Background: Central synucleinopathies, including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), involve alpha-synuclein accumulation and dopaminergic cell loss in the substantia nigra (SN) and locus coeruleus (LC). Pure autonomic failure (PAF), a peripheral synucleinopathy, often precedes central synucleinopathies.
Objectives: To assess early brain involvement in PAF using neuromelanin-sensitive magnetic resonance imaging (NM-MRI) and fluorodopa-positron emission tomography (FDOPA-PET), and to determine whether PAF patients with a high likelihood ratio (LR) for conversion to a central synucleinopathy exhibit reduced NM-MRI contrast in the LC and SN compared with controls and low-LR patients.
The abundance and sequence of satellite DNA at and around centromeres is evolving rapidly despite the highly conserved and essential process through which the centromere directs chromosome inheritance. The impact of such rapid evolution is unclear. Here we find that sequence-dependent DNA shape dictates packaging of pericentromeric satellites in female meiosis through a conserved DNA-shape-recognizing chromatin architectural protein, high mobility group AT-hook 1 (HMGA1).
View Article and Find Full Text PDFBackground: The cholinesterase inhibitor pyridostigmine is used to treat orthostatic hypotension by facilitating cholinergic neurotransmission in autonomic ganglia, thereby harnessing residual sympathetic tone to increase blood pressure (BP) preferentially in the upright posture. We hypothesized that less severe autonomic impairment was associated with greater pressor responses to pyridostigmine.
Methods: To identify predictors of pressor response, linear regression analyses between the effect of pyridostigmine on upright BP and markers of autonomic impairment were retrospectively conducted on 38 patients who had a medication trial with pyridostigmine (60 mg single dose).
Importance: Childhood vaccination rates have declined in recent years; there is also concern that resistance to COVID-19 vaccines could spill over to childhood vaccines.
Objectives: To use local-level data to study trends in childhood vaccination rates and heterogeneity in local rates; including how many areas are below herd-immunity thresholds, and assess the association between COVID-19 vaccine hesitancy and childhood vaccination.
Design: We report, for 11 states with available data, vaccination rates for measles, mumps, rubella (MMR), and diphtheria, tetanus, acellular pertussis (DTaP) vaccines, including percentage of schools/counties with rates ≥95 %, 90-95 %, 80-90 %, and < 80 %.