Longitudinal multi-omics in alpha-synuclein Drosophila model discriminates disease- from age-associated pathologies in Parkinson's disease.

Parkinson's disease (PD) starts decades before symptoms appear, usually in the later decades of life, when age-related changes are occurring. To identify molecular changes early in the disease course and distinguish PD pathologies from aging, we generated Drosophila expressing alpha-synuclein (αSyn) in neurons and performed longitudinal bulk transcriptomics and proteomics on brains at six time points across the lifespan and compared the data to healthy control flies as well as human post-mortem brain datasets. We found that translational and energy metabolism pathways were downregulated in αSyn flies at the earliest timepoints; comparison with the aged control flies suggests that elevated αSyn accelerates changes associated with normal aging.

Relationship between trauma beliefs and distress after an analogue trauma in college students.

The term "trauma" was originally used to describe only the most horrific experiences, but its meaning has expanded in both public and academic circles. This has led to concerns about potential risks associated with defining the term trauma more broadly. However, little research has examined whether the breadth of individuals' trauma beliefs affects their distress after exposure to a potentially traumatic event.

Haploinsufficiency of ITSN1 is associated with a substantial increased risk of Parkinson's disease.

Despite its significant heritability, the genetic basis of Parkinson's disease (PD) remains incompletely understood. Here, in analyzing whole-genome sequence data from 3,809 PD cases and 247,101 controls in the UK Biobank, we discover that protein-truncating variants in ITSN1 confer a substantially increased risk of PD (p = 6.1 × 10; odds ratio [95% confidence interval] = 10.

Tramadol as a fentanyl adulterant: Prevalence and management in a ToxIC Fentalog study prospective cohort.

Background: Tramadol is an adulterant of illicit opioids. As it is a serotonin-norepinephrine reuptake inhibitor as well as a μ-opioid agonist, tramadol adulteration may worsen overdose signs and symptoms or affect the amount of naloxone patients receive.

Methods: This is a multicenter, prospective cohort of adult patients with suspected opioid overdoses who presented to one of eight United States emergency departments and were included in the Toxicology Investigators Consortium's Fentalog Study.

Network modulation at stable states.

Advances in microarray and sequencing technologies have made possible the interrogation of biological processes at increasing levels of complexity. The underlying biomolecular networks contain large numbers of nodes, yet interactions within the networks are not known precisely. In the absence of accurate models, one may inquire if it is possible to find relationships between the states of such networks under external changes, and in particular, if such relationships can be model-independent.

Tau is required for glial lipid droplet formation and resistance to neuronal oxidative stress.

The accumulation of reactive oxygen species (ROS) is a common feature of tauopathies, defined by Tau accumulations in neurons and glia. High ROS in neurons causes lipid production and the export of toxic peroxidated lipids (LPOs). Glia uptake these LPOs and incorporate them into lipid droplets (LDs) for storage and catabolism.

Alzheimer's disease risk gene CD2AP is a dose-sensitive determinant of synaptic structure and plasticity.

CD2-Associated protein (CD2AP) is a candidate susceptibility gene for Alzheimer's disease, but its role in the mammalian central nervous system remains largely unknown. We show that CD2AP protein is broadly expressed in the adult mouse brain, including within cortical and hippocampal neurons, where it is detected at pre-synaptic terminals. Deletion of Cd2ap altered dendritic branching and spine density, and impaired ubiquitin-proteasome system activity.

Parkinson's Disease and Other Alzheimer's Disease and Related Dementia Pathologies and the Progression of Parkinsonism in Older Adults.

Background: The interrelationship of parkinsonism, Parkinson's disease (PD) and other Alzheimer's disease (AD) and Alzheimer's disease and related dementias (ADRD) pathologies is unclear.

Objective: We examined the progression of parkinsonian signs in adults with and without parkinsonism, and their underlying brain pathologies.

Methods: Annual parkinsonian signs were based on a modified Unified Parkinson's Disease Rating Scale.

Psychostimulant drug co-ingestion in non-fatal opioid overdose.

Introduction: In 2019, there were over 16,000 deaths from psychostimulant overdose with 53.5% also involving an opioid. Given the substantial mortality stemming from opioid and psychostimulant co-exposure, evaluation of clinical management in this population is critical but remains understudied.

Hypertensive Disorders of Pregnancy and Risk of Stroke in U.S. Black Women.

BACKGROUND: Black women have a disproportionately higher burden of both preeclamptic pregnancy and stroke compared with White women, but virtually all existing evidence on this possible association has been generated from women of European ancestry. METHODS: In the Black Women’s Health Study, a prospective cohort of U.S.

Research Participants' Perspectives on Precision Diagnostics for Alzheimer's Disease.

Background: Understanding research participants' responses to learning Alzheimer's disease (AD) risk information is important to inform clinical implementation of precision diagnostics given rapid advances in disease modifying therapies.

Objective: We assessed participants' perspectives on the meaning of their amyloid positron emission tomography (PET) imaging results for their health, self-efficacy to understand their results, psychological impact of learning their results, experience receiving their results from the clinical team, and interest in genetic testing for AD risk.

Methods: We surveyed individuals who were being clinically evaluated for AD and received PET imaging six weeks after the return of results.

Frequency of skin cancer among psoriasis, vitiligo, and mycosis fungoides patients treated with narrowband ultraviolet B phototherapy.

Background: Narrowband ultraviolet B (NB-UVB) phototherapy is a popular and relatively contemporary treatment option. However, only a few studies to date have explored the potential risk of skin cancer following NB-UVB treatment.

Objective: This study aimed to investigate the potential long-term risk of skin cancer in patients treated with NB-UVB.

Perceived Interpersonal Racism and Incident Stroke Among US Black Women.

Importance: Black individuals in the US experience stroke and stroke-related mortality at younger ages and more frequently than other racial groups. Studies examining the prospective association of interpersonal racism with stroke are lacking.

Objective: To examine the association of perceived interpersonal racism with incident stroke among US Black women.

Ocular injury from saltwater coral palytoxin.

We describe a case of a young male who presented to the emergency department with unilateral eye pain, blurred vision, conjunctival injection, and ocular pH of 9, one day after direct ocular exposure to palytoxin (PTX) from coral in a home saltwater fish tank. Although uncommon, ocular PTX toxicity is a potentially vision-threatening condition that requires prompt recognition. This case report documents the successful management of presumed ocular PTX exposure and suggests additional workup and treatment considerations for future patients.

Image formation from a concave mirror.

Computing locations and extent of images, except in the most trivial configurations or special cases, is a complex task. Even rays emanating from a point source and passing through an optical system generally fail to converge at a single image point, highlighting the care needed to establish image locations. We use three approaches to study image formation in a simple configuration, that of a point source following reflection from a spherical concave mirror.

Strokes in Patients With Injection Drug Use and Tricuspid Valve Endocarditis - A Case Series.

In this study, we describe patients from a tertiary care safety-net hospital endocarditis registry with tricuspid valve infective endocarditis (TVIE), and concomitant acute or subacute ischemic stroke predominantly associated with injection drug use (IDU). We retrospectively obtained data pertinent to neurologic examinations, history of injection drug use (IDU), blood cultures, transthoracic/transesophageal echocardiography (TTE/TEE), neuroimaging, and Modified Rankin Scale (mRS) scores at discharge. Only those patients with bacteremia, tricuspid valve vegetations, and neuroimaging consistent with acute to subacute ischemic infarction and microhemorrhages in two cases were included in this series.

Tau polarizes an aging transcriptional signature to excitatory neurons and glia.

Aging is a major risk factor for Alzheimer's disease (AD), and cell-type vulnerability underlies its characteristic clinical manifestations. We have performed longitudinal, single-cell RNA-sequencing in with pan-neuronal expression of human tau, which forms AD neurofibrillary tangle pathology. Whereas tau- and aging-induced gene expression strongly overlap (93%), they differ in the affected cell types.

Functional screening of lysosomal storage disorder genes identifies modifiers of alpha-synuclein neurotoxicity.

Heterozygous variants in the glucocerebrosidase (GBA) gene are common and potent risk factors for Parkinson's disease (PD). GBA also causes the autosomal recessive lysosomal storage disorder (LSD), Gaucher disease, and emerging evidence from human genetics implicates many other LSD genes in PD susceptibility. We have systemically tested 86 conserved fly homologs of 37 human LSD genes for requirements in the aging adult Drosophila brain and for potential genetic interactions with neurodegeneration caused by α-synuclein (αSyn), which forms Lewy body pathology in PD.