Plasma proteomic signatures of social isolation and loneliness associated with morbidity and mortality.

The biology underlying the connection between social relationships and health is largely unknown. Here, leveraging data from 42,062 participants across 2,920 plasma proteins in the UK Biobank, we characterized the proteomic signatures of social isolation and loneliness through proteome-wide association study and protein co-expression network analysis. Proteins linked to these constructs were implicated in inflammation, antiviral responses and complement systems.

Systemically circulating 17β-estradiol enhances the neuroprotective effect of the smoking cessation drug cytisine in female parkinsonian mice.

The smoking cessation drug cytisine exerts neuroprotection in substantia nigra pars compacta (SNc) dopaminergic (DA) neurons of female but not male 6-hydroxydopamine (6-OHDA) lesioned parkinsonian mice. To address the important question of whether circulating 17β-estradiol mediates this effect, we employ two mouse models aimed at depleting systemically circulating 17β-estradiol: (i) bilateral ovariectomy (OVX), and (ii) aromatase inhibition with systemically administered letrozole. In both models, depleting systemically circulating 17β-estradiol in female 6-OHDA lesioned parkinsonian mice results in the loss of cytisine-mediated neuroprotection as measured using apomorphine-induced contralateral rotations and SNc DA neurodegeneration.

Neurological and functional outcomes of 32 patients with hemorrhagic brainstem cavernous malformations: a practical guide for surgical planning.

Objective: Brainstem cavernous malformations (BSCMs) were once considered inoperable. Microsurgical resection now represents a valuable option for treating patients with hemorrhagic or symptomatic lesions. The aim of this study was to provide a practical guide for surgical planning by analyzing postoperative neurological and functional outcomes.

Effects of sex on imaging-based intravenous thrombolysis for ischaemic stroke with unknown onset time: a pooled analysis of clinical trials.

Introduction: The effects of imaging-based intravenous thrombolysis on outcomes based on patient sex remain unclear. We aimed to investigate whether outcomes among patients with stroke with an unknown onset time and treated with imaging-based intravenous thrombolysis are influenced by their sex.

Patients And Methods: This study was a pooled analysis of individual patient-level data acquired from the Evaluation of unknown Onset Stroke thrombolysis trials.

Feasibility of at-Home Sleep Monitoring in Adolescents with and without Concussion.

Background: Poor sleep is associated with longer recovery following adolescent concussion, making the longitudinal assessment of sleep important for monitoring recovery and identifying sleep disruptions. An important consideration for successful monitoring of sleep following concussion is the feasibility and adherence of a given sleep monitoring tool when used in an at-home environment. Understanding the usability of different sleep monitoring tools is essential for determining their applicability for longitudinal assessment in an ecologically valid environment.

National Institute of Neurological Disorders and Stroke Clinical Trials Methodology Course: Summary and Accomplishments 2014-2023.

The Clinical Trials Methodology Course (CTMC), given from 2014 to 2023, was conducted to educate early-career clinical investigators from various backgrounds in neurosciences in the design of clinical trials and to provide mentorship to enhance academic careers and retention plus improve research productivity and the likelihood of successful grant applications. This summary describes the rationale, history, structure, and trainee outcomes of the CTMC. The course used small groups, consisting of 1-2 clinical faculty advisor(s), 1 faculty biostatistician, and 2-4 trainees who met remotely approximately weekly over 12 weeks.

Curriculum Innovations: A Novel Neurology Clinician-Educator Program.

Background And Objectives: Neurology residents serve as frontline teachers for junior trainees but often lack formal training in medical education. We developed a novel longitudinal curriculum to enhance the teaching skills and educational leadership of residents interested in pursuing careers as clinician-educators.

Methods And Curriculum Description: We developed and piloted a Neurology Clinician-Educator Program (NCEP) with the following goals: (1) improve resident satisfaction with opportunities to develop teaching skills, (2) improve resident satisfaction with opportunities to transition into a clinician-educator role after training, and (3) enhance resident teaching skills using evidence-based strategies.

Advance Care Planning Billing Codes Associated With Decreased Healthcare Utilization in Neurological Disease.

Goals: Advance care planning (ACP) procedure codes have been established to reimburse meaningful care goal discussions; however, the utilization frequency of these codes in neurological disease is unknown. The objective of this study is to identify the association between ACP codes and healthcare utilization in chronic neurodegenerative diseases.

Methods: This is a multicenter cohort study using real-world electronic health data.

NLS-binding deficient Kapβ2 reduces neurotoxicity via selective interaction with C9orf72-ALS/FTD dipeptide repeats.

Arginine-rich dipeptide repeat proteins (R-DPRs) are highly toxic proteins found in patients with C9orf72-linked amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD). R-DPRs can cause toxicity by disrupting the natural phase behavior of RNA-binding proteins (RBPs). Mitigating this abnormal phase behavior is, therefore, crucial to reduce R-DPR-induced toxicity.

Cytosolic phospholipase A2 in infiltrating monocyte derived macrophages does not impair recovery after spinal cord injury in female mice.

Spinal cord injury (SCI) leads to permanent motor and sensory loss that is exacerbated by intraspinal inflammation and persists months to years after injury. After SCI, monocyte-derived macrophages (MDMs) infiltrate the lesion to aid in myelin-rich debris clearance. During debris clearance, MDMs adopt a proinflammatory phenotype that exacerbates neurodegeneration and hinders recovery.

Dopaminergic signaling to ventral striatum neurons initiates sniffing behavior.

Sniffing is a motivated behavior displayed by nearly all terrestrial vertebrates. While sniffing is associated with acquiring and processing odors, sniffing is also intertwined with affective and motivated states. The systems which influence the display of sniffing are unclear.

A higher order PUF complex is central to regulation of C. elegans germline stem cells.

PUF RNA-binding proteins are broadly conserved stem cell regulators. Nematode PUF proteins maintain germline stem cells (GSCs) and, with key partner proteins, repress differentiation mRNAs, including gld-1. Here we report that PUF protein FBF-2 and its partner LST-1 form a ternary complex that represses gld-1 via a pair of adjacent FBF binding elements (FBEs) in its 3'UTR.

Invasion of glioma cells through confined space requires membrane tension regulation and mechano-electrical coupling via Plexin-B2.

Glioblastoma (GBM) is a malignant brain tumor with diffuse infiltration. Here, we demonstrate how GBM cells usurp guidance receptor Plexin-B2 for confined migration through restricted space. Using live-cell imaging to track GBM cells negotiating microchannels, we reveal endocytic vesicle accumulation at cell front and filamentous actin assembly at cell rear in a polarized manner.

A fiducial-assisted strategy compatible with resolving small MFS transporter structures in multiple conformations using cryo-EM.

Advancements in cryo-EM have stimulated a revolution in structural biology. Yet, for membrane proteins near the cryo-EM size threshold of approximately 40 kDa, including transporters and G-protein coupled receptors, the absence of distinguishable structural features makes image alignment and structure determination a significant challenge. Furthermore, resolving more than one protein conformation within a sample, a major advantage of cryo-EM, represents an even greater degree of difficulty.

A soft thermal sensor for the continuous assessment of flow in vascular access.

Hemodialysis for chronic kidney disease (CKD) relies on vascular access (VA) devices, such as arteriovenous fistulas (AVF), grafts (AVG), or catheters, to maintain blood flow. Nonetheless, unpredictable progressive vascular stenosis due to neointimal formation or complete occlusion from acute thrombosis remains the primary cause of mature VA failure. Despite emergent surgical intervention efforts, the lack of a reliable early detection tool significantly reduces patient outcomes and survival rates.

Tenecteplase Thrombolysis for Stroke up to 24 Hours After Onset With Perfusion Imaging Selection: The CHABLIS-T II Randomized Clinical Trial.

Background: Whether it is effective and safe to extend the time window of intravenous thrombolysis up to 24 hours after the last known well is unknown. We aimed to determine the efficacy and safety of tenecteplase in Chinese patients with acute ischemic stroke due to large/medium vessel occlusion within an extended time window.

Methods: Patients with ischemic stroke presenting 4.

Prevalence and risk factors of covert brain infarction: A community-based cross-sectional study.

Background: Covert brain infarction (CBI) is common and poses a potential and non-negligible burden of disease worldwide. The prevalence and risk factors for CBI have been reported inconsistently in previous studies.

Aims: This study aims to ascertain the prevalence and risk factors of CBI and its imaging phenotypes in community-dwelling adults.

Associations of Traumatic Brain Injury and Hearing: Results From the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS).

Objective: To examine associations of traumatic brain injury (TBI) with self-reported and clinical measures of hearing function.

Setting: Four US communities.

Participants: A total of 3176 Atherosclerosis Risk in Communities Study participants who attended the sixth study visit in 2016-2017, when hearing was assessed.

Minimal presynaptic protein machinery governing diverse kinetics of calcium-evoked neurotransmitter release.

Neurotransmitters are released from synaptic vesicles with remarkable precision in response to presynaptic calcium influx but exhibit significant heterogeneity in exocytosis timing and efficacy based on the recent history of activity. This heterogeneity is critical for information transfer in the brain, yet its molecular basis remains poorly understood. Here, we employ a biochemically-defined fusion assay under physiologically relevant conditions to delineate the minimal protein machinery sufficient to account for various modes of calcium-triggered vesicle fusion dynamics.

DLK-dependent axonal mitochondrial fission drives degeneration after axotomy.

Currently there are no effective treatments for an array of neurodegenerative disorders to a large part because cell-based models fail to recapitulate disease. Here we develop a reproducible human iPSC-based model where laser axotomy causes retrograde axon degeneration leading to neuronal cell death. Time-lapse confocal imaging revealed that damage triggers an apoptotic wave of mitochondrial fission proceeding from the site of injury to the soma.

Design of an equilibrative nucleoside transporter subtype 1 inhibitor for pain relief.

The current opioid crisis urgently calls for developing non-addictive pain medications. Progress has been slow, highlighting the need to uncover targets with unique mechanisms of action. Extracellular adenosine alleviates pain by activating the adenosine A1 receptor (A1R).