A personalized multi-platform assessment of somatic mosaicism in the human frontal cortex.

Somatic mutations in individual cells lead to genomic mosaicism, contributing to the intricate regulatory landscape of genetic disorders and cancers. To evaluate and refine the detection of somatic mosaicism across different technologies with personalized donor-specific assembly (DSA), we obtained tissue from the dorsolateral prefrontal cortex (DLPFC) of a post-mortem neurotypical 31-year-old individual. We sequenced bulk DLPFC tissue using Oxford Nanopore Technologies (∼60X), NovaSeq (∼30X), and linked-read sequencing (∼28X).

Determinants and progression of stigma in amyotrophic lateral sclerosis/motor neuron disease.

: Stigma in amyotrophic lateral sclerosis/motor neurone disease (ALS/MND) may be felt or enacted; felt stigma covers feeling devalued by the illness, whereas enacted stigma refers to being treated differently because of it. Stigma in ALS/MND has been shown to increase social withdrawal, worsen quality of life, and reduce use of assistive devices, so we explored prevalence and factors influencing stigma. : Participants in the Trajectories of Outcome in Neurological Conditions-ALS study completed scales measuring stigma, fatigue, spasticity, functioning, mood, worry, self-esteem, and perceived health, as well as demographic information and symptoms like head drop or emotional lability.

Clinical Pharmacology and Approach to Dose Selection of Emestedastat, a Novel Tissue Cortisol Synthesis Inhibitor for the Treatment of Central Nervous System Disease.

This review demonstrates the value of central pharmacodynamics (PD), including positron emission tomography (PET) and computerized cognitive testing, to supplement pharmacokinetic (PK) and peripheral PD for determining the target dose range for clinical efficacy testing of emestedastat, an 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) inhibitor. Combined data from 6 clinical trials in cognitively normal volunteers and patients with Alzheimer disease included a population PK model, endocrine PD, a human PET trial (11β-HSD1 brain imaging), and computerized cognitive testing. PK and PET findings were similar in volunteers and patients with Alzheimer disease.

Exploration of demographic prevalence of mild cognitive impairment using Montreal cognitive assessment: A cross-sectional pilot study in the Cape Coast Metropolis, Ghana.

Background: The Global prevalence of dementia is projected to rise, particularly in low and middle-income countries like Ghana. Mild cognitive impairment (MCI), an intermediate phase between normal cognitive aging and dementia, is characterized by an objective and subjective decline in cognitive abilities. Individuals with MCI have a greater likelihood of progression to dementia.

Assessing disability progression using the WHODAS 2.0 in multiple sclerosis: Investigating clinical and socio-demographic factors in a large longitudinal cohort study (TONiC-MS).

Background: Identifying influences on disability accumulation in multiple sclerosis (MS), including modifiable factors other than the core features of disease itself, is vital for clinical care, but has often relied on instruments with acknowledged psychometric shortcomings. We model MS disability using the WHO Disability Assessment Schedule (WHODAS) 2.0, a validated measure based on the WHO's biopsychosocial model and sensitive to the breadth of disability-related domains important to people, to investigate the factors associated with its trajectory after diagnosis.