Medicine and Health Sciences Commons^™

Assessing An Online Patient Decision Aid About Upper Extremity Reconstructive Surgery For Cervical Spinal Cord Injury: Pilot Testing Knowledge, Decisional Conflict, And Acceptability, William Moritz, Amanda M Westman, Mary C Politi, Dod Working Group, Ida K Fox

2020-Current year OA Pubs

UNLABELLED:

HIGHLIGHTS: People with cervical spinal cord injury prioritize gaining upper extremity function after injury, but few individuals receive information about treatment options.A newly created patient decision aid (PtDA) provides information about recovery after spinal cord injury and the role of traditional tendon and newer nerve transfer surgery to improve upper extremity upper extremity function.The PtDA improved knowledge and decreased decisional conflict in this pilot study.Future work should focus on studying dissemination and implementation of the ptDA into clinical practice.

Phase I Study Of Anti-Epidermal Growth Factor Receptor Antibody-Drug Conjugate Serclutamab Talirine: Safety, Pharmacokinetics, And Antitumor Activity In Advanced Glioblastoma, Benedito A Carneiro, Saiama N Waqar, Et Al.

2020-Current year OA Pubs

BACKGROUND: Serclutamab talirine (Ser-T, formerly ABBV-321) is an antibody-drug conjugate consisting of an antibody (AM-1-ABT-806) directed against activated epidermal growth factor receptor (EGFR) and a pyrrolobenzodiazepine dimer. We investigated Ser-T monotherapy in a phase I, first-in-human, dose-escalation, and dose-expansion study in patients with advanced solid tumors associated with EGFR overexpression.

METHODS: Eligible patients (≥18 years) had advanced, histologically confirmed solid tumors associated with EGFR overexpression (centralized testing). Patients received Ser-T intravenously once every 4 weeks (Q4W; 5-50 μg/kg) in the dose-escalation phase. Herein, preliminary antitumor activity at the recommended phase II dose (RP2D) is reported only for patients with glioblastoma …

Differential Expression Of Programmed Death 1 (Pd-1) On Various Immune Cells And Its Role In Human Leprosy, Mohammad Tarique, Huma Naz, Mohd Suhail, Ali Turan, Chaman Saini, Naoshad Muhammad, Hari Shankar, Torki A Zughaibi, Tabish H Khan, Neena Khanna, Alpana Sharma

2020-Current year OA Pubs

Leprosy is a chronic bacterial disease caused by

Molecular Techniques Drive Cutting Edge Advancements In Management Of Cutaneous T Cell Lymphoma, Mitchell N Lefebvre, Nicholas Borcherding, Ryan J Reis, Eric Mou, Vincent Liu, Ali Jabbari

2020-Current year OA Pubs

Cutaneous 5T cell lymphoma (CTCL), characterized by malignant T cells infiltrating the skin with potential for dissemination, remains a challenging disease to diagnose and treat due to disease heterogeneity, treatment resistance, and lack of effective and standardized diagnostic and prognostic clinical tools. Currently, diagnosis of CTCL practically relies on clinical presentation, histopathology, and immunohistochemistry. These methods are collectively fraught with limitations in sensitivity and specificity. Fortunately, recent advances in flow cytometry, polymerase chain reaction, high throughput sequencing, and other molecular techniques have shown promise in improving diagnosis and treatment of CTCL. Examples of these advances include T cell receptor clonotyping …

Large-Scale Exome Array Summary Statistics Resources For Glycemic Traits To Aid Effector Gene Prioritization, Sara M. Willems, Ping An, Michael A. Province, Et Al.

2020-Current year OA Pubs

No abstract provided.

Improvement In The Capacity For Activity Versus Improvement In Performance Of Activity In Daily Life During Outpatient Rehabilitation, Catherine E. Lang, Carey L. Holleran, Michael J. Strube, Terry D. Ellis, Caitlin A. Newman, Meghan Fahey, Tamara R. Deangelis, Timothy J. Nordahl, Darcy S. Reisman, Gammon M. Earhart, Keith R. Lohse, Marghuretta D. Bland

2020-Current year OA Pubs

UNLABELLED: We addressed questions about the potential discrepancy between improvements in activity capacity and improvements in activity performance in daily life. We asked whether this discrepancy is: 1. Common in routine, outpatient care, or an artifact of intervention studies? 2. Unique to upper limb (UL) rehabilitation, or is it seen in walking rehabilitation too? 3. Only seen in persons with stroke, or a broader neurorehabilitation problem?

METHODS:: A longitudinal, observational cohort of 156 participants with stroke or Parkinson disease (PD) receiving outpatient rehabilitation at 5 clinics was assessed around admission and monthly during their episode of care. Individual, longitudinal capacity …

Changes In Distribution Of Severe Neurologic Involvement In Us Pediatric Inpatients With Covid-19 Or Multisystem Inflammatory Syndrome In Children In 2021 Vs 2020, Kerri L Larovere, Amanda R Kolmar, Et Al.

2020-Current year OA Pubs

IMPORTANCE: In 2020 during the COVID-19 pandemic, neurologic involvement was common in children and adolescents hospitalized in the United States for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related complications.

OBJECTIVE: To provide an update on the spectrum of SARS-CoV-2-related neurologic involvement among children and adolescents in 2021.

DESIGN, SETTING, AND PARTICIPANTS: Case series investigation of patients reported to public health surveillance hospitalized with SARS-CoV-2-related illness between December 15, 2020, and December 31, 2021, in 55 US hospitals in 31 states with follow-up at hospital discharge. A total of 2253 patients were enrolled during the investigation period. Patients suspected of having …

Eliminating Central Line Associated Bloodstream Infections In Pediatric Oncology Patients: A Quality Improvement Effort, Daniel N. Willis, Karen Looper, Rema A. Malone, Barbara Ricken, Ashley Slater, Amanda Fuller, Meagan Mccaughey, Angela Niesen, Joan R. Smith, Beverly Brozanski

2020-Current year OA Pubs

UNLABELLED: Central Line-Associated Bloodstream Infections (CLABSI) are the largest contributor to harm across the Children's Hospital's Solutions for Patient Safety network. Pediatric hematology/oncology (PHO) patients are at increased risk for CLABSI due to multiple factors. Consequently, traditional CLABSI prevention strategies are insufficient to eliminate CLABSI in this high-risk population.

METHODS: Our SMART aim was to reduce the CLABSI rate by 50% from a baseline of 1.89/1000 central line days to less than 0.9/1000 central line days by December 31, 2021. We created a multidisciplinary team being mindful to identify roles and responsibilities upfront. We developed a key driver diagram and …

Oxidation Driven Reversal Of Pip2-Dependent Gating In Girk2 Channels, Sun-Joo Lee, Shoji Maeda, Jian Gao, Colin G Nichols

2020-Current year OA Pubs

Physiological activity of G protein gated inward rectifier K

Plasma And Cerebrospinal Fluid Proteomic Signatures Of Acutely Sleep-Deprived Humans: An Exploratory Study, Ana Vaquer-Alicea, Jinsheng Yu, Haiyan Liu, Brendan P Lucey

2020-Current year OA Pubs

STUDY OBJECTIVES: Acute sleep deprivation affects both central and peripheral biological processes. Prior research has mainly focused on specific proteins or biological pathways that are dysregulated in the setting of sustained wakefulness. This exploratory study aimed to provide a comprehensive view of the biological processes and proteins impacted by acute sleep deprivation in both plasma and cerebrospinal fluid (CSF).

METHODS: We collected plasma and CSF from human participants during one night of sleep deprivation and controlled normal sleep conditions. One thousand and three hundred proteins were measured at hour 0 and hour 24 using a high-scale aptamer-based proteomics platform (SOMAscan) …

A Critical Scientific Evaluation Of A Purportedly Negative Data Report - Response To Seneviratne Et Al. 2022, Bankole Johnson, Giovanni Addolorato, Otto Lesch, Lei Liu, Zachary A Rodd

2020-Current year OA Pubs

A core principle in the pursuit of scientific knowledge is that science is self-correcting and that important results should be replicable. Hypotheses need to be reinforced, adjusted, or rejected when novel results are obtained. Replication of results confirms hypotheses and enhances their integration into scientific practice. In contrast, publication of substantiated and replicated negative findings (i.e., non-significant or opposite findings) can be the basis to reject erroneous hypotheses or develop alternative strategies for investigation. Replication is a problem in all research fields. The Psychology Reproductivity Project reported that only 36% of 'highly influential' published research in highly ranked journals were …

A Pooled Long-Term Follow-Up After Radiotherapy For Prostate Cancer With And Without A Rectal Hydrogel Spacer: Impact Of Hydrogel On Decline In Sexual Quality Of Life, Zachary A Seymour, Michael Pinkawa, Stephanie Daignault-Newton, Walter Bosch, Jeff M Michalski, Hiram Gay, Daniel A Hamstra

2020-Current year OA Pubs

PURPOSE: The purpose of this study was to analyze the impact of prostate rectal spacers on sexual quality of life (QOL) following external beam radiation therapy (RT).

METHODS AND MATERIALS: Patient- reported QOL was evaluated using the Expanded Prostate Cancer Index Composite (EPIC). Patients were pooled from two sources: a randomized controlled trial and a non-randomized cohort of patients from a single institution. Both cohorts used the same spacing product and QOL instrument. Analysis was limited to those with good baseline pre-treatment sexual QOL (EPIC >/= 60). Differences in QOL summary score and individual items were assessed compared with baseline …

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 …

An Image-Based Modeling Framework For Predicting Spatiotemporal Brain Cancer Biology Within Individual Patients, Kamila M Bond, Lee Curtin, Sara Ranjbar, Ariana E Afshari, Leland S Hu, Joshua B Rubin, Kristin R Swanson

2020-Current year OA Pubs

Imaging is central to the clinical surveillance of brain tumors yet it provides limited insight into a tumor's underlying biology. Machine learning and other mathematical modeling approaches can leverage paired magnetic resonance images and image-localized tissue samples to predict almost any characteristic of a tumor. Image-based modeling takes advantage of the spatial resolution of routine clinical scans and can be applied to measure biological differences within a tumor, changes over time, as well as the variance between patients. This approach is non-invasive and circumvents the intrinsic challenges of inter- and intratumoral heterogeneity that have historically hindered the complete assessment of …

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: …

Vancomycin-Induced Gut Microbial Dysbiosis Alters Enteric Neuron-Macrophage Interactions During A Critical Period Of Postnatal Development, Ellen Merrick Schill, Elisabeth L Joyce, Alexandria N Floyd, Sreeram Udayan, Brigida Rusconi, Shreya Gaddipati, Bibiana E Barrios, Vini John, Mitchell E Kaye, Devesha H Kulkarni, Jocelyn T Pauta, Keely G Mcdonald, Rodney D Newberry

2020-Current year OA Pubs

Vancomycin is a broad-spectrum antibiotic widely used in cases of suspected sepsis in premature neonates. While appropriate and potentially lifesaving in this setting, early-life antibiotic exposure alters the developing microbiome and is associated with an increased risk of deadly complications, including late-onset sepsis (LOS) and necrotizing enterocolitis (NEC). Recent studies show that neonatal vancomycin treatment disrupts postnatal enteric nervous system (ENS) development in mouse pups, which is in part dependent upon neuroimmune interactions. This suggests that early-life antibiotic exposure could disrupt these interactions in the neonatal gut. Notably, a subset of tissue-resident intestinal macrophages, muscularis macrophages, has been identified as …

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. …

Factors Influencing Delayed Clearance Of High Dose Methotrexate (Hdmtx) In Pediatric, Adolescent, And Young Adult Oncology Patients, Ema Mosleh, Stacy Snyder, Ningying Wu, Daniel N Willis, Rema Malone, Robert J Hayashi

2020-Current year OA Pubs

PURPOSE: To identify modifiable risk factors associated with prolonged clearance of methotrexate in pediatric, adolescent, and young adult (AYA) oncology patients receiving high dose methotrexate (HDMTX).

DESIGN/METHOD: A single institution, retrospective chart review of patients receiving HDMTX between 2010-2017. Patients had a diagnosis of either leukemia or osteosarcoma. Data included demographics, concurrent intravenous (IV) medications, IV fluids (IVF) administered, urine output (UO), and rises in serum creatinine (RSC) reflective of renal toxicity (RT). Outcome measures included 1) delayed targeted MTX clearance (DC), 2) actual time to clearance (TTC) and 3) length of stay (LOS).

RESULTS: Data from 447 HDMTX administrations …

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 …

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 …

Rare Predicted Loss-Of-Function Variants Of Type I Ifn Immunity Genes Are Associated With Life-Threatening Covid-19, Daniela Matuozzo, Megan A. Cooper, Et Al.

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 …

Iron Homeostasis And Post-Hemorrhagic Hydrocephalus: A Review, Shelei Pan, Andrew T Hale, Mackenzie E Lemieux, Dhvanii K Raval, Thomas P Garton, Brooke Sadler, Kelly B Mahaney, Jennifer M Strahle

2020-Current year OA Pubs

Iron physiology is regulated by a complex interplay of extracellular transport systems, coordinated transcriptional responses, and iron efflux mechanisms. Dysregulation of iron metabolism can result in defects in myelination, neurotransmitter synthesis, and neuronal maturation. In neonates, germinal matrix-intraventricular hemorrhage (GMH-IVH) causes iron overload as a result of blood breakdown in the ventricles and brain parenchyma which can lead to post-hemorrhagic hydrocephalus (PHH). However, the precise mechanisms by which GMH-IVH results in PHH remain elusive. Understanding the molecular determinants of iron homeostasis in the developing brain may lead to improved therapies. This manuscript reviews the various roles iron has in brain …

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 …

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 …

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.

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 …

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, …

Risk And Protection Of Different Rare Protein-Coding Variants Of Complement Component C4a In Age-Related Macular Degeneration, Johanna M Seddon, Dikha De, William Casazza, Shun-Yun Cheng, Claudio Punzo, Mark Daly, Danlei Zhou, Samantha L Coss, John P Atkinson, Chack-Yung Yu

2020-Current year OA Pubs

No abstract provided.

Understanding Tailoring To Support The Implementation Of Evidence-Based Interventions In Healthcare: The Customise Research Programme Protocol, Sheena M Mchugh, Fiona Riordan, Claire Kerins, Geoff Curran, Cara C Lewis, Justin Presseau, Luke Wolfenden, Byron J Powell

2020-Current year OA Pubs

Although there are effective evidence-based interventions (EBIs) to prevent, treat and coordinate care for chronic conditions they may not be adopted widely and when adopted, implementation challenges can limit their impact. Implementation strategies are "methods or techniques used to enhance the adoption, implementation, and sustainment of a clinical program or practice". There is some evidence to suggest that to be more effective, strategies should be