Efficacy and toxicity of Anatolian propolis on healthy nasal epithelial cells.

OBJECTIVE: In our study we aimed to evaluate the effects of applying propolis topically to epithelial cells of the nasal cells, to discover whether this causes any toxic effect upon the cells. MATERIALS AND METHODS: Samples of healthy human primary nasal epithelium harvested during septoplasty from volunteers were incubated in cell culture. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays may be utilized when assessing cellular damage (toxicity), as evidenced by DNA fragmentation, nuclear condensation, alteration in the outer plasma membrane and cytoskeletal alteration. This was the method used in the study. Cultured epithelial cells were incubated with propolis (Bee&You) for 24 hours at 37°C. The MTT assay was then performed, and the cell morphology was examined by confocal microscopy. In addition, via wound healing assay, cellular proliferation was assessed by the artificial scratch method followed by light microscopy. RESULTS: MTT assay results showed that the primary nasal cells were not affected by the topical application of propolis for 24 hours. All of the applied doses not changed significantly the viability of the cells. The agent was not found to be cytotoxic to the primary nasal cells in the application time of 24 hours. Our confocal microscopy findings supported the MTT findings. According to the confocal images, control cells that were not treated with test agent were with compact morphology and undamaged fusiform cell shape and nucleus. In test group of nasal cells, Propolis was found not to be cytotoxic on the cellular morphology and not changed the cells. When evaluating the results from the wound healing assay, the clear area of scratch obtained at the start of incubation (0th) was closed totally with the proliferated primary nasal cells after incubation of 24 hours with propolis. These findings are supported by our MTT findings that imply to the slight induce of proliferation of the primary cells by Propolis. CONCLUSIONS: Topically applied propolis did not have a cytotoxic effect on nasal epithelium cells. Considering its antibacterial and antioxidant effects, it has been concluded that topical application in sinonasal inflammatory diseases (e.g., acute and chronic rhinosinusitis) may have an auxiliary effect in treatment. Moreover, there is a slight induce of proliferation of the primary cells by propolis which may help wound healing in septal surgeries and epistaxis.

The superiority of Dexpanthenol or Vaseline as excipient in nasal formulations.

OBJECTIVE: Dexpanthenol is an ingredient in multiple topical pharmaceutical preparations thanks to its high penetration and localized concentration. It is included in many ointments or lotions for dermatological use, assisting in healing and reducing pruritus. Vaseline is a synthetic product obtained by distilling crude oil. It is commercially available in several grades. The study presented here examined how topically applied agents (dexpanthenol or vaseline) affect nasal epithelial cells in culture. In particular, the study aimed to identify any alterations to epithelial cells which might indicate toxicity. MATERIALS AND METHODS: The nasal epithelial cells used were sourced from mucosal tissue fragments left over the following septorhinoplasty on five patients not suffering from rhinosinusitis. The first step was to dissect the mucosal fragments into smaller pieces on a sterilized Petri dish. These fragments were then placed into the DMEM-F12 cell culture medium, which had been freshly prepared. The dexpanthenol and vaseline were diluted in dimethylsulfoxide (DMSO) to a concentration of 5 mg/mL. The cells in the wells were exposed to varying concentrations of dexpanthenol or vaseline. The actual concentration of the test reagent to which the epithelial cells were exposed ranged from 0.15 mg/mL to 5 mg/mL. The exposure period was 24 hours. The cells were finally examined using a Leica SP5II confocal microscope. The features sought were DNA fragmentation, condensation of the nuclei, changes in the outer membrane, or cytoskeletal abnormality. These features, if present, indicate cytotoxicity. RESULTS: The viability of the cultured nasal epithelial cells was unaltered by a 24-hour exposure to dexpanthenol, nor was the cellular proliferation rate affected at the level of statistical significance. There was evidence of a cytotoxic effect from exposing nasal epithelial cells to vaseline in liquid form for 24 hours. There was a reduction in cellular viability in the plates where the highest dose of vaseline (5 mg/mL) was used. Cellular viability was not affected significantly at any of the doses below 5 mg/mL. CONCLUSIONS: The absence of cytotoxic effects from the application of dexpanthenol to the nasal mucosa indicates that this agent may be safely used within the nose. The cytotoxic effects of liquid vaseline observed in this trial (condensed nuclear chromatin, loss of cellular volume) indicate that this agent may be harmful when used intranasally. For patients who require nasal packing due to nose bleeds or following endoscopic sinus surgical procedures, dexpanthenol should be preferred to vaseline from the point of view of maximizing healing of a nasal injury.

Prediction of the Cochlear Implant Electrode Insertion Depth: Clinical Applicability of two Analytical Cochlear Models.

Although the spiral anatomy of the human cochlea seems evident, measuring the highly inter-variable true dimensions is still challenging. Today, only a few three-dimensional reconstruction models of the inner ear are available. Previously, spiral equations were applied to two-dimensional computed tomography (CT) images to predict the electrode insertion depth prior to cochlear implantation. The study aimed primarily to compare the clinical applicability of two analytical cochlear models using a recently introduced planning software to predict the insertion depth of the electrode array of 46 cochlear implant recipients. One was based upon the Escudé formula, which relies only on the basal turn diameter, and another based upon the Elliptic-Circular Approximation (ECA), using the diameter and width. Each case was measured twice by two ENT surgeons. Secondly, in order to measure the benefit of the new planning software over the use of the existing clinical routine method, the results were compared to the prediction based upon a two-dimensional CT image. The intra -and inter-observer agreement using the planning software was significantly better when the ECA was applied, compared to the Escudé formula (p < 0.01). As a reference, the predicted insertion depth was compared to the actual insertion depth measured on post-operative images. The mean absolute error was |2.36| (|1.11|) mm in case of the Escudé approach and |1.19| (|0.92|) mm in case of the ECA. The use of a new planning software that allows three-dimensional handling, integrating the diameter and width of the basal turn (ECA formula), resulted in the most accurate predictions of the electrode insertion depths.

Sequential dual-site High-Definition transcranial Direct Current Stimulation (HD-tDCS) treatment in chronic subjective tinnitus: study protocol of a double-blind, randomized, placebo-controlled trial.

BACKGROUND: Chronic tinnitus is a highly prevalent symptom, with many patients reporting considerable effects of tinnitus on quality of life. No clear evidence-based treatment options are currently available. While counseling-based methods are valuable in some cases, they are not sufficiently effective for all tinnitus patients. Neuromodulation techniques such as high-definition transcranial direct current stimulation (HD-tDCS) are proposed to have positive effects on tinnitus severity but, to date, these effects have not been proven conclusively. The proposed trial will investigate the hypothesis that chronic tinnitus patients receiving HD-tDCS will report a positive effect on the impact of tinnitus on daily life, as compared to patients receiving sham stimulation. METHODS: This study proposes a randomized, double-blind, placebo-controlled trial with parallel group design. A total of 100 chronic tinnitus patients will be randomly allocated to an experimental group or a sham group, with allocation stratified according to gender and tinnitus severity. Patient and researcher will be blinded to the patient's allocation. Patients will undergo six sessions of sequential dual-site HD-tDCS of the left temporal area and the right dorsolateral prefrontal cortex. Evaluations will take place at baseline, immediately following treatment, and at three and six months after the start of the therapy. The primary outcome measure is the change in Tinnitus Functional Index (TFI) score. Secondary outcome measures include audiological measurements, cortical auditory evoked potentials, the Repeatable Battery for the Assessment of Neuropsychological Status adjusted for hearing-impaired individuals (RBANS-H), and supplementary questionnaires probing tinnitus severity and additional symptoms. By use of a linear regression model, the effects of HD-tDCS compared to sham stimulation will be assessed. DISCUSSION: The objective of this study is to evaluate whether HD-tDCS can reduce the impact of tinnitus on daily life in chronic tinnitus patients. To date, published trials on the effects of HD-tDCS on tinnitus suffer from a lack of standardization and few randomized controlled trials exist. The proposed study will be the first adequately powered trial to investigate the effects of sequential dual-site HD-tDCS on tinnitus severity. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03754127 . Registered on 22 November 2018.

Prevalence and etiology of sensorineural hearing loss in children with down syndrome: A cross-sectional study.

BACKGROUND: The prevalence and causes of sensorineural hearing loss (SNHL) in children with Down syndrome (DS) are poorly delineated. OBJECTIVE: To describe the prevalence, severity, laterality and underlying etiology of SNHL in a cohort of children with DS. METHODS: A cross-sectional study was performed among all children with DS followed at the multidisciplinary Downteam of the Antwerp University Hospital. Patients' characteristics, risk factors for hearing loss, audiometric data and results of an etiological work-up were collected. RESULTS: Among 291 patients in follow-up, 138 patients (47.4%) presented with hearing loss. In the majority this was caused by middle ear effusion and only 13 patients (4.5%) had sensorineural hearing loss, 7 boys and 6 girls with a mean age of 14.4 ±â€¯7.4 years. Hearing loss was bilateral in 8 cases. Hearing loss severity was graded as mild in 38.5%, moderate in 30.8% and profound in 30.8% of the patients. An etiological work-up was completed in 9 children. Four patients presented with single sided deafness due to cochlear nerve deficiency. One patient had a genetic cause and in 2 patients the hearing loss was attributed to excessive noise exposure. The etiology of hearing loss was unknown in 6 patients. CONCLUSION: Sensorineural hearing loss is uncommon in children with DS with a prevalence of 4.5%. Etiological work-up may allow identifying a specific underlying cause. Cochlear nerve deficiency was found in 4 children with DS and single sided deafness.

Mal de Debarquement Syndrome: a survey on subtypes, misdiagnoses, onset and associated psychological features.

INTRODUCTION: Mal de Debarquement Syndrome (MdDS) is a neurological condition typically characterized by a sensation of motion, that persists longer than a month following exposure to passive motion (e.g., cruise, flight, etc.). The most common form of MdDS is motion triggered (MT). However, recently it has been acknowledged that some patients develop typical MdDS symptoms without an apparent motion trigger. These cases are identified here as spontaneous or other onset (SO) MdDS. This study aimed to address similarities and differences between the MdDS subtypes. Diagnostic procedures were compared and extensive diagnostic guidelines were proposed. Second, potential triggers and associated psychological components of MdDS were revealed. METHODS: This was a retrospective online survey study for MT and SO MdDS patients. Participants were required to respond to a set of comprehensive questions regarding epidemiological details, as well as the diagnostic procedures and onset triggers. RESULTS: There were 370 patients who participated in the surveys. It is indicated that MdDS is often misdiagnosed; more so for the SO group. In addition to the apparent self-motion, both groups reported associated levels of stress, anxiety and depression. DISCUSSION: It appears at present that both MdDS subtypes are still poorly recognised. This was the first attempt to evaluate the diagnostic differences between MdDS subtypes and to propose a set of comprehensive diagnostic guidelines for both MdDS subtypes. In addition, the current research addressed that associated symptoms such as stress, anxiety and depression should also be considered when treating patients. We hope this study will help the medical community to broaden their awareness and diagnostic knowledge of this condition.

How I do it: modified Todd's meatoplasty.

BACKGROUND: Chronic otorrhoea after canal wall down mastoidectomy can be a clinical challenge. Basic principles for canal wall down surgery include establishing a large meatus. Several meatoplasty techniques have been reported. This paper describes this new indication for Todd's meatoplasty with surgical improvements. STUDY DESIGN: Retrospective review. SETTING: Academic tertiary referral centre. METHODS: Modifications of transposition postauricular flap meatoplasty are reported. This technique was applied in a series of patients with chronic otorrhoea after a canal wall down mastoidectomy. RESULTS: In general, a dry radical cavity was successfully created within six weeks and follow-up visits at the out-patient clinic were reduced. Only minor complications occurred, which are all reported. CONCLUSION: The postauricular flap meatoplasty is a valuable tool in the management of chronic otorrhoea after an open cavity approach for cholesteatoma.

Retrospective complication rate comparison between surgical techniques in paediatric cochlear implantation.

OBJECTIVE: To compare paediatric complication occurrence between the Mastoidectomy with Posterior Tympanotomy and the SupraMeatal Approach for cochlear implantation. DESIGN: Retrospective cohort study. SETTING: Children receiving a cochlear implant before 5 years of age between 1996 and 2014 in our tertiary center. PARTICIPANTS: A total of 144 patients receiving a cochlear implant (121 by Mastoidectomy with Posterior Tympanotomy and 23 by SupraMeatal Approach) operated on 165 ears (129 and 39 respectively). MAIN OUTCOME MEASURES: The severity (minor or major) using Cohen and Hoffman criteria and time of occurrence of complications (intraoperative, early postoperative or late postoperative) were identified. Intraoperative surgical challenges were correlated to complication occurrence. RESULTS: The mean age at implantation was 2.13 ± 1.14 years old. Patients operated by the SupraMeatal Approach (1.27 ± 0.69 years old) were significantly (P < .001) younger than those receiving a cochlear implant by Mastoidectomy with Posterior Tympanotomy Approach (2.40 ± 1.12). Most complications were minor (Mastoidectomy with Posterior Tympanotomy Approach: 64.0%; SupraMeatal Approach: 73.1%) and occurred early postoperatively (Mastoidectomy with Posterior Tympanotomy Approach: 61.5%; SupraMeatal Approach: 76.9%). More overall complications occurred in SupraMeatal compared to Mastoidectomy with Posterior Tympanotomy Approach cases (61.5% versus 20.6%; P < .001). Younger SupraMeatal Approach cohort patients (6 - 12 and 18 - 24 months; P < .008 and P = .016) most often developed these complications. When looking at specific complications, more infectious complications occurred in patients receiving a cochlear implant through the SupraMeatal Approach (P < .05). Logistic regression showed that the surgical technique and not the age at implantation was responsible for the documented complications. No relationship between complications and intraoperative difficulties was identified. CONCLUSION: In our institution, cochlear implantation in young patients through the SupraMeatal Approach resulted in significantly more (infectious) complications than those operated through the Mastoidectomy with Posterior Tympanotomy Approach. Outcomes from our institution recommends using the Mastoidectomy with Posterior Tympanotomy Approach when opting for a cochlear implant surgical technique in young children who are more prone to develop infectious complications.

R705H mutation of MYH9 is associated with MYH9-related disease and not only with non-syndromic deafness DFNA17.

MYH9-related disease (MYH9-RD) is a rare autosomal dominant disease caused by mutation of MYH9, the gene encoding for the heavy chain of non-muscle myosin IIA (NMMHC-IIA). MYH9-RD patients have macrothrombocytopenia and granulocyte inclusions (pathognomonic sign of the disease) containing wild-type and mutant NMMHC-IIA. During life they might develop sensorineural hearing loss, cataract, glomerulonephritis, and elevation of liver enzymes. One of the MYH9 mutations, p.R705H, was previously reported to be associated with DFNA17, an autosomal dominant non-syndromic sensorineural hearing loss without any other features associated. We identified the same mutation in two unrelated families, whose four affected individuals had not only hearing impairment but also thrombocytopenia, giant platelets, leukocyte inclusions, as well as mild to moderate elevation of some liver enzymes. Our data suggest that DFNA17 should not be a separate genetic entity but part of the wide phenotypic spectrum of MYH9-RD characterized by congenital hematological manifestations and variable penetrance and expressivity of the extra-hematological features.

Management of repeated trauma to bone-anchored hearing aids in a paediatric patient.

OBJECTIVE: To outline the management options and neurological complications associated with repeated traumatic falls that cause intrusion of bone-anchored hearing aid abutments. CASE REPORT: A three-year-old boy with coloboma, heart defects, atresia of nasal choanae, retarded growth, genital abnormalities, ear defects and deafness was fitted with a bone-anchored hearing aid for severe conductive hearing loss and congenital ear malformations. Six months later, a traumatic fall caused an intrusion injury which rendered the bone-anchored hearing aid abutment unusable. Without removing the original abutment, a second abutment was inserted on the same side to aid his hearing. Two years later, the child fell again and damaged his second bone-anchored hearing aid abutment. Having been offered a surgical option to repair the area, the parents opted to keep the abutments in situ. CONCLUSION: Direct trauma to the fixture of a bone-anchored hearing aid is a relatively common long-term complication in children which can disrupt osseointegration and disable the implant. For young children who are either prone to falling or have behavioural problems, a bone-anchored hearing aid Softband may be more appropriate to non-invasively aid hearing.

Contribution of the N-acetyltransferase 2 polymorphism NAT2*6A to age-related hearing impairment.

BACKGROUND: Age-related hearing impairment (ARHI) is the most common sensory impairment in older people, affecting 50% of those aged 80 years. The proportion of older people is increasing in the general population, and as a consequence, the number of people affected with ARHI is growing. ARHI is a complex disorder, with both environmental and genetic factors contributing to the disease. The first studies to elucidate these genetic factors were recently performed, resulting in the identification of the first two susceptibility genes for ARHI, NAT2 and KCNQ4. METHODS: In the present study, the association between ARHI and polymorphisms in genes that contribute to the defence against reactive oxygen species, including GSTT1, GSTM1 and NAT2, was tested. Samples originated from seven different countries and were combined into two test population samples, the general European population and the Finnish population. Two distinct phenotypes for ARHI were studied, Z(low) and Z(high), representing hearing in the low and high frequencies, respectively. Statistical analysis was performed for single polymorphisms (GSTM1, GSTT1, NAT2*5A, NAT2*6A, and NAT2*7A), haplotypes, and gene-environment and gene-gene interactions. RESULTS: We found an association between ARHI and GSTT1 and GSTM1 in the Finnish population sample, and with NAT2*6A in the general European population sample. The latter finding replicates previously published data. CONCLUSION: As replication is considered the ultimate proof of true associations in the study of complex disorders, this study provides further support for the involvement of NAT2*6A in ARHI.

Prevalence of tinnitus and audiometric shape.

OBJECTIVES: Studies of tinnitus are often conducted on patient populations presenting for treatment. It is, however, difficult to generalise prevalence numbers and aetiological results from these studies to a healthy, elderly population. The first aim of our study was to determine the prevalence of tinnitus in an otologically screened population between 55 and 65 years old. Secondly, both prevalence and the specific characteristics of tinnitus were compared in subjects with either a flat audiogram, a high-frequency gently sloping audiogram or a high-frequency steeply sloping audiogram. METHODS: 1147 subjects (549 males and 598 females) were recruited through population registers and underwent thorough clinical and audiological examinations. Subjects who reported tinnitus in the general questionnaire about medical history and environmental exposure were invited to complete an additional questionnaire on tinnitus history. RESULTS: The prevalence of tinnitus was 19.3% according to the general questionnaire on medical health and environmental exposure and 11.8% according to the additional detailed tinnitus-specific questionnaire. Furthermore, our results indicate that gender has a significant effect (tinnitus is more common in males than in females), as does audiometric configuration (tinnitus is more common in subjects with a high-frequency steeply sloping audiogram than in subjects with a flat audiogram). Both effects were significant in noise-/solvent-exposed subjects, as well as in non-exposed subjects. Finally, comparison of "tinnitus characteristics" in subjects categorised by audiogram configuration revealed significant differences in loudness, pitch, temporal variability and family history of tinnitus.

Familial aggregation of tinnitus: a European multicentre study.

INTRODUCTION AND AIM: Tinnitus is a common condition affecting approximately 20% of the older population. There is increasing evidence that changes in the central auditory system following cochlear malfunctioning are responsible for tinnitus. To date, few investigators have studied the influence of genetic factors on tinnitus. The present report investigates the presence of a familial effect in tinnitus subjects. METHODS: In a European multicentre study, 198 families were recruited in seven European countries. Each family had at least 3 siblings. Subjects were screened for causes of hearing loss other than presbyacusis by clinical examination and a questionnaire. The presence of tinnitus was evaluated with the question "Nowadays, do you ever get noises in your head or ear (tinnitus) which usually last longer than five minutes". Familial aggregation was tested using three methods: a mixed model approach, calculating familial correlations, and estimating the risk of a subject having tinnitus if the disorder is present in another family member. RESULTS: All methods demonstrated a significant familial effect for tinnitus. The effect persisted after correction for the effect of other risk factors such as hearing loss, gender and age. The size of the familial effect is smaller than that for age-related hearing impairment, with a familial correlation of 0.15. CONCLUSION: The presence of a familial effect for tinnitus opens the door to specific studies that can determine whether this effect is due to a shared familial environment or the involvement of genetic factors. Subsequent association studies may result in the identification of the factors responsible. In addition, more emphasis should be placed on the effect of role models in the treatment of tinnitus.

KCNQ4: a gene for age-related hearing impairment?

Age-related hearing impairment (ARHI) is the most common sensory impairment among the elderly. It is a complex disorder influenced by genetic as well as environmental factors. SNPs in a candidate susceptibility gene, KCNQ4, were examined in two independent Caucasian populations. Two quantitative trait locus (QTL) values were investigated: Zhigh and Zlow, a measure of high and respectively low frequency hearing loss. In the first population, the statistical analysis of 23 genotyped SNPs spread across KCNQ4 resulted in significant p-values for two SNPs for Zhigh-SNP9 (NT_004511:g.11244177A > T) and SNP15 (NT_004511:g.11257005C > T; NP_004691:p.Ala259Ala), and one SNP for Zlow-SNP12 (NT_004511:g.11249550A > T). The linkage disequilibrium (LD) structure of KCNQ4 was subsequently determined in a 34-kb region surrounding the significant SNPs, resulting in three LD-blocks. LD-block 1 contains SNP9 and covers an area of 5 kb, LD-block 2 measures 5 kb and surrounds SNP13 (NT_004511:g.11253513A > G) to SNP18 (NT_004511:g.11257509G > A; NP_004691:p.Thr293Thr), and LD-block 3 spans 7 kb. Five tag-SNPs of block 1 and 2, and 2 extra SNPs were subsequently genotyped in the second population. Again, several SNPs were positively associated with ARHI: one SNP (SNP18) for the high frequencies and three SNPs (SNP9, SNP12, and SNP18) for the low frequencies, although only a single SNP (SNP12) resulted in significant p-values in both populations. Nevertheless, the associated SNPs of both populations were all located in the same 13-kb region in the middle of the KCNQ4 gene.

Genetic testing for hearing impairment.

For some patients, genetic testing can reveal the etiology of their hearing impairment, and can provide evidence for a medical diagnosis. However, a gap between fundamental genetic research on hereditary deafness and clinical otology emerges because of the steadily increasing number of discovered genes for hereditary hearing impairment (HHI) and the comparably low clinical differentiation of the HHIs. In an attempt to keep up with the scientific progress, this article enumerates the indications of genetic testing for HHI from a clinical point of view and describes the most frequently encountered HHIs in Belgium. Domains of recent scientific interest, molecular biological aspects, and some pitfalls with HHIs are highlighted. The overview comprises bilateral congenital hearing loss, late-onset progressive high frequency hearing loss, progressive bilateral cochleo-vestibular deficit, and progressive low frequency hearing loss. Also, several syndromal forms of HHI are summarized, and the availability of genetic tests mentioned. Finally, the requirements for successful linkage analysis, an important genetic research tool for localizing the potential genes of a trait on a chromosome, are briefly described.