Design and Evaluation of [F]CHDI-650 as a Positron Emission Tomography Ligand to Image Mutant Huntingtin Aggregates.

Therapeutic interventions are being developed for Huntington's disease (HD), a hallmark of which is mutant huntingtin protein (mHTT) aggregates. Following the advancement to human testing of two [C]-PET ligands for aggregated mHTT, attributes for further optimization were identified. We replaced the pyridazinone ring of CHDI-180 with a pyrimidine ring and minimized off-target binding using brain homogenate derived from Alzheimer's disease patients.

Effects of Unilateral Hearing Loss on Speech-Evoked Auditory Brainstem Responses and Reading: A Preliminary Study.

Purpose: The purpose of this study was to determine whether the speech-evoked auditory brainstem responses (sABRs) obtained by stimulating the ear with normal sensitivity in children with unilateral hearing loss (UHL) were different from that of children with normal hearing (NH), and to explore correlations between the sABR findings and measures of reading.

Method: Eleven children with UHL and 11 children with NH were tested via the BioMARK sABR protocol using the syllable /da/; latency and amplitudes of Waves V, A, C, D, E, F, and O were measured. Participants also were tested on the Phonemic Synthesis Test (PST) and the Woodcock Reading Mastery Test-Revised (WRMT-R), particularly the Reading Readiness, Basic Skills, and Comprehension subtests.

Imaging Mutant Huntingtin Aggregates: Development of a Potential PET Ligand.

Mutant huntingtin (mHTT) protein carrying the elongated N-terminal polyglutamine (polyQ) tract misfolds and forms protein aggregates characteristic of Huntington's disease (HD) pathology. A high-affinity ligand specific for mHTT aggregates could serve as a positron emission tomography (PET) imaging biomarker for HD therapeutic development and disease progression. To identify such compounds with binding affinity for polyQ aggregates, we embarked on systematic structural activity studies; lead optimization of aggregate-binding affinity, unbound fractions in brain, permeability, and low efflux culminated in the discovery of compound , which exhibited target engagement in autoradiography (ARG) studies in brain slices from HD mouse models and postmortem human HD samples.

Older UK sheltered housing tenants' perceptions of well-being and their usage of hospital services.

The aim of this study was to examine sheltered housing tenants' views of health and well-being, the strategies they adopted to support their well-being, and their use of health and social care services through a Health Needs Assessment. Sheltered housing in the UK is a form of service-integrated housing for people, predominantly over 60. The study used a parallel, three-strand mixed method approach to encompass the tenants' perceptions of health and well-being (n = 96 participants), analysis of the service's health and well-being database, and analysis of emergency and elective hospital admissions (n = 978 tenant data sets for the period January to December 2012).