Growth factors with valproic acid restore injury-impaired hearing by promoting neuronal regeneration.

Spiral ganglion neurons (SGNs) are primary auditory neurons in the spiral ganglion that transmit sound information from the inner ear to the brain and play an important role in hearing. Impairment of SGNs causes sensorineural hearing loss (SNHL), and it has been thought until now that SGNs cannot be regenerated once lost. Furthermore, no fundamental therapeutic strategy for SNHL has been established other than inserting devices such as hearing aids and cochlear implants. Here we show that the mouse spiral ganglion contains cells that are able to proliferate and indeed differentiate into neurons in response to injury. We suggest that SRY-box transcription factor 2/SRY-box transcription factor 10-double-positive (Sox2/Sox10-double-positive) Schwann cells sequentially started to proliferate, lost Sox10 expression, and became neurons, although the number of new neurons generated spontaneously was very small. To increase the abundance of new neurons, we treated mice with 2 growth factors in combination with valproic acid, which is known to promote neuronal differentiation and survival. This treatment resulted in a dramatic increase in the number of SGNs, accompanied by a partial recovery of the hearing loss induced by injury. Taken together, our findings offer a step toward developing strategies for treatment of SNHL.

MeCP2 controls neural stem cell fate specification through miR-199a-mediated inhibition of BMP-Smad signaling.

Rett syndrome (RTT) is a severe neurological disorder, with impaired brain development caused by mutations in MECP2; however, the underlying mechanism remains elusive. We know from previous work that MeCP2 facilitates the processing of a specific microRNA, miR-199a, by associating with the Drosha complex to regulate neuronal functions. Here, we show that the MeCP2/miR-199a axis regulates neural stem/precursor cell (NS/PC) differentiation. A shift occurs from neuronal to astrocytic differentiation of MeCP2- and miR-199a-deficient NS/PCs due to the upregulation of a miR-199a target, Smad1, a downstream transcription factor of bone morphogenetic protein (BMP) signaling. Moreover, miR-199a expression and treatment with BMP inhibitors rectify the differentiation of RTT patient-derived NS/PCs and development of brain organoids, respectively, suggesting that facilitation of BMP signaling accounts for the impaired RTT brain development. Our study illuminates the molecular pathology of RTT and reveals the MeCP2/miR-199a/Smad1 axis as a potential therapeutic target for RTT.

[A CASE OF BIRD-RELATED HYPERSENSITIVITY PNEUMONITIS THAT DEVELOPED IN SUBACUTE COURSE AND PRESENTED WITH ACUTE FINDINGS].

A 52-year-old woman presented to a clinic in late August with exacerbated fatigue and dyspnea on exertion for several months. Then, she was referred and admitted to our hospital in late September. Her chest CT showed bilateral diffuse centrilobular micronodules. In her detailed clinical history, she had kept budgerigars indoors for 15 years. These findings suggested she had a bird-related hypersensitivity pneumonitis (BRHP). By a site environmental investigation, 40 budgerigars were kept in a single breeding room and there were large amounts of droppings on the floor. Serum specific antibody for bird antigens and an environmental provocation test were positive. Bronchoalveolar lavage fluid showed lymphocytosis and a low CD4/CD8 ratio. Trans-bronchial lung biopsy showed lymphocytic infiltration of the alveolar wall and interlobular septa. After antigen avoidance as hospitalization, her symptoms and abnormal shadow improved. From these results, the patient was diagnosed as an acute BRHP.BRHP often presents a chronic onset. This case was diagnosed as an acute type despite the 15-years of budgerigars breeding. Increased exposure of antigens due to lack of cleaning after several days' antigen avoidance was suspected with one of the causes of acute onset.

Modified sensory feedback enhances the sense of agency during continuous body movements in virtual reality.

The sense of agency refers to the feeling of control over one's own actions, and through them, the external events. This study examined the effect of modified visual feedback on the sense of agency over one's body movements using virtual reality in healthy individuals whose motor control was disturbed. Participants moved a virtual object using their right hand to trace a trajectory (Experiment 1) or a leading target (Experiment 2). Their motor control was disturbed by a delay in visual feedback (Experiment 1) or a 1-kg weight attached to their wrist (Experiment 2). In the offset conditions, the virtual object was presented at the median point between the desired position and the participants' actual hand position. In both experiments, participants reported improved sense of agency in the offset condition compared to the aligned condition where the visual feedback reflected their actual body movements, despite their motion being less precise in the offset condition. The results show that sense of agency can be enhanced by modifying feedback to motor tasks according to the goal of the task, even when visual feedback is discrepant from the actual body movements. The present study sheds light on the possibility of artificially enhancing body agency to improve voluntary motor control.

COVID-19 pneumonia complicated by bilateral pneumothorax: A case report.

BACKGROUND: Pneumothorax is a rare but life-threatening complication associated with pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). CASE PRESENTATION: Informed consent was obtained from the patient himself.A 50-year-old man presented with a 9-day history of fever, cough, and dyspnoea. He was diagnosed with coronavirus disease 2019 (COVID-19) pneumonia and was admitted to the Medical Hospital, Tokyo Medical and Dental University. Chest CT showed diffuse patchy ground-glass opacities (GGOs). His state of oxygenation deteriorated, and mechanical ventilation was initiated on day 4 after admission (12th day from onset). He improved gradually and was weaned from ventilation on day 15. Sudden onset of bilateral pneumothorax occurred on day 21 with severe respiratory failure, and chest CT revealed pneumatocele formation on both lower lobes. CONCLUSIONS: Pneumothorax is a notable complication in cases of severe COVID-19 pneumonia, especially in those who require positive-pressure ventilation.

Improvement of Sense of Agency During Upper-Limb Movement for Motor Rehabilitation Using Virtual Reality.

Sense of agency refers to the feeling of controlling one's own body. Many patients surviving from a stroke lose the sense of agency over their body. This is due to impairments in both motor control and sensory brain functions. As a result of this lack in the sense of agency, stroke patients tend to lose the intention of moving the paralyzed limb, which results in further deterioration of brain functions and worsening muscles and joints. The present study proposes a motor rehabilitation system using virtual reality to improve the sense of agency during upper-limb movement which is required for various daily life activities such as eating meals and operating devices. Specifically, participants were instructed to move their hand to track a moving target ball in a virtual reality environment, while the position of their real hand was measured via a motion capture system. Participants were shown another ball presenting the position of their hand in virtual reality. We tested the proposed system with healthy participants, of which the motor control was disturbed by a 1-kg weight attached on the wrist. Participants reported their sense of agency after each trial. The results showed that the sense of agency was enhanced by the proposed intervention. Our results pointed out a potentially useful method to improve the sense of agency during body movements using modified visual feedback, which may contribute to the development of rehabilitation for stroke patients.