagged with GFP, and we examined their cellular localization. Results showed that these three proteins co-localized with the vacuole. To further understand the role of the vacuole in fumonisin B1 (FB1) biosynthesis, we disrupted two predicted vacuole associated proteins, FvRab7 and FvVam7, resulting in a significant reduction of FB1 biosynthesis and a lack of Fum1-GFP fluorescence signal. Furthermore, we used the microtubule-targeting drug carbendazim to show that proper microtubule assembly is critical for proper Fum1 protein localization and FB1 biosynthesis. Additionally, we found that α1 tubulin is a negative regulator in FB1 biosynthesis. We concluded that vacuole proteins with optimized microtubule assembly play a crucial role in proper Fum1 protein localization and fumonisin production in F. verticillioides.Fumonisin contamination of corn caused by  Penicillium chrysogenum, penicillin biosynthetic pathway enzymes were shown to be in multiple cell compartments including vesicles, vacuoles, peroxisome, and cytosol . Re. Re1  in the proposed FB1 biosynthetic pathway were studied [F. verticillioides , which is required for the first step of FB1 biosynthesis, was remarkably downregulated in the absence of FvVam7 and FvRab7. Based on these results, we concluded that Fum1 localized in the vacuole and that proper functions of FvVam7 and FvRab7 are indispensable for Fum1 protein expression and FB1 production. In unctions ,29. We itructure , which fo medium C, which ogenitor A. Additiogenitor D. FB1 progenitor B. We tesogenitor . As expeF. verticillioides, carbendazim was used to treat Fum1-GFP, Vam7-mCherry, and mCherry-Rab7 strains to observe their localization and vacuole structure. Our findings showed that Fum1, Vam7, and Rab7 localized to the large vacuole structure in the mock treatment. However, with the treatment of 1.0 μg/mL carbendazim for 24 h, Fum1-GFP was localized to irregular and punctate structures in the cytoplasm, while Vam7-mCherry and mCherry-Rab7 exhibited small and fragmented vacuoles with irregular spheroids structures  led to a 7-fold higher of aflatoxin compared to WT in an aflatoxin-inducing condition [The vacuole is a dynamic cellular compartment that exerts many functions. Plant vacuoles were shown to permanently or temporarily store diverse and numerous secondary metabolites  including chemicals used as defense or attractants . In fungoduction . Taken tmembrane ,38. We plization . As a keoduction . HoweverF. graminearum [F. verticillioides) for 24 h in F. graminearum. This is consistent with vacuole localization in F. verticillioides. We found that MT network participated in vacuole morphology regulation in F. verticillioides. Clear evidence was also found in some plant species that vacuole morphology is regulated by MT [We also examined other factors that may potentially influence vacuole’s function. As an important cytoskeleton, MT and tubulin heterodimers interact with a variety of cellular components (metabolic enzymes or cellular organelles), thereby regulating intracellular metabolic pathways. Evidence revealed that MT binds to most of the glycolytic enzymes and regulates their activities ,41,42. Iminearum . In thised by MT ,34.1 production significantly increased when treated with carbendazim in F. verticillioides. However, the expression of FvFum1 showed no significant difference when compared to the control group by RT-qPCR analysis. The reason is still unclear. In A. parasiticus, two important aflatoxin synthetic enzymes were localized in vesicles. When deleting vb1 (a member of Vps tethering complex) in A. parasiticus or using Vps tethering complex inhibitor Sortin3 to treat A. parasiticus, fragmented vacuoles and increased aflatoxin production were observed, but the expression of aflatoxin biosynthetic genes showed no significant changes in vb1 mutants or under Sortin3 treatment [1 biosynthesis, yet there is no close correlation between the expression levels of FvFum1 and vacuole morphology in F. verticillioides. Additionally, in F. graminearum, low concentrations of carbendazim boosted DON production, but high concentrations significantly reduced it [F. verticillioides could also relate to the concentrations of carbendazim.Interestingly, we found that FBreatment . We specduced it . Our expF. graminearum [F. verticillioides revealed that three tubulin subunits were involved in FB1 biosynthesis. ΔFvα1 showed significantly increased FB1 production, whereas FB1 production in ΔFvα2 and ΔFvβ2 mutants was dramatically reduced. The differences between F. verticillioides and F. graminearum indicated that the regulatory roles of tubulin subunits in secondary metabolism vary among species. Further research is needed to unveil the different FB1 regulating mechanisms in F. verticillioides.Our previous study showed that α1-β2 tubulin heterodimer is critical for toxisome formation and DON biosynthesis in minearum . However1 production. Fvα1 tubulin is a negative regulator in FB1 production. However, further studies are needed to better understand the effect of MT on promoting FB1 production and how the protein–protein interaction network of tubulins interact with MT in regulating FB1 production. In summary, this report revealed the localization of Fum proteins in vacuole. Two vacuole proteins, FvRab7 and FVam7, are required for FB1 biosynthesis. Further study showed that disrupted MT assembly caused the change in Fum1 localization and enhanced FB