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Inverted internal limiting membrane (ILM) flap may constitute a scaffold for Muller cells whose migration and proliferation on its surface begin the process of macular hole closure. The goal of the study was to establish an in vitro model of the interaction between ILM and the Muller cells. Vitrectomy with inverted ILM flap was performed in 23 patients due to a full-thickness macular hole (FTMH). After dissection of the inverted flap, the area of ILM peeling was extended and material was collected for cell culture experiments. Muller cells cultured on adherent cell plates showed significantly better growth than on suspension plates. Our results reveal that the presence of the ILM can overcome the growth inhibitory effect of the non-adhesive surface. Moreover, the ILM appears to be the optimal growth surface under normoxia conditions mimicking the microenvironment after vitrectomy and hypoxia which is natural state for Muller cells. The closure rate of FTMH was 100%. Our study revealed that in non-adhesive culture conditions patient derived ILM constitutes an optimal growth surface for Muller cells. We have demonstrated that the ILM effectively stimulates attachment, proliferation, and survival of Müller cells in conditions of normoxia which is the case after vitrectomy. The results strongly advocate for the use of inverted ILM flap method in macular hole closure surgeries. [ABSTRACT FROM AUTHOR]

In order to test the frequency specificity of the efferent suppressive effect on otoacoustic emissions, changes in the 2f1-f2 distortion product otoacoustic emission (DPOAE) levels induced by contralateral stimuli of different spectra were measured in 10 normally hearing adults. Three types of contralateral stimuli were used: (i) a set of 6 pairs of pure tones with the same frequencies as used for DPOAE stimulation; (ii) 6 narrow-band noise signals with cut-off frequencies equal to the frequencies of the primary tones used for DPOAE stimulation; and (iii) broad-band noise with a bandwidth of 840-6,000 Hz. A small suppressive effect was observed mainly in the mid-frequency region. Broad-band noise was more effective at suppressing DPOAEs than narrow-band noises and two-tone complexes. Occasionally, small enhancements in DPOAE amplitudes were observed. Based on the results of this study, it is concluded that DPOAE changes induced by contralateral stimuli are not frequency-specific, and are too small to have routine clinical value. [ABSTRACT FROM AUTHOR]

Sleep disorders have emerged as a significant public health issue, adversely affecting quality of life and precipitating severe complications. The association between obstructive sleep apnea syndrome (OSAS) and otolaryngological manifestations appears to be underrecognized. This study posits that manifestations in the ear, nose and throat (ENT) among patients with OSAS and users of continuous positive airway pressure (CPAP) therapy are relatively common. Utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement, this systematic review, registered at PROSPERO (No. CRD42023452473), involved a comprehensive search of the MEDLINE databases. We included studies published in English from 1979 to March 2021 that explored the linkages between OSAS, CPAP and otolaryngological manifestations. A total of 29 articles were reviewed, with findings indicating 12 studies on ear dysfunctions, 11 on nose dysfunctions and 6 on pharynx dysfunctions. Reported symptoms included hearing dysfunction, vestibular function disorders, cerebrospinal fluid leak, Eustachian tube (ET) dysfunction, rhinosinusitis, olfaction and taste disorders, dysphagia, dry mouth, and gastroesophageal reflux. The etiology of these ailments varies, yet an understanding of these symptoms can improve the diagnosis to confirm or rule out OSAS. Early identification of ENT symptoms related to OSAS may facilitate prompt diagnosis and mitigate serious complications.

Objective: To develop a methodologically uniform digits-in-noise (DIN) test in 17 different languages., Design: The DIN test was developed for Android devices as an extension to the open-access Hearing Test ™ app, available on the Google Play store. It utilised professionally recorded female speech, speech-shaped noise, a digit scoring method and a variable step size. The test was adaptively optimised and evaluated as the results of tests taken online by users of the app became available., Study Sample: Optimisation using 35,534 ears, evaluation using 6012 ears., Results: Optimisation improved the slopes of the psychometric functions for all languages by an average of 6.8%/dB. Evaluation included calculation of normative speech reception thresholds (SRTs) and estimation of test-retest standard deviations. Normative values for SRTs ranged from -14.2 dB SNR (95% CI -14.3 to -14.0) for Chinese to -11.2 dB SNR (95% CI -11.3 to -11.1) for Japanese, with reliability estimates ranging from 0.48 dB (95% CI 0.36-0.64) for Portuguese to 0.91 dB (95% CI 0.73-1.21) for Romanian., Conclusions: The optimisation of each language version was confirmed by the improvement in the slopes of the psychometric functions. The normative values obtained from the test evaluation were in agreement with literature data., Trial Registration: Science Support Centre of Wroclaw Medical University BW-59/2020.

Background: Quick and appropriate diagnostics and the use of intraoperative monitoring (IM) of hearing during vestibular schwannoma (VS) resection increase the likelihood of hearing preservation. During surgery, various methods of IM can be used, i.e., auditory brainstem responses (ABRs), transtympanic electrocochleography (TT-ECochG), and direct cochlear nerve action potentials. The aim of the study was to evaluate the prognostic values of IM of hearing using ABR and TT-ECochG in predicting postoperative hearing preservation and to evaluate relationships between them during various stages of surgery. Methods: This retrospective study presents the pre- and postoperative audiological test results and IM of hearing records (TT-ECochG and ABR) in 75 (43 women, 32 men, aged 18-69) patients with diagnosed VS. Results: The preoperative pure tone average hearing threshold was 25.02 dB HL, while after VS resection, it worsened on average by 30.03 dB HL. According to the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) Hearing Classification, before and after (pre/post) surgery, there were 47/24 patients in hearing class A, 9/8 in B, 2/1 in C, and 17/42 in D. In speech audiometry, the average preoperative speech discrimination score at an intensity of 60 dB SPL was 70.93%, and after VS resection, it worsened to 38.93%. The analysis of electrophysiological tests showed that before the tumor removal the I-V ABR interlatencies was 5.06 ms, and after VS resection, it was 6.43 ms. Conclusions: The study revealed correlations between worse postoperative hearing and changes in intraoperatively measured ABR and TT-ECochG. IM of hearing is very useful in predicting postoperative hearing in VS patients and increases the chance of postoperative hearing preservation in these patients.

Background: The development of the global digit-in-noise test requires optimization of each language version on a group of normal-hearing native-speakers. An alternative solution may be an adaptive optimization during ongoing tests in a group of subjects with unknown hearing impairments. The objective of the research was to compare the optimization results between these groups., Methods: Digit triplets consisting of three pseudo-randomly selected digits were presented in speech-shaped noise at various signal-to-noise ratios (SNRs), according to the protocol of the final speech test. Digit-specific and position-specific speech reception thresholds (SRTs) were determined and compared between groups., Results: The study sample consisted of 82 subjects, 26 normal-hearing subjects and 56 patients with diverse hearing disorders. Statistically significant differences in digit-specific SRTs between the control and the investigated group were obtained for three digits in continuous noise (digits 0, 4, 6; p -value of 0.04, 0.03, 0.05) and two in modulated noise (digits 1 and 6; p -value of 0.05 and 0.01). An analysis including only ears with SRTs within the range of the normal hearing control group showed no statistically significant differences between digits., Conclusion: Optimization of speech material can be carried out in a group of subjects with unknown hearing impairments, provided the ears with scores outside normal range are rejected.

Significance: Measurements of auditory ossicles displacement are commonly carried out by means of laser-Doppler vibrometry (LDV), which is considered to be a gold standard. The limitation of the LDV method, especially for in vivo measurements, is the necessity to expose an object in a straight line to a laser beam operating from a distance. An alternative to this approach is the use of a handheld laser-fiber vibrometry probe (HLFVP) with a curved tip., Aim: We evaluate the feasibility of an HLFVP with a curved tip for measuring sound-induced displacement of the auditory ossicles., Approach: A handheld vibrometer probe guiding the laser beam with a fiber-optic cable was used for displacement measurements of the incus body and the posterior crus of the stapes. Tonal stimuli at frequencies of 0.5, 1, 2, and 4 kHz were presented by means of an insert earphone positioned in the outer ear canal. The probe was fixed at the measurement site using a tripod or hand-held by one of the two surgeons., Results: The measurements were carried out on six fresh temporal bones. Multivariate analysis of variance showed statistically significant differences for stimulus frequency (F3,143  =  29.37, p  <  0.001, and η2  =  0.35), bone (F5,143  =  4.61, p  =  0.001, and η2  =  0.01), and measurement site (F1,143  =  4.74, p  =  0.03, and η2  =  0.02) in the absence of statistically significant differences for the probe fixation method (F2,143  =  0.15, p  =  0.862, and η2  =  0.001). Standard deviations of the means were 6.9, 2.6, 1.9, and 0.6  nm  /  Pa for frequency, bone, site, and fixation, respectively. Ear transfer functions were found to be consistent with literature data., Conclusions: The feasibility of applying HLFVP to measure the displacement of auditory ossicles has been confirmed. HLFVP offers the possibility of carrying out measurements at various angles; however, this needs to be standardized taking into account anatomical limitations and surgical convenience.

Introduction: Sources of infection of most cases of community-acquired Legionnaires' disease (CALD) are unknown., Objective: Identification of sources of infection of CALD., Setting: Berlin; December 2016-May 2019., Participants: Adult cases of CALD reported to district health authorities and consenting to the study; age and hospital matched controls., Main Outcome Measure: Percentage of cases of CALD with attributed source of infection., Methods: Analysis of secondary patient samples for monoclonal antibody (MAb) type (and sequence type); questionnaire-based interviews, analysis of standard household water samples for Legionella concentration followed by MAb (and sequence) typing of Legionella pneumophila serogroup 1 (Lp1) isolates; among cases taking of additional water samples to identify the infectious source as appropriate; recruitment of control persons for comparison of exposure history and Legionella in standard household water samples. For each case an appraisal matrix was filled in to attribute any of three source types (external (non-residence) source, residential non-drinking water (RnDW) source (not directly from drinking water outlet), residential drinking water (RDW) as source) using three evidence types (microbiological results, cluster evidence, analytical-comparative evidence (using added information from controls))., Results: Inclusion of 111 study cases and 202 controls. Median age of cases was 67 years (range 25-93 years), 74 (67%) were male. Among 65 patients with urine typable for MAb type we found a MAb 3/1-positive strain in all of them. Compared to controls being a case was not associated with a higher Legionella concentration in standard household water samples, however, the presence of a MAb 3/1-positive strain was significantly associated (odds ratio (OR) = 4.9, 95% confidence interval (CI) 1.7 to 11). Thus, a source was attributed by microbiological evidence if it contained a MAb 3/1-positive strain. A source was attributed by cluster evidence if at least two cases were exposed to the same source. Statistically significant general source types were attributed by calculating the population attributable risk (analytical-comparative evidence). We identified an external source in 16 (14%) cases, and RDW as source in 28 (25%). Wearing inadequately disinfected dentures was the only RnDW source significantly associated with cases (OR = 3.2, 95% CI 1.3 to 7.8) and led to an additional 8% of cases with source attribution, for a total of 48% of cases attributed., Conclusion: Using the appraisal matrix we attributed almost half of all cases of CALD to an infectious source, predominantly RDW. Risk for LD seems to be conferred primarily by the type of Legionella rather than the amount. Dentures as a new infectious source needs further, in particular, integrated microbiological, molecular and epidemiological confirmation., Competing Interests: The authors have declared that no competing interests exist.

Background: In addition to the aging process, risk factors for hearing loss in adults include, among others, exposure to noise, use of ototoxic drugs, genetics, and limited access to medical care. Differences in exposure to these factors are bound to be reflected in the prevalence of hearing loss. Assessment of hearing loss can easily be carried out on a large scale and at low cost using mobile apps., Objective: This study aimed to conduct a worldwide assessment of the differences in hearing loss prevalence between countries in a group of mobile device users., Methods: Hearing tests were conducted using the open-access Android-based mobile app Hearing Test. The app is available free of charge in the Google Play store, provided that consent to the use of the results for scientific purposes is given. This study included hearing tests carried out on device models supported by the app with bundled headphones in the set. Calibration factors for supported models were determined using the biological method. The tests consisted of self-determining the quietest audible tone in the frequency range from 250 Hz to 8 kHz by adjusting its intensity using the buttons. The ambient noise level was optionally monitored using a built-in microphone. Following the test, the user could compare his hearing threshold against age norms by providing his or her age. The user's location was identified based on the phone's IP address., Results: From November 23, 2016 to November 22, 2019, 733,716 hearing tests were conducted on 236,716 mobile devices across 212 countries. After rejecting the tests that were incomplete, performed with disconnected headphones, not meeting the time criterion, repeated by the same user, or carried out regularly on one device, 116,733 of 733,716 tests (15.9%) were qualified for further analysis. The prevalence of hearing loss, defined as the average threshold at frequencies 0.5 kHz, 1 kHz, 2 kHz, and 4 kHz above 25 dB HL in the better ear, was calculated at 15.6% (95% CI 15.4-15.8). Statistically significant differences were found between countries (P<.001), with the highest prevalences for Bangladesh, Pakistan, and India (>28%) and the lowest prevalences for Taiwan, Finland, and South Korea (<11%)., Conclusions: Hearing thresholds measured by means of mobile devices were congruent with the literature data on worldwide hearing loss prevalence. Uniform recruitment criteria simplify the comparison of the hearing loss prevalence across countries. Hearing testing on mobile devices may be a valid tool in epidemiological studies carried out on a large scale., (©Marcin Masalski, Krzysztof Morawski. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 23.07.2020.)

The purpose of this study was investigate whether replacing or discontinuing drugs that are inhibitors or substrates of cytochrome P450 3A4 (CYP3A4) may improve the clinical course of central serous chorioretinopathy (CSC). A retrospective observational study included 43 patients with active CSC. Twenty seven patients (32 eyes, group 1) were using drugs that act as substrates or inhibitors of CYP3A4. In 25 of these 27 patients, treatments including steroids, calcium channel blockers, anticoagulants, statins, beta-adrenolytics, angiotensin receptor antagonists, antidepressants, muscarinic receptor antagonists, phosphodiesterase type 5 inhibitors, and others were discontinued or replaced with medications not affecting CYP3A4. Sixteen patients (19 eyes, group 2) not using any medication that affects CYP3A4, were given eplerenone, rifampicin, or laser treatment. Main outcomes measures were assessed by functional and anatomical images obtained using multimodal imaging techniques. The average follow-up time was 12 months. In group I after discontinuing or replacing substrates or inhibitors of CYP3A4, improvements were observed in 18 patients (22 eyes). None of the patients that were using drugs affecting CYP3A4 improved with eplerenone therapy, however, all 18 patients improved after discontinuing the drugs. All these drugs had a blocking effect on eplerenone therapy. Best corrected visual acuity (BCVA) improved in 14 eyes, remained unchanged in 5 eyes, and worsened in 3 eyes. In 21 of the 22 eyes, subretinal fluid absorption was observed with optical coherence tomography (OCT). Mean central retinal thickness decreased from 361 μm to 219 μm. One patient (2 eyes) was unable to change treatment (due to neoplasm), one patient (1 eye) did not agree to change or stop treatment, and seven patients (7 eyes) were lost to follow-up. Of the 16 patients (19 eyes) who were treated with eplerenone, rifampicin, or laser, improvements were observed in 14 patients (16 eyes), two patients (2 eyes) were lost to follow-up, and CSC worsened in 1 eye. We concluded that patients with CSC should not take substrates or inhibitors of CYP3A4. These drugs should be replaced with alternatives that act through other metabolic pathways.

Objectives: Electronic health record (EHR) data have become increasingly available and may help inform clinical prediction. However, predicting hospitalizations among a diverse group of patients remains difficult. We sought to use EHR data to create and internally validate a predictive model for clinical use in predicting hospitalizations., Study Design: Retrospective observational cohort study., Methods: We analyzed EHR data in patients 18 years or older seen at Atrius Health from June 2013 to November 2015. We selected variables among patient demographics, clinical diagnoses, medications, and prior utilization to train a logistic regression model predicting any hospitalization within 6 months and validated the model using a separate validation set. We performed sensitivity analysis on model performance using combinations of EHR-derived, claims-derived, or both EHR- and claims-derived data., Results: After exclusions, 363,855 patient-months were included for analysis, representing 185,388 unique patients. The strongest features included sickle cell anemia (odds ratio [OR], 52.72), lipidoses and glycogenosis (OR, 8.44), heart transplant (OR, 6.12), and age 76 years or older (OR, 5.32). Model testing showed that EHR-only data had an area under the receiver operating characteristic curve (AUC) of 0.84 (95% CI, 0.838-0.853), which was similar to the claims-only data (AUC, 0.84; 95% CI, 0.831-0.848) and combined claims and EHR data (AUC, 0.846; 95% CI, 0.838-0.853)., Conclusions: Prediction models using EHR-only, claims-only, and combined data had similar predictive value and demonstrated strong discrimination for which patients will be hospitalized in the ensuing 6 months.