Digital Commons Network^™

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 …

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 …

Tract-Based Analyses Of White Matter In Schizophrenia, Bipolar Disorder, Aging, And Dementia Using High Spatial And Directional Resolution Diffusion Imaging: A Pilot Study, Daniel Mamah, Shingshiun Chen, Joshua S Shimony, Michael P Harms

2020-Current year OA Pubs

INTRODUCTION: Structural brain connectivity abnormalities have been associated with several psychiatric disorders. Schizophrenia (SCZ) is a chronic disabling disorder associated with accelerated aging and increased risk of dementia, though brain findings in the disorder have rarely been directly compared to those that occur with aging.

METHODS: We used an automated approach to reconstruct key white matter tracts and assessed tract integrity in five participant groups. We acquired one-hour-long high-directional diffusion MRI data from young control (CON, n =28), bipolar disorder (BPD, n =21), and SCZ (n =22) participants aged 18-30, and healthy elderly (ELD, n =15) and dementia (DEM, n …

Janus Kinase Inhibition In The Treatment And Prevention Of Graft-Versus-Host Disease, Elisa De Togni, Oladipo Cole, Ramzi Abboud

2020-Current year OA Pubs

Graft-versus-host disease (GVHD) is a significant cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). For many years, corticosteroids have been the mainstay treatment for GVHD, but cases of steroid-refractory GVHD and the severe adverse effects of high-dose corticosteroids have increased the need for preventative and therapeutic strategies for GVHD. Due to the nature of alloreactive T cells, GVHD is inherently linked to the graft-versus-leukemia (GVL) effect, the therapeutic driving force behind stem cell transplantation. A considerable clinical challenge is to preserve GVL while suppressing GVHD. The field of GVHD research has greatly expanded over the past …

Analyses Of Patients Who Self-Administered Diazepam Nasal Spray For Acute Treatment Of Seizure Clusters, Sunita N Misra, Michael R Sperling, Vikram R Rao, Jurriaan M Peters, Patricia Penovich, James Wheless, R Edward Hogan, Charles S Davis, Enrique Carrazana, Adrian L Rabinowicz

2020-Current year OA Pubs

For acute treatment of seizure clusters in patients with epilepsy, intranasal administration of acute seizure therapies has been shown to provide accessibility and ease of use to care partners as well as the potential for self-administration by patients. Diazepam nasal spray (Valtoco®) was approved by the US Food and Drug Administration for acute treatment of intermittent, stereotypic episodes of frequent seizure activity (ie, seizure clusters, acute repetitive seizures) in patients with epilepsy aged ≥6 years. Self-administration consistent with the prescribing information is feasible and was reported by a subgroup of patients (n = 27 of 163) in a long-term phase …

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-

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

Transcriptional Precision In Photoreceptor Development And Diseases - Lessons From 25 Years Of Crx Research, Yiqiao Zheng, Shiming Chen

2020-Current year OA Pubs

The vertebrate retina is made up of six specialized neuronal cell types and one glia that are generated from a common retinal progenitor. The development of these distinct cell types is programmed by transcription factors that regulate the expression of specific genes essential for cell fate specification and differentiation. Because of the complex nature of transcriptional regulation, understanding transcription factor functions in development and disease is challenging. Research on the

Referent Data For Investigations Of Upper Limb Accelerometry: Harmonized Data From Three Cohorts Of Typically-Developing Children, Catherine E Lang, Catherine R Hoyt, Jeffrey D Konrad, Kayla R Bell, Natasha Marrus, Marghuretta D Bland, Keith R Lohse, Allison E Miller

2020-Current year OA Pubs

AIM: The rise of wearable sensing technology shows promise for addressing the challenges of measuring motor behavior in pediatric populations. The current pediatric wearable sensing literature is highly variable with respect to the number of sensors used, sensor placement, wearing time, and how data extracted from the sensors are analyzed. Many studies derive conceptually similar variables via different calculation methods, making it hard to compare across studies and clinical populations. In hopes of moving the field forward, this report provides referent upper limb wearable sensor data from accelerometers on 25 variables in typically-developing children, ages 3-17 years.

METHODS: This is …

A Structure-Function Analysis Of Hepatocyte Arginase 2 Reveals Mitochondrial Ureahydrolysis As A Determinant Of Glucose Oxidation, Yiming Zhang, Jiameng Sun, Henry D Wasserman, Joshua A Adams, Cassandra B Higgins, Shannon C Kelly, Louise Lantier, Brian J Debosch

2020-Current year OA Pubs

BACKGROUND & AIMS: Restoring hepatic and peripheral insulin sensitivity is critical to prevent or reverse metabolic syndrome and type 2 diabetes. Glucose homeostasis comprises in part the complex regulation of hepatic glucose production and insulin-mediated glucose uptake and oxidation in peripheral tissues. We previously identified hepatocyte arginase 2 (Arg2) as an inducible ureahydrolase that improves glucose homeostasis and enhances glucose oxidation in multiple obese, insulin-resistant models. We therefore examined structure-function determinants through which hepatocyte Arg2 governs systemic insulin action and glucose oxidation.

METHODS: To do this, we generated mice expressing wild-type murine Arg2, enzymatically inactive Arg2 (Arg2

RESULTS: We show …

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 …

An Internet Mantram Repetition Program To Promote Well-Being In Breast Cancer Survivors: A Feasibility Randomized Controlled Trial, Jennifer M Hulett, An-Lin Cheng, Jill E Bormann, Allison B Anbari, Jane M Armer, Brooke M Hartman, B Ann Bettencourt, Leeanne B Sherwin, Edie L Sperling, Natsayakarn Narkthong, Carol Reinero, Hans Rindt, Kathy Schreiber, Lindsay L Peterson, Emily Albright

2020-Current year OA Pubs

No abstract provided.

Bradykinin Receptor Expression And Bradykinin-Mediated Sensitization Of Human Sensory Neurons, Jiwon Yi, Zachariah Bertels, John Smith Del Rosario, Allie J. Widman, Richard A. Slivicki, Maria Payne, Henry M. Susser, Bryan A. Copits, Robert W. Gereau 4th

2020-Current year OA Pubs

Bradykinin is a peptide implicated in inflammatory pain in both humans and rodents. In rodent sensory neurons, activation of B1 and B2 bradykinin receptors induces neuronal hyperexcitability. Recent evidence suggests that human and rodent dorsal root ganglia (DRG), which contain the cell bodies of sensory neurons, differ in the expression and function of key GPCRs and ion channels; whether bradykinin receptor expression and function are conserved across species has not been studied in depth. In this study, we used human DRG tissue from organ donors to provide a detailed characterization of bradykinin receptor expression and bradykinin-induced changes in the excitability …

A Feasibility Trial Of Skin Surface Motion-Gated Stereotactic Body Radiotherapy For Treatment Of Upper Abdominal Or Lower Thoracic Targets Using A Novel O-Ring Gantry, Kendall Kiser, Joshua Schiff, Eric Laugeman, Taeho Kim, Olga Green, Casey Hatscher, Hyun Kim, Shahed Badiyan, Matthew Spraker, Pamela Samson, Clifford Robinson, Alex Price, Lauren Henke

2020-Current year OA Pubs

BACKGROUND AND PURPOSE: A novel O-ring gantry can deliver stereotactic body radiation therapy (SBRT) with artificial intelligence-facilitated, CT-guided online plan adaptation. It gates mobile targets by optically monitoring skin surface motion. However, this gating solution has not been clinically validated. We conducted a trial to evaluate the feasibility of optical skin surface-guided gating for patients with mobile upper abdominal or lower thoracic malignancies treated with SBRT on this platform (NCT05030454).

MATERIALS AND METHODS: Ten patients who were prescribed SBRT to a thoracic or abdominal target and were capable of breath-hold for at least 17 s enrolled. They received SBRT in …

Sirtuin3 Ensures The Metabolic Plasticity Of Neurotransmission During Glucose Deprivation, Anupama Tiwari, Arsalan Hashemiaghdam, Marissa A Laramie, Dario Maschi, Tristaan Haddad, Marion I Stunault, Carmen Bergom, Ali Javaheri, Vitaly Klyachko, Ghazaleh Ashrafi

2020-Current year OA Pubs

Neurotransmission is an energetically expensive process that underlies cognition. During intense electrical activity or dietary restrictions, the glucose level in the brain plummets, forcing neurons to utilize alternative fuels. However, the molecular mechanisms of neuronal metabolic plasticity remain poorly understood. Here, we demonstrate that glucose-deprived neurons activate the CREB and PGC1α transcriptional program, which induces expression of the mitochondrial deacetylase Sirtuin 3 (Sirt3) both in vitro and in vivo. We show that Sirt3 localizes to axonal mitochondria and stimulates mitochondrial oxidative capacity in hippocampal nerve terminals. Sirt3 plays an essential role in sustaining synaptic transmission in the absence of glucose …

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 …

Perspectives From Public Health Practitioners And Advocates On Community Development For Active Living: What Are The Lasting Impacts?, Natalicio Serrano, Laurel Schmidt, Amy A Eyler, Ross C Brownson

2020-Current year OA Pubs

PURPOSE: Evidence suggests differential impacts of community development, including gentrification and displacement. Public health practitioners and advocates are key stakeholders involved in the community development process related to active living, yet little is known about their perceptions of its impacts. We explored the perspectives of relevant leaders of public health departments and key community and advocacy organizations on community development, gentrification, and displacement.

APPROACH: Purposive key informant interviews.

SETTING: CDC State Physical Activity and Nutrition (SPAN) funding recipients.

PARTICIPANTS: CDC SPAN recipient leadership (n = 10 of 16) and advocacy organizations they partnered with (n = 7 of 16).

METHOD: …

Uropathogenic Escherichia Coli Wield Enterobactin-Derived Catabolites As Siderophores, Zongsen Zou, John I Robinson, Lindsey K Steinberg, Jeffrey P Henderson

2020-Current year OA Pubs

Uropathogenic Escherichia coli (UPEC) secrete multiple siderophore types to scavenge extracellular iron(III) ions during clinical urinary tract infections, despite the metabolic costs of biosynthesis. Here, we find the siderophore enterobactin (Ent) and its related products to be prominent components of the iron-responsive extracellular metabolome of a model UPEC strain. Using defined Ent biosynthesis and import mutants, we identify lower molecular weight dimeric exometabolites as products of incomplete siderophore catabolism, rather than prematurely released biosynthetic intermediates. In E. coli, iron acquisition from iron(III)-Ent complexes requires intracellular esterases that hydrolyze the siderophore. Although UPEC are equipped to consume the products of completely …

Harmonization Of Csf And Imaging Biomarkers In Alzheimer's Disease: Need And Practical Applications For Genetics Studies And Preclinical Classification, Jigyasha Timsina, Muhammad Ali, Anh Do, Lihua Wang, Daniel Western, Yun Ju Sung, Carlos Cruchaga

2020-Current year OA Pubs

In Alzheimer's disease (AD) research, cerebrospinal fluid (CSF) Amyloid beta (Aβ), Tau and pTau are the most accepted and well validated biomarkers. Several methods and platforms exist to measure those biomarkers, leading to challenges in combining data across studies. Thus, there is a need to identify methods that harmonize and standardize these values. We used a Z-score based approach to harmonize CSF and amyloid imaging data from multiple cohorts and compared GWAS results using this approach with currently accepted methods. We also used a generalized mixture model to calculate the threshold for biomarker-positivity. Based on our findings, our normalization approach …

An Overview Of The Effects Of Tenapanor On Visceral Hypersensitivity In The Treatment Of Irritable Bowel Syndrome With Constipation, Prashant Singh, Gregory S Sayuk, David P Rosenbaum, Susan Edelstein, Kenji Kozuka, Lin Chang

2020-Current year OA Pubs

BACKGROUND: Patients with irritable bowel syndrome with constipation (IBS-C) experience persistent abdominal pain, a common symptom leading to greater healthcare utilization and reports of treatment non-response. Clinically significant improvements in abdominal pain were observed in clinical trials of tenapanor, a first-in-class inhibitor of sodium/hydrogen exchanger isoform 3 (NHE3), for the treatment of IBS-C in adults.

AIM: This narrative review reports the current knowledge about visceral hypersensitivity as a mechanism for abdominal pain in patients with IBS-C and explores the published evidence for hypothesized mechanisms by which tenapanor may reduce visceral hypersensitivity leading to the observed clinical response of decreased abdominal …

Trans-Ancestry Epigenome-Wide Association Meta-Analysis Of Dna Methylation With Lifetime Cannabis Use, Fang Fang, Laura J Bierut, Et Al.

2020-Current year OA Pubs

Cannabis is widely used worldwide, yet its links to health outcomes are not fully understood. DNA methylation can serve as a mediator to link environmental exposures to health outcomes. We conducted an epigenome-wide association study (EWAS) of peripheral blood-based DNA methylation and lifetime cannabis use (ever vs. never) in a meta-analysis including 9436 participants (7795 European and 1641 African ancestry) from seven cohorts. Accounting for effects of cigarette smoking, our trans-ancestry EWAS meta-analysis revealed four CpG sites significantly associated with lifetime cannabis use at a false discovery rate of 0.05

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.

Leveraging Murine Models Of The Neurofibromatosis Type 1 Cancer Predisposition Syndrome To Elucidate The Cellular Circuits That Drive Pediatric Low-Grade Glioma Formation And Progression, David H Gutmann

2020-Current year OA Pubs

Brain tumors are the leading cause of cancer-related death in children, where low-grade gliomas (LGGs) predominate. One common hereditary cause for LGGs involves neurofibromatosis-1 (NF1) gene mutation, as seen in individuals with the NF1 cancer predisposition syndrome. As such, children with NF1 are at increased risk of developing LGGs of the optic pathway, brainstem, cerebellum, and midline brain structures. Using genetically engineered mouse models, studies have revealed both cell-intrinsic (MEK signaling) and stromal dependencies that underlie their formation and growth. Importantly, these dependencies represent vulnerabilities against which targeted agents can be used for preclinical investigation prior to clinical translation.

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 …

Researching Covid To Enhance Recovery (Recover) Pediatric Study Protocol: Rationale, Objectives And Design, Rachel S Gross, Deanna M. Barch, Andrew C. Heath, Et Al.

2020-Current year OA Pubs

IMPORTANCE: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults.

OBSERVATIONS: We describe the protocol for the Pediatric Observational Cohort Study of the NIH's REsearching COVID to Enhance Recovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of …