A pharynx-to-brain axis controls pharyngeal inflammation-induced anxiety.

Anxiety is a remarkably common condition among patients with pharyngitis, but the relationship between these disorders has received little research attention, and the underlying neural mechanisms remain unknown. Here, we show that the densely innervated pharynx transmits signals induced by pharyngeal inflammation to glossopharyngeal and vagal sensory neurons of the nodose/jugular/petrosal (NJP) superganglia in mice. Specifically, the NJP superganglia project to norepinephrinergic neurons in the nucleus of the solitary tract (NTSNE). These NTSNE neurons project to the ventral bed nucleus of the stria terminalis (vBNST) that induces anxiety-like behaviors in a murine model of pharyngeal inflammation. Inhibiting this pharynx→NJP→NTSNE→vBNST circuit can alleviate anxiety-like behaviors associated with pharyngeal inflammation. This study thus defines a pharynx-to-brain axis that mechanistically links pharyngeal inflammation and emotional response.

Relationships between bilateral auditory brainstem activity and inter-implant interval in children with cochlear implants.

PURPOSE: To investigate the effect of the interval between bilateral cochlear implantation on the development of bilateral peripheral auditory pathways as revealed by the electrically evoked auditory brainstem response (EABR). METHODS: Fifty-eight children with profound bilateral sensorineural hearing loss were recruited. Among them, 33 children received sequential bilateral cochlear implants (CIs), and 25 children received simultaneous bilateral CIs. The bilateral EABRs evoked by electrical stimulation from the CI electrode were recorded on the day of second-side CI activation. RESULTS: The latencies of wave III (eIII) and wave V (eV) were significantly shorter on the first CI side than on the second CI side in children with sequential bilateral CIs but were similar between the two sides in children with simultaneous bilateral CIs. Furthermore, the latencies were prolonged from apical to basal channels along the cochlea in the two groups. In children with sequential CIs, the inter-implant interval was negatively correlated with the eV latency on the first CI side and was positively correlated with bilateral differences in the eIII and eV latencies. CONCLUSIONS: Unilateral CI use promotes the maturation of ipsilateral auditory conduction function. However, a longer inter-implant interval results in more unbalanced development of bilateral auditory brainstem pathways. Bilateral cochlear implantation with no or a short interval is recommended.

The effect of cochlear size on electrically evoked auditory brainstem responses in deaf children.

Objectives: To investigate the relationship between auditory pathway function and cochlear size in deaf children with a radiologically normal inner ear or Mondini malformation. Methods: Thirty-five deaf children without inner ear malformations (IEMs) and forty cases with Mondini malformation were included in this study. The electrically evoked auditory brainstem responses (EABRs) evoked by electrical stimulation at the round window niche (RWN) and round window membrane (RWM) were recorded during cochlear implantation (CI) surgery. The anatomical parameters of the cochlea were assessed by high-resolution computed tomography and OTOPLAN 3-D construction software. Correlations between EABRs and cochlear sizes were analyzed. Results: The EABR thresholds and/or latencies were negatively correlated with the basal cochlear diameter, cochlear width and/or cochlear duct length in both patients without IEMs and those with Mondini malformation. Conclusion: The physiological function of the peripheral auditory system depends on the anatomical structure of the cochlea to an extent. A larger cochlear size appears to be associated with better auditory conduction function. Our findings may be beneficial to selection of the proper electrode type and prediction of postoperative auditory rehabilitation. Level of Evidence: Level 4.

Electrically Evoked Auditory Brainstem Responses in Children Fitted with Hearing Aids Prior to Cochlear Implantation.

This study investigates the effect of hearing aid use on the peripheral auditory pathways in children with sensorineural hearing loss prior to cochlear implantation, as revealed by the electrically evoked auditory brainstem response (EABR). Forty children with hearing aids were recruited. Half of them had normal inner ear structures and the other half had inner ear malformations (IEMs). The EABR was evoked by electrically stimulating the round window niche (RWN) and round window membrane (RWM) during the cochlear implantation operation. The onset age of hearing aid use was significantly correlated with the peak latencies, but not amplitudes, of the wave III (eIII) and wave V (eV). Higher EABR thresholds were found for RWN stimulation than for RWM stimulation and in the children with IEMs than in those without IEMs. Our study provides neurophysiological evidence that earlier use of hearing aids may ameliorate physiological functions of the peripheral auditory pathway in children with and without IEMs. The EABR evoked by the electrical stimulation at RWM is more sensitive compared with that at RWN for evaluating functions of the auditory conduction pathway.

Evidence for predictions established by phantom sound.

Predictions, the bridge between the internal and external worlds, are established by prior experience and updated by sensory stimuli. Responses to omitted but unexpected stimuli, known as omission responses, can break the one-to-one mapping of stimulus-response and can expose predictions established by the preceding stimulus built up. While research into exogenous predictions (driven by external stimuli) is often reported, that into endogenous predictions (driven by internal percepts) is rarely available in the literature. Here, we report evidence for endogenous predictions established by the Zwicker tone illusion, a phantom pure-tone-like auditory percept following notch noises. We found that MMN, P300, and theta oscillations could be recorded using an omission paradigm in subjects who can perceive Zwicker tone illusions, but could not in those who cannot. The MMN and P300 responses relied on attention, but theta oscillations did not. In-depth analysis shows that an increase in single-trial theta power, including total and induced theta, with the endogenous prediction, is lateralized to the left frontal brain areas. Our study depicts that the brain automatically analyzes internal perception, progressively establishes predictions and yields prediction errors in the left frontal region when a violation occurs.

Event-Related Potential Evidence for Involuntary Consciousness During Implicit Memory Retrieval.

Classical notion claims that a memory is implicit if has nothing to do with consciousness during the information retrieval from storage, or is otherwise explicit. Here, we demonstrate event-related potential evidence for involuntary consciousness during implicit memory retrieval. We designed a passive oddball paradigm for retrieval of implicit memory in which an auditory stream of Shepard tones with musical pitch interval contrasts were delivered to the subjects. These contrasts evoked a mismatch negativity response, which is an event-related potential and a neural marker of implicit memory, in the subjects with long-term musical training, but not in the subjects without. Notably, this response was followed by a salient P3 component which implies involvement of involuntary consciousness in the implicit memory retrieval. Finally, source analysis of the P3 revealed moving dipoles from the frontal lobe to the insula, a brain region closely related to conscious attention. Our study presents a case of involvement of involuntary consciousness in the implicit memory retrieval and suggests a potential challenge to the classical definition of implicit memory.

Electrically evoked auditory brainstem responses in deaf patients with Mondini malformation during cochlear implantation.

PURPOSE: To investigate the auditory pathway functions in deaf patients with Mondini malformation using the electrically evoked auditory brainstem response (EABR) during cochlear implantation (CI). METHODS: A total of 58 patients with severe to profound sensorineural hearing loss (SNHL) were included in this study. Of these patients, 27 cases had Mondini malformation and 31 control cases had no inner ear malformations (IEMs). Intraoperative EABRs evoked by electrical stimulation at the round window niche (RWN) and round window membrane (RWM) were recorded. RESULTS: Patients with Mondini malformation showed significantly lower EABR extraction rates than those with no IEMs did. However, for patients who showed EABRs, no significant difference in EABR thresholds, wave III (eIII) latencies, wave V (eV) latencies or eIII-eV latency intervals was found between two groups. CONCLUSION: The physiological functions of the peripheral auditory system in patients with Mondini malformation may divide into opposite extremes, as revealed by a robust EABR and the absence of the EABR, respectively. The auditory conduction function should be objectively and individually evaluated for patients with Mondini malformation by the EABR.

Characteristics of electrically evoked auditory brainstem response in children with large vestibular aqueduct syndrome after cochlear implantation.

BACKGROUND: The vestibular aqueduct (VA) width may affect the auditory conduction pathway of large vestibular aqueduct syndrome (LVAS) children. OBJECTIVE: Analyzing the electrically evoked auditory brainstem response (EABR) after cochlear implantation (CI) in severe to profound sensorineural hearing loss (SNHL) children with LVAS. MATERIALS AND METHODS: Fifty-four children with SNHL who received CI were selected, including 21 children with LVAS and 33 children without inner ear malformations (IEMs). The VA width was measured in LVAS children. The post-operative EABRs were recorded in all children. RESULTS: For the LVAS group, the VA width was positively correlated with wave III (eIII) latency of EABR at the No. 2 electrode (E2), E5, E8, and E11, the VA width was positively correlated with wave V (eV) latency of EABR at E2, E5, E8, and E11. Only the eV latency of E2 showed a significant difference between the two groups. CONCLUSION AND SIGNIFICANCE: SNHL children with LVAS and no IEMs have similar conduction of the auditory pathway. In the LVAS group, the conduction of the auditory pathway becomes better with the decrease of VA width. Rational use of post-operative EABRs and the measurement of anatomical parameters can effectively assess the development of part auditory pathways in LVAS children, which may be helpful in predicting post-operative speech and hearing recovery.

Auditory Sensory Gating in Children With Cochlear Implants: A P50-N100-P200 Study.

Background: While a cochlear implant (CI) can restore access to audibility in deaf children, implanted children may still have difficulty in concentrating. Previous studies have revealed a close relationship between sensory gating and attention. However, whether CI children have deficient auditory sensory gating remains unclear. Methods: To address this issue, we measured the event-related potentials (ERPs), including P50, N100, and P200, evoked by paired tone bursts (S1 and S2) in CI children and normal-hearing (NH) controls. Suppressed amplitudes for S2 compared with S1 in these three ERPs reflected sensory gating during early and later phases, respectively. A Swanson, Nolan, and Pelham IV (SNAP-IV) scale was performed to assess the attentional performance. Results: Significant amplitude differences between S1 and S2 in N100 and P200 were observed in both NH and CI children, indicating the presence of sensory gating in the two groups. However, the P50 suppression was only found in NH children and not in CI children. Furthermore, the duration of deafness was significantly positively correlated with the score of inattention in CI children. Conclusion: Auditory sensory gating can develop but is deficient during the early phase in CI children. Long-term auditory deprivation has a negative effect on sensory gating and attentional performance.

Electrically evoked auditory brainstem responses to electrical stimulation at round window membrane in congenitally deaf children at different ages.

OBJECTIVES: To investigate the usefulness of measuring the electrically evoked auditory brainstem responses (eABRs) to electrical stimulation at the round window niche (RWN) and round window membrane (RWM) and the effect of deafness duration on functions of the auditory pathway to the level of the brainstem. METHODS: According to the age at cochlear implantation (CI), 99 children with profound sensorineural hearing loss were divided into four groups: ≤12 months (group A), 13-36 months (group B), 37-60 months (group C) and >60 months (group D). The eABRs were evoked by electrical stimulation at RWN and RWM during the operation of CI. RESULTS: The higher eABR extraction rate and lower threshold for RWM stimulation was found than those for RWN stimulation. The eⅢ latencies and eⅢ-eⅤ latency intervals for RWM stimulation were similar among four groups. However, children with earlier CI (group A) showed a significantly shorter eⅤ latency than others. CONCLUSION: The eABR evoked by the electrical stimulation at RWM is more stable and sensitive compared with that at RWN for evaluating functions of the auditory conduction pathway. Development in the upper brainstem pathway may be more vulnerable to long-term deafness as revealed by the eⅤ latency.

Deficient sensory and cognitive processing in children with cochlear implants: An event-related potential study.

Compared with children having normal hearing (NH), those with cochlear implants (CIs) perform poorly in spoken language comprehension which involves both low-level acoustic encoding and higher-level cognitive processing. Here, we performed an electroencephalography study to portray this brain dynamics of speech perception in CI children. We presented a Mandarin Chinese monosyllable or four-syllable idiom to CI and NH children, and infrequently varied its lexical tone to form a novel monosyllable or pseudo-idiom in an oddball paradigm. The tone contrast embedded in the monosyllables evoked similar mismatch negativities (MMNs) in CI and NH children at an early stage (~200 ms). However, the amplitude of the MMN evoked by the tone contrast in the idiom context was significantly lower in CI children than in NH children. Furthermore, robust late discriminative negativity (LDN) at a late stage (~500 ms) was found only in NH children, but not in CI children. The MMN and LDN findings indicate deficits of low-level acoustic encoding in a complex context (such as an idiom) and higher-level cognitive processing in CI children, respectively. Both deficient sensory and cognitive processing may contribute to the speech perception difficulties in CI children.

Effect of unilateral cochlear implant use on contralateral electrically evoked auditory brainstem responses to round window membrane electrical stimulation.

BACKGROUND: Long-term use of a unilateral cochlear implant (CI) may lead to abnormal development of contralateral auditory pathway. OBJECTIVES: To investigate the usefulness of measuring the electrically evoked auditory brainstem response (eABR) with the electrical stimulation at the round window membrane and the effect of unilateral CI use on the contralateral auditory pathway functions. MATERIALS AND METHODS: According to duration of unilateral CI use, 45 children with severe or profound sensorineural hearing loss were divided into sCI (≤12 months), lCI (≥24 months) and nCI (no CI use) groups. Intra-operative eABRs evoked by electrical stimulation at the round window membrane were recorded. RESULTS: The latencies of eIII and eV were significantly longer in lCI group than in sCI group and in nCI group, respectively, but not significantly different between sCI group and nCI group. The eABR thresholds and eIII-eV latency intervals were not significantly different among three groups. CONCLUSIONS AND SIGNIFICANCE: The eABR evoked by the electrical stimulation at the round window membrane is a reliable and effective way of evaluating functions of the auditory pathway in deaf children. Long-term use of a unilateral CI may promote the degenerative process of the contralateral auditory pathway to the level of the brainstem.

Serum level and clinical significance of vitamin E in children with allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) is one of the most prevalent allergic diseases in children. This study aimed to investigate the association between serum concentrations of vitamin E and AR to determine if the vitamin E level is correlated with the occurrence and severity of AR. METHODS: A total of 113 children were enrolled in this cross-sectional study. Sixty-five children in the outpatient group were diagnosed with AR, and 48 healthy children were recruited as controls. All subjects underwent serum vitamin E (adjusted for total cholesterol and triglycerides) measurements. Serum to total IgE (tIgE), the five most common allergen-specific IgE (sIgE) levels and skin prick test (SPT) were measured in children with AR. The severity of AR was assessed with the nasal symptoms score, and the situation of exposure to passive smoking were inquired. RESULTS: Serum vitamin E levels were significantly lower in the AR group than in the normal children (P < 0.001). A significant negative correlation was observed between serum vitamin E levels and sIgE as well as the SPT grade. Serum vitamin E levels were also inversely related to the nasal symptoms score; however, statistical significance was not found. CONCLUSIONS: A significantly lower vitamin E level was found in children with AR. Lower serum vitamin E levels may have correlation with the occurrence of AR in children. However, serum vitamin E levels were not statistically correlated with the severity of AR.

Deficit of long-term memory traces for words in children with cochlear implants.

OBJECTIVE: Language experience can develop long-term memory traces for speech units in the brain, to ensure efficient processing of speech sounds. However, prelingually deafened children lack sufficient auditory input before cochlear implantation. Whether the experience-dependent long-term memory traces exist in prelingually deafened children with cochlear implants (CIs) remains unclear. METHODS: We presented CI and normal hearing (NH) children with Mandarin Chinese spoken disyllables in an oddball paradigm and recorded event-related potentials. Each disyllable was defined as a meaningful word or a meaningless pseudoword by the tonal information in the second syllable. RESULTS: The amplitude of mismatch negativity (MMN) elicited by words was larger than that elicited by pseudowords in NH children. However, this enhancement of the MMN amplitude was not found in CI children. Behavioral results showed later recognition points for words and lower accuracies for speech comprehension in CI children than in NH children. Furthermore, increased theta power for words compared with pseudowords was only found in NH children. CONCLUSIONS: Our findings indicate a deficit of long-term memory traces for words in prelingually deafened children with cochlear implants. SIGNIFICANCE: Early speech input may be crucial to the formation of long-term memory traces for speech units.

MiR-196b affects the progression and prognosis of human LSCC through targeting PCDH-17.

OBJECTIVE: To explore the effect of miR-196bon the biological features of human laryngeal squamous cell carcinoma (LSCC) through targeting PCDH-17. METHODS: miR-196b and PCDH-17 expressions were determined in tissues, and the targeting relation of miR-196b and PCDH-17 was verified through dual-luciferase reporter system. In vitro, Hep-2 cells were divided into the Control, miR-196b inhibitors, miR-NC, PCDH-17, and miR-196b mimics+PCDH-17 groups. The miR-196b and PCDH-17 expressions were determined by qRT-PCR or/and Western blot, and the biological features by MTT, Annexin V-FITC/PI, wound-healing and Transwell assays. RESULTS: MiR-196b was found to be up-regulated, while PCDH-17 was down-regulated in a negative correlation in LSCC patients, which was related to histological grade and TNM stage. And low expression of miR-196b and high expression of PCDH-17 contributed to an increase in the 5-year-survival rate of LSCC patients. Besides, miR-196b directly targeted PCDH-17, while miR-196b inhibitors could up-regulate the PCDH-17 in Hep-2 cells. Moreover, miR-196b inhibitors and PCDH-17 curbed Hep-2 cell proliferation but facilitated the apoptosis, with decreases in cell invasion and migration. In addition, no statistical significance was found in cell proliferation, apoptosis, invasion and migration between Control group and miR-196b mimics+PCDH-17 group. CONCLUSION: LSCC patients exhibited the up-regulated miR-196b and down-regulated PCDH-17, which are correlated with the major clinical features and prognosis. Inhibiting miR-196b may suppress proliferation, migration and invasion abilities, and promote apoptosis of Hep-2 cells via targeting PCDH-17.

[Clinical analysis of vocal fold firbrous mass].

OBJECTIVES: To explore the character of laryngoscopy finding, voice, and therapy of vocal fold fibrous mass. METHODS: Clinical data, morphology, voice character, surgery and pathology of 15 cases with vocal fold fibrous mass were analyzed. RESULTS: The morbidity of vocal fold fibrous mass might be related to overuse of voice and laryngopharyngeal reflex. Laryngoscopy revealed shuttle line appearance, smoothness and decreased mucosal wave of vocal fold. These patients were invalid for voice training and might be improved by surgery, but recovery is slow. CONCLUSIONS: The morbidity of vocal fold fibrous mass might be related to overuse of voice and laryngopharyngeal reflex. Conservative treatment is ineffective for this disease, and surgery might improve.

Influence of crocetin on high-cholesterol diet induced atherosclerosis in rats via anti-oxidant activity together with inhibition of inflammatory response and p38 MAPK signaling pathway.

The present study aimed to investigate the effect and possible mechanism of action of crocetin on the high cholesterol diet (HCD) induced atherosclerosis rat. The Wistar rats were used in the current investigation. The rats were divided into following group, Group I: control, Group II: HCD induced AS, Group III: AS + crocetin (25 mg/kg), Group IV: AS + crocetin (50 mg/kg) and Group V: AS + Simvastatin, respectively. AS was induced in the rats using the vitamin D3 and HCD. The rats received the pre-determined treatment for the 10 weeks. After the study period, the level of lipid profile, malonaldehyde (MDA) and superoxide dismutase (SOD) were also estimated. The proinflammatory cytokines viz., tumor necrosis factor (TNF)-α and interleukin (IL)-6 were scrutinized using the ELISA kits. We also estimated the expression of phosphorylated p38 (p-p38) MAPK using the Western blot techniques. The results revealed that the AS was successfully induced in the rats. The AS control group rats showed the modulated level of lipid profile, and decreased the level of the SOD and boost the level of the MDA as compared with the normal control. However, crocetin thrived in enhancing the lipid profile toward the standard value in the normal control group rats. The crocetin and simvastatin group rats significantly inhibited the expression of the p-p38 MAPK as compared to the AS group rats. In conclusion, the current investigation revealed that the crocetin reduced the HCD induced dyslipidemia in the Wistar rats, the possible mechanism of action may be connected to the antioxidative, down regulating of p-p38 MAPK and antiinflammatory effect by crocetin.

Evaluation of the circulating MicroRNA-495 and Stat3 as prognostic and predictive biomarkers for lower extremity deep venous thrombosis.

This study aims to elucidate the prognostic and predictive biomarker of miR-495 and Stat3 in peripheral blood in relation to lower extremity deep venous thrombosis (DVT). Patients with lower limb fractures were assigned into case and control groups. Rats were allocated into blank (normal rats), sham (normal rats), DVT, miR-495 mimic, miR-495 inhibitor, over-Stat3, and si-Stat3 groups. ELISA was used to detect levels of prothrombin time (PT), endothelin-1 (ET-1), Human Fibrinogen (FIB), D-Dimer, blood coagulation factors V and VIII, tissue type plasminogen activator (t-PA), platelet activating factor (PAF), protein C and Stat3. qRT-PCR was employed for the evaluation of the expressions of miR-495 and Stat3, while receiver operating characteristic (ROC) curve was constructed to assess the predictive value of miR-495 and Stat3 as well as the treatment outcomes of patients with lower limb fractures. Logistic regression analyses were conducted in order to correlate indexes and lower extremity DVT. miR-495 overexpression, t-PA, PAF, and protein C were confirmed to be protective factors, while Stat3 overexpression, PT, ET-1, FIB, D-Dimer, blood coagulation factor V, and VIII were all ultimately considered to be risk factors of lower extremity DVT. Stat3 was confirmed to be the target gene of miR-495. Compared with the blank group, the length and weight of the thrombus as well as the ratio between length and weight, mRNA and protein expression of Stat3 were reduced in the miR-495 mimic and si-Stat3 groups. Our findings suggest that through the suppression of Stat3 expression, miR-495 prohibits lower extremity DVT in peripheral blood.