Surface Functional Modification by Ti3 C2 Tx MXene on PLLA Nanofibers for Optimizing Neural Stem Cell Engineering.

Optimizing cell substrates by surface modification of neural stem cells (NSCs), for efficient and oriented neurogenesis, represents a promising strategy for treating neurological diseases. However, developing substrates with the advanced surface functionality, conductivity, and biocompatibility required for practical application is still challenging. Here, Ti3 C2 Tx MXene is introduced as a coating nanomaterial for aligned poly(l-lactide) (PLLA) nanofibers (M-ANF) to enhance NSC neurogenesis and simultaneously tailor the cell growth direction. Ti3 C2 Tx MXene treatment provides a superior conductivity substrate with a surface rich in functional groups, hydrophilicity, and roughness, which can provide biochemical and physical cues to support NSC adhesion and proliferation. Moreover, Ti3 C2 Tx MXene coating significantly promotes NSC differentiation into both neurons and astrocytes. Interestingly, Ti3 C2 Tx MXene acts synergistically with the alignment of nanofibers to promote the growth of neurites, indicating enhanced maturation of these neurons. RNA sequencing analysis further reveals the molecular mechanism by which Ti3 C2 Tx MXene modulates the fate of NSCs. Notably, surface modification by Ti3 C2 Tx MXene mitigates the in vivo foreign body response to implanted PLLA nanofibers. This study confirms that Ti3 C2 Tx MXene provides multiple advantages for decorating the aligned PLLA nanofibers to cooperatively improve neural regeneration.

Removal of biofilm is essential for long-term ventilation tube retention.

BACKGROUND: Although long-term retention of a ventilation tube is required in many ear diseases, spontaneous removal of conventional ventilation tube is observed in patients within 3 to 12 mo. To address this issue, we aimed to determine a new method for long-term retention of the ventilation tube. AIM: To explore the value of removing the biofilm for long-term retention of tympanostomy ventilation tubes. METHODS: A case-control study design was used to evaluate the safety and effectiveness of long-term tube retention by directly removing the biofilm (via surgical exfoliation) in patients who underwent myringotomy with ventilation tube placement. The patients were randomly divided into two groups: Control group and treatment group. Patients in the treatment group underwent regular biofilm exfoliation surgery in the clinic, whereas those in the control group did not have their biofilm removed. Only conventional ventilation tubes were placed in this study. Outcome measures were tube position and patency. Tube retention time and any complications were documented. RESULTS: Eight patients with biofilm removal and eight patients without biofilm removal as a control group were enrolled in the study. The tympanostomy tube retention time was significantly longer in the treatment group (43.5 ± 26.4 mo) than in the control group (9.5 ± 6.9 mo) (P = 0.003). More tympanostomy tubes were found to be patent and in correct position in the treatment group during the follow-up intervals than in the control group (P = 0.01). CONCLUSION: Despite the use of short-term ventilation tubes, direct biofilm removal can be a well-tolerated and effective treatment for long-term tube retention of tympanostomy ventilation tubes in patients who underwent myringotomy.

Surgical Treatment and Outcomes for Sinonasal and Skull Base Phosphaturic Mesenchymal Tumors.

OBJECTIVE: To describe our clinical experience with surgical treatments for sinonasal phosphaturic mesenchymal tumors diagnosed at our institution. STUDY DESIGN: Retrospective case series. SETTING: Affiliated Sixth People's Hospital, Shanghai Jiao Tong University. SUBJECTS AND METHODS: We retrospectively reviewed the medical records of 10 patients diagnosed with phosphaturic mesenchymal tumors associated with tumor-induced osteomalacia between December 2014 and October 2019. RESULTS: There were 4 men and 6 women with a disease course of 1 to 19 years. All patients exhibited hypophosphatemia and tumor-induced osteomalacia. The tumor was located in the sinonasal region, frontal bone, and temporal bone in 8 patients, 1 patient, and 1 patient, respectively. Technetium-99m octreotide scintigraphy was used for tumor localization in 4 cases. Six patients underwent endoscopic resection; the remaining 4 underwent unilateral transorbital anterior and posterior ethmoid artery ligation + endoscopic resection, endoscopic resection + skull base repair, internal carotid artery stenting + transcatheter arterial embolization + temporal bone tumor excision + adipose tissue plugging, and endoscopic resection + transfrontal craniotomy (n = 1 each). Two patients had a history of incomplete endoscopic resection. All patients achieved clinical remission and normalized biochemical indices after surgery. Only 1 patient developed recurrence and died of a brain hernia. CONCLUSIONS: A diagnosis of sinonasal phosphaturic mesenchymal tumors should be based on a combination of clinical, imaging, and pathological findings. Technetium-99m octreotide scintigraphy helps in locating the tumor. Complete surgical excision guarantees clinical remission, and preoperative transcatheter arterial embolization or feeding artery ligation may reduce intraoperative bleeding in cases of highly vascularized tumors.

Changes in tinnitus after vestibular schwannoma surgery.

We designed a prospective study to evaluate changes in tinnitus after vestibular schwannoma (VS) surgery. Subjects included 41 patients who were diagnosed with a VS and underwent translabyrinthine microsurgery (TLM) between January 2015 and May 2016. All patients underwent related examinations and were asked to answer the Tinnitus Handicap Inventory (THI) scale and a visual analog scale (VAS) of tinnitus severity both pre- and postoperatively. Of the 41 patients, 31 (75.6%) suffered from tinnitus before surgery. Microsurgery was associated with an overall decrease in tinnitus (p < 0.001). There was a significant improvement in THI and VAS scores after surgery (p = 0.001 and p = 0.005, respectively). The decrease in THI scores in the low-frequency group was significantly larger than that of the mid- and high-frequency groups after surgery (p = 0.034 and p = 0.001, respectively). The loudness of tinnitus decreased significantly after surgery (p = 0.031). Tinnitus in patients with VS improved after TLM. Patients with mid-/high-frequency tinnitus and louder tinnitus preoperatively seemed to have a worse prognosis than those with low-frequency and quieter tinnitus.

Bilirubin induces auditory neuropathy in neonatal guinea pigs via auditory nerve fiber damage.

Bilirubin can cause temporary or permanent sensorineural deafness in newborn babies with hyperbilirubinemia. However, the underlying targets and physiological effects of bilirubin-induced damage in the peripheral auditory system are unclear. Using cochlear functional assays and electron microscopy imaging of the inner ear in neonatal guinea pigs, we show here that bilirubin exposure resulted in threshold elevation in both compound action potential (CAP) and auditory brainstem response (ABR), which was apparent at 1 hr and peaked 8 hr after drug administration. The threshold elevation was associated with delayed wave latencies and elongated interwave intervals in ABR and CAP. At 72 hr postinjection, these measures returned to control levels, except for the CAP amplitude. Cochlear microphonics remained unchanged during the experiment. Morphological abnormalities were consistent with the electrophysiological dysfunction, revealing fewer auditory nerve fibers (ANFs) in the basal turn, myelin sheath lesions of spiral ganglion neurons (SGNs) and ANFs, and loss of type 1 afferent endings beneath inner hair cells (IHCs) without loss of hair cells at 8 hr posttreatment. Similar to the electrophysiological findings, morphological changes were mostly reversed 10 days after treatment, except for the ANF reduction in the basal turn. These results suggest that hyperbilirubinemia in neonatal guinea pigs impaired auditory peripheral neuromechanisms that targeted mainly the IHC synapses and the myelin sheath of SGNs and their fibers. Our observations indicate a potential connection between hyperbilirubinemia and auditory neuropathy.

Protein kinase A and C signaling induces bilirubin potentiation of GABA/glycinergic synaptic transmission in rat ventral cochlear nucleus neurons.

Previous studies have suggested that bilirubin can potentiate GABA/glycinergic synaptic transmission in lateral superior olivary nucleus neurons, but the cellular mechanism has not been defined. The present study evaluated the possible roles of protein kinase A (PKA) and C (PKC) in bilirubin potentiation of GABA/glycinergic synaptic transmission in rat ventral cochlear nucleus (VCN) neurons. VCN neurons were acutely isolated from postnatal 10-12-day-old (P10-12) rats and were voltage-clamped in whole-cell mode. Miniature inhibitory postsynaptic currents (mIPSC) frequencies, but not amplitude, were increased by bilirubin. Forskolin (PKA activator) and H-89 (PKA inhibitor) also individually increased mIPSCs frequency, with an additional increase induced by co-incubation with bilirubin and H-89. Pretreatment with forskolin blocked bilirubin potentiation. mIPSC frequency was not altered by phorbol 12,13-diacetate (PKC activator), but mIPSC frequency was increased following co-application of bilirubin. The mIPSC frequency was increased by chelerythrine (PKC inhibitor), and then further increased after the addition of bilirubin. Neither H-89, forskolin, nor PDA, nor their co-application with bilirubin affected mIPSC amplitudes of GABA-activated (I(GABA))/glycine-activated (I(gly)) currents, suggesting a presynaptic locus of activity. Chelerythrine decreased the mIPSC amplitudes and I(GABA)/I(gly), suggesting a postsynaptic locus of activity. These data suggest that both PKA and PKC can modulate GABA and glycine release in rat VCN neurons. Bilirubin facilitates transmitter release via presynaptic PKA activation, which might provide insight into the cellular mechanism underlying bilirubin-induced hearing dysfunction.

[Cochlear implantation with suprameatal approach in Chinese children].

OBJECTIVE: To investigate the technique of the suprameatal approach for cochlear implantation in Chinese profound sensory hearing loss children. METHODS: Suprameatal approach for cochlear implantation were used in 50 cases (total 53 ears) with profound sensory hearing loss from May 2005 to January 2007. The electrode was passed through the suprameatal tunnel and went between the incus and chorda tympani into the scala tympani. RESULTS: Electrodes were completely inserted in 51 ears. There were no postoperative complications in all cases. Although the long effect need to be observed, all cases received better hearing and speech development benefit from cochlear implantation in the follow-up period. Among the 50 cases, 26 had speech perception in the open condition; 18 patients could speak short sentences although not clearly; and 6 patients learned to speak individual words only. CONCLUSIONS: The suprameatal approach was found to be a simple and safe technique that does not need mastoidectomy and avoid endangering the facial nerve and the chorda tympani. It enables wide exposure of middle ear and is especially suitable for cases with narrow facial recess or anteriorly located facial nerve.

The effect of noise-induced sloping high-frequency hearing loss on the gap-response in the inferior colliculus and auditory cortex of guinea pigs.

Gap detection has been used as an evaluation tool for temporal processing in subjects with sensorineural hearing loss (SNHL). However, the results from other reports are varied making it difficult to clearly define the impact of SNHL on the temporal processing ability of the auditory system. Specifically, we do not know if and how a high-frequency hearing loss impacts, presumably through off-channel interaction, the temporal processing in low-frequency channels where hearing sensitivity is virtually normal. In this experiment, gap-evoked responses in a low-frequency band (0.5-8 kHz) were recorded in the inferior colliculus (IC) and auditory cortex (AC) of guinea pigs through implanted electrodes, before and after a slopping high-frequency hearing loss, which was induced by over-stimulation using a 12-kHz-tone. The results showed that the gap thresholds in the low-frequency region increased gradually and became significantly higher 8 weeks after the induced high-frequency hearing loss. In addition, the response latency was slightly increased in the IC but this was not true for the AC. These results strongly indicate that a high-frequency hearing loss exerted an off-channel impact on temporal processing in the low-frequency region of the auditory system.

[Duration-tuning of the neurons in the inferior colliculus of guinea pigs and the role of gamma-aminobutyric acid mediated inhibition].

OBJECTIVE: To evaluate duration tuning in the inferior colliculus (IC) of guinea pigs and the role of GABA-mediated inhibition on this tuning. METHODS: Totally 23 healthy albino guinea pigs of either sex were employed in this study. After anesthesia, spikes of neurons in inferior colliculus were recorded using five-barrel glass-pipettes. The characteristic frequency was determined by recording iso-intensity response curves at moderate intensity level (40-70 dB SPL) and duration tuning was measured with signals of fixed intensity and varied durations. GABA-A receptor antagonist, bicuculline, was applied to neurons by means of in vivo micro-iontophoresis through one channel in the five-barrel glass-pipettes. RESULTS: IC neurons of guinea pigs, especially for those who showed sustained temporal response pattern, showed stronger duration tuning in their transient response peak to signal onset. Among 207 neurons recorded, totally 93 neurons were found to show clear duration selectivity. The duration selectivity was eliminated or turned to be weaker in most of the neurons in which the effect of bicuculline was observed successfully. CONCLUSIONS: Unlike what was reported in bats, duration selectivity may be a transient process for most of IC neurons in guinea pigs. Duration selectively of IC neurons in the guinea pig was also largely dependent on the GABAergic inhibition.

Cochlear function after selective spiral ganglion cells degeneration induced by ouabain.

BACKGROUND: Ouabain, a cardiac glycoside that specifically binds to Na/K-ATPase and inhibits its activity, was applied to gerbils to develop a method for studying auditory neuropathy. METHODS: Ouabain was applied to the round window of the cochlea in each gerbil by using a piece of gelfoam with 3 microl or 24 microl (1 mmol/L) ouabain solution. The changes of the threshold of auditory brainstem response, cochlear function round window electrocochleography, as well as the morphological changes of the spiral ganglion cells of the cochlea were observed after application of ouabain for 24 hours or 96 hours. RESULTS: In ouabain treated gerbils, auditory brainstem response and compound action potential thresholds showed either elevation or no response at all. However, the thresholds of cochlear microphonic and distortion product otoacoustic emissions were not affected. Degeneration and necrosis of some spiral ganglion cells in ears with applications of ouabain (24 hours, 3 microl, 1 mmol/L; 96 hours, 24 microl, 1 mmol/L ouabain). The number of spiral ganglion cells was decreased (24 hours, 3 microl, 1 mmol/L ouabain) or near to a total loss (96 hours, 24 microl, 1 mmol/L ouabain). CONCLUSIONS: These results indicate a high degree of independence between the spiral ganglion cells and the outer hair cell systems in the cochlear transduction mechanism. The method used in this study would provide a valuable tool for studying auditory neuropathy.