Digital Commons Network^™

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 …

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.

Case Report: Insulin Hypersensitivity In Youth With Type 1 Diabetes, Einas H Alkhatib, Jody B Grundman, Anna M Adamusiak, Melena D Bellin, Joel P Brooks, Kevin S Buckley, Erin M Janssen, Maleewan Kitcharoensakkul, Kyle P Mcnerney, Thea L Pfeifer, Brooke I Polk, Brynn E Marks

2020-Current year OA Pubs

OBJECTIVE: Immediate type I, type III, and delayed type IV hypersensitivity reactions to insulin are rare, but potentially serious complications of exogenous insulin administration required for the treatment of type 1 diabetes (T1D).

METHODS: We present four cases of insulin hypersensitivity reactions occurring in youth with T1D and a literature review of this topic.

RESULTS: Insulin hypersensitivity reactions included types I, III, and IV with presentations ranging from localized urticaria, erythematous nodules, and eczematous plaques to anaphylaxis with respiratory distress. Reactions occurred in youth with newly diagnosed T1D and in those with long-standing T1D who were using both injection and …

Relationship Between Baseline Plasma P-Tau181 And Longitudinal Changes In Cognition And Structural Brain Measures In A Cohort Of Cognitively Unimpaired Older Adults, Marcos V Pais, Chia-Ling Kuo, Beau M Ances, Julie Loebach Wetherell, Eric J Lenze, Breno S Diniz

2020-Current year OA Pubs

INTRODUCTION: Preclinical Alzheimer's disease (AD) affects a significant proportion of cognitively unimpaired (CU) older adults. Currently, blood-based biomarkers detect very early changes in the AD continuum with great accuracy.

METHODS: We measured baseline plasma phosphorylated tau (p-tau)181 using electrochemiluminescence (ECL)-based assay (MesoScale Discovery) in 533 CU older adults. Follow-up lasted up to 18 months. Cognitive performance assessment included memory and cognitive control. Structural brain measures included cortical thickness, which includes the AD magnetic resonance imaging (AD MRI) signature, and hippocampal volume.

RESULTS: In this cohort of CU older adults, baseline plasma p-tau181 levels were not associated with short-term changes in …

Severe Central Nervous System Demyelination In Sanfilippo Disease, Mahsa Taherzadeh, Erjun Zhang, Irene Londono, Benjamin De Leener, Sophie Wang, Jonathan D Cooper, Timothy E Kennedy, Carlos R Morales, Zesheng Chen, Gregory A Lodygensky, Alexey V Pshezhetsky

2020-Current year OA Pubs

INTRODUCTION: Chronic progressive neuroinflammation is a hallmark of neurological lysosomal storage diseases, including mucopolysaccharidosis III (MPS III or Sanfilippo disease). Since neuroinflammation is linked to white matter tract pathology, we analyzed axonal myelination and white matter density in the mouse model of MPS IIIC

METHODS: Brain and spinal cord tissues of human MPS III patients, 6-month-old

RESULTS: Analyses of CC and spinal cord tissues by immunohistochemistry revealed substantially reduced levels of myelin-associated proteins including Myelin Basic Protein, Myelin Associated Glycoprotein, and Myelin Oligodendrocyte Glycoprotein. Furthermore, ultrastructural analyses revealed disruption of myelin sheath organization and reduced myelin thickness in the brains …

Training, Supervision, And Experience Of Coaches Offering Digital Guided Self-Help For Mental Health Concerns, Ellen E Fitzsimmons-Craft, Elsa Rojas, Naira Topooco, Gavin N Rackoff, Nur Hani Zainal, Daniel Eisenberg, Jillian Shah, Christina Desage, Denise E Wilfley, Craig Barr Taylor, Michelle G Newman

2020-Current year OA Pubs

Accessible, low-cost intervention options are necessary to address the rise in mental health problems among college students. Digital guided self-help, or coached, programs have been developed to provide such services, with many commercially available. As such, there are a large and growing number of individuals coaching these programs. However, an unmet need is to evaluate and assess best practices for training and supervising individuals in these positions. To this end, we describe how we recruited, trained, and supervised coaches as part of a large randomized controlled trial using a widely available digital commercial platform. Coaches were trained to provide digital …

Evaluation Of Gliovascular Functions Of Aqp4 Readthrough Isoforms, Shayna M Mueller, Kelli Mcfarland White, Stuart B Fass, Siyu Chen, Zhan Shi, Xia Ge, John A Engelbach, Seana H Gaines, Annie R Bice, Michael J Vasek, Joel R Garbow, Joseph P Culver, Zila Martinez-Lozada, Martine Cohen-Salmon, Joseph D Dougherty, Darshan Sapkota

2020-Current year OA Pubs

Aquaporin-4 (AQP4) is a water channel protein that links the astrocytic endfeet to the blood-brain barrier (BBB) and regulates water and potassium homeostasis in the brain, as well as the glymphatic clearance of waste products that would otherwise potentiate neurological diseases. Recently, translational readthrough was shown to generate a C-terminally extended variant of AQP4, known as AQP4x, which preferentially localizes around the BBB through interaction with the scaffolding protein α-syntrophin, and loss of AQP4x disrupts waste clearance from the brain. To investigate the function of AQP4x, we generated a novel AQP4 mouse line (AllX) to increase relative levels of the …

The Actin-Bundling Protein, Pls3, Is Part Of The Mechanoresponsive Machinery That Regulates Osteoblast Mineralization, Samantha M Chin, Carmela Unnold-Cofre, Teri Naismith, Silvia Jansen

2020-Current year OA Pubs

Plastin-3 (PLS3) is a calcium-sensitive actin-bundling protein that has recently been linked to the development of childhood-onset osteoporosis. Clinical data suggest that PLS3 mutations lead to a defect in osteoblast function, however the underlying mechanism remains elusive. To investigate the role of PLS3 in bone mineralization, we generated MC3T3-E1 preosteoblast cells that are stably depleted of PLS3. Analysis of osteogenic differentiation of control and PLS3 knockdown (PLS3 KD) cells showed that depletion of PLS3 does not alter the first stage of osteoblast mineralization in which a collagen matrix is deposited, but severely affects the subsequent mineralization of that matrix. During …

Neurobridge: A Prototype Platform For Discovery Of The Long-Tail Neuroimaging Data, Lei Wang, Janine Bijsterbosch, Rick Herrick, Daniel Marcus, Stephen M Moore, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Open science initiatives have enabled sharing of large amounts of already collected data. However, significant gaps remain regarding how to find appropriate data, including underutilized data that exist in the long tail of science. We demonstrate the NeuroBridge prototype and its ability to search PubMed Central full-text papers for information relevant to neuroimaging data collected from schizophrenia and addiction studies.

METHODS: The NeuroBridge architecture contained the following components: (1) Extensible ontology for modeling study metadata: subject population, imaging techniques, and relevant behavioral, cognitive, or clinical data. Details are described in the companion paper in this special issue; (2) A …

Imaging Characterization Of Myocardial Function, Fibrosis, And Perfusion In A Nonhuman Primate Model With Heart Failure-Like Features, Xing-Li Liu, Guan-Zhong Wang, Mao-Ping Rui, Dong Fan, Jie Zhang, Zheng-Hua Zhu, Rosario Perez, Tony Wang, Li-Chuan Yang, Liang Lyu, Jie Zheng, Gang Wang

2020-Current year OA Pubs

INTRODUCTION: The availability of a human-like chronic heart failure (HF) animal model was critical for affiliating development of novel therapeutic drug treatments. With the close physiology relatedness to humans, the non-human primate (NHP) HF model would be valuable to better understand the pathophysiology and pharmacology of HF. The purpose of this work was to present preliminary cardiac image findings using echocardiography and cardiovascular magnetic resonance (CMR) in a HF-like cynomolgus macaque model.

METHODS: The NHP diet-induced model developed cardiac phenotypes that exhibited diastolic dysfunction with reduced left ventricular ejection fraction (LVEF) or preserved LVEF. Twenty cynomolgus monkeys with cardiac dysfunction …

The Role Of Vaccination Route With An Adenovirus-Vectored Vaccine In Protection, Viral Control, And Transmission In The Sars-Cov-2/K18-Hace2 Mouse Infection Model, Alexandria Dickson, Elizabeth Geerling, E Taylor Stone, Mariah Hassert, Tara L Steffen, Taneesh Makkena, Madeleine Smither, Katherine E Schwetye, Jianfeng Zhang, Bertrand Georges, M Scot Roberts, John J Suschak, Amelia K Pinto, James D Brien

2020-Current year OA Pubs

INTRODUCTION: Vaccination is the most effective mechanism to prevent severe COVID-19. However, breakthrough infections and subsequent transmission of SARS-CoV-2 remain a significant problem. Intranasal vaccination has the potential to be more effective in preventing disease and limiting transmission between individuals as it induces potent responses at mucosal sites.

METHODS: Utilizing a replication-deficient adenovirus serotype 5-vectored vaccine expressing the SARS-CoV-2 RBD (AdCOVID) in homozygous and heterozygous transgenic K18-hACE2, we investigated the impact of the route of administration on vaccine immunogenicity, SARS-CoV-2 transmission, and survival.

RESULTS: Mice vaccinated with AdCOVID via the intramuscular or intranasal route and subsequently challenged with SARS-CoV-2 showed …

Recruitment Methods And Yield Rates For A Multisite Clinical Trial Exploring Risk Reduction For Alzheimer's Disease (Rrad), Amanda N Szabo-Reed, Monica Sewell, Ellen F Binder, Et Al.

2020-Current year OA Pubs

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.

RESULTS: Initially, 3290 individuals were screened, of whom 28% were eligible to consent, 805 consented to participate (87.2% of those eligible), and 513 (36.3% of those consented) were randomized. Emails sent from study site listservs/databases yielded the highest amount (20.9%) …

Simple And Complex Cells Revisited: Toward A Selectivity-Invariance Model Of Object Recognition, Xin Li, Shuo Wang

2020-Current year OA Pubs

This paper presents a theoretical perspective on modeling ventral stream processing by revisiting the computational abstraction of simple and complex cells. In parallel to David Marr's vision theory, we organize the new perspective into three levels. At the computational level, we abstract simple and complex cells into space partitioning and composition in a topological space based on the redundancy exploitation hypothesis of Horace Barlow. At the algorithmic level, we present a hierarchical extension of sparse coding by exploiting the manifold constraint in high-dimensional space (i.e., the blessing of dimensionality). The resulting over-parameterized models for object recognition differ from existing hierarchical …

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 …

Interobserver Variability In Target Definition For Stereotactic Arrhythmia Radioablation, Martijn H Van Der Ree, Phillip S Cuculich, Geoffrey D Hugo, Clifford G Robinson, Et Al.

2020-Current year OA Pubs

BACKGROUND: Stereotactic arrhythmia radioablation (STAR) is a potential new therapy for patients with refractory ventricular tachycardia (VT). The arrhythmogenic substrate (target) is synthesized from clinical and electro-anatomical information. This study was designed to evaluate the baseline interobserver variability in target delineation for STAR.

METHODS: Delineation software designed for research purposes was used. The study was split into three phases. Firstly, electrophysiologists delineated a well-defined structure in three patients (spinal canal). Secondly, observers delineated the VT-target in three patients based on case descriptions. To evaluate baseline performance, a basic workflow approach was used, no advanced techniques were allowed. Thirdly, observers delineated …

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. …

Aku Libraries Annual Report - 2023, Office Of The University Librarian

Office of the University Librarian Reports

- Message by Peter Gatiti Associate Vice Provost & University Librarian

- AKU Author’s Day – 2023

- Glimpses of Author’s Day Celebrations

- FAS Library - Welcomes Inaugural Class

- Library Systems

- Collaborations and Partnerships

- Librarian Emeritus

- Library Staff Achievements

- Librarians Get Faculty Status

- Teaching and Learning Commons

- University Archives

- Little is Right Without Copyright

- eScriptorium is the New Way to Encode

- Book Review

- AKU Librarian’s Publications

Evaluating The Efficacy Of Purchased Antisense Oligonucleotides To Reduce Mouse And Human Tau In Vivo, Pranav Vemula, Kathleen M Schoch, Timothy M Miller

2020-Current year OA Pubs

Many preclinical and clinical studies support the use of antisense oligonucleotides (ASOs) as effective therapeutic strategies. However, acquiring ASOs for research purposes may be limited by partnerships with the pharmaceutical companies. Our lab previously developed an effective ASO strategy to lower human tau and reverse pathology in aged tauopathy model mice. Testing the efficacy of purchased tau lowering ASOs would provide support for these reagents as broad research tools. Purchased mouse and human tau lowering ASOs were infused or injected intracerebroventricularly into wildtype and tau transgenic mice. Following treatment, brain tissue evaluated for ASO distribution and levels of tau mRNA, …

Whole Genome Sequence Analysis Of Apparent Treatment Resistant Hypertension Status In Participants From The Trans-Omics For Precision Medicine Program, Nicole D Armstrong, Dabeeru C Rao, Et Al.

2020-Current year OA Pubs

No abstract provided.

A Bone To Pick-Cellular And Molecular Mechanisms Of Bone Pain In Sickle Cell Disease, Jahnavi Gollamudi, Kristine A Karkoska, Oluwabukola T Gbotosho, Wei Zou, Hyacinth I Hyacinth, Steven L Teitelbaum

2020-Current year OA Pubs

The bone is one of the most commonly affected organs in sickle cell disease (SCD). Repeated ischemia, oxidative stress and inflammation within the bone is largely responsible for promoting bone pain. As more individuals with SCD survive into adulthood, they are likely to experience a synergistic impact of both aging and SCD on their bone health. As bone health deteriorates, bone pain will likely exacerbate. Recent mechanistic and observational studies emphasize an intricate relationship between bone remodeling and the peripheral nervous system. Under pathological conditions, abnormal bone remodeling plays a key role in the propagation of bone pain. In this …

Machine Learning Pipelines Developed For The Prediction Of Cancelation Of Inappropriate Parathyroid Hormone-Related Peptide Orders Demonstrate Poor Performance In Predicting Provider Behavior, Nicholas C. Spies, Christopher W. Farnsworth, Ronald Jackups, Mark A. Zaydman

2020-Current year OA Pubs

No abstract provided.

Development Of A Goal Setting And Goal Management System: Intervention Mapping, Eunyoung Kang, Erin R Foster

2020-Current year OA Pubs

BACKGROUND: Although goal setting and goal management (GSGM) is a key component of chronic disease management and rehabilitation practice, there is currently no widely used evidence-based intervention system available. This paper describes the theoretical underpinnings and development of a new intervention called MyGoals. MyGoals is designed to guide occupational therapy (OT) practitioners to implement theory-based, client-engaged GSGM for adults with chronic conditions in community-based OT rehabilitation settings.

METHODS: We first developed a planning team with two adults with chronic conditions, two clinicians, and two researchers. As a collaborative team, we co-developed MyGoals by following Intervention Mapping (IM) steps 1-4 and …

Training In Eight Low-And Middle-Income Countries: Lessons Learned From A Pilot Study Using The Who-Tdr Dissemination And Implementation Massive Open Online Course, Ashlin Rakhra, Victor Davila-Roman, Ana A Baumann, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Non-communicable diseases (NCDs) are a leading cause of morbidity and mortality in low-and middle- income countries (LMICs). Despite this, a lack of funding, training and mentorship for NCD investigators in LMICs exists. In an effort to gain knowledge and skills to address these gaps, participants from the Global Research on Implementation and Translation Science (GRIT), a consortium of studies in eight LMICs and their networks, attended the dissemination and implementation (D&I) massive open online course (MOOC) developed by the Special Programme for Research and Training in Tropical Diseases at the World Health Organization to strengthen D&I capacity building. Here, …

Third-Party Verification Immunization Coverage Survey (Tpvics) - 2023, Sajid Bashir Soofi, Imtiaz Hussain, Muhammad Ahmed Kazi, Ahmad Khan, Muhammad Umer, Khalid Feroz, Imran Ahmed, Dale A. Rhoda, Zulfiqar Ahmed Bhutta

The Aga Khan University Survey Reports

• Background
• Survey Design and Methodology
• Implementation of Survey
• Survey Results
• References