BACKGROUND AND OBJECTIVES: Neuropathology around the cochlea could create variation from site to site in physiological thresholds of cochlear implant users. This variability would be detrimental to speech recognition with a cochlear implant for a variety of reasons, including distortion of the place code and variation in the number of neurons. The purpose of this study is to examine the relationship between thresholds of electrically evoked compound action potential (ECAP) and speech perception in children implanted with the Nucleus Freedom devices. SUBJECTS AND METHOD: Fifty-seven children implanted with the Nucleus Freedom device participated in this study. ECAP thresholds were recorded using the automated neural response telemetry test protocol. We then calculated mean threshold and three metrics to assess across-site variation within subjects: 1) the variance of T levels for all tested sites, 2) the range of T levels (highest minus lowest) across all tested sites and 3) site-to-site variation. For each subject, these measures were compared with performance on tests of word recognition. RESULTS: There was considerable across-site (within-subject) and across-subject variability in thresholds. However, we found no significant correlation between speech recognition and across-site variation of thresholds as well as mean threshold levels. CONCLUSION: These data suggest that the ECAP measures of thresholds may not be an accurate predictor of speech perception ability.
Action Potentials ; Child ; Cochlea ; Cochlear Implants ; Freedom ; Humans ; Hypogonadism ; Mitochondrial Diseases ; Neurons ; Ophthalmoplegia ; Speech Perception ; Telemetry

Isolation of induced pluripotent stem cells (iPSCs) from fully differentiated somatic cells has revolutionized existing concepts of cell differentiation and stem cells. Importantly, iPSCs generated from somatic cells of patients can be used to model different types of human diseases. They may also serve as autologous cell sources that can be used in transplantation therapy. In this study, we investigated the neuronal properties of an iPSC line that is derived from human neonatal foreskin fibroblasts (FS-1). We initially examined the morphology and marker expression of FS-1 cells at undifferentiated stage. We then spontaneously differentiated FS-1 cells in suspension culture and examined the expression of markers representing three germ layers. We finally differentiated FS-1 cells into neuronal lineages by co-culturing them with PA6 stromal cells, and found that, under the conditions we used, they have a tendency to differentiate into more forebrain-type neurons, suggesting that FS-1 iPSC-derived neural cells will be useful to be used in cell therapy of stroke or Huntington's disease, among others. Taken together, FS-1 cells derived from human neonatal fibroblasts exhibit very similar properties with human ES cells, and can provide useful sources for cell therapy and various other applications.
Cell Differentiation ; Fibroblasts ; Foreskin ; Germ Layers ; Humans ; Huntington Disease ; Induced Pluripotent Stem Cells ; Infant, Newborn ; Neurons ; Pluripotent Stem Cells ; Stem Cells ; Stroke ; Stromal Cells ; Tissue Therapy ; Transplants

The transplantation of neural precursor cells (NPCs) is known to be a promising approach to ameliorating behavioral deficits after stroke in a rodent model of middle cerebral artery occlusion (MCAo). Previous studies have shown that transplanted NPCs migrate toward the infarct region, survive and differentiate into mature neurons to some extent. However, the spatiotemporal dynamics of NPC migration following transplantation into stroke animals have yet to be elucidated. In this study, we investigated the fates of human embryonic stem cell (hESC)-derived NPCs (ENStem-A) for 8 weeks following transplantation into the side contralateral to the infarct region using 7.0T animal magnetic resonance imaging (MRI). T2- and T2*-weighted MRI analyses indicated that the migrating cells were clearly detectable at the infarct boundary zone by 1 week, and the intensity of the MRI signals robustly increased within 4 weeks after transplantation. Afterwards, the signals were slightly increased or unchanged. At 8 weeks, we performed Prussian blue staining and immunohistochemical staining using human-specific markers, and found that high percentages of transplanted cells migrated to the infarct boundary. Most of these cells were CXCR4-positive. We also observed that the migrating cells expressed markers for various stages of neural differentiation, including Nestin, Tuj1, NeuN, TH, DARPP-32 and SV38, indicating that the transplanted cells may partially contribute to the reconstruction of the damaged neural tissues after stroke. Interestingly, we found that the extent of gliosis (glial fibrillary acidic protein-positive cells) and apoptosis (TUNEL-positive cells) were significantly decreased in the cell-transplanted group, suggesting that hESC-NPCs have a positive role in reducing glia scar formation and cell death after stroke. No tumors formed in our study. We also performed various behavioral tests, including rotarod, stepping and modified neurological severity score tests, and found that the transplanted animals exhibited significant improvements in sensorimotor functions during the 8 weeks after transplantation. Taken together, these results strongly suggest that hESC-NPCs have the capacity to migrate to the infarct region, form neural tissues efficiently and contribute to behavioral recovery in a rodent model of ischemic stroke.
Animals ; Apoptosis ; Cell Differentiation ; *Cell Movement ; Embryonic Stem Cells/cytology/metabolism/*transplantation ; Glial Fibrillary Acidic Protein/genetics/metabolism ; Humans ; Infarction, Middle Cerebral Artery/metabolism/pathology/physiopathology/*surgery ; Male ; Neural Stem Cells/cytology/metabolism/*transplantation ; *Psychomotor Performance ; Rats ; Rats, Sprague-Dawley ; Receptors, CXCR4/genetics/metabolism

The reproductive tracts have an intimate relationship with reproduction because there are bacterial communities that can affect reproductive health. The differences in the bacterial community of periparturient dairy cows were investigated. Vaginal and fecal samples were collected seven days before and after calving, and DNA was extracted to sequence the V3-V4 regions of the 16S rRNA genes. In the postpartum vaginas, operational taxonomic units, Chao1, Shannon, and Simpson were decreased, and phyla Fusobacteria and Bacteroidetes were increased. In summary, bacterial abundance can affect the periparturient biological differences in dairy cows, suggesting a susceptibility to infection within one week after calving.

The reproductive tracts have an intimate relationship with reproduction because there are bacterial communities that can affect reproductive health. The differences in the bacterial community of periparturient dairy cows were investigated. Vaginal and fecal samples were collected seven days before and after calving, and DNA was extracted to sequence the V3-V4 regions of the 16S rRNA genes. In the postpartum vaginas, operational taxonomic units, Chao1, Shannon, and Simpson were decreased, and phyla Fusobacteria and Bacteroidetes were increased. In summary, bacterial abundance can affect the periparturient biological differences in dairy cows, suggesting a susceptibility to infection within one week after calving.

Purpose: We hypothesized that a radiomics approach could be employed to classify children with growth hormone deficiency (GHD) and idiopathic short stature (ISS) on sella magnetic resonance imaging (MRI). Accordingly, we aimed to develop a radiomics prediction model for differentiating GHD from ISS and to evaluate the diagnostic performance thereof. Materials and Methods: Short stature pediatric patients diagnosed with GHD or ISS from March 2011 to July 2020 at our institution were recruited. We enrolled 312 patients (GHD 210, ISS 102) with normal sella MRI and temporally split them into training and test sets (7:3). Pituitary glands were semi-automatically segmented, and 110 radiomic features were extracted from the coronal T2-weighted images. Feature selection and model development were conducted by applying mutual information (MI) and a light gradient boosting machine, respectively. After training, the model’s performance was validated in the test set. We calculated mean absolute Shapley values for each of the selected input features using the Shapley additive explanations (SHAP) algorithm. Volumetric comparison was performed for GHD and ISS groups. Results: Ten radiomic features were selected by MI. The receiver operating characteristics curve of the developed model in the test set was 0.705, with an accuracy of 70.6%. When analyzing SHAP plots, root mean squared values had the highest impact in the model, followed by various texture features. In volumetric analysis, sagittal height showed a significant difference between GHD and ISS groups. Conclusion Radiomic analysis of sella MRI may be able to differentiate between GHD and ISS in clinical practice for short-statured children.

Background: Although the evidence of treatment for coronavirus disease 2019 (COVID-19) changed rapidly, little is known about the patterns of potential pharmacological treatment during the early period of the COVID-19 pandemic in Korea and the risk factors for ineffective prescription. Methods: Using claims data from the Korean National Health Insurance System, this retrospective cohort study included admission episodes for COVID-19 from February to December 2020. Ineffective antiviral prescriptions for COVID-19 were defined as lopinavir/ ritonavir (LPN/r) and hydroxychloroquine (HCQ) prescribed after July 2020, according to the revised National Institute of Health COVID-19 treatment guidelines. Factors associated with ineffective prescriptions, including patient and hospital factors, were identified by multivariate logistic regression analysis. Results: Of the 15,723 COVID-19 admission episodes from February to June 2020, 4,183 (26.6%) included prescriptions of LPN/r, and 3,312 (21.1%) included prescriptions of HCQ.Of the 48,843 admission episodes from July to December 2020, after the guidelines were revised, 2,258 (4.6%) and 182 (0.4%) included prescriptions of ineffective LPN/r and HCQ, respectively. Patient factors independently associated with ineffective antiviral prescription were older age (adjusted odds ratio [aOR] per 10-year increase, 1.17; 95% confidence interval [CI], 1.14–1.20) and severe condition with an oxygen requirement (aOR, 2.49; 95% CI, 2.24–2.77). The prescription of ineffective antiviral drugs was highly prevalent in primary and nursing hospitals (aOR, 40.58; 95% CI, 31.97–51.50), public sector hospitals (aOR, 15.61; 95% CI, 12.76–19.09), and regions in which these drugs were highly prescribed before July 2020 (aOR, 10.65; 95% CI, 8.26–13.74). Conclusion Ineffective antiviral agents were prescribed to a substantial number of patients during the first year of the COVID-19 pandemic in Korea. Treatment with these ineffective drugs tended to be prolonged in severely ill patients and in primary and public hospitals.

Huntington’s disease (HD) is a dominantly inherited neurodegenerative disorder caused by abnormally expanded CAG repeats in the huntingtin gene. The huntingtin gene mutation leads to the progressive degeneration of striatal GABAergic medium spiny neurons (MSN) and reduces the level of brain-derived neurotrophic factor (BDNF) in HD patient’s brain. BDNF is an essential neurotrophic factor for the cortico-striatal synaptic activity and the survival of GABAergic neurons. In this study, we transplanted BDNF-overexpressing human neural stem cells (HB1.F3.BDNF) into the contra-lateral side of unilateral quinolinic acid (QA)-lesioned striatum of HD rat model. The results of in vivo transplantation were monitored using various behavioral tests, 4.7 T animal magnetic resonance imaging (MRI) and immunohistochemical staining. We observed that the QA-lesioned rats receiving HB1.F3.BDNF cells exhibited significant behavioral improvements in the stepping, rotarod and apomorphine-induced rotation tests. Interestingly, contralaterally transplanted cells were migrated to the QA-lesioned striatum and the size of lateral ventricle was reduced. Histological analyses further revealed that the transplanted cells, which had migrated to the QA lesion site, were differentiated into the cells of GABAergic, MSN-type neurons expressing DARPP-32, and neural networks were established between the transplanted cells and the host brain, as revealed by retrograde tracing. Finally, there was a significant reduction of inflammatory response in HB1.F3.BDNF-transplanted HD animal model, compared with vehicle-transplanted group. Taken together, these results suggest that HB1.F3.BDNF can be an effective therapeutic strategy to treat HD patients in the future.

Background: and Purpose Falls are not uncommon even in patients with early stages of Parkinson’s disease (PD). The aims of this study were to determine the relationships between gait parameters and falls and identify crucial gait parameters for predicting future falls in patients with de novo PD. Methods: We prospectively recruited patients with de novo PD, and evaluated their baseline demographics, global cognitive function on the Montreal Cognitive Assessment test, and parkinsonian motor symptoms including their subtypes. Both forward gait (FG) and backward gait (BG) were measured using the GAITRite system. The history of falls in consecutive patients with de novo PD was examined along with 1 year of follow-up data. Results: Among the 76 patients with de novo PD finally included in the study, 16 (21.1%) were classified as fallers. Fallers had slower gait and shorter stride for FG and BG parameters than did non-fallers, while stride-time variability was greater in fallers but only for BG. Multivariable logistic regression analysis revealed that slow gait was an independent risk factor in BG. Conclusions Among the patients with de novo PD, gait speed and stride length were more impaired for both FG and BG in fallers than in non-fallers. It was particularly notable that slow BG was significantly associated with future fall risk, indicating that BG speed is a potential biomarker for predicting future falls in patients with early-stage PD.

Induced pluripotent stem cells (iPSCs) generated from somatic cells of patients can provide immense opportunities to model human diseases, which may lead to develop novel therapeutics. Huntington's disease (HD) is a devastating neurodegenerative genetic disease, with no available therapeutic options at the moment. We recently reported the characteristics of a HD patient-derived iPSC carrying 72 CAG repeats (HD72-iPSC). In this study, we investigated the in vivo roles of HD72-iPSC in the YAC128 transgenic mice, a commonly used HD mouse model carrying 128 CAG repeats. To do this, we transplanted HD72-iPSC-derived neural precursors into the striatum of YAC128 mice bilaterally and observed a significant behavioral improvement in the grafted mice. Interestingly, the transplanted HD72-iPSC-derived neural precursors formed GABAeric neurons efficiently, but no EM48-positive protein aggregates were detected at 12 weeks after transplantation. Taken together, these results indicate no HD pathology was developed from the grafted cells, or no transmission of HD pathology from the host to the graft occurred at 12 weeks post-transplantation.
Animals ; GABAergic Neurons ; Humans ; Huntington Disease* ; Induced Pluripotent Stem Cells ; Mice ; Mice, Transgenic ; Neurons ; Pathology ; Pluripotent Stem Cells* ; Transplants