Digital Commons Network^™

Human Deprivation Amblyopia: Treatment Insights From Animal Models, Kevin R Duffy, Mark F Bear, Nimesh B Patel, Vallabh E Das, Lawrence Tychsen

2020-Current year OA Pubs

Amblyopia is a common visual impairment that develops during the early years of postnatal life. It emerges as a sequela to eye misalignment, an imbalanced refractive state, or obstruction to form vision. All of these conditions prevent normal vision and derail the typical development of neural connections within the visual system. Among the subtypes of amblyopia, the most debilitating and recalcitrant to treatment is deprivation amblyopia. Nevertheless, human studies focused on advancing the standard of care for amblyopia have largely avoided recruitment of patients with this rare but severe impairment subtype. In this review, we delineate characteristics of deprivation amblyopia …

Case Report: Stereotactic Body Radiation Treatment For Immunotherapy Escaped Oligometastatic Progression In Cutaneous Melanoma And Merkel Cell Carcinoma, Karam Khaddour, Alice Zhou, Omar Butt, Jiayi Huang, George Ansstas

2020-Current year OA Pubs

Oligometastatic progression represents a unique manifestation of tumor immune-escape that can lead to disease progression during treatment with immune checkpoint inhibitor (ICI). The diagnosis and further optimal management of oligometastatic progression through ICI remains unclear. Diagnostic challenges include practical limitations due to the anatomical sites of oligometastatic progression, such as the para-aortic region, where traditional tissue biopsy carries high risk, and circulating-tumor DNA (ctDNA) could aid in diagnosis and disease monitoring as a supplement to surveillance imaging. In this report, we describe two cases of one patient with metastatic melanoma and the other with metastatic Merkel cell carcinoma (MCC) who …

The Immunology Of Takotsubo Syndrome, Kenji Rowel Q Lim, Douglas L Mann, Tsuneaki Kenzaka, Tomohiro Hayashi

2020-Current year OA Pubs

Takotsubo syndrome (TTS) is a disorder characterized by transient cardiac dysfunction with ventricular regional wall motion abnormalities, primarily thought to be caused by the effects of a sudden catecholamine surge on the heart. Although the majority of patients exhibit prompt recovery of their cardiac dysfunction, TTS remains associated with increased mortality rates acutely and at long-term, and there is currently no cure for TTS. Inflammation has been shown to play a key role in determining outcomes in TTS patients, as well as in the early pathogenesis of the disorder. There are also cases of TTS patients that have been successfully …

Leishmania Major- Derived Lipophosphoglycan Influences The Host's Early Immune Response By Inducing Platelet Activation And Dkk1 Production Via Tlr1/2, Olivia C Ihedioha, Anutr Sivakoses, Stephen M Beverley, Diane Mcmahon-Pratt, Alfred L M Bothwell

2020-Current year OA Pubs

BACKGROUND: Platelets are rapidly deployed to infection sites and respond to pathogenic molecules via pattern recognition receptors (TLR, NLRP). Dickkopf1 (DKK1) is a quintessential Wnt antagonist produced by a variety of cell types including platelets, endothelial cells, and is known to modulate pro-inflammatory responses in infectious diseases and cancer. Moreover, DKK1 is critical for forming leukocyte-platelet aggregates and induction of type 2 cell-mediated immune responses. Our previous publication showed activated platelets release DKK1 following

RESULTS: Here we probed the role of the key surface virulence glycoconjugate lipophosphoglycan (LPG), on DKK1 production using null mutants deficient in LPG synthesis (

CONCLUSION: …

Use Of Learner-Driven, Formative, Ad-Hoc, Prospective Assessment Of Competence In Physical Therapist Clinical Education In The United States: A Prospective Cohort Study, Carey Holleran, Jeffrey Konrad, Barbara Norton, Tamara Burlis, Steven Ambler

2020-Current year OA Pubs

PURPOSE: The purpose of this project was to implement a process for learner-driven, formative, prospective, ad-hoc, entrustment assessment in Doctor of Physical Therapy clinical education. Our goals were to develop an innovative entrustment assessment tool, and then explore whether the tool detected (1) differences between learners at different stages of development and (2) differences within learners across the course of a clinical education experience. We also investigated whether there was a relationship between the number of assessments and change in performance.

METHODS: A prospective, observational, cohort of clinical instructors (CIs) was recruited to perform learner-driven, formative, ad-hoc, prospective, entrustment assessments. …

Chronic Gcpii (Glutamate-Carboxypeptidase-Ii) Inhibition Reduces Pt217tau Levels In The Entorhinal And Dorsolateral Prefrontal Cortices Of Aged Macaques, Shveta Bathla, Nicolas Barthelemy, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Current approaches for treating sporadic Alzheimer's disease (sAD) focus on removal of amyloid beta 1-42 (Aβ

METHODS: Aged rhesus macaques were treated daily with the GCPII inhibitor, 2-MPPA (2-3-mercaptopropyl-penanedioic acid (2-MPPA)),Aged rhesus macaques were treated daily with the GCPII inhibitor, 2-MPPA (2-3-mercaptopropyl-penanedioic acid (2-MPPA)).

RESULTS: Aged macaques that received 2-MPPA had significantly lower pT217Tau levels in dlPFC and ERC, and had lowered plasma pT217Tau levels from baseline. pT217Tau levels correlated significantly with GCPII activity in dlPFC. Both 2-MPPA- and vehicle-treated monkeys showed cognitive improvement; 2-MPPA had no apparent side effects. Exploratory CSF analyses indicated reduced pS202Tau with 2-MPPA administration, …

Gene-Educational Attainment Interactions In A Multi-Population Genome-Wide Meta-Analysis Identify Novel Lipid Loci, Lisa De Las Fuentes, Karen L. Schwander, Yun Ju Sung, Mary F. Feitosa, Ahn Do, C. Charles Gu, Treva K. Rice, Mary K. Wojczynski, Michael M. Province, Dabeeru C. Rao, Et Al.

2020-Current year OA Pubs

No abstract provided.

Glial Regulation Of Critical Period Plasticity, Jacob Starkey, Eric J Horstick, Sarah D Ackerman

2020-Current year OA Pubs

Animal behavior, from simple to complex, is dependent on the faithful wiring of neurons into functional neural circuits. Neural circuits undergo dramatic experience-dependent remodeling during brief developmental windows called critical periods. Environmental experience during critical periods of plasticity produces sustained changes to circuit function and behavior. Precocious critical period closure is linked to autism spectrum disorders, whereas extended synaptic remodeling is thought to underlie circuit dysfunction in schizophrenia. Thus, resolving the mechanisms that instruct critical period timing is important to our understanding of neurodevelopmental disorders. Control of critical period timing is modulated by neuron-intrinsic cues, yet recent data suggest that …

Treg-Specific Deletion Of The Phosphatase Shp-1 Impairs Control Of Inflammation In Vivo, Qinlei Gu, Kenneth S Tung, Ulrike M Lorenz

2020-Current year OA Pubs

INTRODUCTION: To achieve a healthy and functional immune system, a delicate balance exists between the activation of conventional T cells (Tcon cells) and the suppression by regulatory T cells (Treg). The tyrosine phosphatase SHP-1, a negative regulator of TCR signaling, shapes this 'activation-suppression' balance by modulating Tcon cell resistance to Treg-mediated suppression. Treg cells also express SHP-1, but its role in influencing Treg function is still not fully understood.

METHODS: We generated a Treg-specific SHP-1 deletion model,

RESULTS: We show that SHP-1 modulates Treg suppressive function at different levels. First, at the intracellular signaling level in Treg cells, SHP-1 attenuates …

Qunex-An Integrative Platform For Reproducible Neuroimaging Analytics, Jie Lisa Ji, Matthew F Glasser, Michael P Harms, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Neuroimaging technology has experienced explosive growth and transformed the study of neural mechanisms across health and disease. However, given the diversity of sophisticated tools for handling neuroimaging data, the field faces challenges in method integration, particularly across multiple modalities and species. Specifically, researchers often have to rely on siloed approaches which limit reproducibility, with idiosyncratic data organization and limited software interoperability.

METHODS: To address these challenges, we have developed Quantitative Neuroimaging Environment & Toolbox (QuNex), a platform for consistent end-to-end processing and analytics. QuNex provides several novel functionalities for neuroimaging analyses, including a "turnkey" command for the reproducible deployment …

The Cerebrospinal Fluid Immune Cell Landscape In Animal Models Of Multiple Sclerosis, Gregory F Wu

2020-Current year OA Pubs

The fluid compartment surrounding the central nervous system (CNS) is a unique source of immune cells capable of reflecting the pathophysiology of neurologic diseases. While human clinical and experimental studies often employ cerebrospinal fluid (CSF) analysis, assessment of CSF in animal models of disease are wholly uncommon, particularly in examining the cellular component. Barriers to routine assessment of CSF in animal models of multiple sclerosis (MS) include limited sample volume, blood contamination, and lack of feasible longitudinal approaches. The few studies characterizing CSF immune cells in animal models of MS are largely outdated, but recent work employing transcriptomics have been …

What Is Operative? Conceptualizing Neuralgia: Neuroma, Compression Neuropathy, Painful Hyperalgesia, And Phantom Nerve Pain, Elspeth J R Hill, J Megan M Patterson, Andrew Yee, Lara W Crock, Susan E Mackinnon

2020-Current year OA Pubs

Neuralgia, or nerve pain, is a common presenting complaint for the hand surgeon. When the nerve at play is easily localized, and the cause of the pain is clear (eg, carpal tunnel syndrome), the patient may be easily treated with excellent results. However, in more complex cases, the underlying pathophysiology and cause of neuralgia can be more difficult to interpret; if incorrectly managed, this leads to frustration for both the patient and surgeon. Here we offer a way to conceptualize neuralgia into 4 categories-compression neuropathy, neuroma, painful hyperalgesia, and phantom nerve pain-and offer an illustrative clinical vignette and strategies for …

Designing Implementation Strategies To Improve Identification, Cascade Testing, And Management Of Families With Familial Hypercholesterolemia: An Intervention Mapping Approach, Laney K Jones, Ross C Brownson, Anne C Goldberg, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Familial hypercholesterolemia (FH) is a common inherited cholesterol disorder that, without early intervention, leads to premature cardiovascular disease. Multilevel strategies that target all components of FH care including identification, cascade testing, and management are needed to address gaps that exist in FH care. We utilized intervention mapping, a systematic implementation science approach, to identify and match strategies to existing barriers and develop programs to improve FH care.

METHODS: Data were collected utilizing two methods: a scoping review of published literature, related to any component of FH care, and a parallel mixed method study using interviews and surveys. The scientific …

Approach To Vaccinating The Pediatric Solid Organ Transplant Candidate And Recipient, Carol M Kao, Marian G Michaels

2020-Current year OA Pubs

Solid organ transplantation (SOT) candidates and recipients are at increased risk for morbidity and mortality from vaccine-preventable infections. Children are at particular risk given that they may not have completed their primary immunization series at time of transplant or have acquired natural immunity to pathogens from community exposures. Multiple society guidelines exist for vaccination of SOT candidate and recipients, although challenges remain given limited safety and efficacy data available for pediatric SOT recipients, particularly for live-vaccines. After transplant, individual patient nuances regarding exposure risks and net state of immunosuppression will impact timing of immunizations. The purpose of this review is …

The Vacc-Seqqc Project: Benchmarking Rna-Seq For Clinical Vaccine Studies, Johannes B Goll, Richard D Head, Et Al.

2020-Current year OA Pubs

[This corrects the article DOI: 10.3389/fimmu.2022.1093242.].

Conserved Gene Signatures Shared Among Mapt Mutations Reveal Defects In Calcium Signaling, Miguel A Minaya, Sidhartha Mahali, Abhirami K Iyer, Abdallah M Eteleeb, Rita Martinez, Guangming Huang, John Budde, Sally Temple, Alissa L Nana, William W Seeley, Salvatore Spina, Lea T Grinberg, Oscar Harari, Celeste M Karch

2020-Current year OA Pubs

No abstract provided.

From Perception To Behavior: The Neural Circuits Underlying Prey Hunting In Larval Zebrafish, Shuyu I Zhu, Geoffrey J Goodhill

2020-Current year OA Pubs

A key challenge for neural systems is to extract relevant information from the environment and make appropriate behavioral responses. The larval zebrafish offers an exciting opportunity for studying these sensing processes and sensory-motor transformations. Prey hunting is an instinctual behavior of zebrafish that requires the brain to extract and combine different attributes of the sensory input and form appropriate motor outputs. Due to its small size and transparency the larval zebrafish brain allows optical recording of whole-brain activity to reveal the neural mechanisms involved in prey hunting and capture. In this review we discuss how the larval zebrafish brain processes …

Slc-0111, An Inhibitor Of Carbonic Anhydrase Ix, Attenuates Hepatoblastoma Cell Viability And Migration, Katja Eloranta, Marjut Pihlajoki, Emmi Liljeström, Ruth Nousiainen, Tea Soini, Jouko Lohi, Stefano Cairo, David B Wilson, Seppo Parkkila, Markku Heikinheimo

2020-Current year OA Pubs

BACKGROUND: In response to hypoxia, tumor cells undergo transcriptional reprogramming including upregulation of carbonic anhydrase (CA) IX, a metalloenzyme that maintains acid-base balance. CAIX overexpression has been shown to correlate with poor prognosis in various cancers, but the role of this CA isoform in hepatoblastoma (HB) has not been examined.

METHODS: We surveyed the expression of CAIX in HB specimens and assessed the impact of SLC-0111, a CAIX inhibitor, on cultured HB cells in normoxic and hypoxic conditions.

RESULTS: CAIX immunoreactivity was detected in 15 out of 21 archival pathology HB specimens. The CAIX-positive cells clustered in the middle of …

Quality Improvements In Radiation Oncology Clinical Trials, Koren Smith, Jeff Michalski, Et Al.

2020-Current year OA Pubs

Clinical trials have become the primary mechanism to validate process improvements in oncology clinical practice. Over the past two decades there have been considerable process improvements in the practice of radiation oncology within the structure of a modern department using advanced technology for patient care. Treatment planning is accomplished with volume definition including fusion of multiple series of diagnostic images into volumetric planning studies to optimize the definition of tumor and define the relationship of tumor to normal tissue. Daily treatment is validated by multiple tools of image guidance. Computer planning has been optimized and supported by the increasing use …

Interactions Of Pathogenic Escherichia Coli With Ceacams, Alaullah Sheikh, James M Fleckenstein

2020-Current year OA Pubs

The pathogenic

The Pace Of Biological Aging Helps Explain The Association Between Insomnia And Chronic Low Back Pain, Edwin N Aroke, Asia M Wiggins, Joanna M Hobson, Vinodh Srinivasasainagendra, Tammie L Quinn, Pooja Kottae, Hemant K Tiwari, Robert E Sorge, Burel R Goodin

2020-Current year OA Pubs

Chronic low back pain (cLBP) is associated with insomnia and advanced age. Emerging evidence suggests that the severity of both sleep disorders (like insomnia) and chronic pain are associated with a faster pace of biological aging. We aimed to determine whether the pace of biological age mediates the relationship between insomnia and the impact of cLBP in a sample of community-dwelling adults ages 19 to 85 years. Participants (49 with no pain, 32 with low-impact pain, and 37 with high-impact pain) completed sociodemographic, pain, insomnia, and short physical performance battery assessments. We calculated the pace of biological aging using DunedinPACE …

Predicting Incident Cardiovascular Disease Among African-American Adults: A Deep Learning Approach To Evaluate Social Determinants Of Health In The Jackson Heart Study, Matthew C. Morris, Hamidreza Moradi, Maryam Aslani, Mario Sims, David Schlundt, Chrystyna D. Kouros, Burel Goodin, Crystal Lim, Kerry Kinney

2020-Current year OA Pubs

The present study sought to leverage machine learning approaches to determine whether social determinants of health improve prediction of incident cardiovascular disease (CVD). Participants in the Jackson Heart study with no history of CVD at baseline were followed over a 10-year period to determine first CVD events (i.e., coronary heart disease, stroke, heart failure). Three modeling algorithms (i.e., Deep Neural Network, Random Survival Forest, Penalized Cox Proportional Hazards) were used to evaluate three feature sets (i.e., demographics and standard/biobehavioral CVD risk factors [FS1], FS1 combined with psychosocial and socioeconomic CVD risk factors [FS2], and FS2 combined with environmental features [FS3]) …

Symmetric Data-Driven Fusion Of Diffusion Tensor Mri: Age Differences In White Matter, Andrea Mendez Colmenares, Michelle B Hefner, Vince D Calhoun, Elizabeth A Salerno, Jason Fanning, Neha P Gothe, Edward Mcauley, Arthur F Kramer, Agnieszka Z Burzynska

2020-Current year OA Pubs

In the past 20 years, white matter (WM) microstructure has been studied predominantly using diffusion tensor imaging (DTI). Decreases in fractional anisotropy (FA) and increases in mean (MD) and radial diffusivity (RD) have been consistently reported in healthy aging and neurodegenerative diseases. To date, DTI parameters have been studied individually (e.g., only FA) and separately (i.e., without using the joint information across them). This approach gives limited insights into WM pathology, increases the number of multiple comparisons, and yields inconsistent correlations with cognition. To take full advantage of the information in a DTI dataset, we present the first application of …

Targeted Aso-Mediated Atp1a2 Knockdown In Astrocytes Reduces Sod1 Aggregation And Accelerates Disease Onset In Mutant Sod1 Mice, Abhirami K. Iyer, Kathleen M. Schoch, Anthony Verbeck, Grant Galasso, Hao Chen, Sarah Smith, Anna Oldenborg, Timothy M. Miller, Celeste M. Karch, Azad Bonni

2020-Current year OA Pubs

Astrocyte-specific ion pump α2-Na+/K+-ATPase plays a critical role in the pathogenesis of amyotrophic lateral sclerosis (ALS). Here, we test the effect of Atp1a2 mRNA-specific antisense oligonucleotides (ASOs) to induce α2-Na+/K+-ATPase knockdown in the widely used ALS animal model, SOD1*G93A mice. Two ASOs led to efficient Atp1a2 knockdown and significantly reduced SOD1 aggregation in vivo. Although Atp1a2 ASO-treated mice displayed no off-target or systemic toxicity, the ASO-treated mice exhibited an accelerated disease onset and shorter lifespan than control mice. Transcriptomics studies reveal downregulation of genes involved in oxidative response, metabolic pathways, trans-synaptic signaling, and upregulation of genes involved in glutamate receptor …

Mora And Ensembletfpredictor: An Ensemble Approach To Reveal Functional Transcription Factor Regulatory Networks, Kevin Boyer, Louis Li, Tiandao Li, Bo Zhang, Guoyan Zhao

2020-Current year OA Pubs

MOTIVATION: Our study aimed to identify biologically relevant transcription factors (TFs) that control the expression of a set of co-expressed or co-regulated genes.

RESULTS: We developed a fully automated pipeline, Motif Over Representation Analysis (MORA), to detect enrichment of known TF binding motifs in any query sequences. MORA performed better than or comparable to five other TF-prediction tools as evaluated using hundreds of differentially expressed gene sets and ChIP-seq datasets derived from known TFs. Additionally, we developed EnsembleTFpredictor to harness the power of multiple TF-prediction tools to provide a list of functional TFs ranked by prediction confidence. When applied to …

Rev-Erb Activation As A Novel Pharmacological Approach For Treating Inflammatory Pain, Sangeet Makhija, Joshua D Griffett, Giri Babu Veerakanellore, Thomas P Burris, Bahaa Elgendy, Kristine Griffett

2020-Current year OA Pubs

Pain is a complex problem affecting millions of people worldwide. The current therapies to reduce pain are limited as many treatment options inadequately address the causes of pain, lead to tolerance of the drug, or have adverse effects including abuse potential. While there are many causes of pain, one underlying mechanism to the pathogenesis and maintenance of pain conditions is chronic inflammation driven by the NLRP3 inflammasome. Several inflammasome inhibitors are currently under investigation however have the potential to suppress the functioning of the innate immune system, which may cause unwanted affects in patients. Here, we show that the nuclear …

Sleep Deprivation, Sleep Fragmentation, And Social Jet Lag Increase Temperature Preference In Drosophila, S Tanner Roach, Melanie C Ford, Vikram Simhambhatla, Vasilios Loutrianakis, Hamza Farah, Zhaoyi Li, Erica M Periandri, Dina Abdalla, Irene Huang, Arjan Kalra, Paul J Shaw

2020-Current year OA Pubs

Despite the fact that sleep deprivation substantially affects the way animals regulate their body temperature, the specific mechanisms behind this phenomenon are not well understood. In both mammals and flies, neural circuits regulating sleep and thermoregulation overlap, suggesting an interdependence that may be relevant for sleep function. To investigate this relationship further, we exposed flies to 12 h of sleep deprivation, or 48 h of sleep fragmentation and evaluated temperature preference in a thermal gradient. Flies exposed to 12 h of sleep deprivation chose warmer temperatures after sleep deprivation. Importantly, sleep fragmentation, which prevents flies from entering deeper stages of …

Feasibility And Acceptability Of Remote Smartphone Cognitive Testing In Frontotemporal Dementia Research, Jack Carson Taylor, Nupur Ghoshal, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Remote smartphone assessments of cognition, speech/language, and motor functioning in frontotemporal dementia (FTD) could enable decentralized clinical trials and improve access to research. We studied the feasibility and acceptability of remote smartphone data collection in FTD research using the ALLFTD Mobile App (ALLFTD-mApp).

METHODS: A diagnostically mixed sample of 214 participants with FTD or from familial FTD kindreds (asymptomatic: CDR®+NACC-FTLD = 0 [

RESULTS: It was feasible for participants to complete the ALLFTD-mApp on their own smartphones. Participants reported high smartphone familiarity, completed ∼ 70% of tasks, and considered the time commitment acceptable (98% of respondents). Greater disease severity …

Vigorous-Intensity Exercise As A Modulator Of Cardiac Adipose Tissue In Women With Obesity: A Cross-Sectional And Randomized Pilot Study, Sumsen Thapa, Bharath S Selvaraj, Paige N Davis, Bryan Smith, Amy H Givan, Jose A Perez-Rivera, Pamela K Woodard, Jon D Klingensmith, Maria Fernandez-Del-Valle

2020-Current year OA Pubs

Cardiac adipose tissue (CAT) has become an important target for the reduction of disease risk. Supervised exercise programs have shown potential to "significantly" reduce CAT; however, the impact of different exercise modalities is not clear, and the relationships between CAT, physical activity (PA) levels and fitness (PFit) remain unknown. Therefore, the purpose of this study was to analyze the relationships between CAT, PA and PFit, and to explore the effects of different exercise modalities in a group of women with obesity. A total of 26 women (age: 23.41 ± 5.78 years-old) were enrolled in the cross-sectional study. PA, cardiorespiratory fitness, …

Nrg/Rtog 0837: Randomized, Phase Ii, Double-Blind, Placebo-Controlled Trial Of Chemoradiation With Or Without Cediranib In Newly Diagnosed Glioblastoma, Tracy T Batchelor, Clifford G Robinson, Et Al.

2020-Current year OA Pubs

BACKGROUND: A randomized, phase II, placebo-controlled, and blinded clinical trial (NCT01062425) was conducted to determine the efficacy of cediranib, an oral pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor, versus placebo in combination with radiation and temozolomide in newly diagnosed glioblastoma.

METHODS: Patients with newly diagnosed glioblastoma were randomly assigned 2:1 to receive (1) cediranib (20 mg) in combination with radiation and temozolomide; (2) placebo in combination with radiation and temozolomide. The primary endpoint was 6-month progression-free survival (PFS) based on blinded, independent radiographic assessment of postcontrast T1-weighted and noncontrast T2-weighted MRI brain scans and was tested using a 1-sided …