The oral bacterial microbiota facilitates the stratification for ulcerative colitis patients with oral ulcers.

BACKGROUND: Clinically, a large part of inflammatory bowel disease (IBD) patients is complicated by oral lesions. Although previous studies proved oral microbial dysbiosis in IBD patients, the bacterial community in the gastrointestinal (GI) tract of those IBD patients combined with oral ulcers has not been profiled yet. METHODS: In this study, we enrolled four groups of subjects, including healthy controls (CON), oral ulcer patients (OU), and ulcerative colitis patients with (UC_OU) and without (UC) oral ulcers. Bio-samples from three GI niches containing salivary, buccal, and fecal samples, were collected for 16S rRNA V3-V4 region sequencing. Bacterial abundance and related bio-functions were compared, and data showed that the fecal microbiota was more potent than salivary and buccal microbes in shaping the host immune system. ~ 22 UC and 10 UC_OU 5-aminosalicylate (5-ASA) routine treated patients were followed-up for six months; according to their treatment response (a decrease in the endoscopic Mayo score), they were further sub-grouped as responding and non-responding patients. RESULTS: We found those UC patients complicated with oral ulcers presented weaker treatment response, and three oral bacterial genera, i.e., Fusobacterium, Oribacterium, and Campylobacter, might be connected with treatment responding. Additionally, the salivary microbiome could be an indicator of treatment responding in 5-ASA routine treatment rather than buccal or fecal ones. CONCLUSIONS: The fecal microbiota had a strong effect on the host's immune indices, while the oral bacterial microbiota could help stratification for ulcerative colitis patients with oral ulcers. Additionally, the oral microbiota had the potential role in reflecting the treatment response of UC patients. Three oral bacteria genera (Fusobacterium, Oribacterium, and Campylobacter) might be involved in UC patients with oral ulcers lacking treatment responses, and monitoring oral microbiota may be meaningful in assessing the therapeutic response in UC patients.

Relative Humidity Affects Acute Otitis Media Visits of Preschool Children to the Emergency Department.

OBJECTIVE: The associations between climate variables and diseases such as respiratory infections, influenza, pediatric seizure, and gastroenteritis have been long appreciated. Infection is the main reason for acute otitis media (AOM) incidence. However, few previous studies explored the correlation between climatic parameters and AOM infections. The most important meteorological factors, temperature, relative humidity, and fine particulate matter (PM2.5), were included in this study. We studied the relationship between these meteorological factors and the AOM visits. MATERIALS AND METHODS: It was a retrospective cross-sectional study. A linear correlation and a linear regression model were used to explore the AOM visits and meteorological factors. RESULTS: A total of 7075 emergency department visits for AOM were identified. Relative humidity was found an independent risk factor for the AOM visits in preschool children (regression coefficient = -10.841<0, P = .039 < .05), but not in infants and school-age children. Average temperature and PM2.5 were not correlated with AOM visits. CONCLUSION: Humidity may have a significant inverse impact on the incidence of AOM in preschool-age children.

The use of vestibular evoked myogenic potentials (VEMP) in the diagnosis of otolithic dysfunction of patients with obstructive sleep apnea: a survey of awareness and recognition of otorhinolaryngology medical staffs.

PURPOSE: To assess awareness and recognition of vestibular function tests in otorhinolaryngology medical staffs, especially the vestibular evoked myogenic potentials (VEMP) testing in patients with obstructive sleep apnea (OSA). METHODS: A survey was delivered via either email or a social media app. The medical staffs of the Chinese Medical Association of Otolaryngology Head and Neck Surgery from various branches were enrolled. Study data were collected and managed with an online data collection tool. RESULTS: A total of 1781 emails and 623 social media messages were sent to 2404 otorhinolaryngology medical staffs. One hundred and fifty-seven of them participated in the survey, including 24 via emails and 133 via the social media app. Regarding the knowledge of VEMP, only 59 (37.6%) of them agreed that OSA could be related to vertigo/dizziness/imbalance and 28 (17.8%) believed that OSA could result in VEMP abnormalities and would factor this in diagnosing the impairment of the vestibular function of OSA patients. A total of 7.6% of the respondents had never heard of the VEMP tests. Responses regarding the minimum age at which VEMP are possible ranged from younger than 6 months to greater than 18 years of age. Beliefs regarding the utility and reliability of VEMP varied, with 'unsure' being the most frequent response. In addition, only 17.8% of otolaryngologists indicated some access to the VEMP test. CONCLUSIONS: Knowledge and beliefs about the role of VEMP in diagnosing otolithic organ dysfunction caused by OSA in otorhinolaryngology vary widely. It is important for otorhinolaryngology medical staffs to learn the latest literatures and updated knowledge through continuing education.

Risk Factors of Difficult Pharyngeal Accidental Fishbones Ingestion.

OBJECTIVE: Accidental pharyngeal fishbone ingestion is a common complaint in ear, nose, and throat clinics. Approximately two-thirds of the accidentally ingested fishbones can be removed using tongue depressors and indirect laryngoscopy. However, the remaining third is challenging to identify and remove using these methods. These difficult fishbones require identification and removal via more advanced approaches. Video-guided laryngoscope is used to deal with difficult fishbones in our center. This study aimed to explore the risk factors for difficult fishbones. METHODS: A prospective study was performed at a teaching hospital on 2080 patients. Univariate and multivariate analyses were performed to identify the risk factors. RESULTS: The common fishbone locations were the tonsils (39.8%; defined as STEP-I), tongue base (37.1%), vallecula (13.3%; STEP-II), and hypopharynx (9.8%; STEP-III). With increasing STEP level, the ratio of difficult fishbones correspondingly increased (Z = 13.919, P < .001), and the proportions were 21.1%, 41.9%, and 70% in STEP-I, II, and III, respectively. In particular, fishbones in STEP-III (vs STEP-I) had a higher risk of difficult fishbones (odds ratio [OR]: 11.573, 95% CI: 7.987-16.769). Complaints of neck pain (yes vs no), foreign body sensation (yes vs no), and shorter length of fishbones always had a lower risk of difficult fishbones (OR: 0.455, 95% CI: 0.367-0.564; OR: 0.284, 95% CI: 0.191-0.422; OR: 0.727, 95% CI: 0.622-0.85). Missing teeth (yes vs no), swallowing behavior after fishbone ingestion (yes vs no), and male patients (vs female) had a higher risk of difficult fishbones (OR: 1.9, 95% CI: 1.47-2.456; OR: 1.631, 95% CI: 1.293-2.059; OR: 1.278, 95% CI: 1.047-1.56). CONCLUSIONS: Neck pain, foreign body sensation, fishbone length, patient age and sex, tooth status, and swallowing behavior after fishbone ingestion are independent risk factors for difficult fishbones.

A Predictive Model Development of Hospital Admission during Triage in a Chinese Ear, Nose, and Throat Emergency Department.

INTRODUCTION: Triaging patients into correct severity categories in an emergency department is an advanced skill that depends on a quick assessment after obtaining very little information. The purpose of this study was to assess specific risk factors associated with hospital admissions in the emergency department environment of the specialized Eye, Ear, Nose, and Throat hospital located in Shanghai, China. METHODS: This study was a retrospective cohort study. Patients visiting the emergency department in a tertiary hospital in eastern China from February 2008 to August 2015 were included. Univariate and multivariate analyses were used to identify the risk factors related to hospital admissions. Combining variables calculated from the regression equation of multivariate analysis (binary logistic regression analysis) enabled the risk factors quantification. The receiver operating characteristic analysis was used to identify the most informative cutoff point of the combining predictors. RESULTS: A total of 188715 patients were enrolled in the study. Of them, 8395 patients (4.4%) required hospital admission. Hour of visit, season, age, sex, chief complaint, anatomical location, and locale of patients were independent risk factors of hospital admission by univariate and multivariate analysis. Combining predictors were calculated from the equation of the multivariate logistic model. The area under the curve of the combining predictors was 0.949, and the 95% confidence interval was 0.947 to 0.951 (P <.001), with a sensitivity of 95.2% and a specificity of 85.6%. A cutoff score of less than -35.1975 was associated with hospital admission. DISCUSSION: This study provided a method to build a feasible predictive model of hospital admission during triage. Understanding risk factors is an important part of the triage process in order to correctly assign priorities to the patients served. The outcomes of this study would add additional information for the triage nurse to consider in assessing the patient and assigning acuity ratings. The model developed here requires validation in future research.

Clinical characteristics of otogenic lateral sinus thrombosis in patients under 18 years old compared with that in adult patients.

BACKGROUND: Otogenic lateral sinus thrombosis (OLST) is a rare complication of otitis media. We do not know whether the disease progress between the pediatric and adult OLST patients is consistent. However, pediatric surgical methods always refer to the adults'. AIMS/OBJECTIVES: This study aimed to seek evidence for suitable surgical methods in pediatric patients. MATERIALS AND METHODS: The clinical manifestation, laboratory findings, and findings in operation between children and adult groups were compared. RESULTS: Ten children and 17 adults OLST patients were included. Most pediatric patients had no history of chronic otitis media or cholesteatoma (p<.001). The ratios of otorrhea, tympanic perforation and sclerotic type mastoid in CT scan were significantly lower in the children group (p<.05). The mean air conduction hearing threshold in the children and adolescent group (31.25 ± 21.27 dB) was significantly lower than that of the adult group (77.6 ± 23.66 dB) (p<.001). The diseases in attics (66.7%) and the ossicular chain destruction (33.3%) were not as severe as those in the adult group (p<.05). The eustachian tube closure was found similar in two groups. CONCLUSIONS AND SIGNIFICANCE: Conservative surgery is recommended to pediatric OLST to obliterate the diseases and improve middle ear and mastoid drainage, preserving hearing function.

Myringoplasty With an Ultrathin Cartilage-Perichondrium Complex Graft Versus Temporalis Fascia Graft: A Propensity Score-Matched Analysis.

OBJECTIVE: To compare endoscopic myringoplasty using the cartilage-perichondrium complex as a graft (test group) with temporalis fascia microscopic myringoplasty (control group). STUDY DESIGN: A retrospective cohort study. SETTING: Department of Otorhinolaryngology in a tertiary Chinese hospital. METHODS: Data were collected on patients between 2017 and 2019. To balance the baseline characteristics between groups, we performed a propensity score-matched analysis, and 44 patients were included in each group. Hearing improvement and eardrum closure rates were compared, and risk factors affecting them were analyzed. RESULTS: In the control and test groups, 90.90% and 86.36% of patients had a mean air-bone gap ≤20 dB after the surgery, respectively (P = .843). The air conduction (AC) threshold gain at each frequency was similar in the 2 groups (P > .05). The closure rates were 95.45% and 93.18%, respectively (P = .645). The air-bone gap improved significantly after surgery, F(1, 61) = 6.729, P = .012. Age, group, middle ear mucosal status, and location of the perforation did not affect the change in air-bone gap or the drum closure rate (P > .05). However, there was an interaction between the change in air-bone gap and the size of the perforation, F(1, 61) = 11.067, P = 0001. CONCLUSION: Endoscopic myringoplasty using a cartilage-perichondrium complex graft is comparable with traditional surgery. Age, location of the perforation, and middle ear mucosal status did not significantly affect the change in air-bone gap or the drum closure rate. A perforation size ≥50% was always associated with a better air-bone gap improvement.

Direct reprogramming adult fibroblast into cells with partial inner ear hair cell characteristics through cell activation and signal directed approach.

Loss of inner ear hair cell (HC) is an irreversible process in mammals and is the most common cause of human hearing and balance disorders especially in the elderly. Cell therapy based on highly scalable generation of HC linage and inner ear transplantation is one of the most promising therapeutic approaches for HC impairment. For fibroblast is quite abundant and readily available in human body, it is an ideal endogenous cell source to generate HC lineage for transplantation purpose. In the present study, by using a cell activation and signaling directed method, we demonstrate that adult fibroblast can be direct reprogrammed into a kind of cell which expresses lots of HC markers. At the same time, an intermediate progenitor stage exists during such a lineage conversion and activation of FGF pathway is critical for its formation. Although these reprogrammed cells still lack some of the key features of HC such as mechanosensitive ion channel hence have not acquired the functional properties of HC, the findings reported here raise the possibility of reprogramming endogenous fibroblasts into functional HC for regenerative purpose.

Mechanisms of Hearing Loss in a Guinea Pig Model of Superior Semicircular Canal Dehiscence.

Defective acoustic transmission in the cochlea is closely related with various auditory and vestibular symptoms. Among them, semicircular canal dehiscence (SCD) with a defective semicircular bone is typical. Currently, the pathogenesis of SCD is usually explained by the third window hypothesis; however, this hypothesis fails to explain the variability in the symptoms and signs experienced by superior SCD (SSCD) patients. We evaluated the mechanism of hearing loss in a guinea pig model of bony dehiscence with various sizes and locations along the superior semicircular canal. Auditory brainstem responses (ABRs) and laser Doppler velocimetry were used to measure hearing loss and vibration changes before and after fenestration, as well as after restorative patching. ABR thresholds at low frequencies (e.g., 1000 Hz) increased after fenestration and decreased back to the normal range after we repaired the defect. Energy leakage from the surgically introduced third window was detected in the range of 300-1500 Hz, accompanied by increased vibration at the umbo, stapes head, and the dehiscence site, while decreased vibration was observed at the round window membrane in the same frequency range. After the patching procedure, the deviant vibrations were recovered. The degree of postfenestration energy leakage was proportional to the size of fenestration and the proximity of the fenestration site to the oval window. These results suggest that the bony fenestration of the superior semicircular canal mimics the hearing loss pattern of patients with SSCD. The decrease in perilymph wave impedance likely accounts for the auditory changes.

Cell proliferation during hair cell regeneration induced by Math1 in vestibular epithelia in vitro.

Hair cell regeneration is the fundamental method of correcting hearing loss and balance disorders caused by hair cell damage or loss. How to promote hair cell regeneration is a hot focus in current research. In mammals, cochlear hair cells cannot be regenerated and few vestibular hair cells can be renewed through spontaneous regeneration. However, Math1 gene transfer allows a few inner ear cells to be transformed into hair cells in vitro or in vivo. Hair cells can be renewed through two possible means in birds: supporting cell differentiation and transdifferentiation with or without cell division. Hair cell regeneration is strongly associated with cell proliferation. Therefore, this study explored the relationship between Math1-induced vestibular hair cell regeneration and cell division in mammals. The mouse vestibule was isolated to harvest vestibular epithelial cells. Ad-Math1-enhanced green fluorescent protein (EGFP) was used to track cell division during hair cell transformation. 5-Bromo-2'-deoxyuridine (BrdU) was added to track cell proliferation at various time points. Immunocytochemistry was utilized to determine cell differentiation and proliferation. Results demonstrated that when epithelial cells were in a higher proliferative stage, more of these cells differentiated into hair cells by Math1 gene transfer. However, in the low proliferation stage, no BrdU-positive cells were seen after Math1 gene transfer. Cell division always occurred before Math1 transfection but not during or after Math1 transfection, when cells were labeled with BrdU before and after Ad-Math1-EGFP transfection. These results confirm that vestibular epithelial cells with high proliferative potential can differentiate into new hair cells by Math1 gene transfer, but this process is independent of cell proliferation.

The Role of the Notch Signal Pathway in Mucosal Cell Metaplasia in Mouse Acute Otitis Media.

Otitis media (OM) is a major cause of morbidity in pediatric and adult patients. This inflammatory condition is characterized by mucous cell hyperplasia that is thought to produce mucins from the middle ear mucosa. We are interested in the role of Notch signalling pathway in this inflammatory process. Using an acute otitis media (AOM) mouse model through injection of Streptococcus Pneumoniae into the middle ear, histopathologic examination and quantitative RT-PCR, acute inflammation with the thickness of mucosa, Goblet cell hyperplasia, and cilia loss were determined and gene expression related to the Notch signaling pathway were evaluated. Upregulation of the mucous cell markers, Argr2 and Muc5AC, and downregulation of the cilia cell marker, Foxj1 and Dnai2, were observed in AOM. In addition, genes encoding Notch receptors and ligands (Notch1, Notch2, Notch3, Notch4 and Dll1) and the Notch target genes (Hes1, Hes5, Hey1, NRARP) in AOM decreased significantly. The expression of the Notch1 and Jagged1 also showed down-regulation throughout the mouse middle ear epithelium. Taken together, this study suggests that downregulation of the Notch signaling pathway is involved in the mucosa hyperplasia during AOM.

Shrinkage of ipsilateral taste buds and hyperplasia of contralateral taste buds following chorda tympani nerve transection.

The morphological changes that occur in the taste buds after denervation are not well understood in rats, especially in the contralateral tongue epithelium. In this study, we investigated the time course of morphological changes in the taste buds following unilateral nerve transection. The role of the trigeminal component of the lingual nerve in maintaining the structural integrity of the taste buds was also examined. Twenty-four Sprague-Dawley rats were randomly divided into three groups: control, unilateral chorda tympani nerve transection and unilateral chorda tympani nerve transection + lingual nerve transection. Rats were allowed up to 42 days of recovery before being euthanized. The taste buds were visualized using a cytokeratin 8 antibody. Taste bud counts, volumes and taste receptor cell numbers were quantified and compared among groups. No significant difference was detected between the chorda tympani nerve transection and chorda tympani nerve transection + lingual nerve transection groups. Taste bud counts, volumes and taste receptor cell numbers on the ipsilateral side all decreased significantly compared with control. On the contralateral side, the number of taste buds remained unchanged over time, but they were larger, and taste receptor cells were more numerous postoperatively. There was no evidence for a role of the trigeminal branch of the lingual nerve in maintaining the structural integrity of the anterior taste buds.

MeCP2 in the rostral striatum maintains local dopamine content critical for psychomotor control.

Methyl-CpG binding protein 2 (MeCP2) is a chromatin regulator highly expressed in mature neurons. Mutations of MECP2 gene cause >90% cases of Rett syndrome, a neurodevelopmental disorder featured by striking psychomotor dysfunction. In Mecp2-null mice, the motor deficits are associated with reduction of dopamine content in the striatum, the input nucleus of basal ganglia mostly composed of GABAergic neurons. Here we investigated the causal role of MeCP2 in modulation of striatal dopamine content and psychomotor function. We found that mice with selective removal of MeCP2 in forebrain GABAergic neurons, predominantly in the striatum, phenocopied Mecp2-null mice in dopamine deregulation and motor dysfunction. Selective expression of MeCP2 in the striatum preserved dopamine content and psychomotor function in both males and females. Notably, the dopamine deregulation was primarily confined to the rostral striatum, and focal deletion or reactivation of MeCP2 expression in the rostral striatum through adeno-associated virus effectively disrupted or restored dopamine content and locomotor activity, respectively. Together, these findings demonstrate that striatal MeCP2 maintains local dopamine content in a non-cell autonomous manner in the rostral striatum and that is critical for psychomotor control.

Changes in ADF/destrin expression in the development of hair cells following Atoh1-induced ectopic regeneration.

The aim of this study was to investigate the effects of actin depolymerizing factor (ADF)/destrin and position changes of kinetosomes in the development of hair cells following Atoh1-induced ectopic regeneration in the basilar membrane of mice. We observed through immunofluorescence at various time-points the expression of ADF/destrin and the specific kinetosome marker, γ-tubulin, in hair cells following ectopic regeneration induced by adenovirus transfection, overexpression of Atoh1 and in vitro culture. Changes of ADF/destrin distribution and kinetosome position during in vitro culture of new hair cells [Myo7a(+)] following Atoh1-induced ectopic regeneration are consistent with the changes in ADF/destrin expression and the polar migration of kinetosomes in hair cells of the cochlear sensory epithelium in normal development. ADF/destrin is involved in the development of the auditory epithelium and the development and structural rearrangement of ectopically regenerated hair cells in mammals. The kinetosomes of hair cells following Atoh1-induced ectopic regeneration show positional changes in vitro at different time-points.

Clinical characteristics of patients with labyrinthine fistulae caused by middle ear cholesteatoma.

BACKGROUND: Labyrinthine fistula (LF) is a very common clinical complication mainly caused by middle ear cholesteatoma. Whether the presence of different degree LF caused by middle ear cholesteatoma aggravates neurosensory hearing loss (NSHL) and what is the degree of the hearing loss caused by LF were still under controversial. This study aimed to investigate whether the LF degree is correlative with the age distribution, disease duration and hearing loss degree for cholesteatomatous patients. METHODS: The files of 143 patients with middle ear cholesteatoma were selected and reviewed in a retrospective study. Seventy-eight patients with LF were divided into three types according to the degree of destruction of labyrinth. Sixty-five patients without LF were randomly chosen for control. Then, we compared the clinical characteristics of patients with or without labyrinthine fistulae caused by middle ear cholesteatoma. RESULTS: According to the study, cholesteatomatous patients with LF were older and suffered longer disease duration than those without LF. Hearing loss is severe with high frequencies both in patients with and without LF. Moreover, inner ear impairment is correlative with the degree of destruction in labyrinth, and more severe destruction in labyrinth follow the more severe symptoms correlative with inner ear impairment. CONCLUSION: Surgical intervention should be performed as early as possible for these cholesteatomatous patients.

Cutaneous neuroendocrine carcinoma of the external auditory canal: a case report and review of the literature.

Cutaneous neuroendocrine carcinoma (cNEC) is rarely seen in the external ear. In this paper, we newly describe a patient with cNEC in his right external auditory canal, followed by a further discussion on the clinical features, diagnosis, and treatments of cNEC of the external ear. A review of the literature showed that cNEC of the external auditory canal generally presents as asymptomatic and that pathology yields the most confirmative diagnosis. A wide resection with adjuvant radiotherapy and chemotherapy is recommended. The overall prognosis of this condition is poor.

Identification of small non-coding RNAs in the planarian Dugesia japonica via deep sequencing.

Freshwater planarian flatworm possesses an extraordinary ability to regenerate lost body parts after amputation; it is perfect organism model in regeneration and stem cell biology. Recently, small RNAs have been an increasing concern and studied in many aspects, including regeneration and stem cell biology, among others. In the current study, the large-scale cloning and sequencing of sRNAs from the intact and regenerative planarian Dugesia japonica are reported. Sequence analysis shows that sRNAs between 18nt and 40nt are mainly microRNAs and piRNAs. In addition, 209 conserved miRNAs and 12 novel miRNAs are identified. Especially, a better screening target method, negative-correlation relationship of miRNAs and mRNA, is adopted to improve target prediction accuracy. Similar to miRNAs, a diverse population of piRNAs and changes in the two samples are also listed. The present study is the first to report on the important role of sRNAs during planarian Dugesia japonica regeneration.

Thiourea based fluorous organocatalyst.

This review deals with general and significant development of the fluorous organocatalysts based on thiourea. The applications of fluorous technology are briefly discussed. The implementations of thiourea based catalysts in organic synthesis are focused on in the chapter.

Expression of Numb and Numb-like in the development of mammalian auditory sensory epithelium.

The Numb and Numb-like are evolutionarily conserved cell fate-determining factors in mammals. For the first time, we investigate the involvement of the Numb and Numb-like in the developing auditory sensory epithelium. We show that both of them are expressed in the rat auditory sensory epithelium, and the four isoforms of the Numb have dynamic expression patterns during cochlear development. At the early stage of the auditory epithelium development, they occur in all progenitor cells. At the late stage of cell differentiation, they are expressed mainly in the cytoplasm of apical cells and their locations are different. Furthermore, we find overexpression of the Numb or Numb-like, in cochlear whole mount cultures, can upregulate mRNA level of Rath1, which is important in the hair-cell development.

Survival and fate of transplanted embryonic neural stem cells by Atoh1 gene transfer in guinea pigs cochlea.

Embryonic neural stem cells (NSCs) were isolated from the neuroepithelium of the dorsal telencephalon of embryonic rats and infected by Ad5-Atoh1-enhanced green fluorescent protein. These NSCs were then delivered into neurosphere culture medium or transplanted into the endolymphatic space of the normal guinea pig cochlea through cochleostomy. Embryonic NSC phenotype of these isolated cells was determined by immunohistochemical detection of cell-specific protein markers. Survival, location and hair cell (HC) differentiation of the implanted NSCs were determined by the expression of the report gene, enhanced green fluorescent protein, and a specific marker for HCs, Myosin VIIa. These implanted cells can survive in the endolymphatic space of the cochlea. Some of the surviving cells differentiated into HCs by Atoh1 gene transfer.