The initial-fit provided by the hearing aid manufacturer’s software is generally a display of measurement done in the ear simulators. The need for verification of hearing aid output and gain in the real ear using probe-microphone measurement to match the prescriptive target is highlighted. The objective of the study was to evaluate the difference in real-ear aided response (REAR), real-ear insertion gain (REIG), aided thresholds, articulation index (AI) and word recognition score (WRS) in quiet, with hearing aid programmed to NAL-NL1 first-fit and NAL-NL1 optimized-fit using the probe-microphone technique.In a repeated measure experimental design, 11 participants with a mean age of 41.09 (SD=±9.95) years having moderate and moderately-severe sensorineural hearing loss were tested monaurally in two aided conditions, with a 16-channel hearing aid programmed for manufacturer’s NAL-NL1 first-fit and optimized-fit to NAL-NL1 using probe-microphone verification. The REAR, REIG, aided threshold, articulation index and word recognition scores in quiet were obtained for both aided conditions.The REAR, REIG, aided threshold, AI and WRS in quiet were significantly better with the NAL-NL1 optimized-fit compared to manufacturer’s NAL-NL1 first-fit.The optimized-fit yields better audibility and improved word recognition in quiet. This supports best practice guidelines of many professional organizations regarding the use of probe-microphone measurement as the “Gold standard” for verification of hearing aid fitting, thereby providing better satisfaction and quality of life to hearing aid users. The probe-microphone measurement is accurate and reliable to verify the gain/output of the hearing matched to the given prescriptive formula like the National Acoustics Laboratory Nonlinear fitting procedures, NAL-NL1 and NAL-NL2 or the Desired Sensation Level input/output formula. Though, the probe-microphone technology is available for more than three decades, a small percentage of audiologists use this to verify the hearing aid fittings.The Independent Hearing Aid Fitting Forum (IHAFF), International Society of Audiology (ISA), American Academy of Audiology (AAA), and American Speech and Hearing Association (ASHA) consider the use of probe-microphone verification as one of the best practices for adult hearing aid fittings. It was found that the measured 2cc coupler output of the manufacturer’s initial-fit was significantly lower than the NAL-NL1 targets by as much as 10-15 dB,9. The real rear measurements of the initial-fit and the verified-fit from various studies were also consistent with the fact that the gain and output provided for the high frequencies are significantly lower with the initial-fit program-13. Hearing aid with initial-fit led to reduced speech recognition and subjective satisfaction. When fitted with programmed-fit to NAL-NL2 targets a significant improvement was observed in speech intelligibility index, speech recognition in quiet and noise, and self-perceived benefit-17.Many hearing aid practitioners prescribe hearing aids based on the manufacturer’s first-fit hearing aid fitting. When the first-fit is alone used, the accuracy of the target match can be low as it is carried out only in ear simulators/coupler and there is no verification of the gain of the hearing aid in real ear suggested that the NAL-NL2 first-fit would have used instead of manufacturer’s proprietary first-fit, the difference in audibility would have been present but not as poor as manufacturer’s proprietary first-fit. It probes further to investigate the difference in performance with first-fit of a given generic prescriptive targets and optimized-fit to those targets. The comparison of objective measures like aided threshold, speech intelligibility index (SII) or articulation index (AI) and word recognition in quiet between hearing aids fitted with first-fit and optimized-fit to NAL-NL1 target is sparse in literature compared to the studies on coupler measures. It is also important to note that when compared to NAL-NL2, the NAL-NL1 prescribes high gain with lower compression ratios for adults to maximize the speech intelligibility. It is important to explore the difference in aided performance with NAL-NL1 first-fit and optimized-fit to NAL-NL1 as it is one of the commonly used prescriptive targets with the adult population. Therefore, the current study aimed to investigate the aided performance with manufacturer NAL-NL1 first-fit and optimized-fit to NAL-NL1 target.Those studies compared the benefit with manufacturer’s proprietary first-fit and programed-fit to a given generic prescriptive target. Valente et al.To compare the real-ear aided response (REAR), the real ear insertion gain (REIG), aided thresholds, articulation index (AI) and the word recognition score (WRS) in quiet obtained with hearing aid set at the manufacturer’s NAL-NL1 first-fit and the optimized-fit to NAL-NL1 target using probe-microphone measurement.The objectives of the study were addressed through a cross-sectional within group repeated-measure experimental design.The study was carried out in 11 native Kannada speaking adults, in the age range from 23 to 55 years (mean age = 41.09±9.95). This sample size was found to be adequate in G*Power analysis using F-family of tests set to 0.80 power at an error rate of 5% for detecting the mean difference in aided threshold and word recognition between hearing aid fittings with a large effect size as demonstrated in this study.The inclusion criteria include (a) bilateral sensorineural hearing loss with either flat or sloping audiogram configuration, (b) pure-tone average (PTA) between 40 and 70 dB HL, (c) greater than 60% speech identification score in quiet, (d) naïve hearing aid user, (e) ‘A’ type tympanogram with reflex present at least in one frequency, (f) post-lingual onset of hearing loss. Those having any history or presence of middle ear infection, neurological (including auditory neuropathy and/or retrocochlear pathology) or psychological complaints were excluded. The experiments were carried out in the right ear if the hearing loss was symmetrical; and only in the better ear of the participants in case the hearing loss was asymmetrical. The demographic details of the participants were given in . Otoscopy was performed to ensure that there was no contraindication for hearing aid testing. Pure-tone audiometry was carried out using modified Hughson-Westlake procedure to establish the air-conduction and bone-conduction thresholds for octave frequencies from 250 Hz to 8000 Hz and 250 Hz to 4000 Hz respectively. Speech audiometry was carried out to obtain Speech Recognition Threshold (SRT) using the Kannada paired-word list and Word Recognition Score (WRS) at 40 dBSL (re: SRT) using phonemically balanced Kannada word identification test for adults. Immittance audiometry was carried out using 226 Hz probe-tone at 85 dB SPL to rule out the middle ear pathology.All procedures carried out in this study adhered to the institutional ethical guidelines for bio-behavioural research on human subjects. The study protocol was also approved by the ethical committee of the institute (ECC-Res.art/03/2020). Informed consent was obtained from the participants prior to the experiments. All testing was carried out in a single- or double- sound treated room situation having ambient noise levels within the permissible limits A 16-channel non-linear digital behind the ear (BTE) hearing aid with a fitting range of mild to severe hearing loss was used for aided testing. The hearing aid was coupled to the test ear with appropriately sized ear-tip. A personal computer with NOAH and the hearing aid specific software installed was used for hearing aid programming. HiPro was used as the interface between the hearing aid and programming computer. The participant’s details and audiogram were entered in the NOAH software. Initially, the hearing aid was programmed for first-fit with the NAL-NL1 prescriptive formula. The acclimatization level was set as ‘2’ as the participants were naïve users of hearing aids. The compression parameters were set according to the NAL-NL1 prescription. The other features like noise reduction, directional microphone was switched off to avoid the influence of these on speech identification testing. Then, the probe-microphone measures, like REAR and REIG, for this setting were carried out. The protocol for probe-microphone measurement is given in Each participant was instructed to sit comfortably with their head held straight forward during the measurements. The participant’s audiogram details were entered in hearing aid test system. The positioning of the probe-tube was made using visually assisted positioning method. A marking was made on the probe-tube at 30 mm from the probe-tube tip. The probe-tube was inserted into the ear canal with the marking on the probe-tube located at the intertragal notch. Thus, it was ensured that the tip of the tube was placed 5-6 mm farther to the tympanic membrane. Then, the real-ear measurement system was leveled to ensure that the input to the hearing aid was controlled across frequency. Followed by leveling, the real-ear unaided response (REUR) was obtained at 60 dB SPL. The hearing aid and ear-tip were inserted into the ear canal without disturbing the probe tube. The REAR and resulting REIG were measured at 60 dB SPL. These probe-microphone measurements were made with the manufacturer NAL-NL1 first-fit. This program was saved as ‘Program 1’ in the hearing aid which was the NAL-NL1 first-fit program.A second program ‘Program 2’ which was a duplicate of the ‘Program 1’ was created in the same hearing aid. The ‘Program 2’ was further programmed to match with the NAL-NL1 targets during verification. The frequency-gain adjustments were carried out until REIG closely matched to NAL-NL1 target at 60 dB SPL input level. The REAR and REIG data were recorded for the ‘Program 2’ which was the optimized-fit to NAL-NL1 target. The Program 1 (Aided 1 condition) and Program 2 (Aided 2 condition) were used to collect data on aided thresholds, AI, and aided WRS. The aided 1 and aided 2 conditions were randomized across participants to avoid the order effect.0 Azimuth. The unaided and the aided thresholds for the initial-fit (Aided 1) and optimized-fit (Aided 2) for octave frequencies from 250 Hz to 4000 Hz were obtained using warble tones. The aided thresholds were then plotted on AI audiogram given by Humes [23] which represents a speech frequency importance function weighted AI. The AI ranges from 0 to 1 or 0.99. The audiogram has a total of 33 dots covering the speech dynamic range and each dot in the audiogram contributes 0.03 times to the AI. The total number of dots below the aided threshold curve was counted and multiplied by 0.03 to get the AI for both aided conditions.The calibrated clinical audiometer was used to assess the unaided and aided performance in sound-field where the loudspeaker was placed 1 meter from the participant at 0. It consisted of four lists of 25 words each. The word lists were presented at 45 dB HL. It was made sure that the word lists were randomly presented across participants and test conditions. Each correct response was given a score of one and incorrect response was scored zero. The maximum word recognition score was 25.The unaided and aided WRS for the two aided conditions were obtained using phonemically balanced Kannada word identification test for adultsp2) and Cohen’s d for ANOVA and paired t-test respectively.The obtained data were analyzed using Statistical Package for the Social Sciences Version 20 software . Descriptive statistics was carried out to obtain the mean and standard deviation for REAR, REIG, aided thresholds, AI and WRS. The Kolmogorov-Smirnov Z-test of normality revealed that the data were in normal distribution (p>0.05), thus parametric inferential statistics was carried out. The effect size was reported using partial eta squared  equaling 0.954 and 0.951 respectively. Pair-wise comparison with the Bonferroni adjustment also indicated that the mean difference in the REAR and REIG between the two aided conditions was significant for all frequencies considered (p < 0.005).The result of repeated measures ANOVA revealed that this difference between the first-fit and optimized-fit was statistically significant for both REAR  and REIG , with an effect size of partial eta squared .The repeated measures ANOVA was carried out with aided threshold dependent variable and the test condition (first-fit and optimized-fit) as independent variable. The results revealed a significant difference in aided threshold between the two test conditions .-10. The difference in the individual ear canal acoustic characteristics would attribute to the reduction in gain measured with manufacturer first-fit setting. This significant reduction in gain especially in high frequency region with the first-fit would lead to a disadvantage in the audibility and speech recognition.The primary objective of the study was to compare the REAR, REIG, aided threshold, articulation index and word recognition score in two aided conditions, i.e., with the manufacturer NAL-NL1 first-fit and optimized-fit to NAL-NL1. There was a substantial difference in the measured REAR and the REIG between the manufacturer NAL-NL1 first-fit and optimized-fit to NAL-NL1 target which was more pronounced for the high frequencies. The findings of previous studies have also showed that the gain/output provided by the manufacturer’s first-fit will be significantly lesser than the generic prescriptive targets when measured both in 2 cc coupler and probe-microphone approach-16. In the present study, the high frequency advantage in the audibility with the optimized-fit was reflected in the advantage seen in the word recognition in quiet.The current findings showed that the audibility for soft sounds was improved with optimized-fit by 10 dB HL as revealed by the aided thresholds. There was more advantage in the high frequency with optimized-fit than the first-fit. Previous research suggests that a first-fit reduces the audibility of high-frequency signals, which could negatively impact speech recognition depicted that the derived speech intelligibility index (SII) from manufacturer’s default fitting was significantly lower than that of the programmed-fit to NAL-NL2 targets. They reported that the average SII obtained for moderate level sound with default fitting ranged from 0.46 to 0.56 compared to 0.65 for the NAL-NL2 fitting. Similar line of findings was observed with the AI in this study suggesting that the manufacturer setting will compromise the speech audibility and speech recognition.Sanders et al. This was because of the improvement in insertion gain at high frequencies as obtained in probe-microphone measurement for the programmed-fit. The gain for the high frequency was increased to 10 to 12 dB from the NAL-NL1 first-fit to match with the NAL-NL1 targets. It is well documented that the high frequency information is important for perception of majority of the consonants. The high frequency advantage with the programmed-fit resulted in improvement in word recognition score.The results on the word recognition revealed a mean programmed-fit advantage of 15% for a 60 dB SPL input level. This agrees with the findings reported by Valente et al., it is very rarely used as a verification tool in hearing aid fitting because of various limitations pertaining to it. A major drawback of aided threshold is the inability to verifying the non-linear hearing aids. The non-linear hearing aids vary the gain depending on the input level. Also, to obtain the true aided thresholds, the sound field audiometer must be calibrated, the patients must be seated with minimal head movements, and the involvement of the non-test ear must be eliminated. In the present study it was ensured that all these factors were controlled. The audiometer was calibrated, participants were instructed to maintain the position of the head throughout the testing, and the better ear was the test ear whenever there was an asymmetrical hearing loss. Though caution is to be exercised while interpreting the aided thresholds, it is one of the commonly used verification method for implantable hearing devices such as bone anchored hearing devices, middle ear implants and cochlear implants, where probe-microphone measures cannot be used as verification option.Though the current study tried to highlight the necessity of routine use of probe-microphone measurement in hearing aid fitting, the limitations in this research need to be discussed. Aided thresholds were used as one of the verification measures. Though aided threshold can draw the information on the aided audibility for soft level sound. However, the aided thresholds can be utilized for calculating the articulation index (AI) or speech intelligibility index (SII) and thereby predict the speech recognition-27. This is based on a same underline theory that speech recognition is related to the audible speech sounds. In this study, the AI was used utilizing the count-the-dot audiogram which is considered as one of the easiest clinically feasible method to estimate AI. AI was calculated from hearing threshold of the listener and the long-term average speech spectrum reaching the listener’s ear.The recognition of speech cannot be directly inferred from the aided thresholds. The SII calculation incorporated updated technical information on spread of masking, standard speech spectrum level, relative importance of various frequencies to speech intelligibility, speech level distortion, and hearing loss desensitization. Thus, make the SII to predict speech recognition appropriate for many conditions of use where the traditional AI does not apply. These procedures are automatized and incorporated in commercially available probe microphone equipment. The display provides SII for different speech level like soft (55 dB SPL), average (65 dB SPL), and loud levels (75 dB SPL) which enables the audiologist to counsel the patient on the effect of hearing loss on unaided and aided speech recognition different input levels.Modifications were made into the calculation of AI to make it more effective for predicting the speech recognition and it was renamed as SII in ANSI S3.5‐1997 standards,14, it can be assumed that other hearing aids models would also exhibit poor aided performance with manufacturer’s first-fit program. It is also important to evaluate perceptual effect of first-fit and optimized-fit with the other available generic formulae in different population, especially in pediatric population.This study was carried out using a single hearing aid model of a manufacturer. It is important to gather more evidence with other hearing aid makes and their default first-fit settings. Based on other reports showing the disadvantage of high frequency gain with manufacturer’s defaults with a variety of hearing aid models found that the measured REAR values were significantly different from the manufacturer predicted initial-fit REAR values in 41 participants with two audiogram configurations using two different input levels (50 and 90 dB SPL). This difference would also influence the aided response and subjective satisfaction in subjects with different degree and configuration of hearing loss which need to be investigated further. In addition, the long-term outcome or acclimatization and real-world benefit with given fittings need to be investigated.The participants recruited for the study were with moderate and moderately severe SNHL. It will be interesting if future research of same kind would target on different degree and configuration of hearing loss. Aarts and Caffee,30.As a health care professional, it is the responsibility of the audiologists to make their clients satisfied with the hearing aid fitting and to encourage them to use the hearing aid regularly. It will further prevent the auditory deprivation, cognitive decline and social isolation associated with hearing loss. A standard hearing aid fitting protocol including the probe-microphone measurement can improve the patient’s self-perceived benefit of their hearing aids, contentment with the hearing care professional and result in better patient loyalty. It was reported that inclusion of probe-microphone measurement in clinical protocol positively influences the user’s trust and improve the acceptance of hearing aid and its useTo conclude, the result of the current study also revealed improvement in aided threshold, articulation index and word recognition when the verification of gain and output was carried out through probe microphone measurement. The probe-microphone measurement is considered as the “Gold Standard” for verification of hearing aid fitting in the best practice guidelines for hearing aid fitting. Many audiologists are not using the probe-microphone technique regularly to verify the hearing aid gain and output when dispensing it. It is depicted that lack of verification will result in underamplification in the higher frequencies, that in turn cause inaudibility for soft and average level sounds and this in turn would compromise the speech recognition. A large number of hearing aid users are now using unverified fit that may be one of the reasons for rejection of amplification and dissatisfaction in adult population. Thus, it can be inferred that the clinical use of probe-microphone measurement is warranted to yield better audibility and speech recognition and in turn better satisfaction and quality of life.


Utriculostomy is a new surgical alternative for Ménière's disease. The basis of this procedure is that the outcome of an electrocautery-induced utricular trauma does not affect cochlear function. However, a demonstration of the hypothesis that this approach to the utricle would preserve hearing is still pending.To determine whether any changes would occur in the electrical potentials evoked in the cochlea and auditory nerve before, during, and 1 month after a surgical procedure in the utricule in an animal model.An experimental study. Eight sheep underwent electrocautery-induced utricular trauma, and their cochlear function was assessed by electrocochleography – recording of electrical evoked potentials, in the preoperative, immediate postoperative and medium-term postoperative periods. The results were analyzed statistically.p = 0.099) and latency (p = 0.591) before and 1 month after the surgical procedure. There was a statistically significant change in the summation of the potential/action potential area ratio (p = 0.0122), a calculated loss of 11.8 dB.There were no statistically significant variations in amplitude (The intervention performed in this study enabled us to conclude that, taking into account the impaired electrophysiological responses observed during and 1 month after the surgical procedure, hearing was preserved in the operated sheep. Since 1878, when Kessel mobilized the stapes in cases of otosclerosis for hearing recovery, otologists have engaged in research to develop surgical techniques that enable the approach to the labyrinth (otic capsule and membranous labyrinth) for recovery of the auditory function and removal of the agent causing organ dysfunction or the patient's clinical symptoms Surgeons, however, were aware that such interventions could damage labyrinthine structures extremely sensitive to vibration, as well as endolymph flow, and tried to avoid a surgical approach to the inner ear, acting fairly distant from the cochlea.Historically, there is a considerable literature on surgical procedures proposed for the treatment of vertigo, according to the underlying diseaseA new surgical alternative for Ménière's disease, which is still in the experimental stage, is the method proposed by Lavinsky et al.In the study by Lavinsky et al.Based on the operational hypothesis that the electrocautery-induced utricular trauma would not affect hearing, the objective of this study was to determine whether any changes would occur in the electrical potentials evoked in the cochlea and auditory nerve in sheep.This experimental study was conducted in the Animal Experiment Unit at our institution, in accordance with the international procedures and regulating rules of research involving living animals.t test was used in the comparison between preoperative and immediate postoperative means, as well as in the evaluation of the preoperative and medium-term (1 month) postoperative periods with magnitude of effect of two standard deviations (SD), α = 0.05, and 90% power.Sample size calculation was determined based on a pilot study including four animals, in which the paired-sample Student Exclusion criteria were: due to anatomical reasons of the external acoustic meatus, the test and surgical procedure could not be performed; the animal died during the experimental study period. The animals which showed normal cochlear potentials before the surgical procedure were included in the study.Eight female Texel sheep, with 40 kg mean live weight and aged around 18 months, were submitted to the assessment of cochlear evoked potentials before, during and 4 weeks after electrocautery-induced utricular trauma. The animals were not killed and were taken to their place of origin as soon as possible after the end of the experiment. One animal was excluded from the study due to death from unknown cause 25 days after the surgical procedure.The anesthetic protocol was the same used by Lavinsky et al.All surgical procedures were performed by the same surgeon (adviser in the present study).The promontory, the oval and round windows, the facial nerve, the chorda tympani, the pyramidal apophysis, and the tensor ligament of the stapes were identified after endaural approach . The tenThe anterior wall of the utricle, which is partially visible during otomicroscopy, was cauterized using the Lavinsky/HCPA otologic microthermocautery with a 0.2-mm pointer for 0.5 seconds at intensity of 3.5 W. The cauterization was repeated in three locations, close to one another.The oval window was closed with adipose tissue taken from the region next to the endoperiauricular incision and then covered with Gelfoam®. The tympanum was restored and the meatus was packed with Gelfoam®. Endoperiauricular incision was sutured with 3.0 mono nylon simple stitches. The region was finally covered with a compressive dressing. The animals received antibiotic prophylaxis with sodium penicillin (40 mg/kg/day) 1 day before and up to 3 days after surgery.Postoperative protocol involved visual observation of the presence or absence of nystagmus, as well as alterations in static and dynamic balance, in the immediate postoperative period ; after 24 hours, additional observations were performed regarding the animal's general status and the presence or absence of nystagmus and alterations in balance.A tone burst stimulus was delivered at the external acoustic meatus in frequencies ranging between 4200–6820 Hz and intensity of 82 SPL, according to the protocol of electrophysiological threshold recording of normal cochlear potentials in sheepSummating potential (SP) and action potential (AP) areas were calculated using the Riemann integral.Leq)To measure the degree of procedure-related hearing loss and to estimate the new hearing threshold, we used the equation to calculate the equivalent sound level (ESL) , with Bonferroni post hoc test. The corresponding nonparametric test was used for the variable area: the Friedman test. The Wilcoxon test was used to find differences by comparing two experimental time points.p values less than or equal to 0.05 were considered to be statistically significant. Statistical analysis was performed using the Statistical Package for Social Sciences (SPSS) 10.0 for Windows.All tests performed were two-tailed, and All animals behaved in a docile way during the preoperative period (anesthetic induction) and immediate postoperative period. There were no cases of bleeding; only one death from unknown cause 25 days after the surgical procedure, during confinement in the breeder's farm.Eight sheep were studied, with measurement of amplitude, latency and SP/AP area ratio before, during and after the procedure .Table 1Rp = 0.011), but not in that of amplitude (p = 0.099). A difference was also found in the comparison of areas, through the Friedman's test (p = 0.012).The analysis of variance of repeated measurements revealed statistically significant differences in the comparison of latency  = 5.95 corresponding to the mean SP/AP area ratio of 11.7 μVIn the immediate postoperative period and 24 hours after surgery, we observed in all animals the presence of horizontal nystagmus rotating counterclockwise to the operated ear, as well as alterations in static and dynamic balance. All animals remained with ipsilateral inclination of the head toward the side of the operated ear for at least 30 days after the surgical procedure.Normal cochlear and vestibular function depends on the integrity of the inner ear, with a physical separation of endolymphatic and perilymphatic compartments by the membranous labyrinth. Disorders occurring between these relationships may lead to a deep loss of function. Therefore, surgical entry into the inner ear has been traditionally avoided.Recent advances in neurotologic surgery in animal models have challenged the traditional belief that violating the labyrinth is incompatible with hearingEndolymphatic shunt procedures, such as sacculotomies (Tack operation) and cochleosacculotomy, a surgery described as a simple technique, effective in the treatment of vertigo in patients with Ménière's disease in whom medical therapy has failed, have been abandoned by some authors who observed significant long-term worsening of hearing thresholds in these patientsThe present study aims to establish the safety of utriculostomy regarding hearing loss. In order to maximize the confidence level of this decision, we opted to produce a relevant injury to the utricle so that, if hearing was preserved, safety regarding utriculostomy could be well grounded, since this procedure is much more conservative, in terms of aggressiveness, to the utricular structure.As in other studies1.amplitude when comparing the results before, during and after 1 month (p = 0.099).There were no statistically significant alterations in the parameter 2.latency, there was alteration during the procedure, but with recovery after 1 month (p = 0.591), revealing that wave propagation time in the cochlea increased during the surgical procedure, with recovery after 1 month. Therefore, we may infer that internal ciliated cells of the cochlea and the auditory nerve were not extensively compromised, which was demonstrated when we associated this result with studies in guineas pigsIn the parameter 3.area was included in our study since it also represents a good parameter of interpretation of nerve conduction studies. The calculation of the SP/AP area ratio, described in some studiesThe analysis of the variable The analysis of cochlear action potential parameters, representing the most important potential obtained by transtympanic electrocochleography and reflecting the sum of the responses of synchronous discharges of thousands of individual nerve fibers, which are limited to high-frequency bands, showed that:p = 0.0122) during the procedure, which remained after 1 month.Since SP/AP area ratio is the integral of a function of the combination between amplitude and duration of action potential, Riemann integral reflects the number and synchronism of activated nerve fibers. In our study, there was a statistically significant decrease in the SP/AP area ratio (This decrease in the number and synchronism of activated nerve fibers may originate from some inflammatory process resulting from surgical trauma, as demonstrated in the histological study of injuries to the vestibule caused by surgery of the inner ear in guinea pigsIt is important to point out that the ESL, defined as a continuous noise level that has the same acoustic energy of initial oscillatory levels for a certain period of time2 and KTP laser irradiation in catsThe association between utricular surgery and hearing preservation is found only in two studies in the literaturePrevious experiments have suggested that the mechanisms of hearing loss after injury to the inner ear involve factors other than only loss of ciliated cellsSurgery of the inner ear with hearing preservation imposes an important challenge on neurotologic procedures. Ability to perform selective procedures in the vestibular organ enhances the potential to develop new procedures for the treatment of disabling labyrinthopathies.The intervention in the utricle performed in this study enabled us to conclude that, taking into account the impaired electrophysiological responses observed during and 1 month after the surgical procedure, there was hearing preservation in the operated sheep.


Lawsonia intracellularis is the etiological agent of proliferative enteropathy, which is globally considered an important enteric disease in pigs and horses. Experimental studies suggest that the organism spreads by subclinical infection of many animals, including rabbits. Despite the importance of rabbits in the epidemiology of L. intracellularis, the extent of exposure to L. intracellularis in the rabbit population is poorly defined and remains unclear. The objective of this cross-sectional study was to investigate the seroprevalence and shedding of L. intracellularis in farmed rabbits. Furthermore, we aimed to identify risk factors associated with seropositivity. Sera from the rabbits were used to measure L. intracellularis-specific antibodies by immunoperoxidase monolayer assay, and rectal swabs were used to detect L. intracellularis DNA using a real-time PCR assay. Antibodies against L. intracellularis were detected in 12.3% of farms (20/163) and 6.3% of rabbits (49/774). Lawsonia intracellularis DNA in rectal swabs was detected in 3.8% of farms (6/156) and 1.2% of rabbits (8/667). The risk factor analysis showed that the presence of pigs or horses on the farm or the neighboring farm was associated with an increase in the risk of seropositivity (p < 0.05). We observed significantly increased odds of positivity for L. intracellularis in rabbits with a history of digestive trouble (diarrhea) on the farm during the 3 months before the samples were obtained (p < 0.05). Collectively, these findings demonstrated that L. intracellularis infection was evident among farmed rabbits and that rabbits might serve as an important reservoir for L. intracellularis epidemiology. Lawsonia intracellularis is a microaerophilic intracellular bacterium that infects the small and also large intestine in pigs and other animals, including hamsters and horses , dogs, artic foxes (Alopex logopus), ferrets, ostriches (Struthio camelus), and rhesus macaques  on the farm.The objective of this cross-sectional study was to investigate the prevalence of antibodies to and the shedding of To obtain the serum and rectal swab samples for this study, farm selection and blood sampling were conducted in close collaboration with local veterinary practitioners and/or government veterinary officers. The study was carried out between March 2020 and February 2022, and we obtained information by carrying out farm visits as a part of veterinary practice, routine health appraisal, and consulting activities on rabbit farms. Informed consent was requested from individuals on every participating farm. Individual information about the breed, sex, age, rearing type , type of rabbitries , or mixed [cage and fence (or free range)], feed type, presence of pigs or horses within the farm or the neighboring farm (within a 0.5 km radius), and history of digestive trouble (diarrhea) in the farm during the 3 months before the samplings was gathered through a detailed survey.L. intracellularis infection among rabbits. The determined sample size needed was calculated as 28 for an unknown population size with a desired precision of 20%, a 95% confidence level and a test assumed with 95% sensitivity and 99% specificity . The cultivation of L. intracellularis and serology using the IPMA technique were performed as described previously  for 30 min at 37°C and washed five times with PBS (pH 7.2). Sera collected from experimentally infected rabbits served as positive controls. Peroxidase-labeled anti-rabbit IgG antibody  was diluted 1:500 in 2% bovine serum albumin and 0.08% Tween 80 in PBS and then applied at a concentration of 50 μl/well. The plate was incubated for 45 min at 37°C. The plate was washed again, and chromogen  solution was added to each well. Then, the plate was incubated at room temperature for 20 min. The plate was washed with distilled water three times, allowed to dry, and examined using a BX50 microscope . Positive samples exhibited red-labeled bacteria in both the cytoplasm of the infected McCoy cells and the extracellular space (Sera from the rabbits were used to detect eviously –27. The ar space –31.Escherichia coli) and one positive extraction sample containing L. intracellularis were included in each experiment to assess for contamination during the DNA extraction process. Nucleic acids were eluted in 50 μl of buffer and stored at −80°C. All purified DNA samples were assayed for the presence of the aspartate ammonia lyase (aspA) gene of L. intracellularis by real-time PCR. All purified DNA samples from the rectal swabs were assayed in triplicate for the presence of the L. intracellularis aspA gene by real-time PCR as described previously (L. intracellularis (GenBank accession no. AM180252).DNA purification was performed using a BioRobot M48 workstation apparatus  with a MagAttract DNA Mini M48 Kit (Qiagen) according to the manufacturer's recommendations. One negative extraction sample containing other bacterial cells (eviously . This reL. intracellularis) and negative  DNA controls. Furthermore, swabs were taken from centrifuges, laminar flow cabinets, and countertops and assayed for the L. intracellularis aspA gene by real-time PCR to assess potential contamination. A real-time PCR assay that targeted a universal sequence of the bacterial 16S rRNA gene was used as a quality control  and as an indicator of fecal inhibition as described previously .Prevalence and Wilson's 95% confidence intervals (CIs)  were calL. intracellularis were detected in 6.3% of farmed rabbits (49/774), as shown in Lawsonia intracellularis DNA in the rectal swabs was detected by PCR in 1.2% farmed rabbits (8/667). Seropositive rabbits were observed in all the provinces surveyed, and the highest seroprevalence values for L. intracellularis were observed in Gyeonggi Province, with rates of 11.9% . Rabbits shedding L. intracellularis were observed in most provinces surveyed except Gangwon Province.Antibodies specific to p < 0.05). We observed significantly increased odds of positivity for L. intracellularis in the rabbits with a history of digestive trouble (diarrhea) on the farm during the 3 months before the samples were acquired . Although there was slightly higher seropositivity in crossbred animals, females, animals younger than 6 months old, animals that were reared outdoors only, animals in rabbitries with a fence or that were free range, or animals that were fed concentrated feed and grass, these associations were not statistically significant (p > 0.05).In the univariate analysis , the risL. intracellularis and as an animal model in the field of proliferative enteropathy research  was found to be one of the main factors affecting the prevalence of L. intracellularis infection (p < 0.05). Another main factor identified in the present study was a history of digestive trouble (diarrhea) on the farm during the 3 months before the samples were acquired (p < 0.05). We observed no significant differences regarding the prevalence of L. intracellularis infection when rabbits were stratified by breed, sex, age, rearing type, type of rabbitries, or feed type (p > 0.05).It has been reported that inically . HoweverL. intracellularis infections. The results of the present study demonstrate that the possibility that the range of susceptible species may broaden further and incorporate more domestic animals by interspecies transmission (spillover) cannot be discounted. In view of the host range of L. intracellularis, lagomorphs may represent a reservoir, amplifying host, or important biological vector of L. intracellularis due to their large population, their short reproductive cycle, and their close contact with pigs or horses.This study may serve as a basis for future epidemiological studies on L. intracellularis infection was evident among the farmed rabbits analyzed, in which ~one in 10 farms exhibited exposure to L. intracellularis. The results of this study indicated that susceptible rabbits are at risk of becoming infected with L. intracellularis, although an outbreak of L. intracellularis among farmed rabbits in South Korea has yet to be reported. These results suggest that rabbit species might serve as an important reservoir for the transmission of L. intracellularis, highlighting the need for closer epidemiological investigation of L. intracellularis infections in rabbits.Collectively, the results of the present study demonstrated that The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.The animal study was reviewed and approved by Animal Research Ethics Committee of Incheon National University. Written informed consent was obtained from the owners for the participation of their animals in this study.J-YY conceived and designed the study, conducted the laboratory experiments, wrote the first draft, and revised the manuscript.


In pediatric audiology, objective techniques for hearing threshold estimation in infants and children with profound or severe hearing loss play a key role. Auditory brainstem responses (ABR) and auditory steady-state responses (ASSR) are available for frequency-dependent hearing threshold estimations and both techniques show strong correlations but sometimes with considerable differences. The aim of the study was to compare hearing threshold estimations in children with and without cochlear and cochlear nerve malformations.® (Denmark) with narrow-band CE-chirps® at 500, 1000, 2000 and 4000 Hz and compared to ASSR at the same center frequencies under similar conditions.Two groups with profound or severe hearing loss were retrospectively compared. In 20 ears (15 children) with malformation of the inner ear and/or cochlear nerve hypoplasia and a control group of 20 ears (11 children) without malformation, ABR were measured with the Interacoustics Eclipse EP25 ABR systemr = 0.413 in malformation group, r = 0.82 in control group). The malformation group showed a significantly lower percentage of “equal” hearing threshold estimations than the control group. In detail, patients with isolated cochlear malformation did not differ significantly from the control group, whereas patients with cochlear nerve hypoplasia showed significantly greater differences.ABR and ASSR correlated significantly in both groups (ABR and ASSR should be used jointly in the diagnostic approach in children with suspected profound or severe hearing loss. A great difference in hearing threshold estimation between these techniques could hint at the involvement of cochlear nerve or cochlear nerve hypoplasia itself. The therapeutic strategy in infants and children with severe-to-profound hearing loss is based on hearing threshold estimations by frequency-specific auditory brainstem responses (ABR) in combination with behavioral measures and other diagnostic tools. Also, auditory steady-state responses (ASSR) offer frequency-dependent hearing threshold estimation and came into play , 2. BothASSR has been reported to show advantages for the threshold detection in profound hearing loss in cochlea implant candidates  and showUntil now, it has not been examined, whether temporal bone or hearing nerve malformations might have an influence on threshold estimations by ABR or ASSR. Approximately 20% of patients with congenital hearing loss show inner ear malformations that can be diagnosed by radiology techniques, and the majority of these patients suffer from profound or severe hearing loss . Inner eIn this study, we compared hearing threshold estimation derived with narrow-band CE chirps evoked ABR and ASSR in children with radiologically proven cochlear malformation (CM), cochlear nerve hypoplasia (CNH) or combined malformation with children without temporal bone and inner ear pathology, both groups suffering from profound or severe hearing loss.We retrospectively evaluated data from 20 ears of 15 children  with an age from 9 months to 7 years with cochlear malformation or/and hearing nerve hypoplasia proven by magnetic resonance imaging (MRI) and/or computer tomography (CT) (see below) and profound or severe hearing loss that was obtained between 07/2014 and 01/2018. As control group, we evaluated 20 ears of 11 children  with an age from 8 months to 6 years without pathological findings in MRI/CT and profound or severe hearing loss. In all children hearing threshold estimations had been obtained by ABR and ASSR measurements because newborns did not pass hearing screening, acoustic hearing testing was pathologic not only due to middle ear effusions, or for follow-up in children with known hearing loss. Only patients with hearing threshold ≥ 70 dB in at least two frequencies in ABR measurements were included . Premature infants and infants with known neurological disorders were excluded. One patient with cochlear nerve hypoplasia showed detectable otoacoustic emissions.The use of data is in accordance with ethical principles stated in the Declaration of Helsinki and was approved by the local ethics committee and the local data protection commissioner (Project No. 17-448).To ensure comparable conditions in ABR and ASSR measurements for retrospective evaluation of both methods, only data sets that were performed at the same day during general intravenous anesthesia were included in the study. Anesthesia had been necessary that day to obtain MRI and CT scans. Measurements were acquired consecutively in a noise-absorbing room which was electrically shielded in.® with center frequencies (CF) at 500 Hz, 1000 Hz, 2000 Hz, and 4000 Hz were used [For both methods standard narrow-band CE-chirpsere used . All ABRThe imputing technique was used for statistical reasons: in data sets without a measurable response up to a stimulus level of 100 dB nHL, the hearing threshold was set to 110 dB nHL and therefore, 110 dB nHL was used for calculations.Magnetic resonance imaging (MRI) was performed on a 3T scanner . The MRI examination protocol included diffusion-weighted-imaging (DWI), T2w-imaging, T1w-imaging pre- and post-gadolinium application, as well as high-resolution 3D T2-SPACE imaging with high-frequency-pulse transmit technique (ZOOMit), which is a single slab 3D TSE sequence with slab selective, variable excitation pulse (flip angle evolution-sequence). The latter MRI technique relies on fast turbo spin imaging sequences with isotropic resolution allowing for equal reconstruction in all planes. In our study voxel size was 0.5 × 0.5 × 0.5 mm, echo train length 54, repetition time 100 ms, echo time 125 ms, flip angle 100, bandwidth 255, 100% sampling, acquisition matrix 320 × 164, number of averages 2. In cases where 3T imaging was not available, patients were scanned on a 1.5T scanner  using an isotropic high-resolution three-dimensional strongly T2-weighted sequence  with a voxel size of 0.5 × 0.5 × 0.5 mm, echo train length 1, repetition time 6.3 ms, echo time 2.81 ms, flip angle 62, bandwidth 420, 100% sampling, acquisition matrix 384 × 288, number of averages 2.Computer tomography (CT) was performed on a Dual-Source CT-scanner (Siemens SOMATOM Definition Flash), a 2 × 128 row CT scanner with a rotation time of 0.28 s, using a dedicated temporal bone scan protocol with a slice thickness of 0.75 mm, 120 kV, variable mAs (111–151 mAs), including selective reconstruction of each temporal bone using a UHR-kernel (V80u3) in three planes.Inner ear malformations were classified as outlined in the introduction according to Sennaroglu et al. , 18 by tp value < 0.05 was considered significant. Differences between malformation patient collectives and control group on an individual value basis were compared by Chi-Square Test. Subgroups of the malformation patient collective itself and control group were compared as “mean of Δ ABR–ASSR (in dB)” and “no. of outliers”, defined as no. of CFs, where Δ ABR–ASSR ≥ 15 dB, by Mann–Whitney-Rank Sum-Test and Kruskal–Wallis-One Way Analysis. In addition, all pairwise multiple comparison procedure (Dunn’s Method) was applied.Data analysis was performed with Excel  and SigmaPlot . Correlations between hearing thresholds of the two methods were calculated by Spearman Rank Order Correlation since data failed normality testing. A Measurements were performed on 20 ears  with radiologically proven CM and/or CNH and on a control group in 20 ears without pathology of the temporal bone. In some ears ABR measurements were not performed for the CF of 500 Hz due to limited time and anesthesia reasons. The malformation group had a mean age of 34 months (range 7 months–7 years) at the day of hearing threshold estimation, the control group a mean age of 33 month (range 8 months–6 years).r = 0.413, p < 0.001 versus 0.82, p < 0.001). In a Bland-Altmann Plot, it becomes obvious, that measurements by ASSR in general estimate better hearing thresholds than by ABR, on the other hand, the difference between ABR and ASSR hearing threshold estimations is lower in ears without malformation . Out of 20 “equal” estimations in 12 (60%) of those cases no hearing threshold could be obtained by neither ABR nor ASSR. Most hearing threshold estimations by ASSR in patients with temporal bone malformations showed a lower/better hearing threshold than estimations by ABR (67% compared to 42% in controls). In 33 of these 43 (78%) cases, no hearing threshold could be obtained by ABR but by ASSR. Only 2% showed a worse hearing threshold estimation in ASSR. 41% of measurements revealed a difference of ≥ 15 dB between ABR and ASSR measurement technique (outliers) in patients with temporal bone malformations compared to 13% in controls (p < 0.001).Table r = 0.915; p < 0.001), CNH , and CM + CNH .Table However, interpreting correlation coefficients on a basis of few data pairs only is limited. Therefore, we looked at two additional parameters to evaluate the individual difference between the groups, which are shown in Table Table p < 0.05) between isolated CM, CNH and CM + CNH, whereas there was no statistical difference between CM and controls (Table p = 0.002), CM and CM + CNH (p = 0.021), between CNH and controls (p = 0.001), and between CM + CNH and controls (p = 0.006). We found the same conditions for the number of outliers  was only seen between CNH and controls and CNH and CM, respectively.In pairwise multiple comparison procedure (Dunn’s Method), the statistically significant difference  by ASSR compared to ABR in these patients.In this study, we evaluated the influence of CM and CNH on hearing threshold estimation by ABR and ASSR in infants and children with severe or profound hearing loss.r = 0.82 (p < 0.001) of ABR and ASSR hearing threshold estimations on all measurements with CFs from 500 Hz to 4 kHz, which is in line with the literature, although these studies used differing stimuli and setups: Rodrigues et al. showed in 17 children with hearing loss correlation coefficients of 0.91, 0.76, 0.81 and 0.89 for 500, 1000, 2000, and 4000 Hz, respectively between ASSR to multiple simultaneous tone-pip stimuli and tone-evoked ABR [r = 0.826 comparing the average of hearing threshold estimation at 1000, 2000, and 4000 Hz by chirp-evoked ASSR and click ABR thresholds [The control group of 20 ears without malformations showed a good correlation of resholds .r = 0.413 (p < 0.001) was revealed between the two techniques . According to Levi et al., 72% of patients with cochlear nerve dysplasia appear with an audiometric profile of ANSD . Jafari This study showed a discrepancy in hearing threshold estimation by ASSR and ABR in children with severe or profound hearing loss and hypoplasia of the cochlear nerve itself or in combination with cochlear malformation. At present, it is unclear, how this discrepancy can be explained and whether ASSR or ABR more likely reflect the “real” hearing threshold. More research on comparison with behavioral and psychoacoustic threshold measures is needed to evaluate the reliability of techniques. For now, ASSR and ABR should be jointly used within the diagnostic test battery of children with severe-to-profound hearing loss and CNH.


Telehealth promises increased access to hearing healthcare services, primarily in areas where hearing healthcare resources are limited, such as within the South African public healthcare system. Telehealth for hearing healthcare is especially important during the COVID-19 pandemic, where physical distancing has been essential. This study aimed to describe audiologists’ perceptions regarding telehealth services for hearing loss within South Africa’s public healthcare system. This study was divided into two phases. During Phase 1, 97 audiologists completed an electronic survey regarding their perceptions of telehealth for hearing loss within South African public sector hospitals. Synchronous virtual focus-group discussions were conducted during Phase 2. Results indicated that audiologists recognized telehealth services’ potential to improve hearing healthcare efficiency within the public sector, and most (84.1%) were willing to use it. However, telehealth’s actual uptake was low despite almost doubling during the COVID-19 pandemic. Prominent perceived barriers to telehealth were primarily related to hospital resources, including the unavailability of equipment for the remote hearing/specialized assessments, internet-related barriers, and limited IT infrastructure. An increased understanding of telehealth in South Africa’s public healthcare system will assist in identifying and in improving potential barriers to telehealth, including hospital resources and infrastructure. Globally, 1.5 billion people are estimated to have a hearing loss, with 430 million requiring rehabilitation services to address their disabling hearing loss ,3,4. At At present, there is a global shortage of hearing loss prevention and treatment programs . Many inHearing healthcare service delivery via telehealth is a promising way to improve access and affordability of hearing healthcare services, and it is recommended as a priority by the recent World Report on Hearing ,14,18,19Despite increasing evidence promoting the use of telehealth in the field of audiology, its clinical uptake has been slow, and there are limited reports of its utilization in everyday clinical practice ,25. The In line with the 2021 World Report on Hearing, which has prioritized telehealth to make hearing care more accessible, understanding the perceptions of hearing healthcare professionals can support guidance for future implementations of telehealth services [Research and ethical approval for this study were obtained from the Research Ethics Committee of the Faculty of Humanities, University of Pretoria, South Africa (HUM005/1019) before any participants were recruited for this study.A survey-based cross sectional study with a subsequent thematic qualitative analysis, applying triangulation, was employed using a two-phase process involving an online survey in Phase 1 followed by focus group discussions in Phase 2. This research design facilitated a deeper and more rigorous understanding of audiologists’ perceptions of telehealth services in South Africa’s public healthcare sector by combining both quantitative (explorative) and qualitative (deepening) data.In 2020, 182 public hospitals across South Africa, including district, regional, provincial tertiary, central, and specialized hospitals, had audiology departments, with approximately 380 audiologists employed across these hospitals . All quaIn Phase 1, data were collected by means of a self-administered survey explicitly developed for the purpose of this study. First, a pilot study involving five volunteering audiologists employed within South African public sector hospitals was conducted to establish the validity of the newly developed survey. The expert panel had some minor recommendations (sentence reconstruction for questions eight and nine for clarity purposes), which were incorporated into the survey. An item content validity index (I-CVI) was computed, which provided the proportion of experts agreeing on an item . An acceThe survey was used to obtain information concerning audiologists’ perceptions of telehealth services for hearing loss in South Africa’s public healthcare system. It included nine closed-ended questions, with one open-ended question included . The surIn Phase 2 of the study, qualitative data were collected to expand and to substantiate findings from the survey. Two virtual focus group discussions were conducted, consisting of four and five audiologists in each respective focus group. A semi-structured focus group guide was compiled, which provided structure and an agenda for audiologists whilst engaged in conversation . The queIn Phase 1 of this study, all 380 audiologists employed within public sector hospitals  in 2020 were invited to participate in the survey via email. The audiologists were sent via email the information letter detailing the nature of the study and their level of involvement, along with the website link to the online survey utilized for this study.Once audiologists clicked on the website link, an informed consent page opened, and only audiologists who electronically consented to participation proceeded to the survey. Data for Phase 1 of the study were collected over a one-month period during the COVID-19 pandemic when the country was under level one lockdown. The response rate was 25.5% in a purposive sample of 97 audiologists who responded to the survey, nine of whom participated in Phase 2 of the study.At the end of the survey, participating audiologists were asked whether they would be interested in participating in the second phase of this study, namely synchronous, virtual focus group discussions. A total of 45 audiologists expressed interest in participating in Phase 2, and they were subsequently sent via email the information letter detailing the nature of Phase 2 and the website link to provide informed consent and indicate their preferred availability for the focus groups. Of the 45 interested audiologists, nine audiologists were available and provided consent allowing for two focus groups. The focus group discussions were conducted and recorded using a web-based virtual communication platform (Microsoft Teams). The primary researcher (A.B) administered the role of the facilitator of each focus group discussion. Each focus group discussion was recorded and transcribed following the discussion for data analyses.p < 0.001), indicating that there is evidence that dimension reduction can be done. After conducting the EFA  and dropping items with low loadings on factors/constructs, a summary of the final set of constructs, item statements, and Cronbach’s Alpha values for Question 9 can be found in The quantitative data of Phase 1 (close-ended questions of the survey) were captured in Microsoft Excel (2017), and Statistical Package for Social Sciences SPSS (Version 26) was used to analyze the data. Cronbach’s Alpha test was used to calculate internal consistency for the scale used for Question 9  in the questionnaire. An exploratory factor analysis (EFA) was subsequently conducted on Question 9 with the Kaiser–Meyer–Olkin (KMO) and Bartlett’s test of sphericity considered to see whether the data is suitable for dimension reduction. The KMO value of 0.759 is middling  , indicatQualitative content analysis of the responses to both the open-ended survey question (Question 10) and the focus group discussions was conducted utilizing the conventional approach as identified by Braun and Clark  Figure .n = 88) held a bachelor’s degree in audiology, or a dual (speech-language pathology and audiology) degree, whilst nine (9.3%) of the audiologists held a master’s degree.Of the 97 participating audiologists, 49 (50.5%) worked at district level, 17 (17.5%) at regional, 23 (23.7%) at tertiary, four (4.1%) at central, and four (4.1%) at specialized levels of care public sector hospitals. The majority of the participating audiologists , and almost one-tenth were unsure  of whether they were using telehealth or not. Both these groups went on to then select the applicable type(s) of telehealth options used from a list provided, although the questionnaire stated that only those that responded ‘yes’ to the question of whether their workplace currently used telehealth should go on to list the types of telehealth they were using. The most frequently reported type was audio or video conferencing , followed by mobile phone technology and applications , and websites   .n = 69/97), 84.1% (n = 53/63) indicated that they would be willing to use it  (n = 67/86) and that internet access at their hospital did not have enough bandwidth 74.4% (n = 64/86)  . Further= 64/86) .Items are shown in order of most significant barrier and are slightly abbreviated from the phrases used in the survey; see For the focus group discussions, four of the audiologists attended the first focus group discussion, and five attended the second. Four audiologists worked in tertiary-, three in district-, one in central-, and one in regional-level hospitals. Seven of the audiologists were production-level therapists, and two audiologists were the heads of their departments.Following inductive thematic content analysis of the two focus group discussions, it became apparent that the identified focus group themes corresponded to the themes identified in the open-ended question analysis: (1) clinical practices, (2) hearing healthcare resources, (3) patient restrictions impacting hearing healthcare, and (4) perceived benefits of telehealth. Therefore, the results from the open-ended question in the survey and focus group responses were integrated .This study investigated audiologists’ perceptions of telehealth for hearing healthcare services within the South African public healthcare system, and it found low use of telehealth services before the COVID-19 pandemic. The use of these services increased during the COVID-19 pandemic. Hospital- and patient-related barriers to telehealth were mentioned by audiologists, and the most prominent perceived benefit of telehealth services was increased accessibility to hearing healthcare services.Telehealth services in hearing healthcare increased as a result of the COVID-19 pandemic, from only 7.2% reporting its use before COVID-19 to almost 19.6% using it during the pandemic. Similarly, other studies have previously reported an increase in telehealth to deliver audiology services during the COVID-19 pandemic ,31. MostDespite a general recognition of the potential telehealth service delivery holds in the field of hearing healthcare, the actual perceived use of telehealth during the COVID-19 pandemic in the current study was significantly lower than that reported in previous studies. The reported telehealth usage of an international survey spanning 44 countries reported that 61.9% of audiologists in their study used telehealth services during the pandemic . When loIdentifying perceived barriers toward telehealth is important to understand the reason behind the low uptake within South Africa’s public healthcare system and address the concerns accordingly. In line with the findings from Eikelboom et al. (2021), the least significant barriers perceived by audiologists in this study were related to the audiologists themselves (audiologists’ confidence and job security). More commonly perceived barriers included training, multiple technologies needed for hearing aids, limited scope for remote aural rehabilitation sessions, and limitations in programming hearing aids remotely. The most significant perceived barriers were external to the audiologists and involved patient-related aspects such as limited/poor patient access to the internet and patients’ lack of confidence to use technology. It also included barriers related to resources, such as the unavailability of equipment for remote hearing and specialized assessments, internet-related barriers, limited IT infrastructure, and limited protocols for telehealth. The majority of these audiologist-perceived barriers toward telehealth were reiterated by audiologists in their open-ended responses and during the focus group discussions, and they were also recently mentioned in other studies as well ,30,31,44The South African health system is dichotomized . Most SoAnother prominent perceived barrier to telehealth was the restrictions faced by patients attending these public sector hospitals, as indicated by both the qualitative and the quantitative data. In line with this study’s findings, uncertainties on the part of audiologists on whether their patients would cope with the technology needed for telehealth were also reported in other studies ,31,44,48Telehealth services are a promising tool for improving the accessibility of hearing healthcare services ,55, espeLimitations of this study include a relatively low response rate (approximately 1 in 4). However, recently , and espThe majority of public sector audiologists reported a willingness to use telehealth services. They were also aware of its potential to improve hearing healthcare accessibility and efficiency within the public sector, especially during the COVID-19 pandemic. However, the uptake of telehealth services was poor despite more than doubling during the COVID-19 pandemic. Prominent barriers that were primarily identified related to limitations in hospitals’ resources and patient-related barriers, including patient restrictions that impacted their means to access required telehealth technology and a lack of confidence that patients were in a favorable position to receive telehealth services.


Fifteen years after their discovery, telocytes (TCs) are yet perceived as a new stromal cell type. Their presence was initially documented peri-digestively, and gradually throughout the interstitia of many (non-)cavitary mammalian, human, and avian organs, including skin. Each time, TCs proved to be involved in diverse spatial relations with elements of interstitial (ultra)structure . To date, transmission electron microscopy (TEM) remained the single main microscopic technique able to correctly and certainly attest TCs by their well-acknowledged (ultra)structure. In skin, dermal TCs reiterate almost all (ultra)structural features ascribed to TCs in other locations, with apparent direct implications in skin physiology and/or pathology. TCs’ uneven distribution within skin, mainly located in stem cell niches, suggests involvement in either skin homeostasis or dermatological pathologies. On the other hand, different skin diseases involve different patterns of disruption of TCs’ structure and ultrastructure. TCs’ cellular cooperation with other interstitial elements, their immunological profile, and their changes during remission of diseases suggest their role(s) in tissue regeneration/repair processes. Thus, expanding the knowledge on dermal TCs could offer new insights into the natural skin capacity of self-repairing. Moreover, it would become attractive to consider that augmenting dermal TCs’ presence/density could become an attractive therapeutic alternative for treating various skin defects. Considering the skin as the largest human organ, which is completely covering the human body, and taking into account at least a few of its most prominent roles , it is natural to consider that skin as being prone to various injuries. These injuries intercept the barrier function and could be either acute or chronic, sometimes emerging abruptly, but also within the context of some dermatological pathologies. Another function of the skin (frequently much augmented) is its social/aesthetic function, since healthy and presentable skin enhances the self-esteem of many individuals, contributing to a better social life . CurrentHowever, a better understanding of the cellular and molecular mechanisms underlying skin wound recovery and repair/regeneration after trauma is necessary. Wound care science could investigate this series of interrelated biological events, which are serially developing as the wound is progressing, in several directions , all of telos’  was assigned for these cells [At least for the histology of human tissues, the year 2005 represented the moment when Interstitial Cajal-like Cells (ICLCs)—a new type of stromal cells (at that time)—were documented within the interstitium of the human pancreas ,17,18,19se cells . This naMastering the Hype Cycle, in 2008). New data are still needed to move forward in defining their roles and identifying biomarkers and, moreover, to define those attributes that could promote them as players in cellular therapies for diverse pathologies. Only a few recent published data suggest that, unlike other interstitial cells, TCs seem to have lost their resistance to tamoxifen, a selective estrogen receptor modulator [However, analyzing the evolution of this concept of Telocytes—as new interstitial cells—it seems that it is closely following the Gartner hype cycle , TCs were frequently described in the deeper reticular dermis (in the proximity of skin adnexa), or being in close relations with connective tissue elements . For accurately attesting TCs and identifying their ultrastructural features, several electron microscopy techniques were employed . Skin TCImmunohistochemistry (IHC) indicates two phenotypical subsets of reticular dermis TCs, both positive for vimentin, but one positive for CD117 and the other positive for CD34 . HoweverPrevious comparative studies showed that skin TCs are a distinct cell population, different from fibroblasts (Fbs), the most common connective tissue cell, since they are not expressing CD90 or procollagen. These data are of keen importance to precisely identify in situ TCs or isolate TCs only for further investigations. Skin TCs localized in the proximity of hair follicles and sebaceous glands show positive expression of PGP 9.5, S100, cytokeratin-19, keratin-5, and MHC II . Their dHowever, it was previously demonstrated in the stroma of other organs that TCs could present a diverse immunophenotypic expression . Within FOXL1 gene encodes transcription factors involved in cellular metabolism, cell proliferation, and ontogenesis [LGR5 gene encodes a protein responsible for the formation of intestinal stem cells and the maintenance of their stemness during postembryonic development [In the lamina propria of the intestinal mucosa, TCs have a positive expression of winged-helix transcription factor forkhead box l1 (FOXL1) and leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) . FOXL1 gogenesis . On the elopment .The c-kit receptor is essential in melanogenesis, among other melanocyte physiological processes, and its involvement in these processes is still under investigation . Some reTo date, there are no reports on a specific TCs’ marker to facilitate the TCs’ identification and isolation and to bring the subject to a new level of functional studies. In vitro studies based on primary cultures of interstitial cells are usually a mixture of cell types, TCs included . A selecThere is sufficient evidence that local transplantation of interstitial cells can promote wound healing by regulating the inflammatory stages. Some studies proved TCs to be responsible for upregulating inflammatory factors in HaCaT cells and Human Dermal Microvascular Endothelial Cells, therefore being implicated in the modulation of inflammatory events and promoting skin wound healing in experimental models .So far, different techniques for isolating TCs have been proposed, including immunomagnetic microbead-based cell separation. This technique was claimed as a safe and easy way to produce pure cellular suspensions of skin TCs. By this technique, the separated cells respect the already mentioned morphological criteria for cultured TCs and their immunophenotype  . This oppuncta adherentia minima, recessus adherents, or gap junctions, or heterocellular junctions connecting TCs with other stromal cells such as immune cells, nerve cells, and endothelial cells in a three-dimensional network [Within the connective tissue of the dermis, TCs are interconnected within a stromal cellular labyrinthine interstitial network either by homocellular junctions such as  network ,47. Besi network ,48. Thes network . Communi network ,50. Thes network ,47. In a network . The clo network . Thus, T network . TCs can network , and con network , evoking network ,54.By paracrine secretion mediated by shedding vesicles with protein content, TCs seem to modulate their microenvironment and the activity of adjacent cells . For exaIn the normal dermis, but also skin lesions, TCs were found in the perivascular space suggesting roles in (neo)angiogenesis  or in blSkin TCs were demonstrated to have an endocytic function, intake pigment of hemosiderin and melanin , or tranHowever, considering the cellular interactions of TCs , or their influencing of the local environment through their paracrine secretion or by intercellular junctions of various types , all preFormer suppositions regarding the relation between TCs and tumor-associated Fb should be assessed through an understanding of molecular and phenotypical interaction between TCs and stem cells within stem cell niches .Outside the skin, in cardiac stem cell niches of the normal heart , in lungMoreover, TCs have positive expression of miR-21, which induces HIF-1α expression , hypoxiaNear another epithelium, within the lamina propria, the stem cell niches are localized near the tip of the intestinal villi . TCs areNg2 gene defects induce failure in the differentiation of stem cells [Moreover, it is well known that overexpression of stem cells’ Wnt signaling molecules could induce tumorigenesis . In the em cells .On the other hand, in the heart, TCs regulation of the WNT signaling pathway (and concomitantly other pathways) conducts cardiomyocyte differentiation and maturation, helping the integration of young cardiac muscle cells into adult heart architecture . HoweverThe presence of TCs, quantitatively and qualitatively, is influenced by different skin conditions, either regular or pathophysiological. Several diseases acknowledged cellularity changes, and these studies showed various (ultra)structural changes of TCs and their spatiality with different components of the interstitium.In systemic sclerosis, the progressive accumulation of collagen type II and III packages within the dermis (either papillary or reticular), the mucoid edema, and panniculitis, leads to disruptions of typical TCs arrangements and the architecture of normal tissue . TCs areOn the other hand, psoriasis—keratinization secondary to dermal inflammation, with immunologic determinants and genetic background, with consequences over the epidermal turnover—is also featured by changes in TCs ultrastructure. The dystrophic changes include disruption of the cellular integrity  and the loss of integrity of Tps with the fragmentation of their continuum at different levels. Interestingly, in microscopical studies, frequently dendritic cells were found in contact with the extruded nuclei of disintegrated TCs. This aspect suggests a series of immune reactions triggered by TCs destruction. These TCs ultrastructural changes are occurring contemporaneously with the increasing density of the dermal dendritic cells and the migration of Langerhans cells from the epidermis to the dermis . MoreovePublished data indicated that the increased density of TCs (positive to PDGFRα) helps improve the evolution of chronic skin wounds, reconfirming previous results regarding myocardial regeneration/repairing processes .The skin carcinomas, either basal cell carcinoma or squamous cell carcinoma, consist of affected TCs less involved in heterocellular junctions, in comparison with TCs in normal tissue . At the Normal skin is aging, and as a natural phenomenon, it becomes wrinkled, especially in the flexural areas, predominantly in sun-exposed areas . Of courIt is already widely accepted that there are excellent outcomes , at least for the skin, of using platelet rich plasma (PRP) for different therapeutic reasons. Usually, the recovery time is significantly shortened, and the positive results are unequivocally visible. PRP benefits are almost dogmatically acknowledged to be exclusively produced due to the activation of only fibroblasts by those granules released by platelets . Furthermore, it is well acknowledged that PRP treatments represent an act of regenerative medicine, in fact, PRP represent an autologous administration of plasma rich in plasmatic proteins, previously centrifuged to remove the red blood cells, but preserving the platelets and their inner granules. Casual studies previously indicated that skin-administered PRP activates Fb , thus increasing the synthesis of collagenic and non-collagenic proteins. However, sensitive, specific data regarding the exact sequence of cellular activation, the molecular fundaments that underline the PRP-induced structural benefits, and the succession of activated cells, are still limited and equivocal. Thus, it will become interesting to also consider TC’s presence and cellular response after administering different skin boosters or local skin procedures that were already documented for their clinical benefits.In case of common skin injuries , both the epidermis and dermis could be intercepted. The skin repairing/regeneration process is an excellent orchestration of dermal/epidermal cell types. Cellular heterogeneity represents a critical element of skin healing progression ,79. IrreHowever, for a deep wound affecting the integrity of the dermis, the pivotal events triggering the reparatory processes are represented by the haemorrhage and clot formation . The fibAll these cellular events are orchestrated by various chemical signals of different origins. The growth factors (either competence or progression growth factors) are mainly provided by platelets (and some by fibroblasts) and can induce the cell cycle in stem cells, but they are also inducing the mitogenic activity of the cells at the wound level . The typc-fos and c-myc (two protooncogenes). PDGF is mainly synthesized and stored within the alpha granules of the thrombocytes, and it can be released by activating the platelets [PDGF is a dimeric glycoprotein that could have different sources. The interaction between PDGF and its receptor is followed by the activation of latelets . Otherwilatelets .Previous studies demonstrated that in experimental acute myocardial infarction, the border zone of myocardial infarction lesion , at given successive time points, is dominated by different types of cells: inflammatory cells, myofibroblasts, fibroblasts, and TCs. However, 30 days after myocardial infarction, the local cellular scenery is mastered by TCs, mainly in close spatial interactions with blood vessels (including the new-formed blood vessels).Thus, further studies must be conducted to elucidate the involvement of skin TCs in reparatory/regeneration processes secondary to an acute injury of the skin, or a chronic skin defect, especially after administering growth factors at the lesion site (like PRP). It is possible that such growth factors augment tissue regeneration by enhancing the presence, distribution, density, and activity of skin TCs. Moreover, such results could be further extrapolated and investigated.TCs represent an entirely distinct cellular population of the dermis, they are being distinct from other stromal cells. To date, skin TCs have been shown to possess a specific ultrastructural profile, different from any other known cell, and an individual immunohistochemical profile, with characteristically double positivity for CD34 and PDGFRα. Their distribution and density are higher within the reticular dermis than papillary dermis, and they are forming in a stromal network by intercellular junctions . Due to all these structural and phenotypical characteristics, it is tempting to ascribe them peculiar roles in skin homeostasis, or in the pathophysiological progression of skin disorders. An attractive research path is to consider TCs (among other cells) as cellular players for skin grafts, transplanted or artificially reconstructed skin substitutes . Therefointer alia, by the disturbance of the regular tissue distribution of dermal TCs. Furthermore, the clinical and/or structural recovery of these dermatological conditions feature  the rehabilitation of dermal TCs’ presence in their previous distribution. Thus, one question that can be raised as to whether TCs are one of the players in the repairing process, or if their recovery is only a consequence of the tissue repair complex cellular orchestration. However, considering the presence of TCs in skin stem cell niches, in respect to the previously published data showing TCs’ involvement in myocardial regeneration  and liver regeneration, it is tempting to hypothesize they may serve the same roles in the skin regeneration/repair processes. Recent studies have already proved that the supplementation of local TCs by transplant can reduce local inflammation [A large body of data indicated that at least few documented skin pathologies are featured, ammation . HoweverOne line of research could derive from the new minimally invasive procedure, platelet rich plasma (PRP) injection. This is improving the tissue regeneration/repair in different dermatological conditions (from skin scars to hair loss) and is usually followed by a smooth local recovery. However, there are no studies on dynamic cellular and molecular changes regarding TCs after such treatment.The skin is one of the most accessible organs that could offer a proof-of-concept for the TCs’ involvement in diseased or injured tissue and thus could offer research insights into other diseases and potential new therapeutic approaches with multiple medical, social, economic, and social benefits.


Phlebotomus papatasi, Scopoli, 1786, the primary proven vector of L. major dynamics. Even if the disease is of public health importance, studies of P. papatasi seasonal dynamics are often local and dispersed in space and time. Therefore, a detailed picture of the biology and behavior of the vector linked with climatic factors and the framework of ZCL outbreaks is still lacking at the North African countries’ level. Our study aims to fill this gap via a systematic review and meta-analysis of the seasonal incidence of ZCL and the activity of P. papatasi in North African countries. We address the relationship between the seasonal number of declared ZCL cases, the seasonal dynamic of P. papatasi, and climatic variables at the North African region scale. Methods: We selected 585 publications, dissertations, and archives data published from 1990 to July 2022. The monthly incidence data of ZCL were extracted from 15 documents and those on the seasonal dynamic of P. papatasi from 11 publications from four North African countries. Results: Our analysis disclosed that for most studied sites, the highest ZCL incidence is recorded from October to February , while the P. papatasi density peaks primarily during the hot season of June to September. Overall, at the North African region scale, two to four months laps are present before the apparition of the scars reminiscent of infection by L. major. Conclusions: Such analysis is of interest to regional decision-makers for planning control of ZCL in North African countries. They can also be a rationale on which future field studies combining ZCL disease incidence, vector activity, and climatic data can be built.Background: In North African countries, zoonotic cutaneous leishmaniasis (ZCL) is a seasonal disease linked to  L. major, L. tropica, and L. infantum, which belong to the Leishmania genus [L. major remains the most frequent in North Africa and Middle East countries. Still, they present a high incidence rate in other territories, such as Afghanistan [Meriones shawi) and the fat sand rat (Psammomys obesus) are the identified reservoirs, while P. papatasi is the proven vector of L. major [Cutaneous leishmaniasis (CL), a skin infection provoking ulcers on exposed body parts, affects annually between 600,000 to 1 million new cases on a global scale [ia genus . Cutaneohanistan , Iran [4hanistan . One or L. major . This diL. major . The infL. major  in arid L. major . SocioecL. major , anthropL. major , and topL. major  are alsoL. major .L. major remains among the most widespread neglected tropical diseases impacting public health. The geographical dispersion of the disease is primarily affected by ecological and socioeconomic drivers that favor vector proliferation and host-reservoir sheltering conditions. In addition, seasonal climatic conditions influence ZCL incidence and dispersion [http://www.emro.who.int/neglected-tropical-diseases/information-resources-leishmaniasis/cl-factsheet.html; accessed on 14 July 2022) reported the incubation period of L. major needs at least one week and usually less than four months, while L. tropica requires at least one week and usually 2–8 months [In North African countries, zoonotic cutaneous leishmaniasis caused by spersion  via the spersion , and Tunspersion . The wor8 months .P. papatasi, whose seasonal activity causes seasonal outbreaks at the North African region scale. To our knowledge, no studies dealing with these aspects were undertaken on such a broad geographic scale. We further analyzed the interplay between seasonal ZCL cases number, P. papatasi density, and climatic data.Most published research papers focus on localized geographical areas in a restricted time range. Here, we collected data on the proven vector of ZCL, The current study was based on a systematic review following the guidelines of the PRISMA initiative (2020)  Figure  and metaP. papatasi density .Monthly data on ZCL case number  and P. p density  were extQuantitative and qualitative information from the selected publications were extracted and presented in two tables; a map of the extracted data is shown in The geographic information, including altitude, latitude, and longitude, was extracted from the literature , and cliData were processed using the Arc-GIS software  and combP. papatasi density were extracted from tables or digitized using ‘digitizelt’ software and represented by country. However, the original values of these different sources are heterogeneous, which requires the normalization of data to be comparable. Therefore, equation 1 was used to calculate the normalized incidence value of ZCL standardizing extracted values for monthly ZCL cases and P. papatasi activity on a scale ranging from 0 to 1, where 0 refers to the absence of data or no recorded activity, and 1 indicates the highest activity. For example, the normalized values of a month’s incidence and vector activity are a ratio between the extracted values for that month and the month with the maximal value.Data on monthly ZCL cases number and The Pearson correlation coefficient and R2, the coefficient of determination, were analyzed with the social science statistics calculator, R.We compiled annual data on published ZCL case numbers in North African countries for 26 years (from 1995 to 2020) . In addiAn overall decreasing trend in ZCL incidence was observed during the period studied and in the sites we reviewed . HoweverP. papatasi dynamic depicted bi- to tri-modal activity from March to November  and the apparition of the ZCL lesions.Morocco and Tunisia are the North African countries with the highest published data, followed by Libya and Algeria. In the Moroccan sites, the high incidence of ZCL was recorded from October to February, coinciding with the vector’s hibernal season. This pattern was also found in the Algerian sites. However, Libyan and Tunisian sites display a pattern with a high incidence ranging from October to January . For theThis increase in seasonal incidence in the North African countries was also found in other regions. For example, in Afghanistan (Mazar-e Sharif), most cases of ZCL occur in mid-October , while iP. papatasi) and the number of ZCL cases, a combination of the normalized average values per country and within the North African region was performed (L. major) and the apparition of the lesion(s) following a medical consultation. There are great laps in time between sandfly density and ZCL incidence with differences between region countries. P. papatasi displays a bi-modal pattern of activity, with the highest activity in June and September, while maximum ZCL cases are recorded in November and January  with an incubation period of 8–12 weeks. In Germany, the incubation period for ZCL was reported to be seven weeks [Overall, in the North African region, two to four months laps are recorded between lesions and scars reminiscent of en weeks .The distribution in time and space of the ZCL follows a seasonal dynamic depending on and following climatic variables, such as rainfall, temperature, or relative humidity. Generally, the rise in cases starts in August and reaches a maximum in September in the Moroccan sites, October in Tunisia and Libya, and December in Algeria. In these countries, the maximum number of cases coincides with the highest amount of rainfall .In the Moroccan site (Ouarzazate), the peak of ZCL cases was recorded in September and coincided with 32.73 °C (maximum temperature), 18.26 °C (minimum temperature), 30.32 mm (monthly precipitation), and 28.6% (relative humidity) . In the The calculated Pearson correlation coefficient displays a moderate to a substantial likelihood of ZCL cases being associated with maximum temperature, precipitation, and relative humidity in Moroccan sites and a positive correlation and mild likelihood with relative humidity in Algerian sites. In contrast, in the Libyan area, a highly positive association is recorded with precipitation . In addiP. papatasi follows a seasonal fluctuation and is dependent on climatic variables, such as rainfall, temperature, and relative humidity. We tested the correlation of these parameters with the P. papatasi density using the available monthly data from four North African country sites. In these sites, the vector density peaks from May to September. In the Moroccan site (Marrakech), the rise of P. papatasi density was recorded in July and coincided with 37 °C (maximum temperature), 20.4 °C (minimum temperature), 2.2 mm (monthly precipitation), and 38.7% (relative humidity) (P. papatasi density was recorded in September. It coincided with 35.6 °C (maximum temperature), 22.3 °C (minimum temperature), 5.7 mm (monthly precipitation), and 47.3% (relative humidity) (The distribution in time and space of umidity) . In the umidity) .P. papatasi activity occurs during the hot season, where both minimum and maximum temperatures are high, and low temperatures during the wet season prevent vector activity. Such observation was already reported [P. papatasi metabolism and the intravectorial development of Leishmania are primarily influenced by temperature [P. papatasi density and temperature (maximum and minimum). A moderate positive association is ascertained in Tunisia (Sidi Bouzid) and Libya (Al Rabta East), suggesting a tendency of P. papatasi density to be somewhat linked to high, maximum, and minimum temperatures  and the activity of its primary proven vector (P. papatasi) were investigated at the North African geographic scale. Using data from the literature, we explore associations between disease incidence, vector activity, and climatic factors to delineate underlying factors playing a role in the ZCL seasonal dynamic and its spread. Nevertheless, the nature of the data we analyzed, dispersed in terms of time and geographic coverage, as well as the differences in time steps between data, particularly those concerning P. papatasi dynamic, limits the strength of our analyses and, therefore, the conclusions raised by the study.North Africa belongs to one of the most impacted geographic areas by ZCL. In this paper, for the first time, the seasonal incidence of P. papatasi peaks mainly in the hot seasons in June and September. Therefore, if the presence of P. papatasi does not always imply the existence of ZCL cases, it can be an alert or an indicator of a high risk for ZCL transmission. Therefore, the outputs can be used as a basis for future field studies about ZCL disease risk and management at a regional scale and decision-making in control planning in North Africa.Our analysis points out that peaks of ZCL cases occur from October to February , while the density of


The retina is a highly specialized tissue which lines the inner surface of the eye. As a projection of the central nervous system, and being part of the brain, the retina shares many of the characteristic traits of neuronal tissue. This makes the retina suitable not only for the study of retinal diseases and physiology, but also for neuroscience studies. The retina is located inside the eye, which is almost completely transparent, making the retina like a “window to the brain”.The retina exhibits a highly organized structure, and the tissue is easily obtained and widely available. A wide range of invasive and non-invasive methods can be utilized to evaluate its morphology and functionality. Thus, it is an excellent option to investigate many neuronal processes to yield novel findings which can then be extrapolated to the brain.It is well-established that many of the underlying mechanisms described in retinal diseases such oxidative stress, inflammation, neuronal development, aging and activation of programmed cell death mechanisms, are common features in both retinal and brain circuitries. The study of these mechanisms in the retina are crucial to obtaining a better understanding of brain research.How Do We See? Morphology and Physiology of Retinal Neurons” covers a variety of research in the retina field . This Research Topic consists of seven original articles.The special Research Topic entitled “Haverkamp, Reinhard et al. aimed to characterize potential aging-associated retinal changes in the common marmoset. This study provides the first descriptions of age-associated changes in quantities, architecture, patterns and decline of different retinal cell populations in this animal model.Characterizing potential changes in retinal morphology due to aging is a mandatory task in order to identify the underlying mechanisms and possible therapeutic targets in many neurodegenerative diseases. The physiological aging process of the retina is accompanied by various and sometimes extensive changes in diseases like macular degeneration, retinopathies and glaucoma. Sox5 in neural development. Kulesh at al. focused on the role of the transcription factor Sox5 to control the morphological differentiation of a specific type of cone bipolar cell, the type 7 cell. They used a conditional knockout mouse line as well as the Gustducin-gfp reporter which labels type 7 bipolar cells to study the regulation of the differentiation during development. Bipolar cells lacking Sox5 developed the characteristic morphological features of type 7 cells, yet their axonal and dendritic field areas were reduced in size, while the axonal arbors exhibited sprouting of vertically oriented processes. These morphological changes would have a significant impact on their specific functions affecting the visual processing.Relatively little is known about the role of +) channels play important roles in all cell types underlying both normal and pathophysiological functions like nerve impulse propagation, muscle contraction, cellular activation and the secretion of biologically active molecules. In addition, various K+ channels are recognized as potential therapeutic targets in the treatment of multiple sclerosis, Alzheimer's disease, Parkinson's disease, epilepsy, stroke, brain tumors, and many other diseases. The paper by Ogata et al. identifies an additional K+ channel subunit in optic nerve and provides evidence that the ion channels it forms in situ are poised to be modulated by lighting conditions that alter CaMKII activation in retinal ganglion cell somata and axons.Potassium  on delaying vascular network degeneration and modulating astrocyte and Müller cells changes associated with retinitis pigmentosa.Inherited retinal diseases exhibit a strong inflammatory component as well as deep remodeling affecting the vascular network. Traditionally, retinal or brain inflammation has been linked mainly to microglia, but the most recent studies indicate that macroglia, astrocytes and even Müller cells may be modulating these responses. The paper presented by Rezeanu et al. presents a computational model that demonstrates how the cortex could use unsupervised learning to efficiently separate the signals from specific ganglion cells (the L vs M midget ganglion cells), into distinct signals for black and white based only on correlation of activity over time, and why it is unlikely that these same ganglion cells could simultaneously mediate our perception of red and green.The paper by Gallego-Ortega et al. identifies and characterizes numerically and topographically the population of alpha retinal ganglion cells and their subtypes with a combination of specific antibodies in the adult pigmented mouse retina. Alpha retinal ganglion cells are distributed throughout the retina with a higher density in the temporal area. This study also shows that the sustained ON and OFF response subtypes are mainly located in the periphery while the transient ON and OFF response subtypes are found in the central regions of the retina.The paper by In summary, this Research Topic for Frontiers in Neuroanatomy presented an overview of the current advances in retina research and ongoing research directions. In a variety of papers discussed above, we have emphasized the importance of this area of research and how the retina is an excellent model by which to advance our understanding of the central nervous system pathways.Editorial was written by LP and LF-S. Both authors contributed to the article and approved the submitted version.