Digital Commons Network^™

Interventions Connecting Young People Living In Africa To Healthcare; A Systematic Review Using The Re-Aim Framework, Titilola Abike Gbaja-Biamila, Chisom Obiezu-Umeh, Ucheoma Nwaozuru, David Oladele, Alexis Engelhart, Thembekile Shato, Stacey Mason, Victoria Carter, Juliet Iwelunmor-Ezepue

2020-Current year OA Pubs

INTRODUCTION: Africa's young people are among the least focused groups in healthcare linkage. The disproportionally high burden of youth-related health problems is a burden, especially in developing regions like Africa, which have a high population of young people. More information is needed about factors that impact linkages in healthcare and the sustainability of health interventions among young people in Africa.

METHODS: A systematic literature search was performed from October 2020 to May 2022 in PubMed, CINAHL, Scopus, Global Health, and the Web of Science. Studies included in the review were conducted among young people aged 10-24 living in Africa, written …

A Novel Crispr/Cas9-Mediated Mouse Model Of Colon Carcinogenesis, Hajime Kashima, Anthony Fischer, Daniel A Veronese-Paniagua, Vered A Gazit, Changqing Ma, Yan Yan, Marc S Levin, Blair B Madison, Deborah C Rubin

2020-Current year OA Pubs

BACKGROUND & AIMS: Human sporadic colorectal cancer (CRC) results from a multistep pathway with sequential acquisition of specific genetic mutations in the colorectal epithelium. Modeling CRC in vivo is critical for understanding the tumor microenvironment. To accurately recapitulate human CRC pathogenesis, mouse models must include these multi-step genetic abnormalities. The aim of this study was to generate a sporadic CRC model that more closely mimics this multi-step process and to use this model to study the role of a novel Let7 target PLAGL2 in CRC pathogenesis.

METHODS: We generated a CRISPR/Cas9 somatic mutagenesis mouse model that is inducible and multiplexed …

Evolution Of Proton Radiation Therapy Brainstem Constraints On The Pediatric Proton/Photon Consortium Registry, Dora Correia, Stephanie M Perkins, Et Al.

2020-Current year OA Pubs

PURPOSE: Increasing concern that brainstem toxicity incidence after proton radiation therapy might be higher than with photons led to a 2014 University of Florida (UF) landmark paper identifying its risk factors and proposing more conservative dose constraints. We evaluated how practice patterns changed among the Pediatric Proton/Photon Consortium Registry (PPCR).

MATERIAL AND METHODS: This prospective multicenter cohort study gathered data from patients under the age of 22 years enrolled on the PPCR, treated between 2002 and 2019 for primary posterior fossa brain tumors. After standardizing brainstem contours, we garnered dosimetry data and correlated those meeting the 2014 proton-specific brainstem constraint …

Ivsight As An Infusion Monitor For Patients Receiving Intravenous Therapy: An Exploratory, Unblinded, Single-Center Trial, Carlos Mejia-Chew, Brett Heuring, Jeffrey Salmons, Lori Weilmuenster, Joe Beggs, Glen Kleinschmidt, Jake Eshelman, Sai Dodda

2020-Current year OA Pubs

BACKGROUND: Intravenous (IV) infusion therapy is commonly used in health care settings. However, IV therapy at home can be challenging because it relies on the patient's ability to manage multiple medications correctly, which may lead to decreased treatment adherence.

OBJECTIVE: We aimed to assess the usability and accuracy of the IVsight monitor in capturing IV infusion data compared to manual recording.

METHODS: A prospective, single-center, usability study involving patients receiving IV infusion therapy at one of the BJC's Home Infusion suites was conducted to evaluate the accuracy, performance, and acceptability of the device IVsight as a monitor for IV infusions. …

Performance Of The Lumipulse Plasma Aβ42/40 And Ptau181 Immunoassays In The Detection Of Amyloid Pathology, Daniel J Figdore, Heather J Wiste, Joshua A Bornhorst, Randall J Bateman, Yan Li, Jonathan Graff-Radford, David S Knopman, Prashanthi Vemuri, Val J Lowe, Clifford R Jack Jr, Ronald C Petersen, Alicia Algeciras-Schimnich

2020-Current year OA Pubs

INTRODUCTION: This study evaluated the performance of the Lumipulse plasma beta-amyloid (Aβ) 42/40 and pTau181 compared to other assays to detect an abnormal amyloid-positron emission tomography (PET).

METHODS: Plasma samples from cognitively unimpaired (

RESULTS: Lumipulse and IP-MS Aβ42/40 exhibited the highest diagnostic accuracy for detecting an abnormal amyloid-PET (areas under the curve [AUCs] of 0.81 and 0.84, respectively). The Lumipulse and Simoa pTau181 assays exhibited lower performance (AUCs of 0.74 and 0.72, respectively). The Simoa Aβ42/40 assay demonstrated the lowest diagnostic accuracy (AUC 0.57). Combining Aβ42/40 and pTau181 did not significantly improve performance over Aβ42/40 alone for Lumipulse (AUC …

Chemotherapy-Induced Neutropenia Management In A Patient With Metastatic Breast Cancer And Shwachman-Diamond Syndrome (Sds): A Case Report, Renee Morecroft, Constantine N. Logothetics, Stefan P. Tarnawsky, Andrew A. Davis

2020-Current year OA Pubs

BACKGROUND: Shwachman-Diamond syndrome (SDS) is a rare inherited bone marrow failure syndrome associated with cytopenia and the development of hematologic malignancies. Solid tumor occurrence is rare and, historically, these patients have had poor outcomes due to chemotherapy-induced myelosuppression and increased susceptibility to infections. We report the administration of cytotoxic systemic therapy with granulocyte colony-stimulating factor (G-CSF) in a patient with SDS and metastatic breast cancer. We describe the risk-benefit profile of utilizing G-CSF in managing this patient to improve her therapeutic outcome and review the prior literature.

CASE DESCRIPTION: A 41-year-old Caucasian female with SDS developed stage IV triple-positive [estrogen …

Lessons Learned From The Moment Study On How To Recruit And Retain A Target Population Online, Across Borders, And With Automated Remote Data Collection, Andrew Belfiglio, Shayleigh Dickson Page, Sara Pettersson, Michelle Van Rijn, Ercole Vellone, Heleen Westland, Kenneth E. Freedland, Christopher Lee, Anna Strömberg, Douglas Wiebe, Subhash Aryal, Barbara Riegel, Tiny Jaarsma

2020-Current year OA Pubs

Increasingly, studies use social media to recruit, enroll, and collect data from participants. This introduces a threat to data integrity: efforts to produce fraudulent data to receive participant compensation, e.g., gift cards. MOMENT is an online symptom-monitoring and self-care study that implemented safeguards to protect data integrity. Facebook, Twitter, and patient organizations were used to recruit participants with chronic health conditions in four countries (USA, Italy, The Netherlands, Sweden). Links to the REDCap baseline survey were posted to social media accounts. The initial study launch, where participants completed the baseline survey and were automatically re-directed to the LifeData ecological momentary …

Translatability Of Findings From Cynomolgus Monkey To Human Suggests A Mechanistic Role For Il-21 In Promoting Immunogenicity To An Anti-Pd-1/Il-21 Mutein Fusion Protein, Mark A Kroenke, Ramaswamy Govindan, Et Al.

2020-Current year OA Pubs

AMG 256 is a bi-specific, heteroimmunoglobulin molecule with an anti-PD-1 antibody domain and a single IL-21 mutein domain on the C-terminus. Nonclinical studies in cynomolgus monkeys revealed that AMG 256 administration led to the development of immunogenicity-mediated responses and indicated that the IL-21 mutein domain of AMG 256 could enhance the anti-drug antibody response directed toward the monoclonal antibody domain. Anti-AMG 256 IgE were also observed in cynomolgus monkeys. A first-in-human (FIH) study in patients with advanced solid tumors was designed with these risks in mind. AMG 256 elicited ADA in 28 of 33 subjects (84.8%). However, ADA responses were …

Graceful Gait: Virtual Ballet Classes Improve Mobility And Reduce Falls More Than Wellness Classes For Older Women, Elinor C Harrison, Allison M Haussler, Lauren E Tueth, Sidney T Baudendistel, Gammon M Earhart

2020-Current year OA Pubs

INTRODUCTION: Dance is an effective and motivating form of exercise for older women, but few studies have quantified the benefits of virtual dance classes nor, specifically, ballet. This study tested the effectiveness of virtual ballet compared to virtual wellness classes, with the goal of reaching underserved populations. It is among the first to explore the effects of virtual classical ballet on functional gait mobility, balance, and quality of life measures in older women.

METHODS: Older women were recruited in two waves and randomized to two groups: a ballet class modified for older adults and a wellness-based control class. Both groups …

A Multisociety Delphi Consensus Statement On New Fatty Liver Disease Nomenclature, Mary E Rinella, Samuel Klein, Et Al.

2020-Current year OA Pubs

The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favor of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panelists from 56 countries participated in 4 …

The Ithildin Library For Efficient Numerical Solution Of Anisotropic Reaction-Diffusion Problems In Excitable Media, Desmond Kabus, Marie Cloet, Christian Zemlin, Olivier Bernus, Hans Dierckx

2020-Current year OA Pubs

Ithildin is an open-source library and framework for efficient parallelized simulations of excitable media, written in the C++ programming language. It uses parallelization on multiple CPU processors via the message passing interface (MPI). We demonstrate the library's versatility through a series of simulations in the context of the monodomain description of cardiac electrophysiology, including the S1S2 protocol, spiral break-up, and spiral waves in ventricular geometry. Our work demonstrates the power of Ithildin as a tool for studying complex wave patterns in cardiac tissue and its potential to inform future experimental and theoretical studies. We publish our full code with this …

Microstructural Analysis Does Not Support Altered Interhemispheric Wiring Of The Human Anterior Commissure In Corpus Callosum Dysgenesis, Timothy J Edwards, Ryan J Dean, Gail A Robinson, Jacquelyn Knight, Simone A Mandelstam, Linda J Richards

2020-Current year OA Pubs

BACKGROUND: Individuals with corpus callosum dysgenesis (CCD) lack the clear disconnection syndrome that is characteristic of individuals in whom the corpus callosum has been surgically severed. One potential explanation for this paradox is that the anterior commissure undergoes neuroplastic remodeling in CCD to improve interhemispheric communication between the brain hemispheres.

METHODS: A cohort of sixteen individuals with CCD (and sixteen sex and age-matched neurotypical controls) underwent multi-shell diffusion magnetic resonance high-field imaging (dMRI) at 7-Tesla to assess the anatomy of the anterior commissure for evidence of neuroplasticity.

RESULTS: No significant group-wise differences in midsagittal anterior commissure volumes were detected between …

Efficacy And Safety Of Bempedoic Acid In Patients With Heterozygous Familial Hypercholesterolemia: Analysis Of Pooled Patient-Level Data From Phase 3 Clinical Trials, P Barton Duell, Maciej Banach, Alberico L Catapano, Ulrich Laufs, G B John Mancini, Kausik K Ray, Christine Broestl, Yang Zhang, Lei Lei, Anne C Goldberg

2020-Current year OA Pubs

BACKGROUND: Patients with heterozygous familial hypercholesterolemia (HeFH) often cannot reach guideline-recommended low-density lipoprotein cholesterol (LDL-C) goals despite multidrug therapy.

OBJECTIVE: To evaluate the efficacy and safety of bempedoic acid as an add-on therapy for lowering LDL-C in patients with HeFH.

METHODS: Pooled data from two 52-week phase 3 clinical trials of patients with atherosclerotic cardiovascular disease and/or HeFH receiving maximally tolerated statin therapy (randomized 2:1 to bempedoic acid or placebo) were analyzed by HeFH status. Endpoints included changes from baseline to week 12 (and up to week 52) in LDL-C and other lipid parameters, achievement of LDL-C goals, and safety. …

Health System Barriers To Hypertension Care In Peru: Rapid Assessment To Inform Organizational-Level Change, Kendra N. Williams, Lindsay J. Underhill, Lisa De Las Fuentes, Elvin H. Geng, Victor G. Davila-Roman, Et Al.

2020-Current year OA Pubs

Traditional patient- and provider-level hypertension interventions have proven insufficient to halt hypertension as the leading cause of morbidity and mortality globally. Systems-level interventions are required to address factors challenging hypertension control across a social ecological framework, an under-studied topic particularly salient in low- and middle-income countries (LMICs) such as Peru. To inform such interventions, we sought to identify key health systems barriers to hypertension care in Puno, Peru. A participatory stakeholder workshop (October 2021) and 21 in-depth interviews (October 2021-March 2022) were conducted with 55 healthcare professionals (i.e., doctors, nurses, midwives, dentists, nutritionists), followed by a deductive qualitative analysis of …

Early-Phase Insulin Secretion During Mixed-Meal Tolerance Testing Predicts Β-Cell Function And Secretory Capacity In Cystic Fibrosis, Saba Sheikh, Darko Stefanovski, Marissa J Kilberg, Denis Hadjiliadis, Ronald C Rubenstein, Michael R Rickels, Andrea Kelly

2020-Current year OA Pubs

UNLABELLED: Insulin secretion within 30 minutes of nutrient ingestion is reduced in people with cystic fibrosis (PwCF) and pancreatic insufficiency and declines with worsening glucose tolerance. The glucose potentiated arginine (GPA) test is validated for quantifying β-cell secretory capacity as an estimate of functional β-cell mass but requires technical expertise and is burdensome. This study sought to compare insulin secretion during mixed-meal tolerance testing (MMTT) to GPA-derived parameters in PwCF.

METHODS: Secondary data analysis of CF-focused prospective studies was performed in PwCF categorized as 1) pancreatic insufficient [PI-CF] or 2) pancreatic sufficient [PS-CF] and in 3) non-CF controls. MMTT: insulin …

Mapping Of A Hybrid Insulin Peptide In The Inflamed Islet Β-Cells From Nod Mice, Janet M Wenzlau, Orion J Peterson, Anthony N Vomund, James E Dilisio, Anita Hohenstein, Kathryn Haskins, Xiaoxiao Wan

2020-Current year OA Pubs

There is accumulating evidence that pathogenic T cells in T1D recognize epitopes formed by post-translational modifications of β-cell antigens, including hybrid insulin peptides (HIPs). The ligands for several CD4 T-cell clones derived from the NOD mouse are HIPs composed of a fragment of proinsulin joined to peptides from endogenous β-cell granule proteins. The diabetogenic T-cell clone BDC-6.9 reacts to a fragment of C-peptide fused to a cleavage product of pro-islet amyloid polypeptide (6.9HIP). In this study, we used a monoclonal antibody (MAb) to the 6.9HIP to determine when and where HIP antigens are present in NOD islets during disease progression …

Characterization Of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels In Oligodendrocytes., Kyle A Lyman, Ye Han, Andrew P Robinson, Samuel E Weinberg, Daniel W Fisher, Robert J Heuermann, Reagan E Lyman, Dong Kyu Kim, Andreas Ludwig, Navdeep S Chandel, Mark D Does, Stephen D Miller, Dane M Chetkovich

2020-Current year OA Pubs

Mature oligodendrocytes (OLG) are the myelin-forming cells of the central nervous system. Recent work has shown a dynamic role for these cells in the plasticity of neural circuits, leading to a renewed interest in voltage-sensitive currents in OLG. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and their respective current (I

Everything But The Kitchen Sink: An Analysis Of Bacterial And Chemical Contaminants Found In Syringe Residue From People Who Inject Drugs, John A Wildenthal, Drew J Schwartz, Nathanial S Nolan, Lingxia Zhao, John I Robinson, Erin Jones, Raagini Jawa, Jeffrey P Henderson, Laura R Marks

2020-Current year OA Pubs

BACKGROUND: People who inject drugs (PWID) are at high risk of severe wounds, invasive infections, and overdoses. To date, there are few data on the bacterial and chemical contaminants PWID are exposed to when using illicitly manufactured fentanyls and stimulants.

METHODS: Previously used injection drug use equipment was recovered in St Louis, Missouri, by harm reduction organizations over a 12-month period. Syringe residue was analyzed for bacterial contaminants by routine culturing followed by whole genome sequencing of single bacterial isolates. Chemical adulterants in syringe residue were identified by liquid chromatography-mass spectrometry.

RESULTS: Bacteria were cultured from 58.75% of 160 syringes …

Age-Related Alterations In Gray Matter Microstructure In Older People With Remitted Major Depression At Risk For Dementia, John A E Anderson, Neda Rashidi-Ranjbar, Arash Nazeri, Jordan A Chad, Peter Zhukovsky, Benoit H Mulsant, Nathan Herrmann, Linda Mah, Alastair J Flint, Corinne E Fischer, Bruce G Pollock, Tarek K Rajji, Aristotle N Voineskos, Pact-Md Study Group

2020-Current year OA Pubs

BACKGROUND: Major depressive disorder (MDD) in late life is a risk factor for mild cognitive impairment (MCI) and Alzheimer's disease. However, studies of gray matter changes have produced varied estimates of which structures are implicated in MDD and dementia. Changes in gray matter volume and cortical thickness are macrostructural measures for the microstructural processes of free water accumulation and dendritic spine loss.

METHODS: We conducted multishell diffusion imaging to assess gray matter microstructure in 244 older adults with remitted MDD (

RESULTS: Results showed that increasing age was correlated with an increase in isotropic volume fraction and a decrease in …

A Search For Bacteria Identified From Cerebrospinal Fluid Shunt Infections In Previous Surgical Events, Paul Hodor, Christopher E. Pope, Kathryn B. Whitlock, Patrick J. Mcdonald, Jason Hauptman, Lucas R. Hoffman, David D. Limbrick Jr., Tamara D. Simon, Cerebrospinal Fluid Microbiota In Shunts (Climb) Study Group

2020-Current year OA Pubs

Shunt infections are a common complication when treating hydrocephalus by cerebrospinal fluid (CSF) shunt placement. The source of infecting pathogens is not well understood. One hypothesis, which we explored here, is that microorganisms persist chronically in the host long before a symptomatic infection occurs and may be detectable in surgical events preceding infection. A cohort of 13 patients was selected, for which CSF samples were available from an infection episode and from a previous surgery event, which was either an initial shunt placement or a revision. Microbiota were analyzed both directly from CSF and from isolates cultured from CSF on …

Predicting Cognitive Decline: Which Is More Useful, Baseline Amyloid Levels Or Longitudinal Change?, Gengsheng Chen, Nicole S Mckay, Brian A Gordon, Jingxia Liu, Nelly Joseph-Mathurin, Suzanne E Schindler, Jason Hassenstab, Andrew J Aschenbrenner, Qing Wang, Stephanie A Schultz, Yi Su, Pamela J Lamontagne, Sarah J Keefe, Parinaz Massoumzadeh, Carlos Cruchaga, Chengjie Xiong, John C Morris, Tammie L S Benzinger

2020-Current year OA Pubs

The use of biomarkers for the early detection of Alzheimer's disease (AD) is crucial for developing potential therapeutic treatments. Positron Emission Tomography (PET) is a well-established tool used to detect β-amyloid (Aβ) plaques in the brain. Previous studies have shown that cross-sectional biomarkers can predict cognitive decline (Schindler et al.,2021). However, it is still unclear whether longitudinal Aβ-PET may have additional value for predicting time to cognitive impairment in AD. The current study aims to evaluate the ability of baseline- versus longitudinal rate of change in-

Stat1 Employs Myeloid Cell-Extrinsic Mechanisms To Regulate The Neutrophil Response And Provide Protection Against Invasive Klebsiella Pneumoniae Lung Infection, Shekina Gonzalez-Ferrer, Zeyu Xiong, Atish Gheware, Janet S Lee, Et Al.

2020-Current year OA Pubs

Klebsiella pneumoniae (KP) is an extracellular Gram-negative bacterium that causes infections in the lower respiratory and urinary tracts and the bloodstream. STAT1 is a master transcription factor that acts to maintain T cell quiescence under homeostatic conditions. Although STAT1 helps defend against systemic spread of acute KP intrapulmonary infection, whether STAT1 regulation of T cell homeostasis impacts pulmonary host defense during acute bacterial infection and injury is less clear. Using a clinical KP respiratory isolate and a pneumonia mouse model, we found that STAT1 deficiency led to an early neutrophil-dominant transcriptional profile and neutrophil recruitment in the lung preceding widespread …

Cep120 Is Essential For Kidney Stromal Progenitor Cell Growth And Differentiation, Ewa Langner, Tao Cheng, Eirini Kefaloyianni, Charles Gluck, Baolin Wang, Moe R Mahjoub

2020-Current year OA Pubs

Mutations in genes that disrupt centrosome structure or function can cause congenital kidney developmental defects and lead to fibrocystic pathologies. Yet, it is unclear how defective centrosome biogenesis impacts renal progenitor cell physiology. Here, we examined the consequences of impaired centrosome duplication on kidney stromal progenitor cell growth, differentiation, and fate. Conditional deletion of the ciliopathy gene Cep120, which is essential for centrosome duplication, in the stromal mesenchyme resulted in reduced abundance of interstitial lineages including pericytes, fibroblasts and mesangial cells. These phenotypes were caused by a combination of delayed mitosis, activation of the mitotic surveillance pathway leading to apoptosis, …

Phosphorylation Regulates Viral Biomolecular Condensates To Promote Infectious Progeny Production, Nicholas Grams, Matthew Charman, Edwin Halko, Richard Lauman, Benjamin A Garcia, Matthew D Weitzman

2020-Current year OA Pubs

Biomolecular condensates (BMCs) play important roles in diverse biological processes. Many viruses form BMCs which have been implicated in various functions critical for the productive infection of host cells. The adenovirus L1-52/55 kilodalton protein (52K) was recently shown to form viral BMCs that coordinate viral genome packaging and capsid assembly. Although critical for packaging, we do not know how viral condensates are regulated during adenovirus infection. Here we show that phosphorylation of serine residues 28 and 75 within the N-terminal intrinsically disordered region of 52K modulates viral condensates in vitro and in cells, promoting liquid-like properties. Furthermore, we demonstrate that …

Non-Invasive Auricular Vagus Nerve Stimulation For Subarachnoid Hemorrhage (Navsah): Protocol For A Prospective, Triple-Blinded, Randomized Controlled Trial, Anna Huguenard, Gansheng Tan, Gabrielle Johnson, Markus Adamek, Andrew Coxon, Terrance Kummer, Joshua Osbun, Ananth Vellimana, David Limbrick, Gregory Zipfel, Peter Brunner, Eric Leuthardt

2020-Current year OA Pubs

BACKGROUND: Inflammation has been implicated in driving the morbidity associated with subarachnoid hemorrhage (SAH). Despite understanding the important role of inflammation in morbidity following SAH, there is no current effective way to modulate this deleterious response. There is a critical need for a novel approach to immunomodulation that can be safely, rapidly, and effectively deployed in SAH patients. Vagus nerve stimulation (VNS) provides a non-pharmacologic approach to immunomodulation, with prior studies demonstrating VNS can reduce systemic inflammatory markers, and VNS has had early success treating inflammatory conditions such as arthritis, sepsis, and inflammatory bowel diseases. The aim of the Non-invasive …

Characterization And Individual-Level Prediction Of Cognitive State In The First Year After 'Mild' Stroke, Juan Pablo Saa, Tamara Tse, Gerald Choon-Huat Koh, Philip Yap, Carolyn M. Baum, David E. Uribe-Rivera, Saras M. Windecker, Henry Ma, Stephen M. Davis, Geoffrey A. Donnan, Leeanne M. Carey

2020-Current year OA Pubs

BACKGROUND: Mild stroke affects more than half the stroke population, yet there is limited evidence characterizing cognition over time in this population, especially with predictive approaches applicable at the individual-level. We aimed to identify patterns of recovery and the best combination of demographic, clinical, and lifestyle factors predicting individual-level cognitive state at 3- and 12-months after mild stroke.

METHODS: In this prospective cohort study, the Montreal Cognitive Assessment (MoCA) was administered at 3-7 days, 3- and 12-months post-stroke. Raw changes in MoCA and impairment rates (defined as MoCA<24 points) were compared between assessment time-points. Trajectory clusters were identified using variations of ≥1 point in MoCA scores. To further compare clusters, additional assessments administered at 3- and 12-months were included. Gamma and Quantile mixed-effects regression were used to predict individual MoCA scores over time, using baseline clinical and demographic variables. Model predictions were fitted for each stroke survivor and evaluated using model cross-validation to identify the overall best predictors of cognitive recovery.

RESULTS: Participants' (n = 119) MoCA scores improved from baseline to 3-months …

Trauma Patients Have Reduced Ex Vivo Flow-Dependent Platelet Hemostatic Capacity In A Microfluidic Model Of Vessel Injury, Kimberly A. Thomas, Rassam M. G. Rassam, Ronit Kar, Devin M. Dishong, Katelin C. Rahn, Ricardo Fonseca, Melissa Canas, Jose Aldana, Hussain Afzal, Kelly Bochicchio, Matthew D. Neal, Grant V. Bochicchio, Philip C. Spinella, Susan M. Shea

2020-Current year OA Pubs

Trauma is the leading cause of death in individuals up to 45 years of age. Alterations in platelet function are a critical component of trauma-induced coagulopathy (TIC), yet these changes and the potential resulting dysfunction is incompletely understood. The lack of clinical assays available to explore platelet function in this patient population has hindered detailed understanding of the role of platelets in TIC. The objective of this study was to assess trauma patient ex vivo flow-dependent platelet hemostatic capacity in a microfluidic model. We hypothesized that trauma patients would have flow-regime dependent alterations in platelet function. Blood was collected from …

Extensive Reactive Cutaneous Histiocytic Infiltrate Resembling Non-Langerhans Cell Histiocytosis As The Presenting Sign Of Underlying Vacuoles, E1 Enzyme, X-Linked, Autoinflammatory, Somatic Syndrome, Cynthia X Wang, Christine C Yokoyama, Ilana S Rosman, Amy C Musiek

2020-Current year OA Pubs

No abstract provided.

Neurosteroids Mediate And Modulate The Effects Of Pro-Inflammatory Stimulation And Toll-Like Receptors On Hippocampal Plasticity And Learning, Yukitoshi Izumi, Kazuko A. O'Dell, Anil G. Cashikar, Steven M. Paul, Douglas F. Covey, Steven J. Mennerick, Charles F. Zorumski

2020-Current year OA Pubs

Pro-inflammatory changes contribute to multiple neuropsychiatric illnesses. Understanding how these changes are involved in illnesses and identifying strategies to alter inflammatory responses offer paths to potentially novel treatments. We previously found that acute pro-inflammatory stimulation with high (μg/ml) lipopolysaccharide (LPS) for 10-15 min dampens long-term potentiation (LTP) in the hippocampus and impairs learning. Effects of LPS involved non-canonical inflammasome signaling but were independent of toll-like receptor 4 (TLR4), a known LPS receptor. Low (ng/ml) LPS also inhibits LTP when administered for 2-4 h, and here we report that this LPS exposure requires TLR4. We also found that effects of low …

Control Of Acute Myeloid Leukemia And Generation Of Immune Memory In Vivo Using Amv564, A Bivalent Bispecific Cd33 X Cd3 T Cell Engager, Linda G. Eissenberg, Julie K. Ritchey, Michael P. Rettig, Dilan A. Patel, Kiran Vij, Feng Gao, Victoria Smith, Tae H Han, John F. Dipersio

2020-Current year OA Pubs

Off-the-shelf immunotherapeutics that suppress tumor growth and provide durable protection against relapse could enhance cancer treatment. We report preclinical studies on a CD33 x CD3 bivalent bispecific diabody, AMV564, that not only suppresses tumor growth, but also facilitates memory responses in a mouse model of acute myelogenous leukemia (AML). Mechanistically, a single 5-day treatment with AMV564 seems to reduce tumor burden by redirection of T cells, providing a time window for allogeneic or other T cells that innately recognize tumor antigens to become activated and proliferate. When the concentration of bispecific becomes negligible, the effector: target ratio has also shifted, …