Triclosan (TCS), a kind of pharmaceuticals and personal care products (PPCPs), is widely used and has had a large production over years. It is an emerging pollutant in the water environment that has attracted global attention due to its toxic effects on organisms and aquatic ecosystems, and its concentrations in the water environment are expected to increase since the COVID-19 pandemic outbreak. Some researchers found that microbial degradation of TCS is an environmentally sustainable technique that results in the mineralization of large amounts of organic pollutants without toxic by-products. In this review, we focus on the fate of TCS in the water environment, the diversity of TCS-degrading microorganisms, biodegradation pathways and molecular mechanisms, in order to provide a reference for the efficient degradation of TCS and other PPCPs by microorganisms. Triclosan  phenol, TCS) is an antibacterial agent that has been widely used in detergents, cosmetics, soaps, toothpaste and other pharmaceuticals and personal care products (PPCPs) since it was first marketed in 1957 . TCS is TCS is a small molecular compound with controversial roles . The bacIn recent years, with the widespread use of TCS, the level of TCS in the water environment has been increasing, especially since the COVID-19 pandemic . WastewaWe searched literatures with the theme of “triclosan degradation”, “triclosan biodegradation”, and “triclosan degrading bacteria” in the Web of Science (WOS), and retrieved 1630 articles and 79 reviews, 375 articles and 24 reviews, and 92 articles and 2 reviews, respectively. We counted the number of literatures published on different topics from 2000–2021 . When wrTherefore, in this review, we focus on the research progress of TCS biodegradation by single microorganisms and microbial consortia, and discuss the research methods and future trends of TCS biodegradation, so as to understand the microbial-mediated TCS-biodegrading mechanisms in the water environment and its applications in remediation.TCS in the water environment comes from the use of the hospital disinfectants, factory production of PPCPs wastewater and the use of PPCPs by humans. Wastewater containing TCS is discharged into Wastewater Treatment Plants (WWTPs), part of which is degraded by microorganisms, another is discharged into natural water with the effluent of WWTPs, and the other is discharged into the soil in the form of excess activated sludge. TCS in the soil enters the surface water and groundwater through the action of rainwater, and the surface water and groundwater are used as reference water sources . The TCSp-dioxin, dibenzodioxin and phenol intermediates, which are harmful to the aquatic organisms by bioaccumulation  center, mostly composed of a terminal oxidase, reductase and ferredoxin [Sphingomonas sp. RD1 belongs to the Rieske-type two-component class IA aromatic dioxygenase Dioxygenasemeta-cleavage pathway of TCS. During TCS degradation, it was found that only the activity of C23O, not catechol 1,2-dioxygenase (C12O), was detected in the cell extract of Sphingopyxis sp. KCY1 (specific enzyme activity = 337 nmol min−1 mg protein−1) [meta-cleavage reactions) at 23 h [−1) in the cell-free extract of Pseudomonas aeruginosa KS2002, and TCS degradation was also ceased in the presence of 3-flurocatechol. These results indicate that C23O is involved in TCS biodegradation via meta-cleavage pathway.Dioxygenases catalyze the incorporation of both oxygen atoms into substrate. According to the catalytic properties, they can be divided into catechol dioxygenases, dihydroxylated aromatic dioxygenases, α-ketoglutarate-dependent dioxygenases, etc. Dioxygenase is involved in the aromatic ring-opening process of TCS biodegradation. Among them, catechol 2,3-dioxygenase (C23O) is involved in the otein−1) . Besides at 23 h . Kumari  at 23 h  detectedortho-cleavage pathway of TCS. Kumari et al. [−1) in the cell-free extract of Citrobacter freundii KS2003. In addition, TCS could not be degraded in the presence of 4-chlorcatechol, an inhibitor of C12O, suggesting that C12O was involved in the degradation of TCS via ortho-cleavage pathway [C12O is involved in the i et al.  detected pathway .(2)MonooxygenaseMycobacterium vaccae JOB5 and alkane monooxygenase (AlkMO) of Rhodococcus jostii RHA1 might be involved in the TCS degradation. Ammonia monooxygenase (AMO) can also degrade TCS [Nitrosomonas europaea and mixed AOB in nitrifying AS. The degradation was observed only in the absence of allylthiourea (an inhibitor for AMO), suggesting that AMO might be responsible for TCS biodegradation [In addition to dioxygenase, some monooxygenases also participate in the TCS biodegradation. Lee et al.  found th(3)Reductive dehalogenaseDehalococcoides mccartyi CG1 could metabolically dechlorinate TCS to diclosan in the AS of the WWTP [At present, only Zhao et al. have studied the dechlorination mechanism of TCS . Dehalocthe WWTP . Both ththe WWTP . A dechlthe WWTP .(4)OthersProvidencia rettgeri MB-IIT, indicating that MnP and LAC might concurrently participate to the TCS degradation.There are also other enzymes involved in the biodegradation of TCS. Balakrishnan et al.  reportedAt present, although many TCS-degrading microorganisms have been isolated, most studies have not been carried out at the molecular level. Subsequently, the enzyme involved in TCS degradation should be studied by molecular biological methods, and its specific function should be verified by gene knockout, complementation, and in vitro enzyme activity, so as to explore the molecular mechanisms of TCS biodegradation.TCS, as an emerging pollutant in the water environment, has attracted significant attention since the outbreak of the COVID-19 pandemic ,25,26,27By studying the interaction mechanisms between functional strains, TCS-degrading synthetic bacterial consortia can be constructed by a “Bottom-up” approach, thus providing the robustness of TCS degradation system and alleviating the stress pressure of environmental changes on TCS-degrading microorganisms.


The functional hearing outcome with hearing implants does not always properly reflect the subjective benefit in everyday listening situations. In this study, the functional hearing gain and the impact on the subjective hearing ability and quality of life were assessed in patients with a Bonebridge. A chart review was performed on 45 patients with a Bonebridge who were provided with questionnaires regarding the hearing quality and health-related quality of life during their last clinical visit. The questionnaires consisted of the Speech, Spatial and Qualities (SSQ) and the Health Utility Index Mark 3 (HUI3). Eleven patients had to be excluded due to missing data. A total of 34 patients (37 ears) were included in the study. Aided hearing thresholds were significantly lower compared with the unaided condition, with a mean functional gain of 26.87 dB for patients with mixed/conductive hearing loss (MHL/CHL). Although patients with single-sided deafness (SSD) scored slightly lower on the SSQ compared with patients with MHL/CHL, all included patients reported improved subjective hearing quality with the BB compared with the hearing situation before implantation. No correlation was found between the functional hearing gain and the subdomains of the SSQ. SSD patients scored the HUI3 subdomain “hearing” slightly lower compared with MHL/CHL patients. Although not significant, a relationship was found between the functional gain and the “hearing” subdomain. No correlation was found for the other subdomains of the HUI3. Audiological measurements showed significantly improved hearing thresholds with the Bonebridge. Most importantly, the subjective benefit achieved in everyday listening situations was superior compared with the previous hearing condition. The lack of correlation between subjective questionnaire results and the functional hearing gain shows the importance of assessing both audiological and subjective hearing quality parameters in clinical routine. Bone conduction implants (BCIs) have been used for the treatment of conductive and mixed hearing loss  as well as single-sided deafness (SSD). Though most people benefit from conventional hearing aids, some cannot wear them due to medical reasons such as chronic otitis media or atresia of the external ear canal. One of the most frequently used implantable devices is the Bonebridge (BB), which is a semi-implantable, transcutaneous bone conduction hearing aid introduced in 2012 . It is approved for CHL, MHL, and SSD in patients above the age of five years ,4. SoundAlthough the improved hearing outcome assessed by audiological measures was previously reported ,5, it doTo date, there are limited data on functional outcomes and the impact on the quality of life of transcutaneous bone conduction devices. An instrument for assessing the health-related QoL is the Health Utility Index (HUI), which is widely used to assess the cost-effectiveness of a treatment. The HUI was recommended for the assessment of health-related QoL in patients with SSD , and wasThe aim of the current study was to evaluate the functional hearing gain and the subjective benefit by means of questionnaires. The HUI was used to evaluate the QoL, and a modified version of the Speech, Spatial and Qualities Questionnaire (SSQ) was used to assess the subjective hearing performance in everyday listening situations.A retrospective chart review was performed in patients with an active bone conduction device, a Bonebridge implant , to assess whether there was a correlation between the functional hearing gain and the subjective hearing quality and QoL. Therefore, all patients implanted with a BB at the department of Otorhinolaryngology, Head and Neck Surgery, at a tertiary care hospital between 2012 and 2016 were assessed for eligibility. Inclusion criteria were implant experience of at least two years and complete data of either the Health Utility Index Mark 3 (HUI3) or the Speech, Spatial and Qualities (SSQ) questionnaire, or both. Exclusion criteria were implant experience of less than two years and missing data of both the HUI3 and SSQ questionnaire. We excluded 11 out of 45 patients from the study due to incomplete data on both questionnaires. Subsequently, a total of 34 patients (37 ears) were included for data analysis see . All incThe following parameters were collected from patients’ charts: preoperative pure-tone thresholds for air and bone conduction, the hearing threshold in sound field in the unaided and aided conditions, word recognition scores in the unaided and aided conditions, the SSQ questionnaire, and the HUI3. Audiological data were collected from measurements performed by the institution’s audiologists. The hearing quality and QoL questionnaires were introduced in clinical routine and were answered during regular follow-up visits.In clinical routine, audiological data were preoperatively and postoperatively assessed during regular follow-up visits. Air-conduction (AC) thresholds were measured for octave frequencies between 125 and 6000 Hertz (Hz), and bone-conduction (BC) thresholds were measured for octave frequencies between 250 and 6000 Hz. Sound field thresholds were assessed for octave frequencies between 250 and 6000 Hz in the unaided and aided conditions. Word recognition scores (WRS) were assessed in quiet using the German Freiburger monosyllable test at 65 decibel (dB) sound pressure level (SPL) and 80 dB, both in the unaided and aided conditions.For the current study, audiological data were collected from measurements preoperatively performed and at the last clinical visit. The HUI is a standardized questionnaire used to measure the health status and health-related QoL ,18. PatiThe SSQ used in this study was a modified version of the original SSQ , which ap value < 0.05 was considered to indicate statistical significance. To examine the relationship between functional hearing gain and subjective benefit, the Spearman’s rho correlation coefficient was calculated.Descriptive statistics such as mean and standard deviation are used to present and summarize the data. The functional hearing gain in MHL/CHL subjects was analyzed using a paired samples t test. The subscores of the modified SSQ questionnaire were analyzed with one-sample t-tests. Prior to that, the Shapiro–Wilk test was used to confirm whether the data were normally distributed. Due to the exploratory nature of this chart review, no correction for multiplicity was applied. A n =32 ears) and SSD (n = 5 ears) for frequencies with octave steps between 0.5 and 4 kHz (PTA4). As only five patients with SSD could be included, no inferential statistical analysis was performed for this group due to the very small sample size. As expected, in SSD subjects, the aided thresholds were considerably better compared with the preoperative AC thresholds of the implanted side. p < 0.0001).n = 26), yielding an average increase of 47.5%. WRS data were available for three SSD patients. In these patients, the mean increase at 65 dB SPL was 58% from 10% ± 7% unaided to 68% ± 11% aided.In total, the postoperative WRS of 29 patients was available for analysis, and are summarized in p = 0.35), spatial , or qualities  subdomains of the SSQ.The SSQ was used to assess the subjective hearing quality in everyday listening situations with the BB compared with the hearing situation before implantation. The total scores and subscores from the last clinical visit are separately depicted for CHL/MHL and SSD patients in HUI3 data were available from all 34 included patients who answered the questionnaire at their last clinical visit. The current audiological outcome is comparable to previous reported hearing gains with bone conduction devices. For patients with CHL/MHL, mean FGs have been reported to be 19.8–50.0 dB, and improvements in WRS ranged from 29.4% to 70.0% ,21,22,23Audiological data do not represent the individual hearing performance in everyday listening situations. How specific aspects of hearing are perceived by patients is frequently measured with the SSQ. Previously published data mostly reported on the original SSQ, in which patients score on a visual analogue scale between 0 and 10, representing complete inability to complete ability in different hearing situations. In the current study, the objective was to assess the subjective hearing benefit with the BB compared with the previous hearing situation, whether it was with a conventional hearing aid, a bone conduction hearing aid, or another implant. The results of the SSQ were generally positive, indicating that patients experienced subjective benefit with the BB compared with the previous hearing situation. Interestingly, the positive results on the SSQ did not correlate with the FG, indicating the importance of assessing both audiological and subjective measurements. Den Besten et al. reported improvements on all subscales, namely “speech hearing”, “spatial hearing”, and “qualities” with the Baha Attract System, though slightly lower pre- and postoperative scores and less improvement were found in SSD patients compared with listeners with CHL/MHL . As in tThe highest scores were assessed for the “speech” and “qualities” domains for patients with CHL/MHL, but slightly lower scores for patients with SSD. These findings are also in line with the results reported by Hougaard et al., with lowest scores in the “spatial” domain for both the CHL/MHL and SSD patients . Laske eA systematic review found limited evidence regarding the QoL benefit of bone-anchored hearing aids . The HUILooking closer to the “hearing” domain, patients with CHL/MHL scored 0.65. This is slightly lower than for a group of patients examined by den Besten . The autA study performed by Schwartz et al. showed a “higher” multi-attribute score of 0.70 based on the HUI3 for unilateral deaf patients with a BAHA compared with the current results . This diThe bias of the current study resulting from recalling the hearing situation before the surgery can be probably neglected as other authors came to similar QoL results, whether it was retrospectively or prospectively assessed ,30. PatiIn conclusion, patients with a BB significantly improved in their aided hearing condition compared with the unaided situation. Although patients with a BB rated their subjective hearing quality better compared with their previous hearing situation, no significant correlation with the FG was observed. Audiological measurements do not sufficiently reflect the subjective benefit in everyday listening situations. Therefore, hearing-related questionnaires should be provided during clinical routine. In terms of health-related QoL, a statistical trend for the “hearing” subdomain of the HUI3 and the FG could be observed.


Hearing Loss: From Pathogenesis to Treatment, encompasses 18 contributions about the mechanisms and prevention of auditory organ injury, new technologies and biomaterials to recover hearing loss in animals and patients, and a range of promising approaches for hearing loss treatment.Damage to the auditory system is associated with many factors, including genetic deficiency, aging, ototoxic drugs, noise, infection, and many other environmental factors. The mammalian inner ear is a highly differentiated organ, particularly the hair cells that cannot regenerate. Therefore, excessive damage to the inner ear cells will lead to permanent hearing loss. At present, there are limited clinical approaches to prevent and treat hearing loss due to the unique nature of the inner ear structure and cells. With the advance of new technologies and methods, including gene therapy, stem cell therapy, biomaterials, and tissue engineering, we hope that future studies will provide theoretical and experimental bases for the prevention and treatment of sensorineural hearing loss and that these basic research findings can be translated into therapeutic applications. This Frontiers Research Topic, entitled Xu and Yang. They introduced some reports about the role of adeno-associated virus (AAV) vectors in improving hearing and summarized the role of transcription factors and epigenetic regulation in hair cell regeneration. Chai et al. have investigated the role of the super elongation complex (SEC) and its three key components in the regulation of inner ear progenitor cell differentiation. The three key components of the SEC can be detected in cochlear hair cells and supporting cells in neonatal mice, and inhibiting the activity of the SEC affects the proliferation ability of Lgr5+ progenitors but not the differentiation ability. Qian et al. have used zebrafish to study dual-specificity phosphatase 14 (DUSP14)-regulated hair cell fate. They found that dusp14 knockdown will reduce the number of hair cells, neuromasts, and supporting cells, eventually causing hearing defects. RNA sequencing was performed to explore the molecular mechanism responsible for regulating the dusp14 gene on hearing function. They found that the p38 signaling pathway plays a vital role in dusp14 knockdown-related hearing defects, and p38 inhibitor treatment could reverse dusp14 knockdown-induced absence of supporting cells and proliferation disability.The regeneration of inner ear hair cells is a hot topic arousing general interest in otology research. In this review, some important regeneration-related signal pathways have been discussed by Gao et al. have explored the protective role of monosialotetrahexosylganglioside (GM1) in aminoglycoside-induced hair cell injury. They found that GM1 could reduce the ROS level by regulating the expression balance of oxidative and antioxidant genes. GM1 also reduces the rate of apoptosis and hair cell death caused by aminoglycoside antibiotics.As commonly used antibacterial drugs, the relationship between aminoglycoside antibiotics and hearing loss has not been fully elucidated. Zheng et al. have found that otitis media (OM) can impair the autophagy pathway in middle ear (ME) tissues. The initial stage of autophagy in OM mice was activated, but downregulation of Rab7 and Syntaxin 17 disrupts the fusion of autophagosomes and lysosomes in OM mice, thereby blocking autophagic flux. Rapamycin treatment was found to protect hearing by inhibiting the activity of mTOR1 and activating autophagy flux to reduce the inflammatory infiltrates and TNF-α expression. Yang et al. have reviewed the role of autophagy in sensorineural hearing loss (SNHL), including noise, ototoxic drugs, and age-related hearing loss. They also introduced the pro-apoptotic effect of autophagy in cisplatin-induced HEI-OC1 cell death. This review concluded the role of TFEB, PTEN, FoxG1, and STAT proteins and miRNAs in the pathogenesis of SNHL by regulating the autophagy pathway.The role of autophagy in the auditory system has received much attention in recent years. Xu et al. have reviewed current developments in promising nanocarrier systems for inner ear disease therapy. Hydrogel delivery systems have the advantage of enabling a higher residence time for drugs so that they reach equilibrium in the inner ear and easy degradation with good biocompatibility. As a novel drug delivery system, nanoparticle-based systems, such as nanosized polymers, peptides, silicas, and metal–organic frameworks, have been widely employed as drug delivery systems for inner ear disease therapy. Those nanoparticles could prolong the half-life of drugs and increase the solubility of drugs for ease of crossing physiological barriers. Tang et al. have discussed the role of superparamagnetic iron oxide nanoparticles (SPIOs), a biomaterial with excellent biocompatibility, in neural stem cell (NSC) proliferation. They found that SPIOs could promote NSC proliferation in the absence of a static magnetic field (SMF). However, when the SMF intensity (over 100 ± 10 mT) and SPIO concentration (more than 500 μg/ml) increased, the proliferation of NSC was suppressed. Uncovering the underlying mechanism could have profound significance for tissue engineering and regenerative medicine for SPIO applications. Ding et al. have reviewed novel materials for auditory disease treatment, including conductive and sensorineural hearing loss and auditory-related conditions. New materials used in clinical otologic surgery have the advantages of excellent biocompatibility, lower incidence of postoperative complications, and shorter postoperative recovery time. Novel drug delivery systems exhibit stable and sustained drug release, capable of transporting the drug into target cells with high selectivity.Lu et al. have found that the systemic administration of mitochondria-target antioxidant mito-TEMPO (MT) mitigated oxidative stress in the cochlea after noise exposure, reduced the hair cell and ribbon synapse loss induced by acoustic trauma, and overall exhibited a protective effect on hearing. MT treatment could restore mtDNA and ATP levels to improve mitochondrial function during noise exposure. Furthermore, they found that MT treatment attenuated TFAM and SOD2 expression reduction after noise exposure independent of the PGC-1α/NRF-1/TFAM pathway. In addition, MT treatment partially recovered the TFAM–mtDNA interaction and reduced the amount of naked mtDNA in the cytoplasm of outer hair cells. Zhang et al. used desmopressin injections to generate an endolymphatic hydrops (EH) model to mimic Meniere's disease. They observed the cochlear structure and hearing changes in the EH model. The increased hearing loss and reduced round window membrane vibration were found to correlate positively with the severity of EH. Then, a mannitol–saline solution was used as a dehydration treatment to recover hearing in the EH model, showing that rehydration can recover the early hearing loss in ER but not after a long duration.Yang et al. have focused on the role of histidyl-tRNA synthetase HARS2 in cochlear hair cell development. They found that Hars2 conditional knockout mice exhibited gradual hearing loss at P30 and complete hearing loss at P60. The abnormal mitochondria began to appear in HCs at P14 of the Hars2 CKO mice, which indicated reduced inner membrane surface and low-density mitochondrial mass. As a result, the expression of the antioxidant genes xCT, Nqo1, Sod2, and Gsr significantly decreased, and apoptosis HCs gradually appeared at P45. They confirmed that Hars2 is a critical gene for hair cell survival and maintaining the normal function of mitochondria. GJB2 gene mutations were the predominant cause of hereditary deafness. However, current research focuses on the role of the GJB2 gene in the morphological development of the organ of Corti. Yang et al. have reported the role of GJB2 in Kölliker's organ. Gjb2loxP/loxP and ROSA26CreER mice were used in this study, and TUNNEL-positive cells were detected in Kölliker's organ at P1. Meanwhile, autophagy flux was also blocked in Cx26-cKD mice. The Cx26 knockdown will reduce the ATP level in lysosomal vesicles and affect the ATP-dependent Ca2+ signaling pathway in Kölliker's organ, which is crucial for hearing acquisition. Yang et al. also used CRISPR/Cas9 technology to generate connexin 30 (Cx30) knockout mice and confirmed the important role of Cx30 in hearing development. Compared with WT mice, Cx30-deficient mice exhibited mild hearing loss from 4 to 16 kHz at 6 months. The expression of the Cx26 protein was decreased in the cochlea of Cx30 knockout mice. The structure of the stria vascularis, endocochlear potential, and ATP release were affected in Cx30 knockout mice.Li et al. have established a “trinomial forced-choice method” to match tinnitus pitch with 16 frequency measurement points from 250 Hz to 16 kHz. They found that clinical patients with normal hearing were almost within the high-frequency range of tinnitus pitch. They have demonstrated a more direct correspondence between tinnitus pitch and hearing frequency deficits.Sun et al. have reviewed the damage mechanism of spiral ganglion neurons (SGNs) in different hearing injury models. They have also introduced some potential therapies to reduce SGN damage. Adenovirus (Ad)-based and AAV-based vectors mediated exogenous NT  and provided good results in SGN protection. Transplanted embryonic stem cells were successfully engrafted into the modiolus and formed ectopic ganglia with differentiated neuronal-type cells. However, many challenges must be overcome before applications can be made for humans. Liu et al. have explored the function of glutathione peroxidase 1 (GPX1) on cochlear SGNs in gpx1 knockout mice (gpx1−/−) after peroxynitrite treatment. They found that after culturing with peroxynitrite, GPX1 expression significantly decreased in cochlear SGNs. In gpx1−/− mice, the cell-counting results showed that SGNs experienced severe damage after peroxynitrite treatment compared with WT mice. Ebselen pretreatment, a GPX1 mimic, can reverse peroxynitrite-induced SGN apoptosis and cell loss. Furthermore, they found that NF-κB pathway activation plays an important role in peroxynitrite-induced SGN damage. NF-κB inhibitors and upregulating GPX1 expression can block NF-κB pathway activation through downstream pro-apoptosis–related gene expression.In hearing protection-related research, the damage mechanism of cochlear hair cells has always been the focus of attention. Sun et al. have performed a cross-sectional population-based study to analyze the link between hearing impairment and air pollution. After adjusting for confounding factors, they found that exposure to PM10, NOX, and NO2 was linked to hearing impairment. However, PM2.5 and PM2.5 absorbance showed no association with hearing loss. They proposed that oxidative stress and pro-inflammatory pathways may be involved in the association between air pollution and hearing loss.In conclusion, the research articles and reviews collected in this Research Topic provide a comprehensive set of information on the damage mechanisms and protection methods of hair cells and SGN, hair cell regeneration, and the application of new materials and approaches in the treatment of hearing diseases. Together, the achievements included in this Research Topic contribute to further understanding of the pathogenesis of hearing loss, attracting the interest of readers in hearing-related research, and providing a reference for the development of novel hearing loss therapies.WK, SZ, and ZH participated in writing the manuscript. ZH, SZ, WK, HH, and SS participated in reviewing the manuscript. All authors contributed to the article 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.


To determine congenital and developmental outcomes of children with Unilateral Hearing Loss (UHL) who were admitted to the Neonatal Intensive Care Unit (NICU).and a NICU admission to a NICU of Nottingham University Hospital. Birth and two-year developmental follow-up data were collected. They were compared to matched control group who had a NICU admission but no hearing loss .Retrospective, single-site study that followed 25 children with permanent congenital UHL and a NICU admission were diagnosed with a congenital anomaly within the first two years of life. Only half (13/25) of these children were diagnosed with a congenital anomaly at discharge. Children with UHL and a NICU admission were more likely than the matched group  to have multiple congenital anomalies. We found a positive association between multiple congenital anomalies and developmental impairment for the NICU graduates with UHL (p = .019). This UHL-NICU group were also more likely than the matched NICU children to have developmental impairment , speech and language therapy , inner ear malformations  or craniofacial anomalies .The median birthweights, gestational ages and number of days spent on the NICU for the UHL population were 2510 g, 36 weeks, and 12 days respectively. Most children  with UHL and a NICU admission were at high risk of congenital anomalies and certain adverse developmental outcomes. Improved congenital anomaly screening is needed at birth for this population. Having multiple congenital anomalies suggests closer developmental monitoring is needed. This study contributes towards producing clinical screening and management guidelines to ensure consistent high-quality care for this unique population.Children with UHL  Currently there are no national hearing or NICU guidelines surrounding the management of this population or of the birth population of children with UHL. UHL is hearing loss in only one ear, it's prevalence in the birth population is estimated at 0.3–1 per 1,000 births  who were admitted to the neonatal intensive care unit (NICU) are a very understudied population, with 0 births , 5.and a NICU admission, although there has been research into the birth population of children with UHL and for children with normal hearing with a NICU admission.There has been no research investigating two-year outcomes of children with UHL Approximately 40% of children with UHL require speech and language therapy (SLT) . A need For children admitted to the NICU, Schiariti et al. found that 12.6% of term babies had a congenital anomaly; 3.1% of them were cardiac and/or circulatory anomalies, 2.7% were gastrointestinal anomalies and 0.4% were face and neck anomalies . Those tand a NICU admission has highlighted the need for this exploratory study. The primary aim is to describe the congenital, anatomical and behavioural outcomes of this population, with the aim to determine a constellation of features specifically associated with this group of children. Genetic screening is not currently funded for children with UHL in the UK.The absence of published literature surrounding the developmental outcomes of children with UHL This information from a larger cohort could inform the development of clinical guidelines on the follow up and management of this understudied population, ensuring effective and consistent care.and a NICU admission to Nottingham University Hospitals. For the UHL infant group the inclusion criteria included a NICU admission and a referral from the UK National Newborn Hearing Screening Programme (NHSP) with a subsequent diagnosis of permanent UHL confirmed via auditory brainstem response (ABR) for birth dates between February 28, 2008, and 12 July 2019. This gave the final cohort of 25 patients .This retrospective, longitudinal case-controlled cohort study documents routinely collected NICU discharge data, two-year developmental follow-up data and hearing aid treatment data which was collected and analysed for patients with UHL and without UHL p > 0.05 for all comparisons).Data was also collected for matched and peer controls. The matched control patients had passed the NHSP screening and were matched on sex, birthweight (±10 g), gestational age (±1 week) and whether they spent ≥48 h NICU, as it is already well established that these variables impact a baby's development. Few exceptions were made when no matched babies fit these criteria; the weight range was increased by 10 g, and one patient was not matched on sex. If more than one baby fit the matched control criteria, then the baby born most recently was chosen. Peer control patients had passed the NHSP screening and were matched on date of birth (±4 days) and sex. Their weights, gestational ages and days spent on the NICU were recorded. No significant difference was detected regarding the birthweights, gestational ages and number of days spent on the NICU between the children with UHL and their matched controls or peer controls .Data recorded between 0 and 2 years included data from (pre-term) birth to 2 years. Data recorded at birth was taken from NICU discharge notes. We analysed all data from birth to the time of the study and utilised paper notes or NHS databases. Demographic data, discharge summaries and the patient's first postcode were recorded from the neonatal database, Badger. If a patient had multiple anomalies within one organ or organ system, this was still recorded as one anomaly.Developmental impairment is a diagnosis of their development which is not in the normal range for their corrected gestational age. Specifically, a child was diagnosed with developmental impairment if their developmental skills fell two SD or more below the population mean in two or more developmental domains. Developmental impairment was included in this study if it was stated in the patient notes that they had a global developmental delay, fine motor delay, delay in communication, developmental impairment or had been referred for developmental needs.In terms of eligibility for SLT in the study area, the local SLT specialist hearing impaired team only accept referrals for children with severe/profound bilateral hearing loss and auditory spectrum neuropathy disorder. Referral to local community SLT is possible for children with other degrees of hearing loss, however this is not done as routine at point of diagnosis by the current service.Home postcode on discharge from NICU was used to determine deprivation index , 17. Theafter 2 years. A consultant neonatologist determined which anomalies were congenital.Follow-up data for the UHL cases and their matched counterparts were collected and used to determine abnormal anatomical features between 0 and 2 years. There were four exceptions in the UHL cohort; three eye problems and one inner ear malformation were detected The date of first fitting of a hearing device and the types of devices trialled were recorded. It was then calculated how many patients had their device fitted before 1 year of age. Patients not recorded on the database were assumed to have never trialled a hearing device.Hearing thresholds for the patients with UHL were recorded and their most recent audiology report was used. The patients with UHL were then split into two groups, those that had mild/moderate hearing loss and those that had severe/profound hearing loss according to the British Society of Audiology guidelines .See Missing data: The number of children with UHL may be higher than we recorded in this population as cases may be missed for a number of reasons: Firstly, while many US screening programmes include babies with permanent mild BHL and UHL in their target group, NHSP in the UK does not. It aims to identify all children with a moderate-profound permanent HL in the better hearing ear. As a by-product, the screen will identify babies who have UHL and, in some cases, mild permanent hearing loss, as well as temporary hearing loss. Babies with UHL may also be missed if they had moved out of area after NICU admission or if their data was not available on Badgernet.U test was performed for non-categorical data and chi-squared for categorical data (or Fischer's Exact if f n ≤ 5 in either group being compared).A power calculation was not performed as the sample size was limited by the number of available UHL cases with NICU admissions registered at the Nottingham University Hospitals, 2008–2019. Mann–Whitney Shapiro-Wilk test indicated that the non-categorical data were not normally distributed.In this study, 14,538 babies were admitted to the NICU, 25 of whom had UHL, making the prevalence of UHL in this NICU cohort approximately 0.17%. This is lower than previous reports (1.23%–4.6%) (n = 7) of patients with UHL were diagnosed with an anomaly that was thought to be congenital, post-discharge, but within the first 2 years of life. Therefore, when the total number of children with UHL with congenital anomalies detected at birth and post-discharge are combined, the majority (20/25) of babies with UHL had a least one congenital anomaly. Most (16/20) of these cases had multiple congenital anomalies. Children with UHL were significantly more likely to have a congenital anomaly that was diagnosed either at birth (p < 0.001) or post NICU discharge between 0 and 2 years (p < 0.001) compared to their matched counterparts. They were also significantly more likely to have multiple congenital anomalies  at birth (p = 0.004) and between 0 and 2 years (p < 0.001) compared with the matched control group.Congenital anomalies that were detected at birth, and between discharge and two years, were documented in p < 0.001). Children with UHL were 6 times more likely to have vision and eye issues, 5 times as likely to have other malformations, 4 times as likely to have neurological and spinal issues, 3.5 times as likely to have gastrointestinal problems, 3 times as likely to have renal anomalies and 2.5 times as likely to have cardiac abnormalities than their matched counterparts. However, these differences were not found to be statistically significant (p > 0.05). Only the differences in inner ear malformations (IEM) and craniofacial anomalies were statistically significant, yielding a p-value of <0.001 and 0.004 respectively. Division of craniofacial anomalies into subgroups revealed a significant difference from matched controls only detected for ear anomalies (p < .05). No statistical differences were found between the patients with UHL and their matched controls for respiratory, metabolic or neuromotor anomalies.p < 0.001) and developmental impairment (p = .01). It was observed that all of the UHL patients with a developmental impairment also had multiple congenital anomalies, with 4/7 (57%) having ≥4 congenital anomalies. Analyses revealed that patients with UHL and a developmental impairment were statistically more likely to have multiple congenital anomalies than those without a developmental impairment (p = .019).Genetic testing was carried out on twelve patients with UHL, and eleven results were obtained. Four of these patients had a genetic variant, two of which were pathogenic and two of uncertain significance. It is not known if these variants were causative of hearing loss. Three out of the four patients that had a genetic variant also had a phenotypic syndrome diagnosed by a paediatrician.Six patients with UHL were diagnosed with a syndrome, four of which are known to be associated with hearing loss. These were Oculo-auriculo-vertebral Syndrome , Large VNo syndromic or genetic data were recorded for the matched controls.p = .047 and p = 0.019 respectively). Five of the seven children with UHL and a developmental impairment also received SLT.Fourteen of the 25 patients with UHL had mild or moderate hearing loss and 11 had severe or profound hearing loss in their affected ear. More than half of the patients (14/25) had an index of multiple deprivation decile of <5 (associated with lower socio-economic status according to their postcode) on discharge from the NICU. Nearly half (12/25) had trialled a hearing device, and most of these patients (10/25) still used a hearing device at the time of the study. The patient's degree of hearing loss or deprivation decile did not significantly affect whether they had a hearing device, their age of fitting of the device or what device they used. Most patients with UHL that were fitted with a hearing device were fitted after their first birthday  irrespective of their degree of hearing loss or deprivation, with an average age of first fitting of 3 years 1 month. Patients with UHL who had SLT or developmental impairment were significantly more likely to have trialled a hearing device than those that did not  of patients with UHL had multiple congenital anomalies but not all congenital anomalies were detected at discharge . This information suggests better screening for congenital anomalies would be advantageous in this population. This would be particularly beneficial as a congenital anomaly was found to be positively associated with a developmental impairment and could be used as an indicator for closer developmental follow up in early life.These data indicate that children with UHL The prevalence of UHL and NICU admission was 0.17%—lower than previous reports 1.23%–4.6%)  showed that 2.4% of babies with UHL (combined well and NICU cohort patients) also had a gastrointestinal problem detected at birth  and 12% for babies who also have a co-existing JCIH – US risk factor . There is little literature surrounding the association between UHL and developmental impairments. One study found one fifth of children with UHL (both well and NICU populations) were diagnosed with developmental delay , which iand NICU admission. One study found that 1 in 110 patients (0.9%) with UHL had a syndrome that was associated with hearing loss, which is much lower than the 16% found in this study  of the UHL cases were diagnosed with a recognised syndrome, 4 of which were found to be associated with hearing loss. It is interesting that these were not the syndromes most associated with UHL , suggesting that perhaps there is a different subset of syndromes yet to be identified, that are more likely to be associated with UHL is study . This suStudies have revealed the percentage of UHL associate with a family history is approximately 3.7%–13% , 24, 25,In this study, 40% of patients with UHL were currently using a hearing device, which is similar to pre-existing literature . Patientand a NICU admission go onto develop congenital anomalies or abnormal anatomical or behavioural outcomes; further research is required into why this is the case and are their neuroprotective factors which help pre or postnatally . It is possible that there is a subset of patients in this cohort that have certain risk factors that increase their chance of having adverse developmental outcomes. For example, further research into the association between multiple congenital anomalies and developmental outcomes could be conducted.Not all patients with UHL Research into the developmental outcomes of patients with UHL has mainly focused on the general population, not the cohort that has also been admitted to the NICU. This longitudinal study identified many adverse outcomes in this unique population, which is a step towards identifying a constellation of features associated with UHL in babies who have been admitted to the NICU. This study can contribute towards developing guidelines surrounding the screening, follow up and management of these patients, which would benefit both clinicians and patients.


Mitochondrial diseases disrupt the process of energy generation by the mitochondria, leading to manifestations that can affect almost any organ in the body. Although various possible clinical phenotypes can result, neurological and neuromuscular affection is most frequently encountered. NARS2 encodes an enzyme responsible for the conjugation of asparagine to its cognate mitochondrial transfer ribonucleic acid (tRNA) molecule, representing an essential step necessary for effective mitochondrial protein synthesis. As such, mutations in this gene can lead to poor mitochondrial gene expression and, consequently, poor energy output resulting in disease. Pathogenic variants in NARS2 have been known to cause neurodegenerative and myopathic syndromes in combined oxidative phosphorylation deficiency 24 (COXPD24). However, nonsyndromic autosomal recessive deafness 94 (DFNB94), with which only one family is known to be affected, has also been reported concerning NARS2. Our report demonstrates the association of a new pathogenic variant in mitochondrial asparaginyl-tRNA synthetase (NARS2) with nonsyndromic sensorineural hearing loss, thus confirming biallelic mutations in NARS2 as a cause of nonsyndromic deafness. Mitochondrial diseases are a large and diverse group of disorders that affect the ability of mitochondria to generate energy, typically by oxidative phosphorylation. This process relies on a host of different mitochondrial and nuclear-encoded proteins responsible for the assembly and functioning of the electron transport chain. Genetic variants in any of these proteins can lead to mitochondrial dysfunction and disease . VariantThe NARS2 gene (MIM: 612803), located on 11q14.1, codes for mitochondrial asparaginyl-tRNA synthetase 2. Like all mt-aaRSs, the enzyme is nuclear encoded and transported to the mitochondria. Its main function is to catalyze the aminoacylation of asparagine to tRNA molecules [COXPD24 is an autosomal recessive mitochondrial disorder that often manifests early in life with seizures, hypotonia, myopathy, hearing impairment, and overall delay and/or regression of cognitive and motor development -7. CompuA three-year-old Saudi boy presented to the clinic at age 14 months with a lack of response to sound, even loud noises, for several months. A pediatric evaluation revealed that language development was delayed compared to that expected for his age, likely due to hearing loss, but motor and cognitive developmental milestones were within the reference range. The patient was born at term by uncomplicated cesarean section to consanguineous healthy parents and was considered normal at birth. However, newborn hearing screening was not performed. He also had a positive family history of sensorineural hearing loss. Physical examination did not reveal abnormalities or deformities. The patient was seen and examined by an otolaryngologist and an audiologist. A normal tympanogram ruled out middle ear pathology. We tested otoacoustic emissions and cochlear microphonics, which were preserved, and auditory brainstem response testing revealed bilateral profound sensorineural hearing loss characteristic of auditory neuropathy. The patient was started on two behind-the-ear hearing aids with a low gain due to an initially mild type of hearing loss; his aided response was satisfactory.After six months, the parents returned due to a lack of benefits from the patient's hearing aids. The results of his laboratory evaluation, including complete blood count and coagulation and biochemical tests, were within reference ranges. A head CT scan and MRI revealed no abnormalities in the middle ear, inner ear, skull, brain, or cerebellopontine angle bilaterally. One month later, he underwent cochlear implant surgery on his right ear and uses MED-EL SONNET 2 .We suspected autosomal recessive disease and performed whole exome sequencing (WES) for the patient and his parents Table . WES revIn this case, we identified a homozygous NARS2 missense mutation: NARS2 c.506T>A; p.Phe169Tyr. This mutation is found in databases with extremely low frequency and has no previous record of any homozygote; it is located in the catalytic domain and affects a moderately conserved amino acid residue. In silico algorithms developed to predict the effect of missense variants show mixed findings. Some, including SIFT  and PolyMitochondrial diseases are a large group of clinically heterogeneous disorders and can involve various organ systems . DiseaseOur patient presented with only bilateral prelingual sensorineural hearing loss without any other signs or symptoms of the central nervous system or muscle involvement  that would typically be found in COXPD24. Furthermore, head and neck CT and MRI scans revealed no abnormal findings indicative of NARS2-associated syndromes such as Alpers or Leigh syndrome. Laboratory tests did not show significant findings and, apart from delayed language development, cognitive and motor development milestones were otherwise within reference ranges. This presentation resembles the only known report of nonsyndromic hearing loss occurring due to a NARS2 mutation, labeled autosomal recessive deafness 94 (DFNB94). In 2015, Simon et al. described a consanguineous family in which five adult members possessed a homozygous missense mutation and had nonsyndromic hearing loss without any other clinical characteristics, apart from possible premature menopause in two family members; thus, the designation of DFNB94 was given -18.An aspect to consider is the patient's age. At age three, it is difficult to predict whether more signs and symptoms will appear as the patient ages. Although sensorineural deafness can be the first sign of COXPD24, neurological and motor manifestations typically appear soon afterward ,9. HowevAs such, in our case, a diagnosis of COXPD24 cannot be definitively ruled out. Although the patient's family history is positive for isolated sensorineural hearing loss that occurs in the absence of other symptoms, suggesting a diagnosis of DFNB94, follow-up of the patient is necessary to exclude other diagnoses reasonably.This report identifies a newly disease-causing variant in the NARS2 gene and validates NARS2 as a cause of early-onset nonsyndromic sensorineural hearing loss (DFNB94), adding to the genotypic and phenotypic variability of NARS2-associated disease. We suggest that using whole exome sequencing (including mt-aaRS genes) is beneficial in evaluating the patient with isolated sensorineural hearing loss by informing further management decisions and counseling for this condition. More studies are necessary to analyze the exact effects of NARS2 variants on mitochondrial protein synthesis, allowing the development of a more targeted approach to managing the condition.


The subcellular sulfur and lead enrichment characteristics in A. alpina were studied by adding sulfur in different forms and concentrations  to Pb-contaminated soil. The results show that the root and shoot biomass increased by 1.94 times under Na2S and Na2SO4 treatment, and the root–shoot ratio of A. alpina increased 1.62 times under the three forms of sulfur treatments, compared with the control. Sulfur content in cell walls and soluble fractions of the root and shoot of A. alpina significantly increased 3.35~5.75 times and decreased 5.85 and 9.28 times in the organelles under 150 mg·kg−1 Na2SO4 treatment. Meanwhile, Pb content in the root and shoot cell walls of A. alpina significantly increased by 3.54 and 2.75 times, respectively. Pb content in the shoot soluble fraction increased by 3.46 times, while it significantly reduced by 3.78 times in the shoot organelle. Pb content in the root organelle and soluble fraction decreased by 2.72 and 2.46 times. Different forms and concentrations of sulfur had no regularity in the effect of Pb and sulfur content in the subcellular components of A. alpina, but the bioconcentration and translocation factors of A. alpina increased compared with the control. Under different concentrations of Na2SO4, there was a significant positive correlation between the contents of sulfur and Pb in the subcellular components of the root of A. alpina (p < 0.05). These results indicate that sulfur application can enhance the Pb resistance of A. alpina by strengthening the cell wall fixation and vacuolar compartmentalization.Sulfur plays a vital role in the phytoremediation of lead-contaminated soil. The effects of different sulfur forms (S Na Elsholtzia chinensis [Pisum sativum) and corn (Zea mays) [Ricinus communis L.) and promoted its growth [Isatis cappadocica Desv and Erysimum allionii L. [Lead has a relatively large molecular weight and migrates slowly, so its chemical cycling in the soil is mainly influenced by human factors. The analysis of lead pollution sources in the environment also confirmed that industry and agriculture are major contributors . Lead mihinensis . Anotherhinensis . Studiesea mays) . Applicas growth . Exogenoionii L. .There are many literature reports on the regulatory role of sulfur in the phytoremediation of soil heavy metals ,12,13. ESoutheastern Sedum [At the subcellular level, sulfur application increases the proportion of heavy metals in cell walls and vacuolar, while changes in sulfur valence in soil also cause changes in soil pH, which has a direct effect on the dissolved sorption of heavy metals and increases the proportion of heavy metals fixed/deposited by plant roots ,15. Furtrn Sedum . Plants rn Sedum . The sulrn Sedum . Lin andrn Sedum  used K-eA. alpina as a Zn, Pb, and Cd hyperaccumulator, could be used for long-term phytoremediation of soils contaminated by Cd, Pb, and Zn, Pb contents in shoot of A. alpina is more than 1000 mg·kg−1, Cd content in shoot >100 mg·kg−1 and Zn contents in shoot >10,000 mg·kg−1, with the enrichment factors and transport coefficients greater than 1 [−1 (as Na2SO4) increased the activities of related enzymes involved in sulfur-containing compounds in A.alpina, including γ-glutamylcysteine synthetase (γ-GCS), Glutathione reductase (GR) and Glutathione S-transferase (GST) activities in the root part of the plant [A.alpina plants following S treatment are not known; particularly, the relationship between these changes and the uptake of accumulated heavy metals by the plants is a topic that needs to be investigated. In this paper, pot experiments were conducted to study the shoot and root biomass of A. alpina under different sulfur forms and treatments, the accumulation characteristics of lead, and the distribution of lead in subcellular components to reveal the influence of sulfur form on the uptake and enrichment of lead by hyperaccumulator plants. The response mechanism of A. alpina to lead stress under the action of sulfur and the mechanism of A. alpina-enriched lead at the subcellular level was explored and used to provide theoretical and technical guidance for using hyperaccumulator plants A. alpina to remediate lead-contaminated soil.r than 1 . Our prehe plant . However2S and Na2SO4 treatments significantly changed the root and shoot biomass of A. alpina compared with the control. Na2S treatment at 75 mg·kg−1 and 150 mg·kg−1 increased the root biomass 1.83 and 2.33 times, Na2SO4 increased 3.00 and 3.28 times, respectively. Compared with the control (CK), 75 mg·kg−1 and 150 mg·kg−1 Na2SO4 treatments significantly increased the shoot biomass of A. alpina by 1.59 and 2.01 times. Different forms of exogenous sulfur increased the root-to-shoot ratio of A. alpina , indicating that sulfur promotes the growth of the root system of A. alpina, which is beneficial to increase the contact of A. alpina with lead-contaminated soil.As shown in A. alpina, but different forms of sulfur had different distributions of sulfur content in the root and shoot cell walls, organelles, and soluble components of A. alpina. Compared with the CK, 75 mg·kg−1 and 150 mg·kg−1 elemental S treatments significantly reduced the sulfur content in the root and shoot organelles of A. alpina by 58% and 49%. Na2S treatment significantly increased the sulfur content of the root cell wall and the soluble component of A. alpina by 116% and 183% and significantly reduced the organelle sulfur content by 68% . Under 150 mg·kg−1 treatment, Na2S had a significant positive correlation with the cell wall and organelles of the A. alpine root. It showed that the sulfur in A. alpina is closely related to the absorption of lead by the roots. Except for Na2SO4 at 75 mg·kg−1 and 150 mg·kg−1, there was a significant positive correlation between the sulfur content and the shoot cell wall of A. alpina. However, there was no significant correlation between the sulfur content and lead content in other shoot subcellular parts.It can be seen from 0-S2O32−-S4O62−-SO42− pathways to be absorbed by the plant [−1 Na2SO4 significantly promoted an increase in the shoot biomass of A. alpina [2S treatment under Pb stress significantly increased the underground biomass of A. alpina. Na2S treatment at 150 mg·kg−1 had a significant effect on the shoot biomass. This is consistent with the significant increase in the Robinia pseudoacacia root system and biomass with Na2S treatment [2SO4 treatment significantly increased the root and shoot biomass of A. alpina. Conversely, the effects of different concentrations of Na2SO4 on the shoot were not significant. It is speculated that the oxidation of Na2S-reducing substances in the rhizosphere affects the microenvironment and Eh  of the rhizosphere soil, which in turn affects the activity of lead. The presence of SO42− can reduce the excessive heavy metals toxicity [42− in the soil accumulates on the root surface of plants, which affects the adsorption, desorption, absorption, and antagonism of lead ions, which affects the bioavailability of lead. In this paper, Na2SO4 treatment significantly increased the biomass of A. alpina, and the root-to-shoot ratio of the three forms of sulfur treatment increased compared with the CK.Elemental sulfur cannot be directly absorbed and utilized by plants. It must be oxidized into sulfate in the soil through the She plant . The addhe plant , signifihe plant . Amounts. alpina . In thisreatment . Na2SO4 toxicity ; SO42− iA. alpina when no sulfur treatment was added, reaching more than 50% in the organelles  between Pb content and cell wall and organelle sulfur content was observed , which affects the bioavailability of lead in A. alpina, and part of the process that affects the microbial activity through sulfur redox reactions changes the physical and chemical properties of soil, such as pH and Eh , and indirectly affects the behavior of lead [A. alpina directly absorbs the SO42– in Na2SO4 to generate sulfur-containing functional groups that combine with lead to form high-affinity and stable compounds; this enhances the lead tolerance of A. alpina. Regarding how different forms of sulfur affect the characteristics of lead enrichment in A. alpina, it is necessary to use the near-side X-ray absorption fine structure absorption spectrometer to understand the geometric configuration of sulfur and lead atoms and reveal how sulfur regulates lead absorption and enrichment in plants.It is speculated that a part of S of lead . A. alpiThe test soil was obtained from an abandoned slag pile in Sanduoduo Village, Zhehai Town, Huize County, Yunnan Province . The collected soil was 0~20 cm tillage soil  of corn-planted farmland near the slag heap. After air drying , the soil was passed through a 2 mm sieve, accurately weighed (5.0 kg), and placed in plastic pots (length 44 cm × width 15 cm × height 19 cm) for later use. The physical and chemical properties of the soil are shown in A. alpina seeds were sown in a seedbed with the substrate. After sprouting 1–2 leaves, seedlings with good growth and a uniform size were transplanted for the pot experiments. The planting method was to set 2 plants in one hole and 18 plants in 9 holes in each pot. The plants were watered with 1/2 Hoagland nutrient solution once every two days. Samples were collected for the experiment 90 days later.A. alpina [0, Na2S, and Na2SO4) were set as 0 mg·kg−1, 75 mg·kg−1, and 150 mg·kg−1 and mixed with the appropriate weight of soil in pots. Each treatment was set with three parallel pots, with a total of 21 pots. The soil was sprayed with 500 mL of different concentrations and forms of sulfur, air dried, and re-mixed to speed up the homogenization process for 20 d.The sulfur concentration was determined based on our previous studies, with the effect of sulfur nutrition on lead accumulation in . alpina . The con3-HClO4 was heated and digested with an adjustable electric heating plate until it was clear, transferred to a 50 mL volumetric flask, and the lead content was determined by an atomic absorption spectrophotometer . A coupled plasma emission spectrometer  was used to determine the available sulfur content; the organic matter was determined volumetrically with potassium dichromate; the available phosphorus was determined using a spectrophotometer (700 nm)  after 0.5 M NaHCO3 leaching; the available nitrogen was determined by using the alkaline diffusion method; the available potassium was determined with flame photometry using 1 M NH4OAc leaching [3)Cl3 leaching (475 nm) [The pH was determined using a pH meter and 1:2.5 (m/v) soil/water mixture, which was shaken for 30 min at room temperature and left for 5 h. In total, 0.1 g of 2 mm air-dried soil was weighted and placed in a 150 mL triangular flask. The soil with 5 mL HNOleaching ; and cat(475 nm) .The soil was brought to a semi-humid state with water, and the whole plant was pulled out from the soil. Plant roots were quickly rinsed with tap water to remove impurities attached to the roots and then rinsed with deionized water. The plant surface moisture was absorbed using filter paper and then evenly divided into two parts. One was deactivated at 105 °C for 30 min and then dried at 70 °C to a constant weight. The dry matter was weighed. Another fresh sample was kept to measure the subcellular sulfur and lead content.A. alpina fresh samples were separated. Exactly 1.00 g of fresh samples in a mortar was weighed. Pre-cooled subcellular extract  (10 mL), sucrose, and Tris-HCl were added to create an environment similar to that inside plant cells. DTT was added as an antioxidant, plant cells were broken using the low-temperature physical fragmentation method, and they were quickly placed in a mortar. They were then ground in an ice bath to a homogenate shape and transferred to a 50 mL centrifuge tube. Because of the lightness of the cell wall fraction, the precipitate was obtained by differential centrifugation at 1000 r·min−1 for 10 min. The supernatant was then removed, and the precipitate contained the cell wall component. The removed supernatant was centrifuged in a high-speed refrigerated centrifuge  at 12,000 r.min−1, at 4 °C, and for 45 min. The supernatant is the soluble fraction of the cell, and the precipitate is the organelle component. The sulfur and lead content measurement method are the same as that described in Differential centrifugation was used to separate the subcellular components. The underground and aboveground parts of the prepared 3-HC1O4 (v:v = 1:4) and determined using atomic absorption spectrophotometry . Similarly, the total Pb content of the soil was digested with HNO3-H2O2 (v:v = 1:4) and determined using atomic absorption spectrophotometry [The Pb content of the roots and shoots are digested with HNOotometry .p = 0.05) were carried out using IBM SPSS Statistics 22 . The data obtained are expressed as mean ± standard deviation (n = 3); figures were drawn using Origin 9.1.The data were collected and analyzed using Microsoft Excel 2010 . One-way analysis of variance (one-way ANOVA) and a significance test (Duncan’s method, The bio-accumulation factor and translocation factor of heavy metals in plants were calculated as follows:0 application had no significant effect on the root-to-shoot ratio or the shoot and root dry weight of A. alpina under Pb stress. With increasing concentration, Na2S and Na2SO4 application promoted the growth of A. alpina and significantly increased the sulfur content in the cell wall of both root and shoot. BCF and TF increased, which promoted the translocation and accumulation of Pb. The correlation between the sulfur and Pb contents of subcellular fractions was found: there is a positive correlation between the sulfur and Pb contents of root and shoot cell walls. This suggests that the sulfur application reduced the transmembrane transport of heavy metals and that Pb fixation by the cell wall was the main way to reduce heavy metal toxicity in the root and shoot parts of A. alpina. In addition, sulfur application increased Pb content in the shoot soluble fraction, which may be a result of the soluble fraction including the vacuoles being the main site of Pb accumulation in the shoot of hyperaccumulators. In summary, these findings provide a reliable basis for the mechanism of Pb enrichment in A. alpina and other hyperaccumulators and for measures to reduce the heavy metal pollution of the environment by exogenous sulfur application.In the present study, exogenous S


Unilateral sensorineural hearing loss affects approximately 9% of the population and is less related to aging than bilateral hearing loss. Prevalence ranges from 0.3 to 1 per 1,000 newborns.Patients with profound unilateral hearing loss or “SSD” (Single-Sided Deafness) have sufficient hearing for communication but have difficulties in sound localization and speech intelligibility in environments with competing noise. Child development is impaired, because it can cause delay in speech acquisition, poor school performance in up to 59% of the children, and behavioral changes.The majority of children with SSD are not rehabilitated. When the diagnosis is made, the school must provide special assistance, placing the child in the first rows, with the normal ear facing the teacher. In some cases, speech therapy should be used when language delay is present. In recent years, the possibilities for treating unilateral hearing loss have increased. In addition to the personal sound amplification device for partial losses and CROS  systems, there are other treatment options for hearing rehabilitation on the affected side in cases of profound hearing loss such as Bone Anchored Hearing Aids (BAHAs) and cochlear implants (CI).The CROS system and BAHAs effectively address the head shadow effect and restore sound perception to the non-listening side. However, they do not restore bilateral auditory input, which is necessary for true binaural hearing. BAHA users have a tendency for the satisfaction and benefit to decrease over time. Desmet et al.A large proportion of cases of children with congenital SSD are associated with structural abnormalities of the cochlear nerve or the VIII cranial nerve. Clemmens et al.It is important to emphasize that many children with SSD can have an absolutely normal life and language development. The cause is usually congenital and, over the years, the child manages to adapt to this condition. For the treatment of these children, one must consider the actual benefit of using a device (implantable or not). As the patient and family sometimes have no complaints, this patient probably won’t use the proposed prosthesis. Although most of these devices are becoming more and more aesthetically adequate, their use in school can stigmatize the child or adult and make their daily use more difficult.The authors declare no conflicts of interest.


Unilateral Sensorineural Hearing Loss (USNHL) is an age-old known entity. Patients with USNHL lack the merits of binaural hearing, i.e., temporal summation, sound localization, and speech recognition in a noisy environment. The lack of binaural hearing affects such individuals' quality of life (QOL). The present study is the most extensive Indian series related to QOL in USNHL patients.  This study aims to assess the impact of USNHL on the QOL of patients in the state of Uttarakhand.  A cross-sectional study was carried out at a tertiary care center in Uttarakhand over a period of 18 months, from January 2018 to July 2019. A total of 115 patients with pure USNHL were evaluated using a validated questionnaire—Hearing Handicap Inventory for Adults-Hindi (HHIA-H).  In our study, patients with higher HHIA-H scores were male, young adults (age group 18–30 years), students, and laborers. Most of our patients (64%) had significant handicaps, followed by moderate handicaps in 25%. However, no significant correlation of degree of handicap was seen with age, duration, and degree of hearing loss. CTRI/2018/06/014396). USNHL can lead to a significant handicap that can severely affect the emotional and social aspects of life. Thus, early diagnosis and rehabilitation are essential to prevent handicap and uplift QOL in patients with USNHL. This trial is registered with Clinical Trials Registry of India (CTRI reg. no.  Hearing is one of the five essential senses of our body that helps us communicate with one another and helps gain awareness of one's surroundings. According to World Health Organization (WHO), a person who is not able to hear as well as someone with normal hearing, i.e., a hearing threshold of 20 decibels (dB) or better in both ears, is said to have hearing loss. This was revised in 2020 over the previous threshold of 25 dB. Hearing loss has emerged as a global health challenge that at present has affected more than 466 million people, around 5% of the world's population . The numOver decades, the definition of health has changed from the mere absence of disease to multifaceted entities comprising of physical, social, and mental well-being. Overall well-being can be assessed by a patient's quality of life (QOL), which is defined by WHO as “individual's perception of their position in life in the context of culture and value systems in which they live and in relation to their goals, expectations, standards, and concerns” . An innuVery limited epidemiological data exists in the literature till date on the prevalence and effect of USNHL in India and QOL. Hence, this particular study aims to assess the impact of USNHL on QOL of patients in India using a previously validated questionnaire, Hearing Handicap Inventory for Adults-Hindi (HHIA-H) . The preAn observational cross-sectional study was conducted in the Department of Otorhinolaryngology in a tertiary care hospital in Uttarakhand, India, over a period of 18 months from January 2018 to June 2019. After clearance from the Institutional Ethical Committee (IEC/18/102), the study was registered with the Clinical Trials Registry of India (CTRI/2018/06/014396). All patients visiting the outpatient department fitting the inclusion criteria: (a) age between 18 and 50 years and (b) USNHL  based on pure tone audiometry (PTA) were enrolled. Patients with comorbidities, conductive or mixed hearing loss in either ear, and any history of ear discharge from either ear were excluded. A detailed history was taken, and examination was performed after taking written informed consent. The patients were then asked to fill HHIA-H. WHO grading of hearing loss was used. Audiometric thresholds were measured at 500, 1000, 2000, and 4000 Hz. The hearing loss was classified as mild (20 to 34.9 dB), moderate (35 to 49.9 dB), moderately severe (50 to 64.5 dB), severe (65 to 79.9 dB), profound (80 to 94.5 dB), and complete deafness (95 dB and above) [HHIA-H questionnaire: the questionnaire comprised of a total of 25 items with scores for responses, which were “Yes” (4 points), “Sometimes” (2 points), and “No” (0 points). The total score ranged from 0 to a maximum of 100. 12 items represented the social subscale (maximum score = 48) and 13 items represented the emotional subscale (maximum score = 52). Handicap was graded as “Nil” (score 0 to 17), “Mild to moderate” (score 18 to 43), and “Significant” (score of 44 and above).Data analysis: the responses of USNHL patients to HHIA-H were documented using Microsoft Excel. Statistical analysis was performed using SPSS Statistics for Windows, version 21.0 .115 patients were studied with a male preponderance of 71%. The majority of patients were aged between 18 and 30 years (50%), with a mean of 31.7 years. 30.4% of the patients who presented with USNHL were students. There was a slight preponderance of left side laterality (54.8%), and the majority were suffering from profound hearing loss of >80 dB (54.8%), with an average hearing loss of 83.46 dB. The duration of hearing loss in most patients ranged from 1 to 5 years (36.5%), with an average of 39.38 months .The overall HHIA-H mean score was 52.21 with a standard deviation of 25.20 and a median score of 56. The social subscale had a mean of 26.21 with a standard deviation of 12.65 and a median of 26. The emotional subscale had a mean of 25.97 with a standard deviation of 13.82 and a median of 26.The majority of the study population was found to be suffering from a significant handicap (63.5%), followed by mild to moderate handicap (25.2%) and nil handicap (11.3%).p=0.052). A similar statistically insignificant, weak positive correlation was seen between HHIA-H social score and average hearing loss . However, a statistically significant weak positive correlation was found between HHIA-H Emotional Subscale and the average hearing loss . For every 1 dB increase in average hearing loss, the HHIA-H score increased by 2.17 units (p=0.257) and duration of hearing loss . The HHIA-H scores were normally distributed in both ears, and hence, parametric tests (t-test) were used to make group comparisons. However, no significant difference was seen in HHIA-H scores between the ears affected .HHIA-H scores were correlated with age, average hearing loss, and duration of hearing loss. Nonparametric tests (Spearman correlation coefficient-rho) were used, as at least one of the variables was not normally distributed. These correlations have been depicted using a scatter plot. A statistically insignificant weak positive correlation was seen between HHIA-H total score and average hearing loss  . HoweverThe auditory input from both ears sums up to show a synergistic effect to amplify the sound almost two times when it reaches the auditory cortex. This summation is absent in USNHL. The interaural time and intensity difference helps a person to localize the sound source. Hence, USNHL patients suffer from impaired sound localization, and this can have an adverse impact on daily routine activities such as crossing a road safely. The binaural squelch effect enables a person to differentiate speech from noise due to the head shadow effect. USNHL patients lack this advantage, and this can cause a significant impact on the patients, both socially as well as emotionally. The disadvantages of lack of binaural hearing can be dealt with hearing rehabilitation options such as hearing aids and bone-anchored hearing aid .To better understand and analyze QOL in multiple aspects of a patient's life with USNHL, we need further studies with a larger sample size to establish such significant correlations.USNHL can have varying impacts on the QOL of patients. The lack of binaural hearing impairs sound localization and understanding speech in a noisy environment. This can profoundly impact all aspects of an individual's life. Significant handicap is seen in young adult males and individuals from low socioeconomic strata. HHIA is a self-report questionnaire. Hence, it needs to be in the native language of the study population. It is essential to diagnose these patients, grade their handicaps, and rehabilitate them appropriately.


The rapid surge of COVID-19 cases in the second wave of the pandemic has crippled the healthcare delivery system in Nepal and neighboring countries. Unlike in the first wave of the pandemic, several cases of mucormycosis have been reported in patients with COVID-19 from Nepal and India. In this report, we briefly describe the clinical presentation, diagnosis, and risk factors for mucormycosis and explore why patients with COVID-19 are at an increased risk for developing the infection. As treatment of mucormycosis is challenging and consumes a lot of resources, prevention of mucormycosis is pivotal in low-income countries like Nepal. We also highlight some basic steps that are easy to perform and important to reduce the risk of infection. Gastrointestinal, pulmonary, renal, isolated central nervous system, cutaneous, and disseminated mucormycosis are less common clinical presentations of mucormycosis.Mucormycosis is an angioinvasive disease caused by fungi of the order Mucorales. The genera commonly implicated in human infections include Rhizopus, Mucor, Rhizomucor, Cunninghamella, and Absidia.6 Symptoms of rhino-orbital mucormycosis include any combinations of unilateral retro-orbital pain, orbital swelling, ptosis, diplopia, decreased vision, facial pain, decreased sensation over cheek, nasal blockage, nasal discharge, blackish discoloration on the face or hard palate. Neurological symptoms will be seen if it has spread intracranially. Tissue necrosis is the hallmark of mucormycosis and is seen as black eschar but may not be found in the early stages. There are no specific biologic markers to identify mucormycosis. Culture report in mucormycosis is usually negative.6 Known risk factors for mucormycosis before the COVID-19 pandemic were diabetes mellitus, hematological malignancy, organ transplantation, autoimmune disorders, immunosuppressant use, iron overload, burns, trauma, and prior treatment with antifungals mainly voriconazole.7The diagnosis is established by a high index of suspicion from the clinical presentation, recognition of host factors, radiologic findings, and microscopic identification of the organism with the typical structure of a Mucorales.3 Nearly 76% of the patients had taken corticosteroids for COVID-19, followed by remdesivir (20%) and tocilizumab (4%).The reason why mucormycosis is common in patients with COVID-19 remains largely speculative. An analysis of 101 cases of mucormycosis in patients with COVID-19 found hyperglycemia at presentation due to pre-existing or new-onset diabetes mellitus, new-onset hyperglycemia, or diabetic ketoacidosis to be the single-most important risk factor in the majority of cases (83.3%).8 thus favoring fungal growth. Similarly, the pro-coagulable state associated with COVID-199 causes thrombosis of feeding arteries leading to necrosis of tissues and secondary invasion by the fungus.It is hypothesized that immune dysregulation associated with COVID-19, such as reduced numbers of T lymphocytes, CD4+T, and CD8+T cells, may alter innate immunity,10 Mucormycosis thrives on freely available iron. Hyperglycemia can cause glycosylation of transferrin and ferritin, reducing their iron affinity and increasing the free iron. Furthermore, the low pH caused by the accumulation of ketone bodies in diabetic ketoacidosis strongly impairs the ability of transferrin to chelate iron, thereby increasing free iron. Also, there is an increase in ferritin levels in patients with COVID-19 due to the surge of cytokines, especially interleukin-6, thus increasing free iron.11The rampant use of high-dose steroids without proper monitoringofbloodglucoselevelsresultsinuncontrolled hyperglycemia andcan precipitate diabetes ketoacidosis. The resultant acidosis acts as a fertile medium for mucor spores to germinate. The concurrent use of steroids and immunomodulatory drugs such as tocilizumab also reduces the phagocytic activity of white blood cells, making a patient with diabetes mellitus vulnerable to mucormycosis.1 Few cases reported in grey literature have speculated other possible reasons for the surge of mucormycosis, such as the supply of contaminated industrial oxygen to the hospitals, use of unsterile water in humidifier and steam inhaler, and intake of zinc. More data is needed to establish an association of these potential risk factors with mucormycosis.Some authors have implicated other possible risk factors, like the use of monoclonal antibodies and the rampant use of broad-spectrum antibiotics as the cause for increase in new-onset fungal infections.12 Cerebral involvement is a significant predictor of mortality in patients with mucormycosis.13The treatment of mucormycosis usually requires early extensive surgical debridement in combination with antifungal medications and rapid control of underlying medical condition. Generally, a multidisciplinary team consisting of otorhinolaryngologists, neurosurgeons, ophthalmologists, anesthesiologists, intensivists, endocrinologists, infectious disease experts, microbiologists, and pathologists are involved in the treatment. Once mucormycosis is suspected clinically, antifungals may be initiated before the formal microbiolgical reporting. It is important to perform appropriate imaging and document the extent of the fungal invasion urgently to help prognosticate and also to guide surgical debridement. Liposomal amphotericin B is recommended as the first-line treatment. Intravenous isavuconazole and intravenous or delayed-release oral posaconazole are recommended with moderate strength as first line treatment if patient is intolerant or refractory to amphotericin B and strongly recommended as salvage therapy. Use of amphotericin B deoxycholate is discouraged whenever alternative therapies are available, because of substantial nephrotoxicity, specifically in the doses and treatment durations needed for mucormycosis. The optimal duration of therapy in mucormycosis is not clear and is guided by the clinical response, tolerability, and radiographic improvement. Even with the best treatment, all-cause mortality ranges from 40% to 80% depending on underlying conditions and sites of infection.As the cost of liposomal amphotericin is high and long-term therapy is needed for cure, treatment of mucormycosis is difficult in Nepal. There are added constraints, such as an acute shortage of the drug. Furthermore, the management of many cases with invasive disease requires a high level of expertise, and a multidisciplinary collaboration, which is not readily available in most parts of the country. Many patients are referred to hospitals in large cities as surgical treatment of patients with COVID-19 is not readily available in Nepal. This not only delays the initiation of therapy but also carries the risk of spread of COVID-19 patients need to travel long distances, often without adequate infection prevention measures. It is not uncommon to have mucormycosis during active stage of COVID-19.During the second wave of the COVID-19 pandemic in Nepal, several cases of mucormycosis have been reported throughout the country. Invasive mucormycosis is difficult to treat and requires exhaustive resources. In resource-limited settings like ours, it is extremely important to adopt all possible measures to prevent mucormycosis in patients with COVID-19. There should be a high index of suspicion of fungal infection in patients with COVID-19 so that timely diagnosis and early initiation of treatment can be done. Evidence-based use of corticosteroids should be advocated and all efforts should be made to maintain normal glucose levels in these patients. Most patients with COVID-19 do not require high doses or prolonged treatment with corticosteroids.10 The use of prophylactic broad-spectrum antibiotics and antifungals, without definite evidence of infection should be discouraged. All other therapeutic agents used should be monitored to achieve a therapeutic effect at the lowest dose and shortest duration possible. Often less-is-more.Without clear evidence of benefit, drugs targeting immune pathways, such as tocilizumab, should be used with caution.


The definition of sudden sensorineural hearing loss (SSNHL) is broadly accepted as acute sensorineural hearing loss of more than 30 dB over at least three consecutive frequencies in a pure-tone audiogram (PTA). Acute audiovestibular loss is common with ischaemic stroke in the territory of the anterior inferior cerebellar artery (AICA). However, cases in which SSNHL and vertigo occur with hypoperfusion alone are very rare. We describe a patient who developed unilateral SSNHL and vertigo as initial symptoms caused by cerebellar hypoperfusion by vertebral artery (VA) dissection without the occurrence of infarction.A 51-year-old man suddenly developed acute hearing loss (AHL) in his left ear and vertigo. On neurological examination, he had vibration-induced right-beating nystagmus and left-beating nystagmus after a head-shaking test. Additionally, he had apogeotropic nystagmus during head turns to either side. The head impulse test (HIT) was normal. PTA showed mild unilateral SSNHL in the left ear. Diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) showed territorial perfusion deficits in the left posterior inferior cerebellar artery (PICA) and anterior inferior cerebellar artery (AICA) without infarction. Two months later, the patient had no vertigo but still had hearing impairment in his left ear. A follow-up PTA documented persistent unilateral SSNHL in the left ear. Additionally, perfusion computed tomography (CT) showed that perfusion deficits remained in the left cerebellum along the PICA and AICA territories.Our case highlights a case of AHL and vertigo presented by isolated cerebellar hypoperfusion without infarction. It is necessary to consider the possibility of a central cause in patients with AHL and vertigo, and it is important to confirm this possibility through brain magnetic resonance imaging (MRI), including PWI, and magnetic resonance angiography (MRA). Sudden sensorineural hearing loss (SSNHL) is a sudden and unexplained hearing loss that is frequently unilateral. The US National Institute for Deafness and Communication Disorders defines SSNHL as an idiopathic hearing loss of at least 30 dB over at least 3 test frequencies within 72 hours . The aetThe evidence suggests that the development of SSNHL can be an initial warning sign of vascular events, such as thromboembolism, vasospasm, and insufficient blood circulation , 3. AudiThere have been reports of SSNHL related to infarction, especially AICA territorial infarction, and although infarction was subsequently observed, it occurred at a site different from the hypoperfusion area; furthermore, it is known that cases in which SSNHL and vertigo occur with hypoperfusion alone are very rare. We describe a patient who developed unilateral SSNHL and vertigo as initial symptoms caused by cerebellar hypoperfusion by vertebral artery (VA) dissection without the occurrence of infarction.A 51-year-old man presented with a sudden loss of hearing in his left ear. He also noted vertigo and imbalance. Approximately three times over the previous week, the patient had experienced transient hearing loss and vertigo lasting between 5 and 10 minutes. The patient had a history of hypertension and heavy smoking but he did not have a history of hearing impairment, head trauma, central nervous system infection, autoimmune diseases, or exposure to ototoxic drugs.On neurological examination, he had vibration-induced right-beating nystagmus and left-beating nystagmus after a head-shaking test. Additionally, he had left-beating nystagmus in the right roll test and right-beating nystagmus in the left roll test. The head impulse test was normal. Analysis of blood contents, including complete blood count, serum electrolytes, liver and kidney function indicators, and high-sensitivity C-reactive protein (hsCRP), were normal, except for an increased LDL-cholesterol level 130 mg/dL). Pure-tone audiogram (PTA) showed a mild unilateral sensorineural, pure-tone average of 37 dB (dB) in the left ear  of the brain was performed 9 hours after the last event. Diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps showed normal findings Fig. B. PerfusWe started treating the patient with 75 mg of clopidogrel and 40 mg of atorvastatin. After starting treatment, his vertigo gradually improved, but his SSNHL did not change. Follow-up DWI and ADC mapping performed 3 days after onset showed multifocal infarctions along the posterior circulation involving the upper cerebellum and occipital lobe, not the PICA and AICA territories Fig. . Two monHearing impairment seriously affects not only the physical and mental health of patients but also the social life and activities of daily living. Circulation system disorders, such as ischemic stroke and myocardial infarction have closely related to SSNHL . BecauseIn this case, the patient had intermittent unilateral hearing loss and vertigo 1 week before the onset of symptoms. This shows that our patient was in the same situation described with infarction of one of the eight subgroups of the AICA area: sudden onset of audiovestibular syndrome with vertigo and hearing loss that is occasionally preceded by a prodromal episode(s) of audiovestibular disturbance , 9. Our In this case, overall hypoperfusion, including in the AICA and PICA territories observed with PWI, is thought to be the cause of the AHL and vertigo due to the prodromal symptoms of infarction. However, the pattern of cerebral infarction observed in follow-up DWI was not the previously known AICA, and the PICA infarction showed the possibility that isolated cerebellar hypoperfusion alone can induce persistent AHL. There are few studies on AHL and isolated cerebellar hypoperfusion. In one study involving acute transient vestibular syndrome (ATVS), The ipsilesional VA stenosis or occlusion may cause unilateral cerebellar hypoperfusion in patients with ATVS. Almost 80% of patients with cerebellar hypoperfusion revealed luminal abnormality or corresponding VA hypoplasia . In addiThere are some reports that an initial normal MRI does not rule out vascular aetiology . HoweverIn a study of patients with AHL due to posterior circulation ischaemia, nearly 80% of the patients who were followed for at least 1 year after the onset of sudden deafness due to vascular cause (mainly cerebellar infarction of the AICA territory) had a partial or complete recovery of hearing. Multivariate analysis revealed that multiple vascular risk factors for ischaemic stroke and profound hearing loss had poorer outcomes regarding recovery from AHL [Although the exact mechanism of the long-term outcome of AHL associated with VBIS is not clearly understood, the maximum improvement is usually seen within the first 2 weeks after the onset of hearing loss . The proThe HINTS examination  provides the earliest collection of physical examination findings developed to reliably rule out a central cause of hearing loss from a peripheral cause . Any othAlthough HINTS has been used academically for more than 10 years, There are still limitations to practical use in clinical practice. Many physicians in acute emergency settings tend to rely on neuroimaging because they lack the confidence to use their examination and interpretation of eye movements to make a critical decision about whether a patient has had a stroke. This means that the usefulness of HINTS strongly depends on the level of expertise of the person performing it . AdditioWe treated the patient with clopidogrel and atorvastatin. Treatment for dissection aims to prevent arterial rupture and further ischaemia and infarction while preserving blood supply to the associated vascular territory . CurrentIn conclusion, we reported a case of AHL and vertigo due to isolated cerebellar hypoperfusion without infarction. If a brain MRI, including PWI, was not performed in this case, the diagnosis and treatment of cerebellar ischaemia may have been delayed. Therefore, it is necessary to consider the possibility of a central cause in patients with AHL and vertigo, and it is important to confirm it through brain MRI, including PWI, and magnetic resonance angiography (MRA).