Ephrin-A3 is required for tonotopic map precision and auditory functions in the mouse auditory brainstem.

Tonotopy is a prominent feature of the vertebrate auditory system and forms the basis for sound discrimination, but the molecular mechanism that underlies its formation remains largely elusive. Ephrin/Eph signaling is known to play important roles in axon guidance during topographic mapping in other sensory systems, so we investigated its possible role in the establishment of tonotopy in the mouse cochlear nucleus. We found that ephrin-A3 molecules are differentially expressed along the tonotopic axis in the cochlear nucleus during innervation. Ephrin-A3 forward signaling is sufficient to repel auditory nerve fibers in a developmental stage-dependent manner. In mice lacking ephrin-A3, the tonotopic map is degraded and isofrequency bands of neuronal activation upon pure tone exposure become imprecise in the anteroventral cochlear nucleus. Ephrin-A3 mutant mice also exhibit a delayed second wave in auditory brainstem responses upon sound stimuli and impaired detection of sound frequency changes. Our findings establish an essential role for ephrin-A3 in forming precise tonotopy in the auditory brainstem to ensure accurate sound discrimination.

Focal Suppression of Epileptiform Activity in the Hippocampus by a High-frequency Magnetic Field.

Electric current has been used for epilepsy treatment by targeting specific neural circuitries. Despite its success, direct contact between the electrode and tissue could cause side effects including pain, inflammation, and adverse biological reactions. Magnetic stimulation overcomes these limitations by offering advantages over biocompatibility and operational feasibility. However, the underlying neurological mechanisms of its action are largely unknown. In this work, a magnetic generating system was assembled that included a miniature coil. The coil was positioned above the CA3 area of mouse hippocampal slices. Epileptiform activity (EFA) was induced with low Mg2+/high K+ perfusion or with 100 µM 4-aminopyridine (4-AP). The miniature coil generated a sizable electric field that suppressed the local EFA in the hippocampus in the low-Mg2+/high-K+ model. The inhibition effect was dependent on the frequency and duration of the magnetic stimulus, with high frequency being more effective in suppressing EFA. EFA suppression by the magnetic field was also observed in the 4-AP model, in a frequency and duration - dependent manner. The study provides a platform for further investigation of cellular and molecular mechanisms underlying epilepsy treatment with time varying magnetic fields.

Establishing the waist as the better location for attaching a single accelerometer to estimate center of pressure trajectories.

BACKGROUND: In this study, we seek to replace conventional force platforms with a single accelerometer for measuring Center of Pressure trajectories, in order to achieve portability and convenience without sacrificing accuracy. METHODS: We measure the actual Anterior/Posterior and Medial/Lateral Center of Pressure trajectories of ten healthy young subjects using a force platform, and compare them with estimated measurements derived from accelerometer signals collected from three body locations (upper trunk, waist, and lower thigh) using three machine learning algorithms (Neural Network, Genetic Algorithm, and Adaptive Network-based Fuzzy Inference System). Error ratios and correlation coefficients corresponding to body locations were compared via one-way repeated-measures ANOVA. The ratios and coefficients corresponding to the three algorithms were also compared using the same approach. FINDINGS: Estimated Anterior/Posterior trajectories indicated that measurements collected from the waist provided the lowest margins of error (8.1-8.4% v. 12.1-13.4%, P ≤ .001) and the highest correlation (.95 v. .82-.86, P ≤ .032). Estimated Medial/Lateral trajectories indicated that measurements collected from both the waist and thigh, as compared to the upper trunk, provided lower margins of error (7.0-7.3% v. 8.5-10.8%). In general, the waist is the better accelerometer attachment location. INTERPRETATION: The results of our study corroborate our deduction that the high correlation between Center of Pressure and body's Center of Mass provides the rationale to place the single accelerometer close to the waist for Center of Pressure estimations. This study also supports the feasibility of using one single accelerometer programmed with algorithms for similar clinical applications.

Hormone replacement therapy decreases the risk of tinnitus in menopausal women: a nationwide study.

The incidence and risk of tinnitus associated with hormone replacement therapy (HRT) in menopausal women have not yet been fully examined. We examined the medical records of menopausal women aged between 45 and 79 years from Taiwan's National Health Insurance Research Database of records between 1 January 2000 and 31 December 2010 to establish matched cohorts (13,920 HRT users and 41,760 nonusers). The incidence of tinnitus in HRT users and nonusers were matched 1:3 based on propensity-score matching over this ten year period. The Cox regression hazard model was used to identify risk factors of tinnitus, and results indicate that a significantly lower percentage of HRT users (P = 0.017) developed tinnitus in comparison with nonusers (0.43%, 60/13, 920 vs. 0.59%, 246/41, 760). Using Cox regressions analysis after adjustments for age and other variables (adjusted hazard ratio: 0.505 (95% confidence interval, 0.342-0.756)), we were also able to show that HRT users appeared to have a reduced risk of developing tinnitus in comparison with nonusers. Based on our observation of the lower incidence of tinnitus among HRT users in this cohort, we speculate that HRT may have provided potential benefits on the management and prevention of tinnitus among menopausal women.