The audiological symptoms presented a prevalence of 74.4% for a sensation of ear fullness, 59.6% for tinnitus, and 51.1% for a sensation of hearing loss.Since the SARS-CoV-19 pandemic, the possibility of audiological involvement by this virus has been speculated without being able to generate a true cause–effect relationship. The objective of this observational, descriptive cross-sectional study is to describe the audiometric findings of post-COVID-19 patients with audiological symptoms. A sample of 47 patients with a diagnosis of COVID-19 infection was included: The age range was between 18 and 50 years old, the mean age was 37.0 years with a standard deviation of ±8.3 years, and 32 patients (68.1%) were female and 15 male patients (31.9%). Patients were recruited by the Otolaryngology service at Civil Fray Antonio Mayor Hospital from September 2020 to December 2022. Tonal audiometry was performed in a window of no more than 3 months from the onset of symptoms. The Chi-square test was used and odds ratios (OR) were established to associate the variables of post-COVID-19 audiological symptoms and the prevalence of hearing loss. A 95% confidence interval (CI) and statistical significance were considered of  Hearing loss is a disease considered to be the fourth cause of disability worldwide, since it conditions difficulty in the person who suffers from it not only to develop socially but educationally and even impacts their ability to earn money . As we eA person is said to have hearing loss when they do not retain or cannot hear as well as a person with normal hearing. Normal hearing is defined when, through an audiometry study, the patient has hearing thresholds of 20 dB or less . Since tStudies have found alterations in hearing thresholds and up to a 15% incidence of audiological symptoms in post-COVID-19 patients without being able to establish a clear relationship , dispropThe present article seeks to find evidence on hearing threshold alterations provided by audiometry that could be associated with COVID-19 infection presenting audiological symptoms.The present observational cross-sectional study focuses on reporting audiometric findings of post-COVID-19 patients who report audiological symptoms, during or after the onset of symptoms, performing an audiometry study in a window of no more than 3 months from the onset of symptoms. Patients with a history of otologic disease or consumption of ototoxic drugs during their illness were excluded. Qualitative methodology using an observational, descriptive method, and cross-sectional study via interviewing was used to explore patients with a positive PCR or antigen COVID test presenting audiological symptoms. This study adheres to the ethical principles for medical research in human beings outlined in the Declaration of Helsinki promulgated by the World Medical Association. The present study approached patients diagnosed with SARS-CoV-2 of fewer than 3 months of evolution and treated at the Civil Fray Antonio Mayor Hospital from September 2020 to December 2022. Patients were recruited by personnel from the otorhinolaryngology and head and neck surgery service. The method of selection was non-probabilistic, and all patients who sought attention at the otorhinolaryngology service during the study period were captured. A total of 47 patients with a diagnosis of COVID-19 infection were included, between 18 and 50 years of age. To comply with legal age regulations, a minimum age requirement of 18 was established. In order to avoid potential bias caused by presbycusis or otosclerosis, which commonly occur around age 50, an age limit was set at that threshold. Patients presented audiological symptoms at the beginning, during, or after the COVID-19 infection, performing audiometry in a window of no more than 3 months from the onset of symptoms.A non-probabilistic, sequential sampling was carried out. There was only one study group determined by the selection criteria. Inclusion criteria were: (a) patients from 18 years to 50 years of age with a positive diagnosis of COVID-19; (b) patients with a positive result for COVID-19 by PCR or antigen test; (c) patients who agreed to be part of the research protocol in question; (d) patients who in the interview referred any of the audiological symptoms from their diagnosis of COVID-19.Although patients had no previous audiometry, they reported a decrease in their hearing clarity during or after their infection. This was identified through the auditory symptomatology questionnaire. The patients never reported any previous auditory symptoms. Further confirmation of any audiological impairment such as hearing loss was confirmed by tonal audiometry. During the clinical evaluation of patients with COVID-19, they were asked if they had experienced tinnitus prior to their infection or if they developed it during or after their illness. The focus was on direct questioning about the presence of tinnitus and its timing in relation to COVID-19. The degree of disability from tinnitus was not explored during this evaluation.Exclusion criteria were: (a) patients with a history of unilateral or bilateral conductive or sensory hearing loss before a diagnosis of COVID-19; (b) previous diagnosis of another cochleovestibulopathy; (c) patients with a history of listed otologic surgery: stapedectomy, cochlear implant; (d) patients who have consumed the following ototoxic drugs during their infection: aminoglycosides: amikacin, gentamicin, kanamycin, neomycin, plazomicin, streptomycin, and tobramycin; quinoline derivatives: chloroquine, quinine, and hydroxychloroquine; loop diuretics: furosemide, ethacrynic acid, and bumetanide; and platinum-derived chemotherapeutics.Elimination criteria were: (a) patients who did not have their audiometry performed within the first 3 months after their diagnosis of COVID-19. This study did not exclude patients who had previously received a COVID-19 vaccine. Out of the 47 patients who were evaluated, 4 (8.5%) did not disclose any prior vaccination for SARS-CoV-2. Meanwhile, 20 (42.5%) reported having completed their vaccination scheme, while 23 patients (48.9%) had an incomplete scheme of their vaccination status.Forty-seven patients were selected for the study, a total of ninety-four ears, and these patients attended the COVID service department and the Otorhinolaryngology service, both from the “Fray Antonio Alcalde” Civil Hospital from September 2020 to December 2022. Patients were then entered into the database met the inclusion criteria and presented complete data.The patient was provided with complete information regarding the study protocol, utility, and eligibility was confirmed by a survey of symptoms . Before First, we explained to the patient what the test consists of and its objective. Secondly, we performed an otoscopy to ensure a permeable external auditory canal. Next, the patient was seated in a soundproof booth and sent a tone produced by the audiometer that reached them through headphones for air conduction and a vibrator for bone conduction, placed in contact with the mastoid process. The order of the frequencies to be studied was the following: 1000, 2000, 4000, 8000, 500, and 250 Hz. The patient had to answer each time they heard the sound, even faintly, by pressing a button, thus detecting the minimum sound stimulus and auditory threshold that the patient perceived at different frequencies, in both air and bone conduction. The tones were not presented rhythmically but randomized to prevent the patient from anticipating the responses. The detected thresholds were recorded using the internationally accepted signs, obtaining a graph of the patient’s hearing known as an audiogram.Speech audiometry was performed, as part of the audiometry study to evaluate the integrated ability of the subject to detect, recognize, and differentiate phonemes in this case, of the Spanish language.Hearing loss was identified by decreased sensitivity of the auditory system to a sound stimulus, resulting in a subjective sensation of increased hearing threshold by the patient. The diagnosis was made with the determination of the hearing threshold through tonal audiometry, determined as present or absent . Types oI.Conduction: Lesion located at the level of the middle ear or external ear, evidenced in the tonal audiometry with an alteration of the thresholds in the airway compared to normal in the bone pathway .II.Sensorineural: Lesion located in any of the areas of the auditory pathway such as cochleopathy (Corti’s organ), neuropathy (acoustic pathway), or corticopathy (auditory cortex), evidenced in the tonal audiometry with an alteration of the tonal thresholds of both the airway and the bone pathway equally .III.Mixed: Lesions in the neurosensory pathway  and conductive pathway  coexisting, presenting in the audiometry a combination of previously described patterns of conductive and neurosensory lesion .p ≤ 0.05 were considered.Using the Shapiro–Wilk test, a non-parametric distribution was established, the Chi-square test was used and odds ratios (OR) were established to associate the variables of post-COVID-19 audiological symptoms and the prevalence of hearing loss. A confidence interval (CI) of 95% and a statistical significance of This study enrolled a total of 47 patients who are from the western region of Mexico. The Civil Fray Antonio Mayor Hospital, one of the largest hospitals in the country, receives a significant number of patients on a daily basis. These patients attended the COVID service and the otorhinolaryngology service, from September 2020 to December 2022, in Mexico. Patients were entered into the database, met the inclusion and exclusion criteria, and presented complete and full data. Out of the total number of patients evaluated, the presence of comorbidities was assessed. Among them, 37 (78.7%) did not suffer from any comorbidities. Meanwhile, 3 (6.4%) had a smoking history, 2 (4.3%) had systemic arterial hypertension, 1 (2.1%) had type II diabetes mellitus, 1 (2.1%) had type I diabetes, 1 (2.1%) had depression, 1 (2.1%) had depression and anxiety, and 1 (2.1%) had both smoking and hypothyroidism.p = 0.033) and the need to repeat words with an OR = 3.802 (p = 0.008) to some degree of hearing loss in the audiometry.Hearing loss was identified by decreased sensitivity of the auditory system to a sound stimulus, resulting in a subjective sensation of increased hearing threshold by the patient. The diagnosis was made with the determination of the hearing threshold through tonal audiometry, determined as present or absent . A totalThe final sample consisted of 47 patients, and audiological symptoms referred by patients were evaluated. First, regarding the presence or absence of tinnitus, 19 patients (40.4%) did not refer tinnitus; 28 patients (59.6%) reported the presence of tinnitus during and/or after COVID-19, of which 10 (21.3%) patients reported left tinnitus, 10 (21.3%) right tinnitus, and 8 (17%) bilateral tinnitus .p = 0.183) being insufficient to establish a relationship between these two variables.Regarding tinnitus, 59.6% of the patients presented this audiological symptom. The relationship of tinnitus  with the presence of hearing loss in the tonal audiometry presented an OR of 1.960  evaluated, 23 patients (48.9%) did not report a sensation of hearing loss; 24 patients (51.1%) did refer it, of which 5 (10.6%) patients reported a sensation of hearing loss in the left ear, 6 (12.8%) a sensation of hearing loss in the right ear, and 13 (27.7%) a sensation of bilateral hearing loss .p = 0.033).The sensation of hearing loss during or after COVID-19 was reported in 39% of the 94 ears studied (51.1% of patients); presenting 2.94 times more risk of presenting a diagnosis of hearing loss in audiometry when presenting said symptom, given by OR = 2.940  met diagnostic criteria for unilateral sudden hearing loss, establishing an incidence of sudden hearing loss in post-COVID-19 patients with audiological symptoms.p = 0.008). This is significant enough to establish a relationship, and strongly suggests the possibility of this symptom is a potential risk factor for hearing loss in post-COVID-19 patients (The necessity of word repeating during a conversation was found in 17 patients (36.2%), the relationship between this symptom and the presence of hearing loss in audiometry presented an OR = 3.802 . According to the classification of the World Health Organization , the degNormal hearing, ≤20 dB.Mild hearing loss, 20 to <35 dB.Moderate hearing loss, 35 to <50 dB. Moderate to severe hearing loss, 50 to <65 dB.Severe hearing loss, 65 to <80 dB.Profound hearing loss, 80 to <95 dB.Anacusis, 95 dB or higher.Of the 94 ears, 74 (78.72%) had normal hearing, from which 70 (74.5%) ears were without underlying pathology, and 4 ears (4.3%) presented ototubaritis. In total, 8 (8.5%) patients had mild conductive hearing loss, 7 (7.4%) mild conductive hearing loss and ototubaritis, 12 (12.76%) patients presented sensorineural hearing loss, 1 (1.1%) had mild sensorineural hearing loss, 5 (5.3%) had moderate sensorineural hearing loss, 4 (4.3%) presented sudden sensorineural hearing loss , and 1 (1.1%) mild sensorineural hearing loss and ototubaritis, 1 (1.1%) moderate mixed hearing loss.This study explored persistent audiological symptoms regarding post-COVID-19 syndrome and audio-metrical involvement. Various studies have shown how feasible the infection of the inner ear by COVID-19 is, as well as its possible involvement not only directly but also due to inflammatory “crossfire” or vascular causes that could culminate in audiovestibular affectations ,12. The The presence of tinnitus is considered one of the most prevalent symptoms in the general population (12 to 30%) and various etiologies are attributed to it, such as upper respiratory tract diseases, hearing loss, or mood factors such as stress and depression . Even chJafari et al. in their systematic review and meta-analysis describe that COVID-19 could cause hearing loss; however, most of the studies that try to establish a relationship between coronavirus and sudden hearing loss are case reports, so care should be taken in result interpretation . AccordiThe necessity of word repeating as an audiological symptom presented a correlation for the development of hearing loss in audiometry and strongly suggests the possibility of this symptom being a potential risk factor for hearing loss in post-COVID-19 patients. Therefore, it is important to specifically ask this question, along with the sensation of hearing loss in the interrogation of patients evaluated for COVID-19, in the event that the patient refers to these two symptoms, and to be able to perform audiometry in a timely manner to rehabilitate the patient if necessary and thus reduce the impact on their quality of life, and professional, social, and educational development.In light of the then-ongoing pandemic and the highly contagious nature of the disease, some patients had expressed reservations about attending their scheduled audiometry appointments, despite having been informed of the extensive precautions in place to ensure a safe and sanitized environment. It is worth noting that any failure of the otolaryngology service’s audiometry equipment could have potentially impeded the progress and recruitment of patients.The prevalence of hearing loss in post-COVID-19 patients with audiological symptoms is 38% in this study. The degree of hearing loss and type of hearing loss in post-COVID-19 patients with audiological symptoms ranges from mild to predominantly sensorineural anacusis as the degree of hearing loss increases. The prevalence of sudden sensorineural hearing loss in post-COVID-19 patients with audiological symptoms in this study is 8.5%. The presence of a sensation of hearing loss is related to a risk factor for presenting some degree of hearing loss in tonal audiometry in post-COVID-19 patients with audiological symptoms, along with a strong correlation with the necessity of word repeating during a conversation. Investigating these diverse audiological manifestations is crucial for a comprehensive understanding of the virus’s impact on the auditory system. Identifying and addressing auditory issues in post-COVID-19 patients can lead to the development of targeted rehabilitation strategies, improving their overall functional outcomes and emotional well-being. Early identification and intervention for audiological issues in post-COVID-19 patients can lead to better outcomes. Audiological research can help identify risk factors and symptoms associated with auditory complications, enabling healthcare providers to initiate timely interventions and reduce the burden of long-term auditory problems. This is the initial stage of comprehensive research that will thoroughly analyze variables researched within this study such as tinnitus, over a prolonged period.


Hearing aids are the most commonly used treatment for people with age-related hearing loss, however, hearing aid uptake is low, primarily due to high cost of the device, stigma, and a lack of perceived need. To address accessibility and affordability issues, the U.S. Food and Drug Administration created a new over-the-counter (OTC) hearing aid category. Various types of hearing devices are available for both individuals with hearing loss and for those with normal hearing, as hearing enhancement devices. Hearing aids  are regulated by the FDA. The purpose of this article is to (a) provide a summary of existing research on direct-to-consumer (DTC) hearing devices such as Personal Sound Amplification Products (PSAPs) that informs OTC service delivery models; (b) provide an update on existing and ongoing randomized controlled trials on currently marketed OTC hearing aids; and (c) highlight the need for immediate research on OTC hearing aids and service delivery models to inform policy and clinical care. It remains to be seen what effect OTC hearing aids have on improving the uptake of hearing aids by individuals with mild-to-moderate hearing loss. However, there is scant research on all aspects of OTC hearing aids that are currently on the market. We conclude that high quality independent research must be prioritized to supplement evidence provided by the OTC hearing aid manufacturers for regulatory approval purposes. Aging is the leading cause of hearing loss which affects an estimated 1.5 billion persons globally and age-related hearing loss is one of the most common chronic health conditions affecting nearly one third of the world’s population over 60 years . Age-relHearing devices have seen tremendous evolution in the last decade including rapid development in features, functionalities as well as look and feel of the device. Modern hearing aids have many new features such as Bluetooth connectivity, rechargeability and fitness tracking. Interestingly, several devices look more like an earbud rather than a traditional hearing aid. This has been possible due to the convergence of traditional hearing aids, which are medical devices, with consumer audio devices, creating a whole array of hybrid devices such as Personal Sound Amplification Products (PSAPs) and hearables. Currently, there are several hearing devices on the market, of which some are medical devices intended for individuals with hearing loss and regulated by the FDA , and other devices that serve as hearing enhancement devices for individuals with normal hearing who have an average hearing thresholds of 25 dB or better in frequencies 500 Hz, 1,000 Hz, 2000 and 4,000 Hz  or those used mainly for entertainment purpose   Figure . Some maSome of these devices have been available to consumers through direct-to-consumer (DTC) channels for several years  including a category of DTC online hearing aids. The OTC hearing aid category has now superseded the DTC online hearing aid category with devices becoming available in-store and online to consumers in the United States starting 17 October 2022 following the historic ruling of the U.S. Food and Drug Administration . The OTCvia channels such as supermarkets, pharmacies, consumer electronic stores or online. Third, users may have to select one of the pre-set programs or self-fit the hearing aid via an accompanying smartphone app. Fourth, users have to self-learn handling skills such as putting on the hearing aid appropriately, charging, cleaning, etc. Finally, users must monitor on-going issues with the device  and troubleshoot them as necessary. OTC hearing aids do come with instruction manuals and/or step-by-step help in the smartphone app. Moreover, users may also have remote customer support by a technician and/or remote clinical support by hearing healthcare professionals. Nevertheless, these are still pre-requisites that users need to be able to comply with to obtain optimal benefits. For these reasons, both consumers as well as the licensed hearing care professionals/providers (HCPs) who are assisting the consumers must consider aspects related to the (a) device, (b) service delivery model and (c) user when deliberating on the appropriateness of OTC hearing aids for specific persons.There are some important pre-requisites for successful use of OTC hearing aids to achieve optimal benefit and satisfaction as illustrated in In this article, we aim to 1) provide a summary of existing research on DTC hearing devices that informs OTC service delivery models; 2) provide an update on existing and ongoing randomized controlled trials (RCTs) on currently marketed OTC hearing aids based on the clinical trials registration; and 3) highlight the need for immediate research on OTC hearing aids and service delivery models to inform policy and clinical care.via DTC channel, we can call them as DTC hearing devices. Nevertheless, a few systematic reviews on consumer hearing devices suggested that the available literature can be grouped into three key themes focusing on 1) acoustic quality of hearing devices, 2) consumer surveys, and 3) clinical trials as discussed below  used in the research discussed below were available to consumers ed below . First, ed below , whereased below . These red below . It is aed below  and Japaed below  show thaed below . These sed below .n = 154 across all groups). Participants from all three groups used prescription hearing aids, although the self-fit group used a device with pre-set programs and the placebo group used a device with no functional gain. The study results showed that the self-fit group presented with only slightly poorer outcomes in self-reported and behavioral measures when compared to an audiologist-fitted group demonstrating the efficacy of the OTC service delivery model. In a follow-up study, n = 40). Participants were asked to choose one of the pre-programed hearing aids (like a pre-set OTC hearing aid) one of which included a placebo device with functional gain. The outcomes of the two groups with pre-programmed hearing aids with gain were comparable and were superior to the placebo group. The study also highlighted that the presence of red-flag conditions  did not impact the purchase decision of the users raising some concerns about consumers ability to self-identify their candidacy for OTC hearing aids.In another study, All the studies discussed above used either early generation DTC hearing devices  or prescn = 240–591) and aim to investigate service delivery models. In most of the studies, OTC hearing aids that are currently on the market or likely to come to the market in the near future are being investigated which increases their ecological validity. All of the studies include self-reported and/or behavioral measures as primary and secondary outcome measures. Unlike blinded RCTs , other pressing questions should be prioritized. Important questions should consider for whom OTC devices and respective service delivery models work and what the predictors of success are. We outline some specific questions below:⁃ What is the range in electroacoustic characteristics of OTC hearing aids that are currently on the market and how many of them are appropriate for individuals with mild-to-moderate hearing loss?in-situ audiometry-based fitting vs. direct methods)?⁃ How effective are self-fitting algorithms in personalizing hearing aid gain for individual users when compared to the gold standard prescription targets (NAL-NL2) based on pure tone audiometry thresholds? Also, is there a difference in different self-fitting methods ?⁃ Are there measures  that can be administered over the internet (web or mobile phone) that can predict who will benefit from OTC hearing aids as well can be used as an outcome measure?Service delivery model related:⁃ Are there specific users based on their biographical, demographic, and audiological variables who are more likely to seek OTC hearing aids and successfully navigate the OTC service delivery model in terms of key prerequisites?⁃ How and where will consumers find OTC hearing aid models? How will they make decisions on which device to purchase?⁃ How will users determine whether they are benefitting from OTC hearing aids or whether they should return or exchange the hearing aids during the federally mandated trial period? It is possible to design a self-testing method that consumers can use for this purpose?⁃ Will there be a difference with respect to when and where users are more likely to wear OTC vs. prescription hearing aid? For example, are OTC hearing aids more likely to be used situationally while prescription hearing aids used daily? How does the duration of hearing aid use impact core outcomes?⁃ What is the cost-benefit ratio and for which users when it comes to lower versus higher cost OTC hearing aids and which features, and functionalities are most relevant?⁃ Can customized or personalized educational programs increase user uptake and motivation, supplement self-fitting and management of OTC hearing aids and enhance outcomes e.g., ?User related:OTC hearing aids have opened a new service-delivery avenue for hearing care with many potential consumer benefits especially for those with age-related hearing loss. The limited available research on OTC hearing aids currently on the market emphasizes the need for a stronger evidence-base to support the efficacy of these devices and their service-delivery models. In this article, we propose several questions regarding OTC hearing aids as well as service delivery models that need to be answered rigorously and urgently to inform hearing healthcare policy and clinical care. High quality independent research is important to supplement the evidence that is currently being provided by the OTC hearing aid manufacturers for regulatory approval. Moreover, Patient and Public Involvement (PPI) or Consumer and Community Involvement (CCI) should be considered in shaping future research priorities .


In our study, we aimed to evaluate the hearing aid benefit and speech intelligibility with hearing aids using objective and subjective measurements, according to the type of hearing loss in elderly individuals who used different types of hearing aids.The objective and subjective findings from a total of 47 elderly individuals between the ages of 60 and 84, who used regular hearing aids for at least six months, and who were diagnosed with different types and degrees of hearing loss were evaluated by scanning them retrospectively.0N90 and S0N270) and asymmetric hearing loss (S0N0 and S0N270) in the free area. A significant difference was found between abbreviated profile of hearing aid benefit satisfaction questionnaires before and after hearing aid use in all groups.In our study, the Adaptive Turkish matrix sentence test (ATMST) was carried out with binaural headphones, and a statistically significant difference was observed between the ATMST scores of individuals with symmetrical hearing loss. A significant difference was found between the ATMST score averages for individuals with symmetrical hearing loss (SThe Turkish matrix sentence test (TMST) in noise can be used routinely in clinics in order to evaluate the possible hearing loss from the daily environment and the hearing aid effectiveness. Hearing loss, which is one of the most common neurological diseases and emerges with old age , is a heIn accordance with the aim of this study, the speech intelligibilities of geriatric individuals with hearing loss were determined through sentence tests by performing TMST in noise with constant talk simulation. Then, it was also aimed to decide the appropriate amplification for every patient and to determine how much they benefit from the use of hearing aids and the superiority of the single-sided/bilateral hearing aids.In our study, the patients (47 patients with hearing loss), who applied to the Audiology Unit of Hacettepe University Adult Hospital between 2015 and 2018 due to hearing loss and were given hearing aids and were followed for 6 months at least, were scanned retrospectively. Among those individuals, 44 individuals with hearing loss , 8 individuals with asymmetrical sensorineural hearing loss (4 men and 4 women), and 7 single-sided sensorineural hearing loss (3 men 4 women)), who came to follow-ups regularly and who had other tests done besides routine ones, were included in the study. Individuals were divided into three groups  according to hearing loss type. Patients’ pure-tone air conduction thresholds (between 125 and 8kHz octave frequency) were tested via a GSI audiometry device. The air conduction pure tone averages (PTA) of individuals with asymmetrical hearing loss were determined as such; for right ear 40.31 ± 29.05; for the left ear, 71.87 ± 21.82. The PTA of individuals with left ear single-sided sensorineural hearing loss was determined as such: for right ear 33.75 ± 8.75, for left ear 92.50 ± 10.68. The PTA of individuals with right ear single-sided sensorineural hearing loss was determined as such: for the right ear, 10 ± 1.44; for the left ear, 120. The PTA of individuals with symmetrical hearing loss was determined as such: for the left ear, 46.29 ± 11.03: for the right ear, 46.89 ± 9.99. Age averages of all the individuals were determined to be 68.02 ± 5.45 (between the ages of 60 and 84). MOBID tests were done on all of the patients, who were given hearing aid and came to their follow-up appointments, and only one of the patients’ test scores was less than 21 in this test. However, the patient who got less than 21 was not included in the study as he did not come to the follow-up. Demographic information about the individuals is shown in The EQ-5D-3L scale for general life quality and the satisfaction questionnaire for hearing aid (abbreviated profile of hearing aid benefit (APHAP)), which were carried out with the patients’ permission, were scanned retrospectively.The Turkish satisfaction questionnaire for hearing aids given to the patients for the assessment was examined retrospectively. APHAB, which evaluates different situations with and without hearing aids, consists of 4 subgroups  and 24 items. Those items help patients and clinicians assess performance with and without hearing aids. In the questionnaire interpretation, the averages of the questions asked in each of the subgroups (averages of 4 subgroups) show the APHAB score .The validity and reliability studies of the EQ-5D-3L scale for general life quality, which was developed to assess the general life quality of many disease groups, were carried out by H. Kahyaoğlu Süt (2009) . The scaThe TMCT, developed by Zokoll et al. 2015), was applied to the patients in order to evaluate their skills of distinguishing speech in noise and speech intelligibility . TMCT wa15, was a0N0); then when the signal came from the front, the noise came from the right side of the patient (S0N90); and lastly, the patient turned to the speaker on his or her right side and the signal came from the front and noise came from the left side of the patient (S0N270). The ATMST in noise –with and without a device- was performed and questionnaires were given to all of the patients 1 month, 6 months, and 12 months after the application of hearing aids. However, since among the patients who were included in the study, only 2 of them came to annual control, the results for 6 months were given and annual results were discussed. The TMST was tested through Sennheiser HDA200 headphones by using an otometrics audiometry device  connected to a PC. Calibration of the device was carried out regularly and monthly in accordance with American Speech Hearing Association (ASHA) standards 0N90 and 0N0,S0N90, and S0N270) SNR rates of the individuals with single-sided/bilateral hearing loss  was found compatible with the other studies [Not observing a significant difference between free field ATMST in noise  using the matrix sentence test. In our study, an increase in the speech intelligibility of the individuals using BICROS hearing aids was observed compared to their earlier situations without the hearing aids. Giving hearing aids to geriatric individuals, whose one ear is functional and who have single-sided hearing loss, not only provides an increase in the speech intelligibility in noise but also increases their life quality. It is believed that the inclusion of Turkish matrix sentence test, which is different from other routine audiological tests, in routine clinic usage for determining the amplification can give useful results for evaluating and following the patients with different types of hearing loss. The findings obtained were compatible with the study of Prates et al., in which the authors evaluated speech intelligibility and SNR rates of patients with hearing loss who used hearing aids for three months .The Turkish matrix sentence test showed that there was an improvement in the speech intelligibility of elderly individuals with hearing loss after hearing aid use.The use of bilateral hearing aids provides more benefits than a unilateral hearing aid.Objective and subjective evaluation is done together to evaluate the benefit of hearing aids in elderly individuals.


In a previous study, an inner ear catheter was used to deliver low- and high-dose steroids into the cochlea prior to cochlear implant electrode insertion. With this approach, more apical regions of the cochlea could be reached and a reduction of electrode impedances in the short term was achieved in cochlear implant recipients. Whether intracochlear application of drugs via the catheter is a safe method also for patients with residual hearing has not been investigated hitherto. The aim of the present study was therefore to investigate the effect of intracochlear triamcinolone application in cochlear implant recipients with residual hearing.n = 10) via an inner ear catheter just prior to insertion of a MED-EL FLEX28 electrode. Impedances were measured at defined time points  and retrospectively compared with a control group (no steroid application) and low- and high-dose group. Hearing thresholds were measured preoperatively, 3 days after surgery and at first fitting by pure tone audiometry. Pre- to postoperative hearing loss was determined at first fitting and compared to results from a previous study.Patients with residual hearing were administered triamcinolone-acetonide  was 20.6 dB. Four patients (40%) showed a median hearing loss of less than 15 dB, three patients (30%) between 15 and 30 dB and three patients (30%) more than 30 dB. The median hearing loss was similar to the results obtained from our previous study showing a median hearing loss of 24 dB when using FLEX28 electrode arrays.No difference in residual hearing loss was found when comparing application of triamcinolone-acetonide using an inner ear catheter prior to the insertion of a FLEX28 electrode array to the use of the FLEX28 electrode array without the catheter. Thus, we conclude that application of drugs to the cochlea with an inner ear catheter could be a feasible approach in patients with residual hearing. If not Pharmacological treatment to prevent loss of residual hearing includes the administration of steroids via different modalities, i.e., systemic, intratympanic, and intracochlear . Systemi2.Ten adult patients (age ranging from 36.9–86.5 years (mean 59 ± 15 STD (standard deviation)), 4 female, 6 male) were included in the retrospective analysis. All patients underwent a CI surgery with an indication for a Flex28 electrode array. They had preoperative residual hearing in the low frequencies with a median low-frequency air-conduction threshold averaged across the frequencies  of 75 dB HL  see also . For allAll patients were prepared for cochlear implantation according to our standard as follows: performing the mastoidectomy, drilling of the implant bed, performing the posterior tympanotomy, drilling the bony notch for fixating the electrode array at the chorda-facial angle and exposure of the round window membrane. Thereafter, the catheter was connected to a 1 mL syringe containing a triamcinolone-acetonide solution at a concentration of 20 mg/mL and preloaded with the steroid [Triamhexal ® 40 mg/ml ] diluted at a ratio of 1:9 with Ringer solution . For detailed information on the inner ear catheter, the reader is referred to our previous publications , 2020. TUntil the first fitting appointment (approximately 6 weeks post-op), no audio processor was worn. To document hearing preservation, the hearing loss after cochlear implantation  was determined by subtraction and subsequent averaging of the preoperative air conduction threshold the frequencies 125, 500, 1,000 and 1,500 Hz from the threshold measured at first fitting using pure-tone audiometry. For the measurements, patients were seated in a sound proof chamber and instructed to press the button immediately when hearing a pure tone. The contralateral ear was plugged and muffled when necessary. Pure-tone audiometer limits were 95 dB at 125 Hz, 100 dB at 250 Hz, and 110 dB at 500 to 1,500 Hz. If no hearing could be measured up to the audiometer limit, the thresholds were set to audiometer limit +5 dB. This is a best-case assumption and corresponds to the audiometer limit + the minimum audiometer step size. If hearing thresholds for a specific frequency was not measurable preoperatively, this frequency was not considered for the calculation of the PTA shift. A change in the preoperative to postoperative air conduction was evaluated arithmetically.Impedances were measured for each electrode contact intraoperatively (intra-OP), postoperatively (3 days), at the first fitting before activation (FF) and after activation of the device electrode (FF-el). Electrode impedances were obtained using the standard MED-EL telemetry system .The impedance results were compared to our previous results obtained from patients, who received a deep intracochlear administration of triamcinolone-acetonide at a concentration of 4 mg/mL (“low-dose”) prior to insertion of the Flex28 electrode . As a coAll data were pseudonymized prior to analysis.To classify hearing preservation, the pre-to postoperative low-frequency hearing loss was clustered as previously reported : PTA shiper se exhibit different impedance values. The three groups  were treated as independent samples. To test for equality of variances, the Levene’s test was used. One-way analysis of variance (ANOVA) was used to test for significant differences among the groups. No post-hoc test was performed as no significant difference was detected between the groups. p < 0.05 were considered significant. All data were analyzed statistically using IBM SPSS Statistics 22.Impedance measurements of all 12 electrode contacts were averaged per patient for every time point for each impedance value. To assess different regions of the cochlea, the electrode contacts were furthermore clustered and averaged as follows: apical (C1–C5), medial (C6–C8), and basal (C9–C12). The clustering of the electrode contacts was performed accounting not only the different regions that are covered intra-cochlearly but also the fact that C1–C5 in the Flex28 electrode array are single (on one side) and C6–C12 are double electrode contacts (on both sides). Thus, contact C5 was added to the apical contacts, since the single sided contacts might 3.As in our previous studies, none of the patients enrolled in this analysis experienced any perioperative complications. All patients included in the study showed a correct position of the electrode array inside the cochlea as determined by postoperative cone beam CT scans.3.1.n = 10) was 20.6 dB (The median pre- and postoperative (first fitting appointment) air-conduction thresholds up to 1.5 kHz are shown in  20.6 dB . The maj 20.6 dB .3.2.A rise of the impedances at the first fitting prior to electrode activation was observed for all groups. After initial activation of the electrode, impedance values decreased immediately (FF-el) for all groups. A similar behavior of the impedances was also observed for the control group (patients treated with the FLEX28 electrode array without any steroids and without the use of the catheter) .F = 1.156, p = 0.338; 3 days: F = 0.015, p = 0.985; FF: F = 0.648, p = 0.536; FF-el: F = 0.476, p = 0.629].No significant difference was found between the three groups for the mean impedances across all electrodes (C1-C12) for the observed appointments , medial region (C6–C8)  and basal region (C9–C12) .There were no significant differences found between control group and the two catheter groups for the different regions of the cochlea: apical region (C1–C5): [ANOVA: Intra-OP: 4.p = 0.689) and at 12 months (p = 0.219) after implantation , as partial up to 75% of the hearing was lost (in 39.1% of the patients) and minimal when more than 75% of the residual hearing was lost (in 30.4% of the patients) according to the HEARRING criteria up to 1 year after implantation. Complete loss of hearing  was observed in 17.4% of the adult population . In the Cochlear pharmacokinetics may be different in the implanted cochlea as has been shown in a guinea pig model . The volOne major concern with the application of intracochlear steroids via a catheter is an increase in intracochlear pressure leading to microtrauma, inflammation, fibrosis formation and loss of residual hearing. The herein presented results of hearing preservation after the use of the catheter for deep intracochlear steroid injection could be one indicator against such microtraumata. However, a direct measure for cochlear microtrauma does not exist and therefore, the presence or absence of microtraumata cannot be proven. Using the catheter, we applied triamcinolone-acetonide that can - due to its lipophilic attributes - pass anatomic boundaries more readily than dexamethasone . HoweverThere are several limitations associated with this study. Only a limited number of patients with residual hearing were treated with the inner ear catheter and included in this retrospective analysis. The follow up period of the patients reported and analyzed in this study is rather short limiting the strength of the findings. In addition, the amount of the drug and the pace of drug instillation was not controlled in this study and therefore considerable differences may exist that could influence the results. Despite the fact that considerable data on drug distribution, clearance and metabolism exist from preclinical experiments, such information after drug application to the human cochlea is not available hitherto and cannot be taken into account in the discussion of the results. Other factors that could influence hearing preservation such as age, underlying disease, individual cochlear anatomy and surgical expertise have not been controlled in the present study. Despite these limitations, our study is -to our knowledge- the first and only to demonstrate the feasibility of catheter-based application of glucocorticoids in human cochlear implantation.Despite the presence of benzyl alcohol, the degree of hearing preservation that was achieved after the use of deep intracochlear injections of triamcinolone-acetonide via the inner ear catheter is similar to the one achieved in our previous study . This suBased on the prototype discussed in this publication, the Inner Ear Catheter was CE-marked (INCAT from MED-EL GmbH) and is available for clinical application in the EU and several other countries.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. The patients/participants provided their written informed consent to participate in this study.NP, TL, and AW: conception or design of the work. NP, TL, AW, and RS: acquisition of data. LG and AL-S: analysis and interpretation of data. AW: drafting the work. NP, RS, TL, LG, and AL-S: revising the manuscript critically for important intellectual content. All authors provided approval for publication of the content and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.This work was supported by the German Research Foundation, Cluster of Excellence “Hearing 4 All” (DFG Exc. 2177), Hanover, Germany. NP and AW received travel grants from MED-EL.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.


Colonic self-expandable metallic stent (SEMS) placement enables preoperative total colonoscopy (TCS) in patients with obstructive colorectal cancer. Following SEMS placement, it is possible to assess the presence or absence of synchronous proximal colon cancers and perform preoperative endoscopic resection (ER) for neoplastic lesions proximal to the primary lesion. The objective of this study was to determine the usefulness and safety of preoperative TCS and ER after SEMS placement in patients with obstructive colorectal cancer.From April 2016 to March 2022, we enrolled 100 patients with obstructive colorectal cancer who underwent SEMS placement, including 86 patients who underwent preoperative TCS after SEMS placement. Complications associated with preoperative TCS and ER after SEMS placement and the characteristics of the neoplastic lesions were assessed.The success rate of SEMS placement as bridge-to-surgery was 98.0%; six patients had associated complications. Preoperative TCS was performed 8 (range: 1–30) days after SEMS placement. Four patients had synchronous advanced cancers. Nine non-advanced synchronous cancers, 116 adenomas, and 18 sessile-serrated lesions were treated by preoperative TCS and ER after SEMS placement. No procedure-related complications, namely stent migration, bleeding, and perforation were observed. Forty-five patients underwent follow-up TCS 1 year after surgery. Only one patient with submucosal invasive cancer required a second surgery.Preoperative TCS and ER after SEMS placement was performed with no complications. This approach allows preoperative evaluation of the entire colon and the treatment of precancerous lesions. (240 words) Placement of colonic self-expandable metallic stents (SEMS) is widely performed in patients with obstructive colorectal cancer as a bridge-to-surgery (BTS). This procedure avoids emergency surgery by resolving obstruction to the passage of stool and obstructive enterocolitis. Colonic SEMS placement for BTS not only minimizes postoperative complications and the risk of colostomy compared with emergency surgery –3, but aFrom April 2016 to March 2022, 100 patients with obstructive colorectal cancer admitted to our hospital underwent colonic SEMS placement for BTS. The Niti-S colonic stent  or HANAROSTENT Naturfit colonic stent  were used. In all cases, plain abdominal X-rays were obtained 2 days after colonic SEMS placement to confirm sufficient expansion. Eighty-six patients underwent preoperative TCS after preparation with an osmotic laxative . Forty-seven patients underwent ER, which comprised CSP, EMR, or ESD, after stent placement (Table Of the 100 patients with obstructive colorectal cancer, colonic SEMS placement for BTS was performed successfully in 98 patients Fig. . PreoperIn obstructive colorectal cancer, the reported frequency of synchronous colon cancers is 9% . RecentlIt is important to note that colorectal cancer can be detected even in patients who undergo TCS between 6 months and several years before the diagnosis, namely post-colonoscopy colorectal cancer. Patients with a history of colorectal cancer surgery have a risk of developing post-colonoscopy colorectal cancer . The JapBeing able to perform colonoscopy with a thin-diameter colonoscope through the SEMS provides very important advantages for the treatment of the patient, but colonic SEMS placement for the sole purpose of proximal colon observation or ER, but not for BTS, should be avoided. There were no complications associated with preoperative TCS and ER after SEMS placement in the present study. However, colonic SEMS placement is not recommended for patients with obstructive colorectal cancer without obstructive symptoms in accordance with the Japanese Society for Cancer of the Colon and Rectum Guideline 2022 for the treatment of colorectal cancer. This is because the procedure-related perforation rate is reported to be 1.6%, and the rate of the risk of deviation is reported to be 1.3% .The limitations of this study are small sample size, for there is no data for long-term course but only short follow-up after surgery. More statistical analysis of those patients by longer follow-up is necessary.In conclusion, preoperative TCS and ER after SEMS placement was performed without complications, in this study. This approach permits preoperative evaluation of the entire colon and the treatment of precancerous lesions, which can avoid unnecessary multiple surgeries in patients with obstructive colorectal cancer.


Understanding how spatial patterns of gene expression emerge from the interaction of individual gene networks is a fundamental challenge in biology. Developing a synthetic experimental system with a common theoretical framework that captures the emergence of short- and long-range spatial correlations (and anti-correlations) from interacting gene networks could serve to uncover generic scaling properties of these ubiquitous phenomena.Escherichia coli quasi-2D colonies growing on hard agar surfaces. Guided by the combined mechanisms of the contact process lattice simulation and two-dimensional Ising model (CPIM), we describe the spatial behavior of bi-stable and chemically coupled SGNs that self-organize into patterns of long-range correlations with power-law scaling or short-range anti-correlations. These patterns, resembling ferromagnetic and anti-ferromagnetic configurations of the Ising model near critical points, maintain their scaling properties upon changes in growth rate and cell shape.Here, we combine synthetic biology, statistical mechanics models, and computational simulations to study the spatial behavior of synthetic gene networks (SGNs) in Our findings shed light on the spatial biology of coupled and bistable gene networks in growing cell populations. This emergent spatial behavior could provide insights into the study and engineering of self-organizing gene patterns in eukaryotic tissues and bacterial consortia.The online version contains supplementary material available at 10.1186/s12915-023-01681-4. The emergence of spatially correlated structures is a phenomenon that pervades biology from molecular to ecological scales e.g., –4). An e. An e4])Escherichia coli growing on hard agar as quasi-2D colonies. By analogy with the two-state interacting particles of the model, we construct synthetic toggle switches [Here, we apply a theoretical framework based on the Ising model to study how spatial correlations emerge from chemically coupled, bistable SGNs in switches  whose stswitches . These SN sites  of a certain spatial configuration of spins x is defined by Z is the partition function T is the absolute temperature of the system. Together with Eq. J and T to the probability distribution of spatial configurations: for a given value of J, varying T determines the transition between ordered and disordered configurations of the system , which represents the order parameter of the system, is determined by the degree of alignment of the cells and is given by T) and the type of interaction (ferromagnetic or anti-ferromagnetic). In a ferromagnetic population  . This beIn anti-ferromagnetic populations, an ordered configuration emerges under strong interactions between cells and a disordered configuration is observed when the interaction is weak Fig. c bottom.These CPIM simulations showed that growing cell populations with ferromagnetic and antiferromagnetic Ising-like interactions give rise to short and long-range correlations around critical points. This suggests that SGNs with two states coupled through chemical signals that capture ferromagnetic and antiferromagnetic interactions should lead to spatial patterns of positive or negative correlations, respectively.i) a state reporter, responsible for the synthesis of a red fluorescent protein  or a green fluorescent protein  to report the state of SGNs; (ii) a switch module, composed of two repressors (LacI and TetR) that repress the expression of each other, allowing cells to adopt only one of the two possible states at a time; and (iii) a coupling module, which allows the production of one of the two coupling signals for each state (3-oxo-C6-homoserine lactone (C6HSL), synthesized by LuxI from Vibrio fischeri, or 3-oxo-C12-homoserine lactone (C12HSL), synthesized by LasI from Pseudomonas aeruginosa). These functions are contained in two vectors: the reporter vector and the ferromagnetic or anti-ferromagnetic vector ; n is a Hill exponent to represent cooperative binding [To test the bi-stability condition and coupling properties of the ferromagnetic and anti-ferromagnetic systems, we calculated the red and green fluorescent protein synthesis rate  in E. co binding .RFP and GFP promoters active in absence of the inducers C6HSL and C12HSL is close to zero, and it increases as the concentration of its inducer increases  Fig. .E. coli cells carrying the reporter and ferromagnetic or anti-ferromagnetic vectors. In order to discard any bias related to the properties of the reporters, we constructed another version of the reporter vector in which the promoters directing the expression of the red and green fluorescent proteins are swapped  of C6HSL   Fig. 4aa4a and bb corresponds to the length constant, which is an estimation of the mean size of cellular state clusters that emerge in the colonies. As suggested by the patterns observed in the colonies    of cluster size S for ferromagnetic colonies of rod-shaped and spherical cells shows a scale-invariant distribution of the form To further characterize the behavior of the ferromagnetic system, we analyzed the size distribution of the cellular state clusters. As seen in Fig. of 2.055   Contact Process (CP) model incorporating Ising mechanisms to represent gene expression, we show how Synthetic Gene Networks (SGNs) with two states, which are positively or negatively coupled, give rise to a rich repertoire of short- and long-range correlations (and anticorrelations). These SGNs are capable of self-organizing into long-range correlations with power-law scaling properties or checkerboard-like patterns similar to ferromagnetic and anti-ferromagnetic configurations of the Ising Model (IM) near critical points, respectively. Near the critical point, the spatial autocorrelation function of simulated “ferromagnetic populations” follows a power-law decay with an exponent consistent with the value of the IM at the critical temperature. On the other hand, the scaling exponent reshold , 51). At. At\docud, the CPIM shifts its d, extra vacancy introduces noise in the IM behavior, and thus stronger coupling or lower temperature is needed to compensate.To further understand the behavior at the critical point as to investigate the value of the critical exponents of the CPIM model, we performed a finite-size scaling analysis  as showe 2-D IM . Note hoThese theoretical results combined with our experimental ones suggest that the “ferromagnetic” genetic system can pose colonies near the critical point of a phase transition in which far regions in the colony are correlated. These findings are in agreement with the theoretical work of WB , who fouAnother interesting observation is that although the CPIM considers flipping rates between spin states which only depend on local energy differences, the dynamics of the empirical pattern of gene expression of our SGNs within the growing colonies varies with both spatial coordinates within the colony as well as its age. When comparing colonies at 14, 18, and 22 h post-inoculation , 5711, 5https://github.com/jekeymer/Contact-Process-Ising-Model). Additional information on the simulation of the Ising model during quasi-2D colony growth can be found in Additional file https://developer.gnome.org/gtk3/stable/).The code for the simulation of the Ising model during the growth of a bacterial colony was written in the C programming language, and it is available in GitHub (mCherry2 was obtained from [https://iorodeo.com) using SYBR Safe (Thermofisher). The purification of the vectors was performed using the Wizard Plus SV Minipreps DNA Purification System (Promega), while the purification of the PCR fragments was performed using the Wizard SV Gel and PCR Clean-Up System (Promega).All the vectors used in this work, listed in Additional file ned from . DiffereE. coli TOP10 (Invitrogen) or KJB24 strains. KJB24 strain contains a stop codon mutation in the cell wall protein RodA, which results in the generation of spherical cells, and a second mutation that allows cells to grow in rich medium [http://openwetware.org/wiki/TOP10_chemically_competent_cells). Cells were grown on LB liquid medium  or on M9-glucose liquid medium , where 1.5% w/v agar was added to the corresponding liquid medium to prepare LB agar or M9-glucose agar medium. When necessary, the medium was supplemented with 50 All experiments were performed using the h medium . To tranCells were grown overnight in a shaking incubator at 37 https://github.com/vivien-walter/autocorrelation) to calculate the spatial Autocorrelation Function (sACF) of binarized images of whole colonies. A value of 1 or http://www.gnuplot.info/) to fit the data of the sACF to the one phase exponential decay equation b is the length constant, which correspond to the average size of the cellular states domains generated in the colonies.A Nikon Ti microscope equipped with 10×, 20×, and 40× objectives, and FITC and TRITC Filter Cube Sets were used to obtain the images of the colonies. Images were acquired using the Nikon NIS-Elements BR software. The processing and analysis of the images was performed using the Fiji distribution of ImageJ . Single-http://homepages.inf.ed.ac.uk/s9808248/imagej/find-connected-regions/). The values of the power-law exponents To obtain the probability distribution of cluster sizes, we calculate the number and size of the clusters of binarized images of colonies and simulations using the Find Connected Regions Plugin of ImageJ  of two images. If in that position both images have the same pixel value, the program adds a 0, but if the values are different, the program adds a 1. The total number of pixels in which the images are different is then divided by the total number of pixels to obtain the Hamming distance. For this analysis, 42 colonies of ferromagnetic cells with reporter vector 1 and 65 colonies of ferromagnetic cells with reporter vector 2 were compared with 10 simulated populations for each value of the control parameter between 2 and 2.54. To find the smallest value of the Hamming distance between a colony and a simulated population, the image of the simulated population was rotated every 15°, generating a total of 24 versions for each simulated population. Thus, the final value of the Hamming distance corresponds to the smallest value obtained from the calculation of the distance between the colony and each version of the simulated population. One-way ANOVA followed by Dunnett’s multiple comparisons test, and non-parametric, unpaired two-tailed Mann-Whitney test (https://doi.org/10.5281/zenodo.8121516).All the raw data is available in an open data repository in Zenodo . Supplementary figures S14. Magnetization and Neighborhood size. Supplementary figures S15. Time series of colonies of spherical E. coli cells carrying the ferromagnetic system with reporter vector 1. Supplementary figures S16. Dynamics of reporter gene expression (spin flipping rates) in ferromagnetic colonies of spherical E. coli cells. Supplementary figures S17. Neighborhoods and Probability. Supplementary figures S18. Colony size expansion in a 3 point time series. Supplementary figures S19. Average size of spherical E. coli cells. Supplementary figures S20. Colonies of rod-shaped E. coli cells carrying the ferromagnetic system with reporter vector 1 or 2. Supplementary figures S21. Colonies of rod-shaped E. coli cells carrying the anti-ferromagnetic system with reporter vector 1 or 2. Supplementary figures S22. Colonies of spherical E. coli cells carrying the ferromagnetic system with reporter vector 1 or 2. Supplementary figures S23. Colonies of spherical E. coli cells carrying the anti-ferromagnetic system with reporter vector 1 or 2.Additional file 4:Supplementary Note 1. Simulation of the Ising model during the growth of a quasi 2D colony. Supplementary Note 2. Finite-size scaling analysis. Supplementary Note 3. Time series analysis. Supplementary Note 4. Comparison of our work with the work of Weber and Buceta. Supplementary table S1. Reporter vector. Supplementary table S2. Ferromagnetic vector. Supplementary table S3. Anti-Ferromagnetic vector. Supplementary table S4. Scaling exponent γ of populations with ferromagnetic interactions. Supplementary table S5. Scaling exponent γ of simulated populations with ferromagnetic interactions at different birth rates. Supplementary table S6. Numerical critical exponents and critical temperature of the two-dimensional Ising model, Weber-Buceta model, and the Contact Process Ising Model (CPIM). Supplementary table S7. Plasmids used in this study.


Chronic venous disease, with varicose veins as its archetypal manifestation, stands as a pervasive and intricate health quandary, encompassing a vast array of contributing factors. Age, genetics, obesity, pregnancy, and prolonged immobility weave a complex tapestry, underscoring the omnipresence of this ailment. Its societal and economic footprint is undeniably formidable, as diverse classifications underscore its multifaceted character. The intricate interplay of chronic venous disease with diabetes mellitus and neuropathy compounds the challenge, fostering soaring healthcare expenditures and a palpable erosion of quality of life, particularly among women harboring cardiometabolic risk factors. Despite research shedding light on heightened susceptibility within certain demographics, the enigmatic determinants orchestrating the transition from mild to severe chronic venous disease continue to elude us.Varicose veins, marked by the presence of dilated and tortuous subcutaneous vessels, precipitate both physical discomfort and cosmetic concerns, frequently necessitating meticulous clinical evaluation coupled with ultrasound studies to secure a precise diagnosis. Treatment strategies are strategically crafted to ameliorate distressing symptoms, enhance aesthetic concerns, and forestall potential complications. Nevertheless, the prognostication of chronic venous disease remains ensconced in a degree of ambiguity, hinting at the vast terrain yet to be charted in this medical domain. The quest to fathom the intricacies of this condition uncovers an ever-evolving panorama where conservative interventions play an indispensable role in managing mild cases, while interventional procedures like endovenous laser ablation and sclerotherapy step onto the stage for patients grappling with severe symptoms, thus treading the fine line between efficacy and invasiveness. Moreover, a meticulous economic analysis underscores the cost-effectiveness of various therapeutic modalities, thereby bolstering the imperative of a patient-centered approach. As we navigate the labyrinthine complexities of chronic venous disease and varicose vein management, we are inexorably drawn to the pivotal role of customized treatment approaches, as well as the dynamic interplay between scientific progress, patient preferences, and therapeutic innovations in the relentless pursuit of optimized outcomes and an enhanced quality of life. Chronic venous disease looms as an alarmingly pervasive and intricate health concern, casting its shadow over millions of individuals and, alas, often revealing itself only in its advanced stages, complicating the path to effective intervention. At the heart of this condition lies the omnipresent manifestation of varicose veins, a visual marker of venous insufficiency that spans a wide-ranging spectrum, with their prevalence oscillating between 5% and 30% in the general population. Traditionally, a striking female predilection was observed, with a reported female-to-male ratio of 3:1 . The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines used in research methodology are depicted in Figure Patient approachWhen patients embark on the path to seek treatment for varicose veins, the importance of a meticulous and comprehensive assessment cannot be overstated. While a clinical examination can offer valuable insights, it is often the judicious use of Doppler ultrasound that serves as the cornerstone for a thorough evaluation. This widely employed diagnostic technique allows healthcare professionals to delve deep into the intricacies of venous dynamics by scrutinizing blood flow during specific maneuvers. Of particular significance is the identification of sites prone to valve incompetence, with the saphenofemoral junction in the groin being a focal point where such incompetence is more frequently encountered. The integration of Doppler ultrasound into the diagnostic process ensures a precise understanding of the patient's condition, paving the way for informed decisions regarding the most suitable treatment options .The choice of treatment modalities hinges on the nature of the varicose veins and the underlying physiological intricacies. In instances where valve incompetence is not detected in upstream regions and the issue predominantly resides below the knee, injection treatment in the form of compression sclerotherapy emerges as a compelling option. This non-invasive approach yields promising results, significantly alleviating symptoms and cosmetic concerns. However, it is important to acknowledge that due to the underlying valve issues, the specter of recurrence looms over these cases. For those confronted with more complex varicose vein scenarios, characterized by the incompetence of valves between deep and superficial veins, surgery offers a pathway to enduring relief. Surgical interventions typically involve the precise division of superficial veins at the sites of incompetence, the stripping of long saphenous veins, and the meticulous removal of varicosities through discreet small incisions. It is worth noting that bilateral varicose vein operations can be a time-consuming endeavor, necessitating a collaborative team approach to ensure the best possible outcomes. Additionally, the prioritization of patients with complications such as skin changes or ulcers is paramount, as their conditions warrant specialized attention and timely interventions ,7.Simultaneously, the realm of varicose vein treatment encompasses individuals with different needs and aspirations. Patients grappling with concerns of a cosmetic nature or mild discomfort deserve the same level of expert assessment to tailor their treatment strategies effectively. Their journey involves a nuanced evaluation that takes into account local circumstances and individual preferences. The reassuring guidance provided by healthcare professionals plays a pivotal role in this phase, ensuring that patients are well-informed about their options and potential outcomes. For those individuals presenting with harmless varicose veins and expressing the desire for treatment, reassurance is coupled with a range of therapeutic alternatives. This includes the prospect of temporary symptom alleviation through sclerotherapy or the option to await surgical intervention if they are more inclined towards a lasting solution. In cases where a patient's eagerness for active treatment persists even after being assured of the benign nature of their condition, a prudent referral to a hospital-based setting is a recommended course of action. This comprehensive approach to patient care is underpinned by a commitment to providing tailored solutions and compassionate support throughout the varicose vein treatment journey .Assessment and decision-makingIn the realm of assessing and determining the most suitable course of action for individuals dealing with varicose veins, venous duplex ultrasound has emerged as the gold standard. This advanced diagnostic tool has revolutionized the investigation of varicose veins, enabling a comprehensive evaluation of both deep and superficial systems, including critical junctions and perforators. Its role is pivotal in deciphering the patency and competence of the venous network. With a nuanced understanding of the underlying pathophysiology, healthcare professionals are well-equipped to make informed decisions tailored to the specific needs and complications of each patient ,7.However, the approach to varicose vein management is not one-size-fits-all, and it must be fine-tuned to the individual's unique circumstances. When faced with uncomplicated, painless veins, providing reassurance often suffices. It's noteworthy that in the age of readily accessible information and the influence of anecdotal advice, some patients may be inclined to pursue specific treatments driven by recommendations from acquaintances or online research, even in the absence of clear medical indications. In these instances, the expertise of specialists becomes invaluable, ensuring that decisions are rooted in sound medical judgment rather than anecdotal evidence ,4,7.Within the domain of public health systems, there is an ongoing need for discourse regarding the management of uncomplicated varicose veins. Guidelines advocate for conservative approaches, reserving more invasive treatments for advanced cases or when debilitating symptoms are present. The key lies in striking a balance between the principles of conservative management and the necessity for intervention, guided by the unique needs of each patient. Patients grappling with varicose vein complications such as venous eczema, ulcers, insufficiency, thrombophlebitis, bleeding, or discomfort should find their path leading to a vascular team. This is a critical step in ensuring that specialized care is administered, addressing the complexities of their conditions effectively .Pre-referral discussions between healthcare professionals and patients are valuable, particularly in scenarios where individuals might harbor reservations about further interventions. These dialogues help in allaying concerns, elucidating the potential benefits of treatment, and addressing any lingering doubts. For those experiencing symptoms and whose foot pulses remain palpable or possess an ankle-brachial index abnormality above 0.6, below-the-knee compression stockings, often of class 2, can offer substantial relief and symptom management. It is a conservative yet effective approach to enhancing the patient's quality of life. The landscape of treatment options is further shaped by patient comorbidities, influencing the suitability of various interventions. Typically, surgical treatments are reserved for those who, apart from their varicose veins, grapple with severe medical conditions or obesity. Exceptions to this rule exist in cases where non-healing venous ulcers are a prevailing concern, warranting a more aggressive approach to care ,8.In the intricate realm of varicose vein management, the assessment and decision-making process is as diverse as the patients themselves, necessitating a nuanced approach that blends state-of-the-art diagnostics with a patient-centric ethos. It's through these carefully considered decisions that individuals receive the personalized care they require, ensuring that their varicose vein journey is one of empowerment and effective intervention. Future developments in the endovenous field might influence this approach . The genConservative management: a pillar of varicose vein careExternal compression therapy remains a cornerstone in the holistic approach to managing varicose veins. This therapeutic approach involves various tools, including bandages, support/compression stockings, and intermittent compression devices. These methods have consistently demonstrated their efficacy in alleviating the complications associated with this condition and can be employed either as standalone treatments or in conjunction with other interventions . HoweverOvercoming Challenges: Customization and ComplianceChallenges may arise with compression therapy, primarily related to patient compliance. Some individuals find compression stockings cumbersome, time-consuming, and uncomfortable. Poor compliance can compromise treatment outcomes. Therefore, healthcare professionals should consider these challenges and provide guidance and support to enhance patient adherence . CompresDrug Therapy: A Limited but Promising AvenueAesculus hippocastanum), has emerged as a potential solution [While drug therapy for varicose veins has limitations, there are promising options that deserve consideration. Traditional diuretics, used for managing edema, fall short of providing substantial relief from the pain and discomfort associated with varicose veins. However, horse chestnut extract, derived from the seeds of the horse chestnut tree  the junctions where these veins meet the femoral and popliteal veins. It is a well-established procedure indicated for patients with incompetent long or short saphenous veins, reflux through saphenofemoral or saphenopopliteal junctions, or superficial thrombophlebitis, identified through duplex Doppler ultrasound . TraditiEndovenous chemical ablation, often employed following endovenous laser ablation, aims to manage any remaining abnormal dilatations. The procedure is well-suited for effectively addressing more prominent varicose veins, particularly in the trunk region, where high blood flow may limit the effectiveness of alternative treatments like sclerotherapy . AmbulatEndovenous Saphenous Vein Obliteration: A Minimally Invasive OptionEndovenous saphenous vein obliteration represents an advanced surgical technique to reduce the invasiveness of traditional varicose vein treatments. The procedure utilizes endovenous thermal ablation, employing lasers or high-frequency radio waves to generate higher temperatures. Laser ablation transfers heat to the vessel wall . In contDuplex Doppler ultrasonography is indispensable before and during surgery to ensure precise visualization and planning. Specific vein diameter and depth requirements must be met for the procedure. The depth requirement, in particular, limits the procedure's applicability in the calf and ankle regions. Access to the greater saphenous vein is typically established just below the knee crease through a venous cut-down or direct puncture using a large-bore needle. Recent developments have expanded the range of options by enabling punching at the ankle, providing additional treatment possibilities .Transilluminated Power Phlebectomy: Minimizing Discomfort and ScarringTransilluminated power phlebectomy is tailored to treat varicose veins in the thigh region. Distinguishing itself from stab phlebectomy, which entails multiple incisions and potential pain, hematomas, and scarring, transilluminated power phlebectomy aims to reduce complications by minimizing the number of incisions while effectively removing varicose veins . During The surgical management of varicose veins has seen significant developments over the years, offering patients a range of options tailored to their specific needs. Traditional procedures like saphenous vein ligation and ambulatory phlebectomy continue to be effective treatments for varicose veins, while newer techniques like endovenous saphenous vein obliteration and transilluminated power phlebectomy are enhancing the field with their minimally invasive and patient-friendly approaches ,37. WhenOverall analysis of the available treatment optionsThe excerpt provided by some researchers across the United States of America and the United Kingdom discusses a detailed economic analysis and comparison of different treatment options for varicose veins. The study evaluates the costs and effectiveness of various interventions over a specific period for varicose veins ,37. CompResults and discussionConservative TreatmentConservative management options include lifestyle modifications, compression stockings, and phlebotonics. These methods suit mild cases, pregnant patients, and individuals unwilling to undergo surgery. They offer a non-invasive approach with minimal risk. However, they may not provide long-term relief, making them more appropriate for managing mild symptoms and preventing further deterioration ,23.Endovenous Laser AblationEndovenous laser ablation is a highly effective treatment option for patients with severe varicose vein symptoms. It involves using heat to close the affected veins, resulting in minimal scarring. While this method offers significant benefits, some patients may experience post-treatment pain during recovery ,26.SclerotherapySclerotherapy is the injection of a solution to collapse and close smaller veins, making it a viable option for patients with smaller veins or cosmetic concerns. It is effective for smaller veins, and downtime is minimal. However, multiple sessions may be necessary for optimal results ,30.Surgical StrippingSurgical stripping is recommended for severe cases with prominent veins. It provides immediate relief but is an invasive procedure with longer recovery times and scarring ,30.Laser Ablation TreatmentLaser ablation treatment is more suitable for minor to medium-sized veins and is less invasive, resulting in minimal scarring. However, patients should know the potential for post-treatment pigmentation ,38,39.Economic AnalysisAn economic analysis compared the costs and effectiveness of different varicose vein treatment options over a specified period. Various interventional procedures were assessed, including ultrasound-guided foam sclerotherapy, radiofrequency ablation, conventional surgery, mechanochemical ablation, endovenous laser ablation, high ligation and stripping, and cyanoacrylate closure ,40.The study found that ultrasound-guided foam sclerotherapy is the least expensive and most effective treatment option, leading to a higher probability of additional interventions. In contrast, radiofrequency ablation was considered cost-effective. Mechanochemical ablation, endovenous laser ablation, and high ligation and stripping were found to have similar costs and outcomes, making them comparable in terms of value for money. Varicose vein management requires a tailored approach, considering the patient's condition, preferences, and the available treatment options. Conservative management is a non-invasive starting point, particularly for mild cases, pregnant patients, and those opposed to surgery. For patients with severe symptoms and more prominent veins, interventional procedures like endovenous laser ablation, sclerotherapy, surgical stripping, and laser ablation treatment offer effective solutions ,38,40.In this narrative exploration, we have meticulously traversed the multifaceted realm of chronic venous insufficiency and the therapeutic avenues for varicose veins. Our journey commenced by shedding light on the prevalence of chronic venous disease, a condition most prominently manifesting as varicose veins and elucidating the intricate web of risk factors intricately woven into the fabric of these vascular disorders. Our scholarly voyage then ventured into the diverse spectrum of treatment modalities, encompassing established surgical procedures like saphenous vein ligation and ambulatory phlebectomy while embracing the evolution of medical science through contemporary techniques such as endovenous saphenous vein obliteration and transilluminated power phlebectomy. Moreover, we navigated the financial landscape of varicose vein treatments, dissecting the pivotal realm of cost-effectiveness and therapeutic outcomes. Throughout this odyssey, one constant remained evident: the paramount significance of precise diagnosis, comprehensive patient assessment, and tailoring treatment plans to meet everyone’s unique needs, preferences, and medical necessities. It is unequivocally clear that the management of chronic venous disease is an endeavor of profound complexity, demanding an integrated approach that harmonizes the patient's journey with the relentless march of medical progress, continuously reshaping the landscape of varicose vein treatment and, in doing so, bestowing upon patients a broader array of options and elevated prospects for enhanced outcomes.


Sudden sensorineural hearing loss (SSNHL) is considered an otolaryngologic emergency that must be treated within 72 hours. Failure to treat within that time frame typically results in permanent hearing loss. Here, we present a case of SSNHL confirmed by an audiogram that was treated as eustachian tube dysfunction. Aggressive management measures started at follow-up failed to improve the hearing loss. This case demonstrates the need for early recognition and ENT referral for SSNHL. Sudden sensorineural hearing loss (SSNHL) is considered an otolaryngologic emergency with high morbidity if missed . This isThe small space of the middle ear makes the study of the pathophysiology of SSNHL difficult. At this moment, little is known about the etiology of the disease. In up to 71% of cases, the cause is idiopathic and can resolve without any intervention . VasculaThe patient is a 45-year-old male who presented to the neurology clinic with a five-day history of gradual onset hearing loss in his left ear that began while he was on vacation in North Carolina. He reported that his left ear felt “muffled” and described his hearing as though there was a “tin can” placed over his ear. This caused him to have sounds that echoed in his hearing. He had trouble hearing out of the affected ear. He had no history of permanent hearing loss but did have a history of eustachian tube dysfunction (ETD) that caused temporary hearing loss, which was treated successfully with nasal sprays several years prior. There were no other complaints or no traumatic events prior to his decrease in hearing. On physical examination, there was a small amount of fluid noted behind the left tympanic membrane.The patient was given a topical nasal steroid (TNS) as well as saline nasal sprays for treatment of suspected ETD with a one-week follow-up. At his follow-up appointment, his audiogram showed an approximately 10 dB difference between the left ear and the right ear at 250 Hz. Overall, the left ear showed mild-to-moderate hearing loss. The left ear had a 20 dB loss in the low frequencies and close to a 50 dB loss in the high frequencies. There was no significant hearing loss in the right ear. Word scores were significantly decreased on the left in comparison with the right. A tympanogram on the left showed a type AS (reduced peak height) tympanogram classification secondary to a peak between ±100 daPa  with a compliance less than 0.3 mL. The pure tone average was 22 dB on the left and normal on the right.A repeat audiogram from several months later showed moderate-to-severe hearing loss. There was a 15 dB difference between the left ear and right ear at 250 Hz. The left ear showed a 30 dB loss in the low frequencies and an 80 dB loss in the high frequencies  . HyperbaIn this case, the patient presented outside of the 72-hour window for treatment. ETD was suspected, and the patient was treated accordingly using TNS. The patient did not improve from treatment after one week, and his hearing never returned to baseline, despite delayed treatment with oral prednisone. A left hearing aid was required to improve the patient’s quality of life. This case illustrates the necessity of considering SSNHL in a patient who presents with unilateral sudden hearing loss. Otolaryngology (ENT) referral for a hearing test and oral/intratympanic steroid therapy is the best possible treatment outcome for the patient. Starting the patient on a five-day course of oral prednisone is sufficient if ENT referral within the timeframe is not feasible.In the treatment of SSNHL, please refer to Figure This case helps to demonstrate the incredible need for physicians, and especially primary care providers, to not overlook the possibility of SSNHL in a patient who presents with hearing loss. The need for accurate diagnosis and quick treatment cannot be overstated. It is important to understand that hearing loss can present in a variety of ways, including tinnitus, "muffled" hearing, and even pain. Sudden hearing loss may need to be considered an ENT emergency. When a patient presents with hearing loss, all causes of hearing loss must be entertained, including SSNHL, anterior inferior cerebellar stroke, noise damage, presbycusis, otitis media, and cerumen impaction.


A joint longitudinal and survival model showed that during a median follow up of 10 years (SD = 4.67 years) increased PD risk (p < 0.001), but not self-reported hearing capability (p = 0.402). Additionally, an exploratory binary logistic regression modelling the influence of hearing loss identified using a screening test (n = 4812) on incident PD indicated that neither moderate (p = 0.794), nor moderately severe/severe hearing loss (p = 0.5210), increased PD risk, compared with normal hearing. Whilst discrepancies with prior literature may suggest a neurological link between hearing loss and PD, further large-scale analyses using clinically derived hearing loss are needed.Observations that hearing loss is a substantial risk factor for dementia may be accounted for by a common pathology. Mitochondrial oxidative stress and alterations in α-synuclein pathology may be common pathology candidates. Crucially, these candidate pathologies are implicated in Parkinson’s disease (PD). Consequently, hearing loss may be a risk factor for PD. Subsequently, this prospective cohort study of the English Longitudinal Study of Ageing examines whether hearing loss is a risk factor for PD longitudinally. Participants reporting self-reported hearing capabilities and no PD diagnosis prior to entry ( Hearing loss is oftentimes considered an inevitable sequela of ageing. However, an accumulation of evidence has revealed that hearing loss is a substantial, potentially modifiable, risk factor for incident all-cause dementia . SpecifiThe underlying mechanism relating hearing loss and dementia remains unclear. The common cause hypothesis suggests that a common pathology affects both the cochlea and ascending auditory pathway (causing hearing loss) and the cortex (causing dementia) ,4,5. MitOxidative stress, a biological state, occurs when the production and accumulation of reactive oxygen species (ROS) within cells outweighs detoxification of these molecules . This stPD is pathologically hallmarked by accelerated dopaminergic neuronal cell death, particularly within the substantia nigra of the basal ganglia . Whilst Another potential common pathological candidate, for the relation between hearing loss and dementia, is alterations in the production, and aggregation, of ligomers . Notablyy bodies .Importantly, sporadic ,29 and ~sporadic , Alzheim disease  and mild disease ,33 relat disease  observedl et al.  found siCritically, in addition to accelerated dopaminergic neuronal degeneration, PD is also neuropathologically hallmarked by intracellular Lewy body inclusions and Lewy neurites . Moreoveinant PD , and varinant PD . Subsequgy of PD .Thus far, mitochondrial oxidative damage and alterations in  process ,40,41. Gogenesis , followiogenesis , we may Consideration of the relation between essential tremor and hearing loss may further support the assumption that hearing loss will be intricately related to PD. Evidence suggests that patients with essential tremor, which can be defined as “bilateral upper extremity action tremor” , are at Indeed, a meta-analytical review concluded that sensorineural hearing loss and cochlear impairment are more severe in PD patients compared to age-matched controls . MoreoveRecent prospective studies indicate that hearing loss may antedate, and be a risk factor for PD. For example, Schrag et al.  found thhttps://doi.org/10.17605/OSF.IO/MJGQ6, accessed on 1 February 2023), and the data analysed in this study are openly available in the UK Data Service at https://doi.org/10.5255/UKDA-SN-5050-25, accessed on 18 November 2022. The OSF page for this project includes details regarding the variables analysed, planned statistical analyses, and the data analysis code book. We summarise the implementation below. This study deviated from the pre-registration only in the number of covariates embedded within both the primary and exploratory analyses and the exclusion criteria for missing data. Please refer to This study was pre-registered on the Open Science Framework .The final analytical sample was TM Screener data from wave 7 and incident PD data from wave 9 of ELSA. Participants reporting a PD diagnosis at wave 7 who did not complete the HearCheckTM Screener test, or who did not have age data available, were excluded. The final analytical sample was n = 4812 .We used HearCheckParticipants disclosed whether they had a diagnosis of PD at all waves. PD diagnosis was confirmed at subsequent waves.Participant reported PD in wave 9.Participants self-reported hearing capabilities at each wave by indicating on a five-point Likert scale “Is your hearing [using a hearing aid as usual] (1) excellent, (2) very good, (3) good, (4) fair, or (5) poor”.TM screener generates a series of six tones: three mid-frequency tones of decreasing volume at 1 kHz  and three high-frequency tones of decreasing volume at 3 kHz . Participants indicate when they hear the tone by raising their finger. Audibility testing occurs separately for each ear. Participants are required to remove any hearing aid(s) prior to completion of the screening test, thus the obtained results reflect hearing capabilities in the absence of corrective hearing devices. Evidence indicates that hearing loss, defined as >35 dB at 3 kHz in the better-hearing ear, is a robust and justifiable cut off criterion at which intervention is beneficial , nor moderately severe/severe hearing loss , increased risk of incident PD over a four-year follow-up.The assumption of linearity for the age variable was assumed by observing conditional density plots and using the Box Tidwell test  may not affect PD progression. However, due to fundamental limitations in the dataset analyses  we observed that as age and length of time in the study increased, self-reported hearing capabilities decreased. Age-related hearing loss is characterised by degenerative pathology in the cochlear hair cells, supporting cells, and auditory nerve endings [The present study examined whether hearing loss is a risk factor for incident PD. Regarding the incidence of PD, we observed that self-reported hearing capability was not a significant risk factor for incident PD over ~10 years of follow up. Similarly, HearCheck endings , and age endings . Thus, tAlthough the present study did not observe a relation between hearing loss and incident PD, some previous literature suggests that hearing loss increases the future risk of incident PD by 1.14–1.6 fold ,54,55. CTM screener constitutes a substantially more objective hearing loss measure than self-report questionnaires, the accuracy and sensitivity of the HearCheckTM are, at the lowest, 83 percent [n = 24). Additional larger-scale cohort analyses that draw on a more reliable diagnosis of hearing loss  are required to further elucidate whether hearing loss is a risk factor for incident PD.Exploratory analyses also found that screening-test-derived hearing loss was not a significant risk factor for incident PD. Yet, whilst the HearCheck percent . ConsequThe discrepancies between the current findings and those of previous research could speak to the mechanism underlying hearing loss and antedating PD motor manifestations. Pure tone audiometry assessment is thought to depend primarily upon the health of the outer hair cells, and additionally cochlear transduction by the inner hair cells . AlthougImportantly, both the present study and previous research ,54,55 haopathies . Moreoveopathies ,76, PSP opathies ,78 and Copathies ,80 .Although hearing loss may play a small role in the clinical manifestation of Parkinsonism disorders, observations of a differential influence of hearing loss on symptom onset across Parkinsonism disorders may be useful for clinicians to consider when differentiating such symptomatically similar conditions. Furthermore, ascertaining the relation between hearing loss and multiple Parkinsonism disorders may provide invaluable insights for the differential clinical management of Parkinsonism disorders. Therefore, the predictions made here should be investigated formally.Within this study, PD was indicated by self-disclosure of a clinical diagnosis. In the UK, in accordance with UK Parkinson’s Disease Society Brain Bank guidelines, a probable diagnosis of PD is provided if any given individual presents with bradykinesia (slowed movement) and at least one of the following: muscular rigidity, rest tremor, or postural instability . Whilst Clinical heterogeneity is well recognised in PD. Such heterogeneity presents a major barrier in terms of understanding disease mechanisms, developing treatments, and clinical management. Consequently, a set of clinical criteria for PD subtype categorization has been developed. The most frequently referred to subtyping system categorises patients into three subtypes: (1) mild-motor predominant, (2) diffuse malignant, and (3) intermediate, with categorization being based on motor impairment, cognitive function, rapid eye movement behaviour disorder, and autonomic symptoms . Given tIt is important to also consider the potential role of addressed versus unaddressed hearing loss  on symptom onset and the results obtained here. When accounting for the relation between hearing loss and dementia, it is increasingly acknowledged that prolonged auditory deprivation, due to hearing loss, may give rise to chronic cortical reorganisation, which hinders cognitive processes in favour of auditory perception ,88. Althn = 151). However, it is unlikely that this substantially biased our findings. Specifically, in 2018, the incidence rate of PD in the English population was 0.22 percent [This study is not without limitations. First, incident PD cases within the final analytical sample were low ( percent . Within  percent . Althoug percent ,93. TherTo conclude, the present study observed that self-reported hearing loss is not a substantial risk factor for incident PD. However, sample limitations necessitate further analyses in alternative populations to substantiate this finding. Should findings be replicated, treatment of hearing loss may not substantially reduce the risk of developing PD. Additionally, exploratory analyses indicated that more objectively derived hearing loss is also not a risk factor for incident PD. However, given the small number of incident PD cases in this sample, further large-scale, planned, analyses are needed to corroborate this conclusion.