Stepwise regression models explored predictors of ADL and their awareness.PwD showed impairment in all ADL levels, particularly when measured through informant-report. No differences were seen between controls and PwMCI regardless of measurement type. PwD differed in awareness of instrumental and basic, but not of advanced ADL, compared to controls. Age, gender, education and fluency were the most consistent predictors for ADL. Diagnosis was a significant predictor only for instrumental ADL. Awareness of basic ADL was predicted by memory, and awareness of instrumental ADL was predicted by general cognitive status, educational level, and diagnosis.Results reinforce the presence of lack of awareness of ADL in PwD. Use of informant-reports and cognitive testing for fluency are suggested for the clinical assessment of ADL performance. Finally, assessment of instrumental ADL may be crucial for diagnostic purposes. Functional capacity, i.e., the ability to perform activities of daily living (ADL), is an important variable in the context of aging, being affected by a variety of chronic conditions linked to older age. Loss of functional ability is commonly associated with cognitive decline in older adults , and canOne important issue when considering the relationship between ADL performance and cognitive impairment is the existence of different levels of functional capacity according to the complexity of the activity . TypicalThe notion of a hierarchy of ADL is particularly important for the diagnosis of MCI. Initially, it was believed that all levels of ADL would be preserved in this condition . HoweverStudies that analyze the cognitive processes related to loss of functional capacity vary in their conclusions. In general, some evidence suggests that executive functioning is the best predictor of functional capacity , 8, but One potential issue leading to heterogeneity of results may be that cognitively impaired patients do not fully acknowledge the extent to which they have functional impairments. This lack of awareness about the diagnosis and its consequences has been termed anosognosia. Although findings are mixed, it has been shown that people with MCI (PwMCI) may have limited awareness about their abilities . A recenA better understanding of the association between cognitive impairment, ADL performance and its awareness is critical to aid the development of better interventions, rehabilitation programs and compensatory strategies. These studies are especially relevant for low- and middle-income countries (LMIC), considering the scarcity of data from these world regions in comparison to developed countries . StudiesAccordingly, the current study aimed to investigate functional capacity and awareness in dementia and MCI with a sample from a LMIC. Specifically, three levels of ADL were explored , measured both by self- and informant-report. In addition to exploring differences between patient groups, sociodemographic and cognitive correlates for each type of ADL and awareness of functional ability were also investigated.The sample for this study was obtained from the Frailty in Brazilian Older People—Rio de Janeiro Section (FIBRA Study) stage II database , 24. FIBn = 44) was drawn randomly for evaluation in Stage II, to check for the presence of false negatives (none of them were diagnosed as having dementia). The second group—271 subjects with MMSE scores < 28 and FAQ ≥ 5—were considered suspected of having dementia or MCI and were invited to be assessed by clinical and neuropsychological evaluations (stage II). The assessment was carried out by a multidisciplinary team led by a geriatrician.During stage I, the sample was divided into two groups based on MMSE and FAQ performances. The first one—250 subjects with MMSE ≥ 28, and 215 with MMSE < 28, but without loss of functional capacity (FAQ < 5)—were regarded as cognitively unimpaired and thus negative for dementia syndrome and MCI. From this group, a sample  when their contact initiated]. Some participants had missing informant or self-report measures of ADL and were also excluded.The present study analyzed data from 243 participants who fulfilled all these criteria. Based on these assessments, the sample was split into the following subgroups: 104 participants diagnosed with dementia; 45 diagnosed with MCI and 94 healthy older adults . Although information about dementia subtype was not fully available for the dementia group, most had a diagnosis of Alzheimer’s Disease.General cognitive level was measured through the MMSE , 26, witActivities of daily living (ADL) were assessed through three different instruments. For all instruments, self-report and informant report were obtained. Informants were people in close contact with the participants (see previous section), typically relatives (partners and children).Were measured with Reuben’s advanced ADL scale . This 12Were measured with the Lawton instrumental ADL scale , 39. TheWere measured with The Katz Index of Independence in ADL. The scale has six items assessing bathing, dressing, personal hygiene, feeding, mobility and continence , 41. To Awareness was assessed through the discrepancy between self-report and informant-report, a method widely used in the literature . For eacpost hoc t-tests, or a chi-square test in the case of gender.Data analysis was carried out using SPSS software (version 20.0). Descriptive statistics were used to illustrate the sample characteristics, with differences between groups being tested with one-way ANOVAs, followed by For each ADL type , differences between groups  were calculated with one-way ANOVAs, followed by pairwise comparisons adjusted with Bonferroni corrections. This was done for self-report, informant-report and discrepancy scores (awareness variables).R2), highest cross-validity (adjusted R2) and Akaike’s Information Criterion (AIC).Finally, stepwise regression models were calculated to explore predictors of functional capacity and awareness. Predictors included demographic , clinical (diagnostic group) and cognitive variables . Models were run separately for each type of ADL  and variable . In all models, to avoid inflation of type II error and exclusion of predictors involved in suppressor effects, we used a backward regression method. The best models were selected on the basis of a trade-off between highest explained variance  = 27.94, p < 0.001], with PwD being older than controls and MCI group (p < 0.001). Educational level was also significantly different between groups, , with fewer years of education in the PwD group in relation to controls. There were no differences in terms of gender distribution between groups .The demographic characteristics and clinical profile of the sample are described in p < 0.001 for all ANOVAs). For the memory variables , PwD performed worse than MCI and control participants, and MCI participants performed worse than controls . For the MMSE, IQCODE, digit to symbol and fluency tasks, PwD performed worse than controls and participants with MCI , but there were no significant differences between these two groups.Regarding clinical and cognitive variables, as expected there were significant differences between groups  = 9.77, p < 0.001], instrumental  and basic ADL . Means can be seen in Post hoc tests indicated that for advanced ADL PwD reported less preserved abilities than controls (p < 0.001), but there were no significant differences between participants with MCI and controls (p = 0.495) or PwD (p = 0.070). Pairwise comparisons of instrumental ADL indicated less preserved abilities for PwD in relation to both MCI and control participants (p < 0.001 in both cases), but no significant differences between these two groups (p = 0.999). For basic ADL, there were no differences between controls and PwD (p = 0.135) or MCI participants (p = 0.999), but a significant difference between the latter group and PwD (p = 0.036).ANOVA results indicated significant differences between groups for advanced , instrumental  and basic ADL . Means can be seen in Post hoc tests indicated a similar pattern for all types of ADL, with no significant differences between controls and PwMCI (p > 0.05), but PwD having less preserved abilities than controls and PwMCI .ANOVA results indicated significant differences between groups for advanced  and instrumental , but not for advanced ADL awareness . Means can be seen in Post hoc tests indicated significant differences in awareness of basic ADL abilities between controls and PwD (p < 0.001), and between PwMCI and PwD (p = 0.002), but not between controls and MCI (p = 0.999). Differences in instrumental ADL awareness were significant only between controls and PwD (p < 0.001).ANOVA results indicated significant differences between groups for basic [There was no evidence of collinearity in the data, with VIF and tolerance values within the recommended range . Signifip < 0.01 in all models). For advanced ADL, the model with the best trade-off between AIC score, explained variance (R2 = 0.28) and highest cross-validity (adjusted R2 = 0.27) included phonemic fluency , age , and categorical fluency, but the latter variable did not give a significant contribution to the model (p = 0.181).All regression models significantly predicted advanced, instrumental and basic ADLs (R2 = 0.39) and highest cross-validity (adjusted R2 = 0.37) included female gender , age , categorical fluency , immediate recall , and variables which did not give a significant contribution to the model, such as phonemic fluency (p = 0.194), delayed recall (p = 0.371) and educational level (p = 0.182).For instrumental ADL, the model with the best (lowest) AIC score, highest explained variance (R2 = 0.13) and highest cross-validity (adjusted R2 = 0.10) included educational level , phonemic fluency  and variables which did not give a significant contribution, such as age (p = 0.051), diagnosis (p = 0.387), categorical fluency (p = 0.563) and delayed recall (p = 0.064).For basic ADL, the model with the best (lowest) AIC score, highest explained variance . For advanced ADL, the model with the best (lowest) AIC score, highest explained variance (R2 = 0.30) and highest cross-validity (adjusted R2 = 0.28) included phonemic fluency , female gender , age , and variables which did not give a significant contribution to the model, such as categorical fluency (p = 0.297) and educational level (p = 0.514).All regression models significantly predicted advanced, instrumental and basic ADLs (R2 = 0.54) and highest cross-validity (adjusted R2 = 0.52) included all variables, except delayed recall, with significant contributions of diagnosis , female gender , age , educational level , categorical fluency , MMSE , immediate recall , but not of phonemic fluency (p = 0.056) or digit span (p = 0.199).For instrumental ADL, the model with the best trade-off between AIC score, highest explained variance (R2 = 0.15) and highest cross-validity (adjusted R2 = 0.12) included educational level , phonemic fluency  and variables which did not give a significant contribution, such as age (p = 0.060), categorical fluency (p = 0.391), MMSE (p = 0.360) and delayed recall (p = 0.708).For basic ADL, the model with the best trade-off between AIC score, highest explained variance , but not advanced ADL awareness. For instrumental ADL awareness, the model with the best trade-off between AIC score, highest explained variance (R2 = 0.27) and highest cross-validity (adjusted R2 = 0.24) included diagnosis , educational level , MMSE  and variables which did not give a significant contribution, such as digit span (p = 0.120), phonemic fluency (p = 0.306), and delayed recall (p = 0.082).The regression models significantly predicted instrumental and basic ADL awareness (R2 = 0.09) and highest cross-validity (adjusted R2 = 0.07) included only delayed recall as a significant predictor , and variables which did not give a significant contribution, such as educational level (p = 0.095), categorical fluency (p = 0.318), and MMSE (p = 0.276).For basic ADL, the model with the best trade-off between AIC score, highest explained variance .Lack of significant differences in ADL between control participants and PwMCI is consistent with the definition of this condition, with MCI being characterized by cognitive impairment in the absence of functional deficits . NeverthCognitive and demographic predictors of functional ability were generally consistent across measurement type and ADL level. Higher phonemic fluency and lower age predicted better advanced ADL for both measurement types; in the informant variable, women showed better functional capacity. Older age may lead to decreases in advanced ADL since it is the greatest risk factor for cognitive decline . By its The presence of phonemic fluency in the models may suggest cognitive processes that are at some level linked to advanced ADL performance. This statement, however, should be considered with three caveats. First, fluency tests are influenced by a variety of different cognitive processes , 48, andIn the informant report, gender was also a predictor, with women showing better functional ability. Although biological hypotheses could be made, this finding may be more readily explained by differences in perception due to psychosocial and cultural roles. Men usually engage more in work-life  and lessInstrumental activities abilities were, in both models, also predicted by age and gender, as well as by categorical fluency, immediate recall and education. Diagnosis and MMSE were present in the informant-report model as well. Age and gender are present in this model probably for the same reasons they were present as predictors for advanced activities. The presence of gender for both informant and self-report may be explained by the fact that men are commonly and consciously less involved in housework than women , with inInstrumental ADL models included more cognitive variables than for advanced and basic ADL. Both self- and informant-report models included categorical fluency and immediate recall. This is consistent with previous findings that relate instrumental abilities primarily to executive functioning and memory , 45. CatEducation is a variable that may often be undetected as a predictor of functional capacity because most studies about the theme have been conducted in developed countries, characterized by higher educational homogeneity. In this study, the variable appeared in instrumental and basic ADL models, both in self- and informant- report. Higher education is one of the factors known to provide higher cognitive reserve , a proteIn addition to education, both basic ADL prediction models included also phonemic fluency. First, it is important to highlight that phonemic fluency is associated with education . It has Regarding awareness, general cognitive level was a significant predictor of instrumental ADL awareness, and memory was the only predictor of awareness of basic ADL, although explained variance was low for the latter. Altogether these findings suggest that awareness in can be considered a neurocognitive ability, as proposed by theoretical models . AdditioOne limitation of the current study refers to the measurement of the main variables explored. The neuropsychological test battery could have been more diverse, exploring also cognitive abilities such as inhibitory control and planning. Nevertheless, a briefer battery was chosen considering application time and the populational approach used in the current study. Questionnaire measurements of ADL also may be criticized for reduced ecological validity, and, ideally, observational measures should be applied. Nevertheless, in the current setting, such measures were not possible, so future community-based work should consider the applicability of ADL outcomes with increased ecological validity. Another limitation is the lack of information regarding specific diagnosis for all participants within the dementia group. Different types of dementia could have led to distinct profiles in terms of ADL and awareness impairment. Nevertheless, where information is available, most participants had Alzheimer’s disease, the most common form of dementia in older adults. Future studies could explore ADL performance and awareness, as well as their predictors, in different types of dementia.In conclusion, the results imply lack of awareness of ADL ability, as well as poorer performance, in PwD, with a subtle decrease in performance in PwMCI in advanced activities. As informant-report consistently showed differences between PwD and both other diagnostic groups in all ADL levels, using informant measures may be crucial for clinical assessment of functional capacity. Using ADL screening may be especially important to LMIC countries, where more expensive methods are not available . RegardiThe raw data supporting the conclusions of this article will be made available by the authors, upon reasonable request.Stage I of the FIBRA study was approved by the Pedro Ernesto University Hospital Ethics Committee (1850-CEP HUPE/2007), with subsequent approval for stage II (0163.2008-COEP UERJ 027/2008). All participants and their caregivers provided informed consent.RL was responsible for the conception and design of the study. CF and PR were responsible for data acquisition and the database organization. LH was responsible for the writing. DM and LH were responsible for data analysis. DM, LH, HF, MS, and RL contributed to the interpretation. All authors contributed to the manuscript revision, read, and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


EIF2B3: the previously known pathogenic variant c c.260C>T  and the novel variant c.673C>T (p.Arg225Trp). Based on the American College of Medical Genetics (ACMG) recommendations, we classified p.Arg225Trp as likely pathogenic. We report a novel variant in a patient with CACH/VWM and highlight the importance of genetic testing in patients with leukodystrophies.Leukodystrophies are a group of heterogeneous disorders affecting brain myelin. Among those, childhood ataxia with central nervous system hypomyelination/vanishing white matter (CACH/VWM) is one of the more common inherited leukodystrophies. Pathogenic variants in one of the genes encoding five subunits of EIF2B are associated with CACH/VWM. Herein, we presented a case of CACH/VWM who developed ataxia following a minor head injury. Brain magnetic resonance imaging showed extensive white matter signal abnormality. Diagnosis of CACH/VWM was confirmed by the presence of compound heterozygous variants in  Inherited leukodystrophies  are a grEIF2B1, EIF2B2, EIF2B3, EIF2B4, and EIF2B5, encoding the five subunits of the eukaryotic translation initiation factor 2B (eIF2B), are found to be associated with CACH/VWM  is one of the more common leukodystrophies . In the CACH/VWM .Herein, we report a child with CACH/VWM who developed ataxia following minor head trauma. He was found to be a compound heterozygote for a known pathogenic variant and a novel variant that is classified as likely pathogenic.via vaginal delivery. Antenatal and neonatal courses were uncomplicated. He was meeting developmental milestones appropriately. At 2 years and 11 months, he had a minor accidental fall when he fell off the couch. The parents denied loss of consciousness; however, they noticed that he was unsteady. He remained unsteady for 3 h after the fall. His gait was improving over time; however, he remained unstable. He was referred to orthopedic surgery, and gait ataxia was confirmed. The child was referred to neurology for further evaluation. The initial examination was notable for positive Romberg signs with normal cranial nerve function, muscle tone and strength, cerebellar signs, and downgoing plantar reflex. Brain MRI revealed diffuse bilateral T2-weighted and FLAIR hyperintensity in a symmetrical distribution involving the supratentorial and the cerebellar white matter with sparing of the basal ganglia  was at the 24th percentile. Neurological examination was notable for normal mental status, normal cognition, and normal speech content with mild dysarthria, mild tremor on the finger-to-nose test, mild hyperreflexia with normal functional motor strength, and wide-based gait, but he was able to ambulate without assistance for 10–12 steps. Biochemical profiles including lysosomal enzyme panel, urine ceramide trihexoside and sulfatide profiles, and leukocyte arylsulfatase A were normal.Clinical targeted sequencing using the leukodystrophy panel was performed by Invitae . The variants were confirmed by Sanger sequencing. Bioinformatic analysis was performed by using combined annotation-dependent depletion (CADD) . Variantp.Ala87Val) and c.673C>T (p.Arg225Trp). Parental testing confirmed trans configuration (In silico analysis supported the deleteriousness of p.Ala87Val and p.Arg225Trp, with CADD scores of 26.4 and 32, respectively.Two variants were found in EIF2B3, designated as c.260C>T (guration . In siliTwo months after the first evaluation, he developed worsening ataxia following 2 days of low-grade fever and upper respiratory infection symptoms. Interval changes in his examination included worsening hyperreflexia, extremity weakness, intension tremor, and very wide-based gait in addition to respiratory distress and wheezing on auscultation. He was admitted for dehydration and monitoring of respiratory status. He received a course of steroids for 5 days for presumed reactive airway disease. A follow-up examination demonstrated resolution of weakness and respiratory symptoms and improvement of his gait and reflexes. He was enrolled in the clinical trial shortly after his recovery from illness.p.Ala87Val and p.Arg225Trp. The variant p.Ala87Val is known to be pathogenic and is a founder variant among French–Canadians (p.Arg225Trp, has been reported in one heterozygote in the population database (p.Arg225Gln has been reported to be pathogenic (eif2b3 mutant zebrafish rescued morphological phenotypes; however, overexpression of human EIF2B3 harboring pathogenic variants, including p.Ala87Val and p.Arg225Gln, could not. The residue Arg225 is highly conserved (In silico prediction supports that the change from Arg to Trp is likely to be disruptive (p.Arg225Trp as likely pathogenic using the following criteria: PM2, PM3, PM5, PP3, and PP4 (Herein, we describe a child with CACH/VWM whose symptoms were triggered by minor head trauma. His MRI demonstrated diffuse T2 and FLAIR hyperintensity in cerebral white matter with secondary cavitation, which are typical findings of CACH/VWM. He has compound heterozygous variants, namely, anadians . The resanadians . A noveldatabase . Althougthogenic . Overexponserved . In silisruptive . Based o and PP4 .Our patient presented at the age of 3 years with ataxia following minor head trauma. The age of 2–4 years is the most common age of presentation in patients with CACH/VWM . The majA recent study reported a case with CACH/VWM who received intravenous immunoglobulin and systemic corticosteroids with partial improvement in clinical and neuroimaging . Our patEIF2B5 variants are associated with milder or more severe diseases, the age of onset and survival are not significantly different among the patients with pathogenic variants in EIF2B1, EIF2B2, EIF2B3, EIF2B4, or EIF2B5 (Five genes that encode eIF2B are associated with CACH/VWM in an autosomal recessive manner . Althougr EIF2B5 . The patr EIF2B5 .In eukaryotic cells, eIF2B acts as a guanine nucleotide exchange factor for eIF2. The formation of eIF2-GTP is required for translation initiation . eIF2B aIn the past, the diagnosis of leukodystrophies relies mostly on the clinical course and brain imaging. Brain MRI is a crucial diagnostic step and helps determine the subgroup of leukodystrophies; however, the characteristics of brain MRI may not be able to distinguish specific leukodystrophies . The recIn conclusion, we report a patient with leukodystrophy. CACH/VWM was diagnosed based on targeted sequencing, elucidating the role of genetic diagnosis in patients with leukodystrophies.


Oral Submucous fibrosis (OSMF) is a chronic insidious disease of oral mucosa that occurs due to areca-nut chewing, consumption of chillies, autoimmunity and genetic predisposition. The disease starts with burning sensation and inability to tolerate spicy foods with gradual reduction in mouth opening due to fibrosis of the oral mucosa. The extension of fibrosis into the naso pharynx leads to reduction in hearing efficiency. As very few studies had been done to evaluate the hearing disability in OSMF patients, this study had been undertaken to prove the same. To evaluate hearing efficiency in patients with Oral Submucous Fibrosis of various grades of severity. Presentation includes 30 patients of osmf with various grades and evaluated for hearing efficacy by audiometry. Hearing threshold was compared in different grades of osmf. The present study revealed a significant association between OSMF and hearing deficit. Involvement of the palatal muscles with OSMF may decrease the patency of the Eustachian tube, leading to conductive hearing loss. Therefore, the protocol for managing OSMF patients should include ENT consultation and treatment for hearing deficit in order to increase the success rate of treatment. Oral submucous fibrosis (OSMF) is a chronic insidious disease, affecting any part of the oral cavity and sometimes the pharynx. Although occasionally preceded by and/or associated with vesicle formation, it is always associated with a juxta-epithelial inflammatory reaction followed by fibroelastic changes of the lamina propria, with epithelial atrophy leading to stiffness of the oral mucosa and causing trismus and inability to eat , 2.Symptoms of this disease include burning sensation of the oral mucosa, ulceration and pain, reduced movement and depapillation of tongue, blanching and leathery texture of oral mucosa, loss of pigmentation of oral mucosa, and progressive reduction of mouth opening. Advanced cases show signs of loss of hearing due to blockage of eustachian tubes and difficulty swallowing because of esophageal fibrosis .Amongst structures communicating with the oral cavity the eustachian tube (pharyngotympanic tube) connects the middle ear cavity with the nasopharynx. Opening and closing functions of the eustachian tube are physiologically important . Normal However there is a paucity of information related to the involvement by fibrosis of areas adjoining the oral cavity eg. Ear (Eustachian tube), Oro-pharynx, Pharynx and very few studies available correlating the eustachian tube dysfunction with various clinical stages of OSMF and its association with increase or decrease in the severity of the disease process. Therefore, this study was designed to evaluate eustachian tube function in OSMF patients and to correlate it with various clinical stages of the disease which may be helpful in assessing the morbidity and in identifying the overall prognosis to find more appropriate therapeutic interventions , 4.The present study was carried out in the Department of Oral medicine and radiology, Government Dental College and Hospital Ahmedabad on 30 patients of OSMF after ethical approval by the Institutional Ethical Committee. After obtaining written informed consent, the clinical data of the patients was obtained by taking thorough case history and clinical examination. After the clinical examination, the diagnosis of OSMF was made on the basis of history and characteristic clinical features of the disease. Depending on the clinical findings, cases were divided into grade I, II and III. Burning sensation on hot and spicy food, blanching, palpable fibrosis of buccal mucosa and fibrosis of faucial pillars, pterygomandibular raphae and soft palate; Mouth opening 25–35 mm.Burning sensation on hot and spicy food; Palpable fibrosis of buccal mucosa, faucial pillars, pterygomandibular raphae and soft palate extends anteriorly to involve labial mucosa, floor of the mouth and tongue; Tongue movements are restricted to some extents; Loss of flexibility of buccal mucosa; Mouth opening 15 mm–25 mm.Burning sensation on absence of stimuli; Severe fibrosis of entire oral cavity; Severe restriction of tongue movements; Severe loss of flexibility of buccal mucosa; Circular band (fibrotic rim) around lips and mouth; Fibrosis of soft palate and shrunken uvula; Difficulty in swallowing and deglutition; Difficulty in speech and nasal voice; Restricted mouth opening less than 15 mm.10–15 dB—Normal Hearing.16–25 dB—Minimal Hearing Loss.26–40 dB—Mild.41–55 dB—Moderate.56–70 dB—Moderate to Severe.71–90 dB—Severe.Above 90 dB is profound deafness.Examination of the ear was done in ENT Department and they were ruled out other causes of hearing loss such as tympanic membrane perforation, cholesteatoma, previous surgery and ear infections. Pure tone audiometry (PTA) was performed in all selected cases. Both the right and left ears  were evaluated for hearing loss. Hearing level in decibel above the normal threshold is plotted. Fig. a, b, c TAll subjects were evaluated for hearing loss according to age, and grades of OSMF and it tabulated as shown below.OSMF is predominantly a disease of the oral cavity and oropharynx. The disease is characterized by progressive fibrosis involving the mucus membrane of the mouth, mainly the buccal mucosa, soft palate, lip mucosa, and anterior pillars. It rarely affects the membrane lining of the pharyngeal box or vocal cords, but is capable of involving the eustachian tube , 5–7. ItP ≤ 0.005) Most of these patients were in the second and third decade of life [83.33%] patients being in the age group of 15–45 years. This is in accordance with the studies by Gupta et al. and Shah et al. [OSMF mainly affects in the second and third decades of life having male predominance , 5, 7. Th et al. , 7.TableP > 0.05).Table In the present study there was significant difference noticed in hearing loss for group 1 and group 3 (early OSMF and severe OSMF) Group 3 was significantly associated with moderate hearing loss as compared with any other group in both the right and left ears. These results were in accordance with those of Chaudhary et al. Dysfunction of the eustachian tube in OSMF may be due to fibrosis of the palatal muscles.Palatal involvement is seen in more than 50% of patients with fibrosis evident in the faucial pillars. Involvement of the palatal and paratubal muscles , which regulate the patency and function of the pharyngeal orifice. Fig.  In OSMF P > 0.05. Hearing efficiency reduces as age advances. Therefore it might be a compounding factor too.Table Involvement of the palatal muscles with OSMF may decrease the patency of the Eustachian tube, leading to conductive hearing loss. Therefore, as the test is non-invasive, painless and less time consuming, it can be effectively used for educating the patient, which may be helpful in assessing the morbidity and in identifying the overall prognosis to find more appropriate therapeutic interventions for hearing deficit in order to increase the success rate of treatment.


Arabidopsis plant, we could use a gene-relatedness search to pinpoint only those genes residing within the relevant regions of the genome in both species. Follow-up tests verified the identity of four genes that modify root gravitropism. The new information could help us understand how gravity shapes root system architectures.Plants use the Earth’s gravitational field to orient their growth, but there are large gaps in our understanding of the mechanism. We measured thousands of corn seedling roots, changing their growth direction in response to gravity (gravitropism) with machine vision methods, and we used genetic information about the seedlings to coarsely map the genomic positions of influential genes. Because we had previously performed the same experiment with the distantly related  Zea mays (maize) recombinant inbred lines with machine vision and compared the results with those obtained in a similar study of Arabidopsis thaliana. Each of the several quantitative trait loci that we mapped in both species spanned many hundreds of genes, too many to test individually for causality. We reasoned that orthologous genes may be responsible for natural variation in monocot and dicot root gravitropism. If so, pairs of orthologous genes affecting gravitropism may be present within the maize and Arabidopsis QTL intervals. A reciprocal comparison of sequences within the QTL intervals identified seven pairs of such one-to-one orthologs. Analysis of knockout mutants demonstrated a role in gravitropism for four of the seven: CCT2 functions in phosphatidylcholine biosynthesis, ATG5 functions in membrane remodeling during autophagy, UGP2 produces the substrate for cellulose and callose polymer extension, and FAMA is a transcription factor. Automated phenotyping enabled this discovery of four naturally varying components of a conserved process (gravitropism) by making it feasible to conduct the same large-scale experiment in two species.Plants typically orient their organs with respect to the Earth’s gravity field by a dynamic process called gravitropism. To discover conserved genetic elements affecting seedling root gravitropism, we measured the process in a set of  Gravity provides a constant guide for plant growth on Earth. A plant determines the direction of the gravity vector primarily by registering where dense plastids called statoliths settle in some endodermal cells of shoots and cap cells of roots . In rootDRO1, which is related to the LAZY genes in Arabidopsis that are required for gravitropism . The genomic intervals that Moore et al. (Zea mays (maize) as the monocot to compare with the previous Moore et al. .We created a custom image-acquisition platform that made it feasible to measure maize root gravitropism in the Intermated B73 x Mo17 (IBM) population of RILs. Each computer-controlled camera in the platform acquired images every 3 min beginning when the seedlings were rotated 90° to initiate a gravitropic response . The B73 and Mo17 inbred parents displayed significantly different gravitropism time courses  detected in the three maize datasets.The stepwise QTL method  as impleSI Appendix, Table S2). The 10 tQTLs that matched pQTL were long-lasting, averaging 44 ± 9 min. The tQTL that were not also detected by parameter analysis persisted on average only 4 ± 5 min. Thus, genetic loci that affected gravitropism for many minutes were more likely to be detected by a parameter-trait analysis. Some pQTLs for µ such as Chr1-1, Chr8-1, and Chr10-1 were evident as tQTL during the curvature development phase. Variation in these loci may represent variation in the mechanism that establishes differential growth across the root. In contrast, pQTL for λ such as Chr3-1 and Chr9-2 matched tQTL that appeared early in the time course. These may reflect genetic variation in the gravity-signaling mechanism that precedes differential growth. QTL for the overshoot (P-A) trait, such as the late-appearing Chr2-1, may play a role in swinging the root tip back after peaking.We fit logistics and Gompertz sigmoidal functions to the mean response curve of each RIL to produce three parameters that could be mapped as quantitative traits. Lambda (λ) is a measure of the response lag phase, µ is the maximum slope, and A is the final (steady state) angle. A spline-fitting method quantified P, the peak angle in time courses that displayed an overshoot phase. Subtracting A from P produced a measure of the overshoot that we treated as a phenotype to map. We also measured the integral (I) of each fitted curve. Using these fit-based metrics as phenotypes, we mapped 14 different parameter QTLs, or pQTLs . The analogous Moore et al. study  sequence similarity search  gravitropism QTL intervals. From 233 Arabidopsis candidate genes and 5,483 maize candidate genes, the search identified only 7 BBH pairs  for each of the four genes. SI Appendix, Table S3 also shows expression information for each of the four genes.The QTL intervals were broad. Two contained >1,000 gene models and 12 contained >100  and heterozygous (FAMA/fama) root responses were indistinguishable, but homozygous mutant siblings (fama/fama) showed an overshoot in the tip angle curve  wild-type background  in GK_061G06 than in wild type. If the overexpressed mRNA produces more active ATG5 protein, then this mutant further supports our conclusion that ATG5 affects root curvature during gravitropism and that the ATG5 gene is responsible for the Chr5-2 QTL in maize and 5@61 in Arabidopsis. The elongation rates were not significantly different , we identified two potentially causal genes using the reciprocal sequence comparison method  also did not display a gravitropism phenotype, compared to the W22 wild type  that evolution subsequently involved in one lineage but not another. A QTL orthology approach would probably not be effective if the species being compared were more closely related and their genomes more syntenic, nor would it be expected to identify genes that participate in a process that was poorly conserved between them. Gravitropism may be especially amenable to study by a QTL orthology approach because it would have been key to the original specialization of shoots and roots after the successful colonization of land, and at least within seed plants, it appears to be based on a homologous architecture of statolith-based sensing in the root tip and auxin redistribution in a more basal growth zone . The QTLATG5, CCT2, FAMA, and UGP2  for orthology identification discriminates well against genes with one-to-many or many-to-many orthology relationships, although it is prone to false-negative errors . An apprand UGP2 .atg5 mutants. Jiménez-Nopala et al. . ATG5 is expressed in the columella, meristem, and elongation zone cells of Arabidopsis roots . The primary root of 3-d-old maize seedlings, the same stage used in this study, contains significant amounts of ATG5 mRNA . The ATG5 protein was not detected in the maize seedling root, but it was evident in the germinating kernel .ATG5 plays a rate-limiting role in the formation of autophagosomes, which are membrane-delimited structures that degrade and recycle cellular components . A compla et al.  reportedis roots  . Perhaps variation in CCT2 expression in roots varies a membrane property or changes the production of a signaling factor important to gravitropism.The CCT2 enzyme associates with the face of lipid bilayers in some membranes. Its activity maintains the characteristically high percentage of PC relative to other phospholipid species in membranes. s >50%/h . Perhapse leaves , so it me leaves . Knockinr vision . The QTLArabidopsis cotyledons, where it ceases division of stomatal cell precursors and promotes guard cell differentiation . Perhaps some effect of FAMA action in cotyledons influences how roots respond to a gravity stimulus. Alternatively, a low level of FAMA in roots may directly participate in the gravitropism mechanism. This possibility is supported by the finding that FLP and MYB88, two other bHLH transcriptions that function in stomatal development at the same stage as FAMA, affect gravitropism and the expression of PIN auxin efflux transporters , consistent with our measurements of greater root elongation .The QTL that contains ild type , 27. UGPongation  and a pr mutants , but the mutants , so whetArabidopsis or maize, even though the very closely related PIP5K2 (At1g77740) has been shown to play a role in gravitropism (pip5k1pip5k2 double mutants have an even clearer gravitropism phenotype than the pip5k2 single mutant (PIP5K1 in maize and Arabidopsis is the cause of QTL Chr5-1 (1@64), then the lack of a gravitropism phenotype in pip5k1 mutants may be due to the genetic backgrounds of the alleles (Col-0 in Arabidopsis and W22 in maize) being different from the populations used to map the QTL. Ideally, reverse genetic tests of candidate genes would be performed in the genetic backgrounds of the parent of the RILs used to map the QTL.Mutant analysis failed to confirm a gravitropism phenotype for PIP5K1 in either 2 At1g777 has beene mutant . If natuPrecisely measuring gravitropism in mapping populations of two distantly related species, identifying one-to-one orthologs within the QTL intervals by reciprocal BLAST, and testing their functions by reverse genetics identified genes not previously known to affect this fundamental process. As data-sharing infrastructure and open-data practices make reusing phenotype data more feasible, this approach may be found to be generally useful, enabling two QTL studies to be much more powerful than the sum of their results.cct2 Mutator transposon mutant in the B73 inbred background (mu-illumina_231033.6) was obtained from the Mu-illumina team (teosinte.uoregon.edu/mu-illumina/). The pip5k1 (mu1045297) Mu transposon maize mutant in the W22 inbred background was obtained through the maize gene database (The maize ina team  through database . Both mu−2 s−1) was applied so that germination and photomorphogenesis would proceed in the absence of any phototropic stimuli. Recording chambers, one per camera, were prepared using square Petri dishes (13.5 × 13 × 1.5 cm) and 1% agar with no added nutrients. Removal of an upper portion of the agar in the dish produced an empty headspace and a horizontal agar ledge. Seedlings having a root between 5 and 15 mm were removed from the germination box and placed on the agar ledge of the recording plate such that the roots could grow down along the surface of the vertical agar slab. The original orientation of the primary root, which was not always vertical, was maintained as best as possible during transfer to the measuring plate. Up to eight seedlings were spaced along the ledge of one recording plate.Maize kernels were submerged in continuously aerated deionized water maintained at 28 °C. All of the subsequent steps were performed in a photobiology darkroom. Imbibed kernels were mounted on a plastic strip that suspended the kernel tip-down, overlaid with wet paper (Kimwipe), and placed in a clear plastic box (16 × 16 × 3 cm). Dim red light  to the shoot side of each kernel. The seedlings were maintained vertically in this fixture for 2 h before the plate was rotated by 90° within the frame of the fixture to induce gravitropism. The top-edge red LEDs were switched off and a row of red LEDs on the side of the frame was switched on so that red light continued to illuminate the shoot side of each seedling. A computer collected and stored images from each of the 7 cameras every 3 min for 3 h. A completely automated method identified each root tip at each time point in the series and measured its angle. The image processing and machine learning-based method is presented in SI Appendix, SI Methods.A bank of seven Marlin F-146B charge-coupled device cameras (AVT Corporation) collected images of seedlings on seven agar plates, each held vertically in a sample holding fixture. Each camera was equipped with an 18-mm focal length lens , which produced an image of the entire plate at a resolution of 10 pixels per millimeter. A longpass filter made with infrared-transmitting Plexiglas  was placed in front of the lens. A custom-built array of infrared light-emitting diodes (LEDs) having a peak output at 940 nm backlit each translucent agar plate. Each camera thereby collected an image of the seedlings using infrared radiation delivered from behind the sample. The top edge of the square-frame fixture holding the sample plates was fitted with LEDs that provided continuous dim red light  were identified using Perl scripts to perform reciprocal protein-protein BLAST   of the pus pairs  were calArabidopsis (Col-0) was transformed with the construct by floral dipping  and its sequence was confirmed to be identical to that in the wild type, N60000 (Col-0). The verified fragment was inserted into the PacI/AgeI site of the pEGAD vector . Arabido dipping .SI Appendix, Table S4. For genotyping of the maize mutant alleles, genomic DNA was extracted using the cetyltrimethylammonium bromide (CTAB) method as previously described  using the KAPA SYBR FAST one-step qRT-PCR kit (Roche). Beta-TUB  with RNase-Free DNase Set (Qiagen). For Beta-TUB  and ACT8Beta-TUB  were useFor confocal imaging, roots were stained with propidium iodide (10 µg/mL) for 5 min. pCCT2:CCT2-eGFP (enhanced green fluorescent protein) was observed by the Zeiss 780 confocal laser scanning microscope. We used the optics C-Apochromat 40x/1.1 W Korr M27 lens. The excitation-emission settings used for eGFP and propidium iodide were excitation 488 nm, emission 536 nm and excitation 561 nm, and emission 648 nm, respectively. A Zeiss AxioZoom was used to collect an image of fluorescence from the entire root. The pCCT2:CCT2-eGFP was visualized using a short-wavelength emission filter set .https://www.arabidopsis.org (file “Araport11_GFF3_genes_transposons.May2022.gff.gz”). Finally, the multiple alignment between the DNA sequences of the three accessions was carried out with MAFFT version 7 (https://benchling.com).We obtained the Ler-0 and Cvi-0 genome assemblies with their corresponding gene annotations from Jiao and Schneeberger . The locersion 7  and visuSupplementary FileSupplementary File


Ginkgo biloba extract during the 12 days of hospitalization. The clinical and audiometric profiles were compared between recovered patients and their unrecovered counterparts. The overall recovery rate was 57.3% in the study. Accompanying vertigo  and body mass index  were two independent predictors of hearing outcomes of the therapy. The male gender and cigarette-smoking history were marginally associated with good hearing prognosis . Patients with BMI ≥ 22.4 kg/m2 had a better chance of hearing recovery (p = 0.02). Conclusions: Accompanying vertigo and low BMI (<22.4 kg/m2) were independently associated with poor prognosis for full-frequency ISSNHL in combination therapy. Male gender and cigarette-smoking history might be considered positive effects on hearing prognosis.We aimed to characterize the clinical profiles and short-term outcomes of adult patients with full-frequency idiopathic sudden sensorineural hearing loss (ISSNHL) treated uniformly with combination therapy, and to determine the prognostic predictors for the combination therapy. A total of 131 eligible cases hospitalized in our department from January 2018 to June 2021 were retrospectively reviewed. All enrolled cases received a standardized combination therapy employing intravenous methylprednisolone, batroxobin, and  Ginkgo biloba extract, and nerve growth factors (NGFs), are also selectively used among institutions [Sudden sensorineural hearing loss (SSNHL), defined as a rapid onset of sensorineural hearing loss of no less than 30 dB affecting at least three consecutive frequencies on an audiogram between 250 and 8000 Hz within 72 h , is a tyitutions ,7,8,9,10Ginkgo biloba extract has been recommended as the first-line option in treating full-frequency ISSNHL [Ginkgo biloba 761 (EGb 761), containing approximately 24% flavonoid and 6% terpenes lactones, could improve cochlear blood flow by promoting vasodilation. It also acts as an antioxidant to attenuate oxidative stress provoked in ISSNHL. Additionally, batroxobin is a thrombin-like serine protease isolated from the venom of the snakes Bothrops atrox and B. moojeni. It is applied in clinical treatment to the management of thrombotic conditions as a defibrinogenating agent [According to the affected frequencies on the audiogram, ISSNHL can be classified as low-frequency , high-frequency , and full-frequency , with different underlying etiology . In Chinng agent . HoweverIn this study, we aimed to report the clinical profiles and short-term hearing outcomes of patients with full-frequency ISSNHL receiving combination therapy and to determine the prognostic factors associated with hearing improvements.Adult patients diagnosed with unilateral full-frequency ISSNHL admitted to our department from January 2018 to June 2021 were enrolled in the study. The medical records were retrospectively investigated. Eligible subjects must not have had either a prior episode of SSNHL or a history of Ménière’s disease or other cochlear lesions, and must have received prompt treatment within two weeks of symptom onset. Otoscopy and audiometric examinations were performed in all involved patients, including pure tone and speech audiometry, tympanometry, distortion product otoacoustic emission (DPOAE), and auditory brainstem response (ABR), to confirm the diagnosis of ISSNHL. Magnetic resonance imaging (MRI) of the brain and internal auditory canals was also conducted to evaluate the presence of retrocochlear pathology. Those with middle ear diseases or abnormal MRI findings, such as labyrinthine hemorrhage, vestibular schwannoma, or other cerebellopontine angle tumors, were excluded. Patients with comorbidities of hypertension or diabetes, or taking any lipid-lowering drugs, anticoagulants, antiplatelet or fibrinolytic agents, were also excluded. Clinical data of all enrolled patients were collected and analyzed, including age, sex, laterality, the time to initial treatment, the severity of hearing loss, accompanying tinnitus, vertigo, and aural fullness, and cigarette-smoking history. Peripheral blood samples were obtained on admission for basic blood tests and biochemistry studies.Ginkgo biloba extract EGb 761 was infused intravenously at 87.5 mg/d.All enrolled patients received a standardized combination therapy during the 12 days of hospitalization. Methylprednisolone was dripped intravenously at 120 mg/d for the first four days, followed by a 40 mg taper every four days. Up to five shots of alternate-day batroxobin were given intravenously at 10 Bu for the first shot, then reduced to 5 Bu for the following shots. The plasma fibrinogen (Fg) level was closely monitored before each shot. Once the Fg level fell below 1.0 g/L, batroxobin injection was skipped to the next day to avoid the risk of hemorrhage. Additional Hearing thresholds were determined by measuring air conduction pure tone average (PTA) at 250, 500, 1000, 2000, 4000, and 8000 Hz. According to the revised grading system recently released by World Health Organization (WHO) , the sevt-test was carried out to compare the means of metric variables between two groups when complying with a normal distribution. Otherwise, non-parametric tests were used. The Pearson χ2 test was conducted to compare frequencies of categorical variables between different groups. Spearman’s rank correlation coefficient 𝜌 was used when one variable had a continuous normal distribution and the other was non-normally distributed. Kendall’s 𝜏 was calculated to measure correlations between two non-normally distributed variables. In addition, multivariate logistic regression was employed to determine the independent prognostic factors on early hearing outcomes. The receiver operating characteristic (ROC) curve was further used to calculate the optimal cut-off points  in the continuous variables predicting the hearing prognosis. Any p-value less than 0.05 was considered to be of statistical significance.Statistical analysis was performed using SPSS 22.0 software. The independent samples Clinical and audiometric profiles of the patients and their short-term hearing outcomesA total of 131 eligible patients were enrolled in the study, consisting of 74 (56.5%) males and 57 (43.5%) females, aged between 19 and 64 years old, with a median age of 47. Their clinical profiles are presented in χ2 = 0.593, df = 1, p = 0.441).Over 90% of enrolled patients had severe to complete hearing loss regarding their initial PTA. No adverse events were observed during treatment. Hearing outcomes were presented as follows according to CSOHNS criteria: 9 (6.9%) patients made a complete recovery; 23 (17.6%), a marked recovery; 43 (32.8%), a partial recovery; and 56 (42.7%), no recovery. The overall recovery rate of the enrolled patients was 57.3% in our study. The linear-by-linear association indicated no significant trend for hearing recovery with the alleviating severity of hearing loss . Similarly, patients with cigarette-smoking history revealed a better hearing prognosis . Furthermore, accompanying vertigo significantly reduced the hearing recovery rate . Other factors, including age, affected side, time to initial treatment, initial PTA, and presence of associated tinnitus and aural fullness seemed to have little impact on the hearing prognosis (p > 0.05).Univariate analysis demonstrated a higher recovery rate in male patients compared to female counterparts . The Mann–Whitney U test indicated a similar reduction in the fibrinogen levels between the two groups  of baseline plasma fibrinogen levels (Fg1) before the first shot of 10-Bu batroxobin a. The avCorrelation of body mass index (BMI) and serum lipid levels with hearing outcomes of the combination therapyt = 2.601, df = 129, p = 0.010). Furthermore, the BMI points were positively correlated with hearing gains in the presented study . Recovered patients were similar to their unrecovered counterparts in terms of serum TG levels . The male gender and cigarette-smoking history also seemed to be associated with a good hearing prognosis; however, their statistical significance levels were marginal . As shown in 2, predicting that patients with BMI ≥ 22.4 km/m2 tended to have hearing recovery after the therapy , all the enrolled patients were subdivided into four groups: V+B+, V+B-, V-B+, and V-B-. The overall recovery rate reached 75% (27/36) in the group of V-B+, but decreased to 62.5% (20/32) and 51.5% (17/33), respectively, in V-B- and V+B+. The lowest recovery rate of 36.7% (11/30) was found in V+B- . In parallel with this, V-B+ patients had the greatest hearing gain of 22.5 (36) dB, while the least hearing gain of 9.0 (15) dB was observed in V+B- counterparts  and BMI  . The mulThe majority of patients (59.5%) were middle-aged (46 to 65 years old); thus, age had little impact on the hearing outcomes in this study. Interestingly, a significantly higher hearing recovery rate was found in male patients than in female ones, and there was a more significant proportion of smoking patients in the recovered group. Multivariate analysis further revealed that both the male gender and cigarette-smoking history were marginally associated with a good hearing prognosis. Such findings have seldom been reported in the literature. There was an equal prevalence of ISSNHL between the left and right ears. No significant association was found between hearing recovery and affected sides, which aligns with the literature ,21. All The presence of vertigo at the time of symptom onset was proven to be an independent predictor for poor hearing prognosis in the presented study, which matches the finding from previous studies. Possible theories include occlusion of the internal auditory artery, labyrinthine membrane rupture, and concurrence of vestibular neuritis. Tinnitus was nearly a universal accompanying complaint among patients, and about half of the patients reported a feeling of ear fullness. There was no significant association of hearing recovery with either tinnitus or aural fullness. All these findings were already well-known ,22.Prior studies have stated that high BMI and serum TC concentration correlate with poor hearing recovery in corticosteroid therapy ,24. HoweThe discrepancy unveiled in our study could be partly explained by the cochlear microcirculation thrombosis theory. Theoretically, atherosclerosis, which induces vascular occlusion of coronary and cerebral arteries resulting in angina, myocardial infarction, and stroke, could play a similar role in blocking the terminal arteries supplying the cochlea, thus interrupting cochlear perfusion and eventually resulting in full-frequency ISSNHL . Obesity2). The findings from our study provide preliminary clinical guidance for physicians to make individualized treatment decisions for patients with full-frequency ISSNHL and support the theory of cochlear microcirculation disturbance as a vital cause of ISSNHL.Although this study is limited by its retrospective design, short observational window, and relatively small sample size, it is the first clinical research addressing the correlation of the short-term hearing outcomes of the triad combination therapy for full-frequency ISSNHL with atherosclerotic risk factors in Chinese patients, and suggesting that combination therapy could be recommended for full-frequency ISSNHL patients with a high BMI (≥ 22.4 km/m2) as two independent prognostic factors for poor hearing outcomes in combination therapy employing methylprednisolone, batroxobin, and Ginkgo biloba extract. Additionally, male patients and those with cigarette-smoking history may also tend to have better hearing outcomes after combination treatment.Our study identified the presence of concurrent vertigo and low BMI (<22.4 kg/m


The A1555G mitochondrial mutation is the main alteration associated with aminoglycoside-induced deafness.to investigate the prevalence of the A1555G mutation in patients sensorineural hearing loss patients with and without aminoglycosides antibiotic use.a study of 27 cases with deafness as the sample, and 100 neonates with normal hearing as the control group. DNA was extracted from blood leukocyte samples, and specific oligonucleotide primers were designed to amplify the cytochrome b gene and the region which encloses the A1555G mutation of the mitocondrial DNA using the polymerase chain reaction and restriction fragment length polymorphism.a cross-sectional case study.a region of the cytochrome b gene was amplified and the presence of the mtDNA was confirmed in all of the 127 cases. The A1555G mutation was not found in any of the 27 patients with hearing loss or the control group with 100 neonates.the results agree with studies stating that the A1555G mutation is not prevalent in the Americas. There is interest in establishing the real prevalence of this mutation and to investigate other mutations that may cause hearing loss, associated or not with the use of aminoglycosides, in the Brazilian population. It is estimated that in developed countries, one child in 750 births presents sensorineural hearing loss, and that one child in each 1,000 births becomes deaf before adulthood. The prevalence increases further and reaches 50% in octogenarians.Mitochondrial mutations, especially those in the 12S rRNA and tRNASer(UCN) genes, are important causes of non-syndromic sensorineural hearing loss in some population groups.Many studies have suggested that the A1555G mutation by nitrogenated base substitution generates a new pair of C-G bases, making the secondary structure of the human 12S rRNA gene strictly similar to the corresponding region of the E. coli 16S rRNA gene; this is referred to as the decoding bacterial rRNA region and an important action site for aminoglycosides.In contrast with systemic mitochondrial mutations, which usually affect only a fraction of all mitochondrial DNA molecules (heteroplasmia), mutations associated with non-syndromic sensorineural hearing loss are generally homoplasmic, and phenotypes may differ considerably among members of the same family, ranging from deep hearing loss to normal hearing. Many factors, such as nuclear genes, mitochondrial DNA haplotypes, environmental factors or tissue-specific factors, may operate independently or in association, and may alter the clinical expression. However, research has not found nuclear modifying genes or correlations among mutations and mitochondrial haplotypes. The only known environmental factors affecting the A1555G mutation are the aminoglycosides.Although mitochondrial mutations are etiologically relevant in sensorineural hearing loss, few studies have been made in developing countries, especially in Brazil. The purpose of this study, therefore, was to investigate the prevalence of the mitochondrial A1555G mutation in patients with non-syndromic sensorineural hearing loss with and with no exposure to aminoglycosides.A cross-sectional study was made between September and October 2006 of 20 index cases of non-syndromic sensorineural hearing loss  aged from 1 to 37 years, previously submitted to GJB2 gene and D(GJB6-D13S1830) mutation molecular analysis; the cases had no molecular changes.A complete history was taken from each patient to investigate the age of onset of hearing loss, other cases in the family, the use of ototoxic drugs (aminoglycosides), and to exclude other environmental causes such as maternal-fetal infections, perinatal complications, meningitis, acoustic trauma and consanguineous marriages. Patients underwent a physical examination  and laboratory exams, to exclude syndromic forms of hearing loss . Other tests were an ophthalmologic evaluation (including fundoscopy), vestibular tests, and temporal bone computed tomography. Thus, a complete clinical assessment was made to exclude patients with hearing loss due to environmental factors except for aminoglycoside use, consanguinity, congenital inner ear malformations and genetic syndromes. Audiological testing consisted of pure tone audiometry, based on which patients with non-syndromic sensorineural hearing loss were included in the study and classified as mild (25–40 dB), moderate (41–60 dB), severe (61–80 dB) or profound (>81 dB).HLG group Ipatients that used aminoglycosides (n=13).HLG group IIpatients that did not use aminoglycosides (n=14).The patients in the sample were identified as the Hearing Loss Group (HLG) and divided into two subgroups:One hundred term neonates with one-minute Apgar scores ≥7 and normal otoacoustic emissions tests (done within three days of birth) were selected as the control group (CG).The Research Ethics Committee of our institution approved this study (protocol nº 2784/2006). Parents or legal caretakers read and signed a free informed consent form, after which 4.0 ml of whole blood  was taken and placed on a VacutainerÒ tube containing anticoagulant (EDTA). Genomic DNA was extracted from the blood samples of both groups using the GFXTM Genomic Blood DNA Purification Kit (Amersham Pharmacia Biotech Inc.) according to the manufacturer’s instructions. Mitochondrial DNA fragments including the mutation region were amplified using the polymerase chain reaction (PCR) technique in a thermocycler (Applied Biosystems - GeneAmp PCR System 9700Ò) to detect the A1555G mutation.A 643 bp fragment was amplified as a PCR product and then submitted to restriction fragment length polymorphism (RFLP) analysis, using the BsmAIA second primer pair was also synthesized to amplify a specific cytochrome b region.Both primer pairs used in the PCR include regions in the “Human Mitochondrial DNA Revised Cambridge Reference Sequence.”The products of both reactions (PCR and RFLP) were analyzed using 2% agarose gel electrophoresis in a TBE 1X buffer containing ethidium bromide, at 0.5mg/mL concentration, submitted to ultraviolet light, to confirm the success of the reaction and gel; photographic documentation was done.A pilot study was done to assess 100 newborns to estimate the proportion (p) of probable A1555G mutation carriers in the initial sample. The statistical formula “sample size with a known population” was applied to the proportion (p) to obtain the final sample size (n) needed for statistically representing the total population (Np) of newborns born within the study period (Np=352 neonates). The final sample (n) was calculated using the abovementioned statistical formula with the following parameters: p=0.00 (estimated by the pilot sample); q=1.00; zc=3.00 (99.74% reliability); e=0.03 (3% estimated error); Np=352 (population size within the study period).2 × p × q × NpFormula: n = zc2 × (Np - 1) zc2 × p × qeResults were expressed as percentages.PCR was done for amplification of the b cytochrome gene region to visualize the corresponding 161 bp fragment to confirm the presence of mitochondrial DNA in all 127 samples of the study - 100% (HLG I and II groups - n=27 and the control group - n=100).PCR enabled amplification of the mitochondrial DNA 643 bp fragment encompassing the mutation area in all of the samples (100%) of HLG I and II groups (n=27) and the control group (n=100).The A1555G mitochondrial mutation was not found in the study sample (100%); 413 bp and 230 bp fragments were found after enzymatic digestion, which were amplified in the absence of mutation in all samples within both groups (HLG I and II groups - n=27 and the control group - n=100).Clinical and audiometric data from the index cases, such as sex, age, onset and degree of hearing loss, use of aminoglycosides and family cases are shown in Research in population groups in various European countries has found that conexin 26 (Cx26) gene mutations may cause hearing loss in a significant proportion of cases. Continued research has led to the discovery of other mutations, which has made possible molecular etiological identification in many patients; thus, early rehabilitation and genetic counseling have become feasible in these cases. It is interesting to note that the frequency of genes and mutations that cause hearing loss varies significantly among populations. The 35delG mutation in the Cx26 gene, for example, is highly prevalent among deaf persons of European descent,16Similarly, the frequency of mitochondrial mutations also differs among populations; the A1555G mutation is found mostly in patients with maternally inherited hearing loss, although it has been sporadically identified in patients with hereditary autosomal recessive conditions. There are major differences in ethnic origin in both transmission modes, as revealed by recent studies showing the mutation to be a frequent cause of non-syndromic hearing loss, associated or not with aminoglycoside use, in Asian,25A study in 32 Asians with hearing loss and in 100 American controls  found the A1555G mutation in 87.5% of Asians that were deaf, and in none of the subjects in the control group, concluding that the mutation is not prevalent in non-Asian populations.Two mutation screening program have been done in neonates in the USA. The first of these sampled umbilical cord blood of 1,773 neonates, of which only one carried the mutation.Our method has already been described in the literature;11 it includes amplifying a specific cytochrome b gene region - a highly conserved mitochondrial genome area - to serve as an amplification control for identifying mitochondrial DNA in all of the samples.29There is a single study in Brazil reporting the findings of five families with hearing loss cases in which the prevalence of the mutation was 2% (4 cases). Only one of these positive cases was associated with an assumed aminoglycoside exposure; no mutation was found in the control group composed by black, white or Asian (Japanese or Chinese) ethnic groups.Many mutations may result in hearing loss; the A1555G mitochondrial mutation, which is related to aminoglycoside use, may be only one of them.The PCR/RFLP molecular techniques, such as the protocol we used in this study, are simple methods for tracking the A1555G mutation, supporting the molecular investigation of hearing loss.There has been considerable interest in establishing the true prevalence of the A1555G mitochondrial mutation in the Brazilian population by means of molecular testing, as well as investigating other mutations that may result in hearing loss associated or not with aminoglycoside use. These tests may become a valuable adjunct for neonatal audiometric screening.


Age-related hearing loss, mental health conditions, and loneliness commonly affect older adults. This study aimed to determine whether untreated hearing loss is independently associated with depression, anxiety, stress, and loneliness in tonal language-speaking older adults in China.Observational, cross-sectional study.M = 70.33 ± 4.90 years; 182 females, M = 69.02 ± 4.08 years) were recruited. All participants completed a pure tone audiometric hearing assessment, and provided information on living arrangements, marital status, leisure activities, tobacco and alcohol use, and medical history. The Mandarin version of the De Jong Gierveld Loneliness Scale was used to measure loneliness, and the Mandarin version of the 21-item Depression Anxiety Stress Scale (DASS-21) was used to assess a range of symptoms common to depression, stress, and anxiety of the participants. The analysis focused on determining the predictors of depression, anxiety, and stress, and the predictors of measures of loneliness.293 older adults  and living status  significantly predicted DASS depression scores; emotional loneliness  and a history of vascular disease  were significantly related to DASS anxiety scores; emotional loneliness  and a history of vascular disease  significantly predicted DASS stress scores. Furthermore, multiple stepwise regression analyses showed that DASS stress scores , education years , marriage status , and a history of vascular disease  significantly predicted emotional loneliness; four-frequency average hearing loss  and DASS stress scores  significantly predicted social loneliness scale; and four-frequency average hearing loss  and DASS stress scores  also significantly predicted overall loneliness. There were no significant associations with high-frequency hearing loss.Multiple stepwise regression analyses revealed that the emotional loneliness (This study revealed that loneliness has a significant relationship both with hearing loss and aspects of mental health in an older adult Mandarin-speaking population. However, mental health was not significantly associated with hearing loss in this population. The increasing human lifespan has resulted in a growing number of older people with health problems associated with aging. According to World Health Organization (WHO), in 2019, the number of people aged 65 years and above was estimated to be 703 million, which is expected to double in 2050. Most of the estimated increase in population is expected to occur in Eastern and South-Eastern Asia . China hWorldwide more than 1.5 billion people experience some degree of hearing loss, equivalent to 20% of the global population, of whom at least 430 million have a hearing loss of moderate or higher severity in the better ear . For oldIt is estimated that 4.4% of the global population suffers from depressive disorders , and 3.6Recent evidence suggests that there is a relationship between hearing loss and depression in non-tonal language speakers in Western countries . PreviouLoneliness is a subjective negative feeling associated with perceived limitations in a wider social network  or the absence of a specific desired companion or relationship  . ApproxiAlthough loneliness is experienced by people across the world regardless of culture, gender, and age, there are substantial differences across cultures in the ways loneliness is experienced and coped with . For exaTraditional and contemporary Chinese culture places great importance on family members’ dependence, marital mutual support, and filial piety of offspring . With thMandarin is the dominant dialect of what is commonly known as Chinese, and is considered the standard language in China. The Chinese (or Sinitic) family of dialects is tonal in nature. Tonal languages employ lexical tones or pitch variations to indicate different meanings at the suprasegmental level . The numAs it is the case for the implications of culture on the relationship between hearing loss and aspects of mental health and loneliness, the influence of tonal language on these associations has not been properly explored yet. A cross-sectional study investigated the impact of hearing loss on loneliness in older people in China, showing that living arrangements had a significant modifying effect on loneliness . Having The nature of tonal languages also suggests further investigation is required into hearing sensitivity in the different bands of frequencies. For the most part, studies in non-tonal language settings that have investigated the association between hearing loss and mental health in older adults, have employed the average of the pure-tone hearing thresholds between 0.5 and 4 kHz (speech-frequency) or even self-reported hearing impairment  as measuThe purpose of this study was to determine whether untreated hearing loss is independently associated with depression, anxiety, stress , and loneliness in Mandarin-speaking older adults in China.The protocols for this study have previously been reported for a study on hearing loss and cognitive function in an adult Chinese population . ParticiNative Mandarin speakers aged 60 years and above were invited to participate in the study. Those not in a general state of good health, or unable to perform tasks required in the mental health evaluation session due to an underlying physical or mental condition, or those who had previously worn or currently wearing hearing aids or a hearing implant were excluded from the study, or those with single-side deafness were also excluded, which refers to subjects with severe-to-profound hearing loss on one side and normal hearing on the other side.After enrolment, all participants completed a baseline questionnaire capturing data on demographic characteristics , alcohol consumption  , smokingThe assessment of participants comprised measurements of hearing ability, loneliness, and mental health.Pure-tone audiometry (PTA) was assessed with an audiometer  and supra-aural earphone (TDH-39). For all participants, bilateral pure-tone air-conduction thresholds were measured at 0.25, 0.5, 1, 2, 4, 6, and 8 kHz; and bone-conduction thresholds were measured at 0.5, 1, 2, and 4 kHz, through a standard audiometric assessment conducted by a qualified audiologist in a soundproof booth at the audiology center of the Beijing Institute of Otolaryngology.Hearing loss data were summarized by two different methods: four frequency average of hearing thresholds at 0.5, 1, 2, and 4 kHz (speech frequencies), and the three high-frequency average of hearing thresholds at 4, 6, and 8 kHz (high frequencies), noted, respectively, as 4FA and 3HFA. In both cases, the value for the better ear was used for further analysis, being a measure of bilateral hearing loss. These were analyzed as continuous variables. Furthermore, for the purpose of describing the hearing loss of the study cohort, the 4FA hearing loss was classified using the World Health Organization (WHO) grades of hearing impairment , respectThe Mandarin version of the six-item De Jong Gierveld Loneliness Scale was used to measure the loneliness of the participants . In thisThe Depression Anxiety Stress Scales (DASS-21) is a 21-item questionnaire used to assess the symptoms of depression, anxiety, and stress . A ChineAll statistical analyses were performed using SPSS version 25 . The Kruskal Wallis H test for non-normally distributed data was used to investigate whether DASS-21, and loneliness scores were significantly different across three groups of participants classified by the severity of hearing loss .p < 0.1 were included in the multiple regression analyses.A multiple forward stepwise regression analysis was firstly used to examine the relationship among mental health-related variables  as the dependent variables, and these independent variables: age, gender, chronic medical history, education, 4FA, 3HFA, self-reported hearing loss, living status, marital status, emotional loneliness, social loneliness, overall loneliness, and the four activity scores . The collinearities of factors were examined for each stepwise regression analysis, by using the variance inflation factor (VIF). Univariate ANOVA was used to test each independent variable against each of the dependent variables. Only those with p < 0.1 were included in the multiple forward regression analysis. The candidate independent variables were age, gender, chronic medical history, clinically diagnosed depression, education, 4FA, 3HFA, self-reported hearing loss, living status, marital status, DASS depression, DASS anxiety, DASS stress, and the four activity scores .Secondly, a similar multiple forward regression analysis was conducted to examine the relationship between loneliness and the other variables. Emotional loneliness, social loneliness, and overall loneliness scores were entered as dependent variables. For the independent variables, a univariate ANOVA was used to test each independent variable against the dependent variables, and only those with Multiple forward regression analysis was conducted to examine the relationship between mental health, loneliness, and the other independent variables, across the three classifications of hearing loss: normal, mild, and moderate, and moderately severe.A total of 293 people aged between 60 and 87 years were included in the study. The study cohort consisted of 111 males (mean age = 70.33 ± 4.90 years) and 182 females (mean age = 69.02 ± 4.08 years). A summary of the demographic information, classifications of hearing, mental health scores, loneliness scales, and other descriptive data of this study population are presented in p < 0.05) between the three hearing loss groups, but not between emotional loneliness and hearing loss , and social and overall loneliness were significantly different (loss see .p > 0.1).Univariate ANOVA indicated for the following variables to be included in the multiple stepwise regression analysis; (i) For DASS depression: emotional loneliness, overall loneliness, history of vascular disease, and living status, (ii) for DASS anxiety: emotional loneliness, overall loneliness, and history of vascular disease, (iii) for DASS stress: emotional loneliness, social loneliness, overall loneliness, and history of vascular disease, (iv) for emotional loneliness: DASS depression, DASS anxiety, DASS stress, education years, marital status, history of vascular disease, 4FA, recreational activities, and history of mental health, (v) for social loneliness, DASS depression, DASS stress, 4FA, 3HFA, recreational activities, and social activities, and (vi) for overall loneliness, DASS depression, DASS anxiety, DASS stress, 4FA, 3HFA, history of vascular disease, and the social activities. All other independent variables were not significantly associated (All the tolerances and variance inflation factor (VIF) values met the prerequisites for the multiple regression analysis, to exclude collinearity between predictors. Multiple stepwise regression analysis revealed the following significant predictor of the dependent variables see : (i) ForOnly the last model of the stepwise regression is shown in Regression analysis using the hearing loss classified by severity rather than hearing loss as a continuous variable showed similar results to the above, except that 4FA was not significantly related to loneliness scores in normal hearing and moderately severe or above hearing loss group see –S-10.This study investigated the association between untreated hearing loss and loneliness and mental health in Mandarin speaking older adults in China. To the best of our knowledge, this is the first study to examine the association between hearing loss, loneliness, and mental health by employing both speech-frequency and high-frequency audiometry in a Chinese-setting population.Our results revealed that whether speech or higher frequency losses were considered, mental health scores, including depression, anxiety, and stress were not significantly associated with hearing loss. Our findings in this tonal language population do not align with those of cross-sectional studies of pure-tone audiometric hearing loss and mental health in non-tonal language speakers . These rSex, education level, and marital status were not significantly associated with mental health in these Chinese participants. These findings are partially corroborated by a previous study in which gender, marital status, and education are not related to depression in a Chinese oldest-old population, although the mean age of the subjects in this study was higher .The loneliness scores from the present study were slightly higher than those reported by All three mental health scales were significantly associated with emotional loneliness, but not social loneliness . This asOur results also demonstrated that social and overall loneliness was significantly associated with speech-frequency hearing sensitivity. This finding accord with other studies, which have shown that greater hearing impairment was associated with greater degrees of loneliness . Two of The analysis showed that only speech-frequency hearing was associated with loneliness, not with the high frequency. High frequencies decline at least a decade earlier than the speech frequencies , which dStress was observed to be associated with both the two dimensions of loneliness and overall loneliness. In accordance with the present results, previous studies have demonstrated that stress is causally related to loneliness, and it is hypothesized that changes produced in the hypothalamic–pituitary-adrenocortical (HPA) axis is related to stress .This study contributes to the growing global body of evidence that loneliness was significantly associated with hearing loss and mental health in tonal language-speaking older adults in China. Given the high burden of loneliness and mental health problems, interventions to alleviate these problems for seniors may have significant public health impacts. Hearing may be a modifiable solution for loneliness. Both otolaryngologists and physicians should discuss the long-term benefits of hearing loss treatment when managing and counseling their patients.One of the limitations of the current study is that results are based on cross-sectional analyses rather than longitudinal assessments of hearing, loneliness, and mental health over time. Furthermore, the study would have benefited with the inclusion of more physically and mentally healthy participants, even though they are much more difficult to recruit from an older adult population. The study had a gender imbalance and had a relatively small sample size. Another limitation is that there were relatively fewer participants with untreated severe-to-profound hearing loss. These, too, are difficult to recruit from an older adult population. A longitudinal large-scale study, with a gender-balanced cohort that included physical and mental health participants, and a suitable representation of those with untreated severe to profound hearing loss, will help to examine a potential causal relationship between hearing loss, loneliness and mental health scores over time.Our research provides more evidence for the association between loneliness and hearing loss, and also between loneliness and mental health in Mandarin-speaking older adults in China. This study revealed that loneliness has a significant relationship with hearing loss and mental health in a Mandarin-speaking population.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by the University of Western Australia-Human Research Ethics Committee (RA/4/20/5538) and Beijing Tongren Hospital, Capital Medical University (TRECKY2019-090). The patients/participants provided their written informed consent to participate in this study.DJ and XF designed the experiments. XF carried out the experiments. XF, RE, DJ, SW, and BL analyzed the experimental data. XF wrote the manuscript. RE, DJ, SW, and BL reviewed the manuscript. All authors contributed to the article and approved the submitted version.This research was supported by the Reform and Development Grant of Beijing Institute of Otolaryngology, Natural Science Foundation of China (Grant No. 81200754), and National Key Research and Development Program (Grant No. 2020YFC2005200).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Hearing loss is a common problem that everyone faces at some point in their life. There are three main types of hearing loss: conductive, sensorineural, and mixed. Conductive hearing loss occurs when an external sound is not able to gain access to the inner ear because of some type of obstruction, e.g., cerumen in the auditory canal and fluid in the middle ear. Sensorineural hearing loss (SNHL) is due to damage to the inner ear, which affects the nerve conduction pathway from the inner ear to the brain. Mixed hearing loss is a combination of both conductive and sensorineural hearing loss. Sensorineural hearing loss (SNHL) is one of the most common types of hearing loss. A kiss on an external auditory canal can create a negative pressure that can affect the bones in the inner ear, therefore causing tinnitus and hearing loss. This case report will discuss sensorineural hearing loss ) caused by an innocent kiss on the patient’s ear. Sensorineural hearing loss (SNHL) is basically of two types: acquired and congenital. A congenital SNHL is usually genetic, and patients are born with this hearing loss. In some cases, prematurity and infections during pregnancy can be passed from mother to child and cause congenital hearing loss. An acquired SNHL is defined as a hearing loss later in life. Common causes of acquired SNHL include aging, noise, trauma, tumors, and medications. Usually, an acquired SNHL occurs gradually and later in life. Still, in some cases, patients develop sudden acquired SNHL or sudden sensory neural hearing loss (SSNHL), which causes deafness in the unilateral ear, e.g., trauma or an innocent loving kiss ,2.The patient is a 50-year-old female with a past medical history of only hypertension controlled on lisinopril 20 mg daily who presented to the hospital with a chief complaint of severe tinnitus and hearing loss in her right ear. The patient stated that she and her husband were watching a movie at home when her husband suddenly kissed her on the right ear. She stated that suddenly after the kiss, she had an almost complete hearing loss in the right ear along with severe tinnitus and nausea. The patient stated that this happened a few hours ago at home, and her tinnitus and hearing loss do not seem to be getting any better, so she decided to come to the hospital. The patient, in general, is healthy besides her hypertension, which is very well controlled on lisinopril 20 mg daily. She stated that she had a normal hearing before this episode. The patient has never worn any hearing aid. She has never had any significant ear infections in the past. She denied neurological symptoms such as headache, diplopia, vertigo, history of meningioma, cancer, autoimmune disease, vasculitis, history of Lyme disease, fever, or any changes in recent medications. The patient denied diabetes, stroke, recent infection, or any recent travel outside her state or outside the United States. The patient is a software engineer and works from home. The patient had a blood test performed, which was normal, as can be seen in Table On physical examination, the patient had a normal tympanic membrane, as can be seen in Figure There were no signs of trauma in either ear inside or outside. A full physical examination and skin check were performed, and no signs of physical abuse were found either. Cranial nerves II to XII are all intact. The patient then had CT temporal bone with the brain stem, and an MRI of the brain with contrast was performed as well, but no significant abnormalities were found. In the emergency room, an otolaryngologist was consulted, and the patient was admitted for nausea and severe tinnitus.The patient was given 4 mg of Zofran IV to help with nausea. The Weber and Rinne tests were performed by the otolaryngologist in the hospital, and the patient was found to have a sensorineural hearing loss only. She was also started on 60 mg prednisone daily by the otolaryngologist. The patient has then discharged from the hospital with a prescription for a tapering dose of prednisone over two weeks and a follow-up appointment with the otolaryngologist outpatient clinic the very next day. The patient had an audiogram performed, which showed a sensorineural hearing loss of 30 decibels (dB) at 500 and 1,000 Hz. The otolaryngologist stated that she had a decrease in stapedial reflex in the right ear, but normal reflex was present in the left ear.The patient was followed one week later to the outpatient clinic. She stated that she was feeling much better. There was a significant reduction in tinnitus since the incidents, but she can still hear it when she is alone. The patient followed up with ENT again and had the audiological evaluation performed, which showed that she still had sensorineural hearing loss from 15-20 DB at 1,000-2,000 Hz. The patient was advised by ENT to follow up again in two months for reevaluation. The patient stated that she was feeling much better and could work almost normally now.Sudden sensorineural hearing loss (SSNHL) usually presents as an acute unilateral hearing loss that is sensorineural in nature. Most cases of SSNHL are idiopathic, although it can also occur from multiple other reasons, e.g., infections, cancer, vascular diseases, metabolic, drugs, and trauma.A kiss on the patient’s external auditory canal creates a large vacuum or negative pressure, which causes an outward pressure on the tympanic membrane. This pressure on the tympanic membrane also creates negative pressure on the small ear bones attached to the tympanic membrane, i.e., stapes, incus, and malleus. This causes dislodging of the stapes in the inner ear, and the fluid in the inner ear  leaks out and causes damage to the hair cells, leading to tinnitus and hearing loss .The diagnostic criteria for SSNHL include diagnosing hearing loss as sensorineural, at least 30 dB of hearing loss, and loss of hearing within a 72-hour timeframe .Patients who presented with sudden hearing loss should be evaluated within the next few days after symptom onset. The first step is the evaluation of hearing loss itself; this can be achieved using audiometric equipment such as a tone-emitting otoscope or a whisper test. The next step is distinguishing sensorineural hearing loss from conductive hearing loss, which can be achieved by a simple Weber and Rinne test. A focused clinical history and physical examination must be performed on the patient who presents with suspected sudden sensorineural hearing loss (SSNHL), as was in this case. Audiometric testing is necessary to establish the diagnosis of sensorineural hearing loss. Also, an MRI of the brain must be performed with contrast to evaluate for any cochlear pathology .All patients who have SSNHL, including identifiable causes, should be treated with glucocorticoids. For example, patients who have identifiable causes of SSNHL such as meningitis should be treated with antibiotics along with steroids . TreatmeA sudden innocent kiss on a person’s external auditory canal can lead to sensorineural hearing loss, which can be devastating and life-altering for the patient. This is also known as Reiter’s ear kiss syndrome first described by Levi Reiter in 2008. Patients such as small children and infants have small and narrow ear canals and are, therefore, at higher risk of this hearing loss. Physicians, medical professionals, parents, and partners should be made aware of the risk associated with this innocent kiss. We should be able to quickly identify and start the treatment as soon as possible once the diagnosis is made to have a better chance of full recovery.