Regenerating Family Member 3 Alpha Is Predictive of Mortality Following Emergent Large Vessel Occlusion.

Regenerating Family Member 3 Alpha (REG3A) is an antimicrobial protein secreted by the intestine and pancreas with additional immunomodulatory properties. Previously, we published that REG3A expression in ischemic stroke patient systemic blood, during mechanical thrombectomy (MT), is significantly associated with inflammatory cytokines and patient function on admission. This paper, however, did not investigate post-acute death rates.

Temporal Immune Profiling in the CSF and Blood of Patients with Aneurysmal Subarachnoid Hemorrhage.

Background: Delayed cerebral ischemia (DCI) is a significant complication of aneurysmal subarachnoid hemorrhage (aSAH). This study profiled immune responses after aSAH and evaluated their association with DCI onset.

Methods: Twelve aSAH patients were enrolled.

The differential proteomic response to ischemic stroke in appalachian subjects treated with mechanical thrombectomy.

Introduction: The Appalachia region of North America is known to have significant health disparities, specifically, worse risk factors and outcomes for stroke. Appalachians are more likely to have comorbidities related to stroke, such as diabetes, obesity, and tobacco use, and are often less likely to have stroke interventions, such as mechanical thrombectomy (MT), for emergent large vessel occlusion (ELVO). As our Comprehensive Stroke Center directly serves stroke subjects from both Appalachian and non-Appalachian areas, inflammatory proteomic biomarkers were identified associated with stroke outcomes specific to subjects residing in Appalachia.

Venous Thromboembolism Rates in Trauma Patients Significantly Increase With Missed Prophylactic Enoxaparin Doses.

Current literature demonstrates prophylactic enoxaparin to be efficacious in reducing venous thromboembolism (VTE) rates without significantly increasing risk for bleeding complications. Despite this evidence, prophylactic enoxaparin doses are frequently withheld for surgery or procedures. This exploratory study aims to quantify the risk of a VTE event in trauma patients associated with missed doses of prophylactic enoxaparin.

Astrocytic stress response is induced by exposure to astrocyte-binding antibodies expressed by plasmablasts from pediatric patients with acute transverse myelitis.

Background: Pediatric acute transverse myelitis (ATM) accounts for 20-30% of children presenting with a first acquired demyelinating syndrome (ADS) and may be the first clinical presentation of a relapsing ADS such as multiple sclerosis (MS). B cells have been strongly implicated in the pathogenesis of adult MS. However, little is known about B cells in pediatric MS, and even less so in pediatric ATM.

Terminally differentiated effector memory T cells associate with cognitive and AD-related biomarkers in an aging-based community cohort.

Background And Purpose: The immune response changes during aging and the progression of Alzheimer's disease (AD) and related dementia (ADRD). Terminally differentiated effector memory T cells (called T) are important during aging and AD due to their cytotoxic phenotype and association with cognitive decline. However, it is not clear if the changes seen in T are specific to AD-related cognitive decline specifically or are more generally correlated with cognitive decline.

Evaluating Independent Double Checks in the Pediatric Intensive Care Unit: A Human Factors Engineering Approach.

Objectives: The goal of this human factors engineering-led improvement initiative was to examine whether the independent double check (IDC) during administration of high alert medications afforded improved patient safety when compared with a single check process.

Methods: The initiative was completed at a 24-bed pediatric intensive care unit and included all patients who were on the unit and received a medication historically requiring an IDC. The total review examined 37,968 high-risk medications administrations to 4417 pediatric intensive care unit patients over a 40-month period.

Terminally differentiated effector memory T cells associate with cognitive and AD-related biomarkers in an aging-based community cohort.

Background And Purpose: The immune response changes during aging and the progression of Alzheimer's disease (AD) and related dementia (ADRD). Terminally differentiated effector memory T cells (called TEMRA) are important during aging and AD due to their cytotoxic phenotype and association with cognitive decline. However, it is not clear if the changes seen in T are specific to AD-related cognitive decline specifically or are more generally correlated with cognitive decline.

Association between goal nutrition and intubation in patients with bronchiolitis on noninvasive ventilation: A retrospective cohort study.

Background: Acute bronchiolitis causes many hospitalizations in children younger than 2 years. Early enteral nutrition is associated with improved outcomes in these patients. However, often nutrition is withheld when patients require noninvasive respiratory support because of the risk of aspiration worsening respiratory failure, possibly requiring intubation.

Recruitment methods and yield rates for a multisite clinical trial exploring risk reduction for Alzheimer's disease (rrAD).

Introduction: The risk reduction for Alzheimer's disease (rrAD) trial was a multisite clinical trial to assess exercise and intensive vascular pharmacological treatment on cognitive function in community-dwelling older adults at increased risk for Alzheimer's disease.

Methods: Eligibility, consent, and randomization rates across different referral sources were compared. Informal interviews conducted with each site's project team were conducted upon study completion.

Iron-sensitive protein conjugates formed with a Wittig reaction precursor in ionic liquid.

In this report, formation of protein conjugates with an iron-sensitive enamine linkage is demonstrated through the ionic liquid-based bioconjugation method.

Neuronal binding by antibodies can be influenced by low pH stress during the isolation procedure.

Low pH stress and its influence on antibody binding is a common consideration among chemists, but is only recently emerging as a consideration in Immunological studies. Antibody characterizations in Multiple Sclerosis (MS), an autoimmune disease of the Central Nervous System (CNS) has revealed that antibodies in the cerebrospinal fluid (CSF) of patients with Multiple Sclerosis bind to myelin-related and non-myelin antigen targets. Many laboratories have used molecular biology techniques to generate recombinant human antibodies (rhAbs) expressed by individual B cells from healthy donors and patients with systemic autoimmune disease to identify antigen targets.

Sex-based differences in effector cells of the adaptive immune system during Alzheimer's disease and related dementias.

Neurological conditions such as Alzheimer's disease (AD) and related dementias (ADRD) present with many challenges due to the heterogeneity of the related disease(s), making it difficult to develop effective treatments. Additionally, the progression of ADRD-related pathologies presents differently between men and women. With two-thirds of the population affected with ADRD being women, ADRD has presented itself with a bias toward the female population.

Inflammatory-associated proteomic predictors of cognitive outcome in subjects with ELVO treated by mechanical thrombectomy.

Background: Emergent Large Vessel Occlusion (ELVO) stroke causes devastating vascular events which can lead to significant cognitive decline and dementia. In the subset of ELVO subjects treated with mechanical thrombectomy (MT) at our institution, we aimed to identify systemic and intracranial proteins predictive of cognitive function at time of discharge and at 90-days. These proteomic biomarkers may serve as prognostic indicators of recovery, as well as potential targets for novel/existing therapeutics to be delivered during the subacute stage of stroke recovery.

Spared Premotor Areas Undergo Rapid Nonlinear Changes in Functional Organization Following a Focal Ischemic Infarct in Primary Motor Cortex of Squirrel Monkeys.

Recovery of motor function after stroke is accompanied by reorganization of movement representations in spared cortical motor regions. It is widely assumed that map reorganization parallels recovery, suggesting a causal relationship. We examined this assumption by measuring changes in motor representations in eight male and six female squirrel monkeys in the first few weeks after injury, a time when motor recovery is most rapid.

Using Operant Reach Chambers to Assess Mouse Skilled Forelimb Use After Stroke.

Skilled forelimb reaching and grasping are important components of rodent motor performance. The isometric pull task can serve as a tool for quantifying forelimb function following stroke or other CNS injury as well as in forelimb rehabilitation. This task has been extensively developed for use in rats.

Co-culturing Immune Cells and Mouse-Derived Mixed Cortical Cultures with Oxygen-Glucose Deprivation to In Vitro Simulate Neuroinflammatory Interactions After Stroke.

Studying interactions between neural cells and glial cells in vitro remains an essential tool for scientists worldwide, and with the addition of oxygen-glucose deprivation (OGD) can be particularly useful for identifying mechanisms related to ischemic stroke-related injury and repair. In developing these protocols in the lab, however, we discovered the limitation of co-culturing immune cells with pure neuronal cultures as the standard media for immune cells impair neuronal growth and vice versa. Thus, we optimized a mixed cortical cell culture system that does not require the use of glial-conditioned media to support the viability and growth of neurons but can nonetheless be used to quantify neuronal survival and dendritic arborization.

A Guide on Analyzing Flow Cytometry Data Using Clustering Methods and Nonlinear Dimensionality Reduction (tSNE or UMAP).

Flow cytometry has been used for the last two decades to identify which immune cell subsets diapedese from the periphery into the brain parenchyma following injuries, including ischemic and hemorrhagic stroke. Recent developments have moved the analysis of high-parameter flow cytometry data sets from the traditional analysis method of manual gating to using unbiased analyses to improve scientific rigor. This chapter gives a step-by-step guide on using modern computational approaches to analyze complex flow cytometry data sets in FlowJo™ Software v10.

FACS to Identify Immune Subsets in Mouse Brain and Spleen.

Flow cytometry enables the multi-parametric quantification of cell types, especially in immunophenotyping of unique immune cell subsets that can either contribute to or ameliorate pathology. For tissues to be used in such analyses, single-cell suspensions must be created. Here we describe protocols for preparing single-cell suspensions of mouse spleen and brain tissue, as well as the steps for fluorescently activated cell staining/sorting (FACS).

Rodent Stroke Models to Study Functional Recovery and Neural Repair.

Rodent ischemic stroke models are essential research tools for studying this highly prevalent disease and represent a critical element in the translational pipeline for development of new therapies. The majority of ischemic stroke models have been developed to study the acute phase of the disease and neuroprotective strategies, but a subset of models is better suited for studying stroke recovery. Each model therefore has characteristics that lend itself to certain types of investigations and outcome measures, and it is important to consider both explicit and implicit details when designing experiments that utilize each model.

Thermosensitive Biodegradable Hydrogels for Local and Controlled Cerebral Delivery of Proteins: MRI-Based Monitoring of and Protein Release.

Hydrogels have been suggested as novel drug delivery systems for sustained release of therapeutic proteins in various neurological disorders. The main advantage these systems offer is the controlled, prolonged exposure to a therapeutically effective dose of the released drug after a single intracerebral injection. Characterization of controlled release of therapeutics from a hydrogel is generally performed , as current methods do not allow for measurements of spatiotemporal distribution and release kinetics of a loaded protein.