Extracellular vesicles-based point-of-care testing for the diagnosis and monitoring of Alzheimer's disease.

Alzheimer's disease (AD) is a debilitating condition that affects millions of people worldwide. One promising strategy for detecting and monitoring AD early on is using extracellular vesicles (EVs)-based point-of-care testing; however, diagnosing AD using EVs poses a challenge due to the low abundance of EV-biomarkers. Here, we present a fully integrated organic electrochemical transistor (OECT) that enables high accuracy, speed, and convenience in the detection of EVs from AD patients. We incorporated self-aligned acoustoelectric enhancement of EVs on a chip that rapidly propels, enriches, and specifically binds EVs to the OECT detection area. With our enhancement of pre-concentration, we increased the sensitivity to a limit of detection of 500 EV particles/µL and reduced the required detection time to just two minutes. We also tested the sensor on an AD mouse model to monitor AD progression, examined mouse Aß EVs at different time courses, and compared them with intraneuronal Aß cumulation using MRI. This innovative technology has the potential to diagnose Alzheimer's and other neurodegenerative diseases accurately and quickly, enabling monitoring of disease progression and treatment response.

Integrating multimodality magnetic resonance imaging to the Allen Mouse Brain Common Coordinate Framework.

High-resolution magnetic resonance imaging (MRI) affords unique image contrasts to nondestructively probe the tissue microstructure; validation of MRI findings with conventional histology is essential to better understand the MRI contrasts. However, the dramatic difference in the spatial resolution and image contrast of these two techniques impedes accurate comparison between MRI metrics and traditional histology. To better validate various MRI metrics, we acquired whole mouse brain multigradient recalled-echo and multishell diffusion MRI datasets at 25-µm isotropic resolution. The recently developed Allen Mouse Brain Common Coordinate Framework (CCFv3) provides opportunities to integrate multimodal and multiscale datasets of the whole mouse brain in a common three-dimensional (3D) space. The T2*, quantitative susceptibility mapping, diffusion tensor imaging, and neurite orientation dispersion and density imaging parameters were compared with both serial two-photon tomography images and 3D Nissl staining images in the CCFv3 at the same spatial resolution. The correlation between MRI and Nissl staining strongly depends on different metrics and different regions of the brain. Integrating different imaging modalities to the same space may substantially improve our understanding of the complexity of the brain at different scales.

A Comparison of Prompting Strategies to Teach Intraverbals to an Adolescent with Down Syndrome.

Ingvarsson and Hollobaugh (2011) investigated tact- or echoic-to-intraverbal transfer of stimulus control to "wh" questions for three preschool-aged boys with autism. The current study was a systematic replication of this study with an adolescent girl with Down syndrome. A multielement design was used to compare the effectiveness and efficiency of picture or echoic prompts presented on an iPad or in vivo to teach "wh" questions. All prompt conditions were effective. Conclusions and recommendations for practice are presented.

Otolith end organ projections to auditory neurons in the descending octaval nucleus of the goldfish, Carassius auratus: a confocal analysis.

The distribution of axons from the saccule, lagena, and utricle to descending octaval nucleus neurons that project to the auditory midbrain in the goldfish is reported. We have divided these auditory projection neurons, located in the dorsal portion of the descending octaval nucleus (dDO), into two groups, medial and lateral, each of which contains several neuronal populations based on morphology and location. At most levels of the dDO, there are three medial and three lateral populations; the rostral dDO contains an additional lateral population. The saccule provides input to each of the seven medial and lateral populations but appears to be the exclusive/nearly exclusive source of primary input to the most dorsal cell group of the medial population. Along with the saccule, the lagena and utricle each supply the remaining six medial and lateral populations. Neurons in each of these populations receive input from more than one end organ. One medial and one lateral population include neurons that receive remarkably large contacts from utricular afferents. Overall, the results reveal a more substantial input from the lagena and utricle to the main first-order auditory nucleus in the goldfish than was previously recognized, suggest this nucleus is composed of functionally distinct populations, and relate to functional and evolutionary issues about hearing in early vertebrates.