Basic Science and Pathogenesis.

Background: Activation of the mTOR pathway is pivotal for microglia to induce and sustain neuroprotective functions (Ulland et al., 2017; Wang et al., 2022).

Longitudinal Assessment of Pain in Rheumatoid Arthritis: Increases in Pain and Their Relationship to Functional Declines and Medication Changes.

Objective: Electronic health applications (apps) allow patients with rheumatoid arthritis (RA) to report patient-reported outcomes (PROs) between visits. However, almost no data exist on patients' report of pain between visits and how that correlates with change in function and/or modifications to medication.

Methods: Patients with RA from one rheumatology practice provided data as part of a study of an app.

Validation of the 11+ Myco MS-PREP® Method for Determination of Aflatoxins, Fumonisins, Deoxynivalenol, Ochratoxin A, Zearalenone, HT-2, and T-2 Toxins in Cereals, Baby Food, Spices, and Animal Feed by Immunoaffinity Column with LC-MS/MS: AOAC Performance Tested MethodsSM 112401.

Background: The 11+Myco MS-PREP® Immunoaffinity Column (IAC) contains a gel suspension of monoclonal antibodies specific to the toxins of interest. Following sample extraction, the IAC is used for cleanup and concentration of mycotoxins prior to analysis by Liquid Chromatography with Tandem Mass Spectrometry (LC-MS/MS).

Objective: This study evaluated the IAC with LC-MS/MS method for Performance Tested Methods  SM certification for simultaneous determination and confirmation of Aflatoxins B1, B2, G1, G2, and M1; Deoxynivalenol, Fumonisins B1, B2, and B3; Ochratoxin A; T-2; HT-2; and Zearalenone from corn, wheat, cereal-based baby food (with and without dairy ingredients), paprika, chili powder and animal feed.

Neuropathological and cerebrospinal fluid correlates of choroid plexus inflammation in progressive multiple sclerosis.

Among the intrathecal inflammatory niches where compartmentalized inflammation persists and plays a pivotal role in progressive multiple sclerosis (MS), choroid plexus (CP) has recently received renewed attention. To better characterize the neuropathological/molecular correlates of CP in progressive MS and its potential link with other brain inflammatory compartments, such as perivascular spaces and leptomeninges, the levels, composition and phenotype of CP immune infiltration in lateral ventricles of the hippocampus were examined in 40 post-mortem pathologically confirmed MS and 10 healthy donors, using immunochemistry/immunofluorescence and in-situ sequencing. Significant inflammation was detected in the CP of 21 out of the 40 MS cases (52%).

Coding-Sequence Evolution Does Not Explain Divergence in Petal Anthocyanin Pigmentation Between Mimulus luteus Var luteus and M. l. variegatus.

Biologists have long been interested in understanding genetic constraints on the evolution of development. For example, noncoding changes in a gene might be favored over coding changes if they are less constrained by pleiotropic effects. Here, we evaluate the importance of coding-sequence changes to the recent evolution of a novel anthocyanin pigmentation trait in the monkeyflower genus Mimulus.

Follow the CSF flow: probing multiciliated ependymal cells in brain pathology.

Multiciliated ependymal cells regulate cerebrospinal fluid (CSF) microcirculation and form a dynamic CSF-brain interface. Emerging evidence suggests that ependymal cells enter reactive states in response to pathology that are associated with ciliary and junctional protein alterations. The drivers of these alterations, likely from both acquired and inherited mechanisms, remain elusive.

Senolytic treatment diminishes microglia and decreases severity of experimental autoimmune encephalomyelitis.

Background: The role of senescence in disease contexts is complex, however there is considerable evidence that depletion of senescent cells improves outcomes in a variety of contexts particularly related to aging, cognition, and neurodegeneration. Much research has shown previously that inflammation can promote cellular senescence. Microglia are a central nervous system innate immune cell that undergo senescence with aging and during neurodegeneration.

Crosstalk between bone metastatic cancer cells and sensory nerves in bone metastatic progression.

Although the role of peripheral nerves in cancer progression has been appreciated, little is known regarding cancer/sensory nerve crosstalk and its contribution to bone metastasis and associated pain. In this study, we revealed that the cancer/sensory nerve crosstalk plays a crucial role in bone metastatic progression. We found that (i) periosteal sensory nerves expressing calcitonin gene-related peptide (CGRP) are enriched in mice with bone metastasis; (ii) cancer patients with bone metastasis have elevated CGRP serum levels; (iii) bone metastatic patient tumor samples express elevated calcitonin receptor-like receptor (CRLR, a CGRP receptor component); (iv) higher CRLR levels in cancer patients are negatively correlated with recurrence-free survival; (v) CGRP induces cancer cell proliferation through the CRLR/p38/HSP27 pathway; and (vi) blocking sensory neuron-derived CGRP reduces cancer cell proliferation in vitro and bone metastatic progression in vivo.

Multiciliated ependymal cells: an update on biology and pathology in the adult brain.

Mature multiciliated ependymal cells line the cerebral ventricles where they form a partial barrier between the cerebrospinal fluid (CSF) and brain parenchyma and regulate local CSF microcirculation through coordinated ciliary beating. Although the ependyma is a highly specialized brain interface with barrier, trophic, and perhaps even regenerative capacity, it remains a misfit in the canon of glial neurobiology. We provide an update to seminal reviews in the field by conducting a scoping review of the post-2010 mature multiciliated ependymal cell literature.

A Preliminary Investigation of a Tool to Measure BCBA Supervisory Behaviors.

Board certified behavior analysts (BCBAs) are in high demand. However, given the fast growth of the field, most behavior analysts who serve as supervisors have recently been certified and thus, have had limited opportunities to refine their supervisory repertoires. Although supervision best practices have been a topic of frequent discussion in behavior analytic publications, little research has been conducted to empirically assess these recommendations with BCBA supervisors.

The chromatin regulator Ankrd11 controls cardiac neural crest cell-mediated outflow tract remodeling and heart function.

ANKRD11 (Ankyrin Repeat Domain 11) is a chromatin regulator and a causative gene for KBG syndrome, a rare developmental disorder characterized by multiple organ abnormalities, including cardiac defects. However, the role of ANKRD11 in heart development is unknown. The neural crest plays a leading role in embryonic heart development, and its dysfunction is implicated in congenital heart defects.

Heterogeneity of mature oligodendrocytes in the central nervous system.

Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous system. Recent evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to axons. Despite the recognition of potential heterogeneity in mature oligodendrocyte function, a comprehensive summary of mature oligodendrocyte diversity is lacking.

Cognitive performance and mortality among patients receiving autologous hematopoietic stem cell transplant.

Objectives: Patients undergoing autologous hematopoietic stem cell transplant (HCT) are at risk for death and remain understudied relative to those undergoing allogeneic HCT. Cognitive functioning may be a useful indicator of mortality risk. We examined cognition among patients who underwent autologous HCT and its relationship to mortality.

Supervised latent factor modeling isolates cell-type-specific transcriptomic modules that underlie Alzheimer's disease progression.

Late onset Alzheimer's disease (AD) is a progressive neurodegenerative disease, with brain changes beginning years before symptoms surface. AD is characterized by neuronal loss, the classic feature of the disease that underlies brain atrophy. However, GWAS reports and recent single-nucleus RNA sequencing (snRNA-seq) efforts have highlighted that glial cells, particularly microglia, claim a central role in AD pathophysiology.

Glycerol Trinitrate Acts Downstream of Calcitonin Gene-Related Peptide in Trigeminal Nociception-Evidence from Rodent Experiments with Anti-CGRP Antibody Fremanezumab.

Calcitonin gene-related peptide (CGRP) and nitric oxide (NO) have been recognized as important mediators in migraine but their mechanisms of action and interaction have not been fully elucidated. Monoclonal anti-CGRP antibodies like fremanezumab are successful preventives of frequent migraine and can be used to study CGRP actions in preclinical experiments. Fremanezumab (30 mg/kg) or an isotype control monoclonal antibody was subcutaneously injected to Wistar rats of both sexes.

Neurocognitive change over the course of a multiday external lumbar drain trial in patients with suspected normal pressure hydrocephalus.

To characterize neurocognitive response to cerebrospinal fluid (CSF) diversion during a multiday external lumbar drainage (ELD) trial in patients with suspected normal pressure hydrocephalus (NPH). Inpatients ( = 70) undergoing an ELD trial as part of NPH evaluation participated. Cognition and balance were assessed using standardized measures before and after a three-day ELD trial.

Comparative analysis of methods to reduce activation signature gene expression in PBMCs.

Preserving the in vivo cell transcriptome is essential for accurate profiling, yet factors during cell isolation including time ex vivo and temperature induce artifactual gene expression, particularly in stress-responsive immune cells. In this study, we investigated two methods to mitigate ex vivo activation signature gene (ASG) expression in peripheral blood mononuclear cells (PBMCs): transcription and translation inhibitors (TTis) and cold temperatures during isolation. Comparative analysis of PBMCs isolated with TTis revealed reduced ASG expression.