Medicine and Health Sciences Commons^™

The Structural Basis Of Long-Term Potentiation In Hippocampal Synapses, Revealed By Electron Microscopy Imaging Of Lanthanum-Induced Synaptic Vesicle Recycling, John E Heuser

2020-Current year OA Pubs

Hippocampal neurons in dissociated cell cultures were exposed to the trivalent cation lanthanum for short periods (15-30 min) and prepared for electron microscopy (EM), to evaluate the stimulatory effects of this cation on synaptic ultrastructure. Not only were characteristic ultrastructural changes of exaggerated synaptic vesicle turnover seen within the presynapses of these cultures-including synaptic vesicle depletion and proliferation of vesicle-recycling structures-but the overall architecture of a large proportion of the synapses in the cultures was dramatically altered, due to large postsynaptic "bulges" or herniations into the presynapses. Moreover, in most cases, these postsynaptic herniations or protrusions produced by lanthanum were …

Association Between Recent Overdose And Chronic Pain Among Individuals In Treatment For Opioid Use Disorder, Sarah M. Hartz, Robert C. Culverhouse, Carrie M. Mintz, Matthew S. Ellis, Zachary A. Kasper, Patricia Cavazos-Rehg, Richard A. Grucza, Laura J. Bierut, Theodore J. Cicero

2020-Current year OA Pubs

Chronic pain increases risk for opioid overdose among individuals with opioid use disorder. The purpose of this study is to evaluate the relationship between recent overdose and whether or not chronic pain is active. 3,577 individuals in treatment for opioid use disorder in 2017 or 2018 were surveyed regarding recent overdoses and chronic pain. Demographics from the 2017 Treatment Episode Data Set, which includes all U.S. facilities licensed or certified to provide substance use care, were used to evaluate the generalizability of the sample. χ2 tests and logistic regression models were used to compare associations between recent overdoses and chronic …

Mitochondrial Fitness And Cancer Risk, Andrew V. Kossenkov, Andrew Milcarek, Faiyaz Notta, Gun-Ho Jang, Julie M. Wilson, Steven Gallinger, Daniel Cui Zhou, Li Ding, Jagadish C. Ghosh, Michela Perego, Annamaria Morotti, Marco Locatelli, Marie E. Robert, Valentina Vaira, Dario C. Altieri

2020-Current year OA Pubs

Changes in metabolism are a hallmark of cancer, but molecular signatures of altered bioenergetics to aid in clinical decision-making do not currently exist. We recently identified a group of human tumors with constitutively reduced expression of the mitochondrial structural protein, Mic60, also called mitofilin or inner membrane mitochondrial protein (IMMT). These Mic60-low tumors exhibit severe loss of mitochondrial fitness, paradoxically accompanied by increased metastatic propensity and upregulation of a unique transcriptome of Interferon (IFN) signaling and Senescence-Associated Secretory Phenotype (SASP). Here, we show that an optimized, 11-gene signature of Mic60-low tumors is differentially expressed in multiple malignancies, compared to normal …

Children With Supratentorial Midline Pilocytic Astrocytomas Exhibit Multiple Progressions And Acquisition Of Neurologic Deficits Over Time, Nicole M Brossier, Jennifer M Strahle, Samuel J Cler, Michael Wallendorf, David H Gutmann

2020-Current year OA Pubs

No abstract provided.

The Impact Of A Virtual Orthopaedic Surgery Symposium On Medical Students: Increasing Awareness And Knowledge Of The Field, Theodore Quan, Alex Gu, Amil R. Agarwal, Simone A. Bernstein, Alisa Malyavko, William N. Levine, Lisa K. Cannada, Medical Student Orthopedic Society

2020-Current year OA Pubs

UNLABELLED: Orthopaedic surgery has become an increasingly popular field of residency training for medical students. Many institutions offer elective time to explore areas of interest through clinical rotations and research; however, most of these opportunities are reserved for senior medical students. The purpose of this study was to evaluate the impact of a dedicated medical student orthopaedic surgery symposium to increase awareness about the field and to assess students' interest and knowledge of orthopaedic surgery before and after the symposium.

METHODS: Medical students were invited to submit orthopaedic surgery-related research to a free, 1-day virtual symposium held in April 2022. …

Age Differences In The Association Between Sleep And Alzheimer's Disease Biomarkers In The Epad Cohort, Sharon L Naismith, Yue Leng, Jake R Palmer, Brendan P Lucey

2020-Current year OA Pubs

INTRODUCTION: We aimed to determine the independent association between sleep quality and Alzheimer's disease (AD) biomarkers, and whether the associations differ with age.

METHODS: We included 1240 individuals aged ≥50, without dementia from the

RESULTS: For the youngest age tertile, shorter sleep duration and higher sleep efficiency were associated with greater p-tau/Aβ42 ratio. For the oldest tertile, longer sleep latency was associated with greater p-tau/Aβ42.

DISCUSSION: Differential relationships between sleep and AD pathology depend on age. Short sleep duration and sleep efficiency are relevant in middle age whereas time taken to fall asleep is more closely linked to AD biomarkers …

Clinical And Molecular Characteristics Of A Novel Rare De Novo Variant In Ppp2ca In A Patient With A Developmental Disorder, Autism, And Epilepsy, Iris Verbinnen, Sara S Procknow, Lisa Lenaerts, Sara Reynhout, Aujan Mehregan, Chris Ulens, Veerle Janssens, Katherine A King

2020-Current year OA Pubs

PP2A-related (neuro) developmental disorders are a family of genetic diseases caused by a heterozygous alteration in one of several genes encoding a subunit of type 2A protein phosphatases. Reported affected genes, so far, are

Donor Chimerism And Immune Reconstitution Following Haploidentical Transplantation In Sickle Cell Disease, Yaya Chu, Brenda Grossman, Shalini Shenoy, Et Al

2020-Current year OA Pubs

INTRODUCTION: We previously reported the initial results of a phase II multicenter transplant trial using haploidentical parental donors for children and aolescents with high-risk sickle cell disease achieving excellent survival with exceptionally low rates of graft-versus-host disease and resolution of sickle cell disease symptoms. To investigate human leukocyte antigen (HLA) sensitization, graft characteristics, donor chimerism, and immune reconstitution in these recipients.

METHODS: CD34 cells were enriched using the CliniMACS

RESULTS: HLA antibodies were detected in 7 of 11 (64%) evaluable patients but rarely were against donor antigens. Myeloid engraftment was rapid (100%) at a median of 9 days. At 30 …

Resting State Network Mapping In Individuals Using Deep Learning, Patrick H Luckett, John J Lee, Ki Yun Park, Ryan V Raut, Karin L Meeker, Evan M Gordon, Abraham Z Snyder, Beau M Ances, Eric C Leuthardt, Joshua S Shimony

2020-Current year OA Pubs

INTRODUCTION: Resting state functional MRI (RS-fMRI) is currently used in numerous clinical and research settings. The localization of resting state networks (RSNs) has been utilized in applications ranging from group analysis of neurodegenerative diseases to individual network mapping for pre-surgical planning of tumor resections. Reproducibility of these results has been shown to require a substantial amount of high-quality data, which is not often available in clinical or research settings.

METHODS: In this work, we report voxelwise mapping of a standard set of RSNs using a novel deep 3D convolutional neural network (3DCNN). The 3DCNN was trained on publicly available functional …

Expert Guidance On Prophylaxis And Treatment Of Dermatologic Adverse Events With Tumor Treating Fields (Ttfields) Therapy In The Thoracic Region, Milan J Anadkat, Mario Lacouture, Adam Friedman, Zachary D Horne, Jae Jung, Benjamin Kaffenberger, Sujith Kalmadi, Liza Ovington, Rupesh Kotecha, Huda Ismail Abdullah, Federica Grosso

2020-Current year OA Pubs

Tumor Treating Fields (TTFields) are electric fields, delivered via wearable arrays placed on or near the tumor site, that exert physical forces to disrupt cellular processes critical for cancer cell viability and tumor progression. As a first-in-class treatment, TTFields therapy is approved for use in newly diagnosed glioblastoma, recurrent glioblastoma, and pleural mesothelioma. Additionally, TTFields therapy is being investigated in non-small cell lung cancer (NSCLC), brain metastases from NSCLC, pancreatic cancer, ovarian cancer, hepatocellular carcinoma, and gastric adenocarcinoma. Because TTFields therapy is well tolerated and delivery is locoregional, there is low risk of additive systemic adverse events (AEs) when used …

Sars-Cov-2 Booster Vaccination Rescues Attenuated Igg1 Memory B Cell Response In Primary Antibody Deficiency Patients, Frank J Lin, Alexa Michelle Altman Doss, Hannah G Davis-Adams, Lucas J Adams, Christopher H Hanson, Laura A Vanblargan, Chieh-Yu Liang, Rita E Chen, Jennifer Marie Monroy, H James Wedner, Anthony Kulczycki, Tarisa L Mantia, Caitlin C O'Shaughnessy, Saravanan Raju, Fang R Zhao, Elise Rizzi, Christopher J Rigell, Tiffany Biason Dy, Andrew L Kau, Zhen Ren, Jackson S Turner, Jane A O'Halloran, Rachel M Presti, Daved H Fremont, Peggy L Kendall, Ali H Ellebedy, Philip A Mudd, Michael S Diamond, Ofer Zimmerman, Brian J Laidlaw

2020-Current year OA Pubs

BACKGROUND: Although SARS-CoV-2 vaccines have proven effective in eliciting a protective immune response in healthy individuals, their ability to induce a durable immune response in immunocompromised individuals remains poorly understood. Primary antibody deficiency (PAD) syndromes are among the most common primary immunodeficiency disorders in adults and are characterized by hypogammaglobulinemia and impaired ability to mount robust antibody responses following infection or vaccination.

METHODS: Here, we present an analysis of both the B and T cell response in a prospective cohort of 30 individuals with PAD up to 150 days following initial COVID-19 vaccination and 150 days post mRNA booster vaccination. …

Postnatal Osterix But Not Dmp1 Lineage Cells Significantly Contribute To Intramembranous Ossification In Three Preclinical Models Of Bone Injury, Evan G Buettmann, Susumu Yoneda, Pei Hu, Jennifer A Mckenzie, Matthew J Silva

2020-Current year OA Pubs

Murine models of long-bone fracture, stress fracture, and cortical defect are used to discern the cellular and molecular mediators of intramembranous and endochondral bone healing. Previous work has shown that Osterix (Osx

Stat3 Gain-Of-Function Syndrome, Tiphanie P Vogel, Jennifer W Leiding, Megan A Cooper, Lisa R Forbes Satter

2020-Current year OA Pubs

STAT3 gain-of-function (GOF) syndrome is a multi-organ primary immune regulatory disorder characterized by early onset autoimmunity. Patients present early in life, most commonly with lymphoproliferation, autoimmune cytopenias, and growth delay. However, disease is often progressive and can encompass a wide range of clinical manifestations such as: enteropathy, skin disease, pulmonary disease, endocrinopathy, arthritis, autoimmune hepatitis, and rarely neurologic disease, vasculopathy, and malignancy. Treatment of the autoimmune and immune dysregulatory features of STAT3-GOF patients relies heavily on immunosuppression and is often challenging and fraught with complications including severe infections. Defects in the T cell compartment leading to effector T cell accumulation …

Do The Expert Recommendations For Implementing Change (Eric) Strategies Adequately Address Sustainment?, Nicole Nathan, Byron J Powell, Rachel C Shelton, Celia V Laur, Luke Wolfenden, Maji Hailemariam, Sze Lin Yoong, Rachel Sutherland, Melanie Kingsland, Thomas J Waltz, Alix Hall

2020-Current year OA Pubs

BACKGROUND: Sustainability science is an emerging area within implementation science. There is limited evidence regarding strategies to best support the continued delivery and sustained impact of evidence-based interventions (EBIs). To build such evidence, clear definitions, and ways to operationalize strategies specific and/or relevant to sustainment are required. Taxonomies and compilations such as the Expert Recommendations for Implementing Change (ERIC) were developed to describe and organize implementation strategies. This study aimed to adapt, refine, and extend the ERIC compilation to incorporate an explicit focus on sustainment. We also sought to classify the specific phase(s) of implementation when the ERIC strategies could …

Sustainability In Pediatric Hospitals: An Exploration At The Intersection Of Quality Improvement And Implementation Science, Sara Malone, Jason Newland, Sapna R Kudchadkar, Kim Prewitt, Virginia Mckay, Beth Prusaczyk, Enola Proctor, Ross C Brownson, Douglas A Luke

2020-Current year OA Pubs

BACKGROUND: Although new evidence-based practices are frequently implemented in clinical settings, many are not sustained, limiting the intended impact. Within implementation science, there is a gap in understanding sustainability. Pediatric healthcare settings have a robust history of quality improvement (QI), which includes a focus on continuation of change efforts. QI capability and sustainability capacity, therefore, serve as a useful concept for connecting the broader fields of QI and implementation science to provide insights on improving care. This study addresses these gaps in understanding of sustainability in pediatric settings and its relationship to QI.

METHODS: This is a cross-sectional observational study …

Low Risk For Developing Diabetes Among The Offspring Of Individuals With Exceptional Longevity And Their Spouses, Iva Miljkovic, Ryan Cvejkus, Ping An, Bharat Thyagarajan, Kaare Christensen, Mary Wojczynski, Nicole Schupf, Joseph M Zmuda

2020-Current year OA Pubs

Little is known about the risk of type 2 diabetes (T2D) among the offspring of individuals with exceptional longevity. We determined the incidence of and potential risk and protective factors for T2D among the offspring of probands and offspring's spouses (mean age=60 years, range 32-88 years) in the Long Life Family Study (LLFS), a multicenter cohort study of 583 two-generation families with a clustering of healthy aging and exceptional longevity. Incident T2D was defined as fasting serum glucose ≥126 mg/dl, or HbA1c of ≥6.5%, or self-reported with doctor diagnosis of T2D, or the use of anti-diabetic medication during a mean …

Neurology Resident Eeg Training In Europe, Fábio A Nascimento, Jay R Gavvala, Hatice Tankisi, Sándor Beniczky

2020-Current year OA Pubs

OBJECTIVE: To detail current European EEG education practices and compare European and U.S. EEG teaching systems.

METHODS: A 19-question online survey focused on EEG clinical practices and residency training was emailed to all 47 European Academy of Neurology Societies.

RESULTS: Thirty-two (68 %) out of the 47 Societies completed the survey. In half of countries, general neurologists are either among the providers or the only providers who typically read EEGs. The number of weeks devoted to EEG learning required to graduate ranged from none to 26, and it was expected to be continuous in one country. In most countries (n …

Calorie Restriction Improves Lipid-Related Emerging Cardiometabolic Risk Factors In Healthy Adults Without Obesity: Distinct Influences Of Bmi And Sex From Calerie™ A Multicentre, Phase 2, Randomised Controlled Trial, Kim M Huffman, Susan B Racette, Et Al.

2020-Current year OA Pubs

BACKGROUND: For many cardiovascular risk factors there is no lower limit to which further reduction will result in decreased disease risk; this includes values within ranges considered normal for healthy adults. This seems to be true for new emerging metabolic risk factors identified by innovative technological advances. Further, there seems to be ever evolving evidence of differential responses to lifestyle interventions by sex and body compositions in the normal range. In this secondary analysis, we had the opportunity to test these principles for newly identified molecular biomarkers of cardiometabolic risk in a young (21-50 years), normal weight healthy population undergoing …

Management Of Acute Promyelocytic Leukemia In The Setting Of Acute Covid-19 Infection, Kevin G Shim, Mallory Crain, Kristan Augustin, Karolyn A Oetjen

2020-Current year OA Pubs

Acute promyelocytic leukemia (APL) often presents with significant coagulopathy which may result in both hemorrhagic and thrombotic complications. The emergence of the COVID-19 pandemic has complicated the initial treatment and diagnosis of APL owing to the viral infection's own associated coagulopathy. Here we report two cases of APL newly diagnosed in the setting of COVID-19 infection and considerations in their management. Included is a discussion of strategies for the dosing of arsenic trioxide in patients with significant obesity and renal insufficiency. The case series submitted does not represent a study on patients and thus no specific informed consents or permissions …

Functional Tic-Like Presentations Differ Strikingly From Provisional Tic Disorder, Amanda L Arbuckle, Emily C Bihun, Bradley L Schlaggar, Kevin J. Black

2020-Current year OA Pubs

No abstract provided.

Protocol For The Ketamine For Postoperative Avoidance Of Depressive Symptoms (K-Pass) Feasibility Study: A Randomized Clinical Trial, Bradley A Fritz, Bethany R Tellor Pennington, Ben J A Palanca, Julie A Schweiger, Jon T Willie, Nuri B Farber

2020-Current year OA Pubs

No abstract provided.

Automated Detection Of Vaping-Related Tweets On Twitter During The 2019 Evali Outbreak Using Machine Learning Classification, Yang Ren, Dezhi Wu, Avineet Singh, Erin Kasson, Ming Huang, Patricia Cavazos-Rehg

2020-Current year OA Pubs

There are increasingly strict regulations surrounding the purchase and use of combustible tobacco products (i.e., cigarettes); simultaneously, the use of other tobacco products, including e-cigarettes (i.e., vaping products), has dramatically increased. However, public attitudes toward vaping vary widely, and the health effects of vaping are still largely unknown. As a popular social media, Twitter contains rich information shared by users about their behaviors and experiences, including opinions on vaping. It is very challenging to identify vaping-related tweets to source useful information manually. In the current study, we proposed to develop a detection model to accurately identify vaping-related tweets using machine …

Isotopically Nonstationary 13c Metabolic Flux Analysis In Resting And Activated Human Platelets, Cara L Sake, Alexander J Metcalf, Michelle Meagher, Jorge Di Paola, Keith B Neeves, Nanette R Boyle

2020-Current year OA Pubs

Platelet metabolism is linked to platelet hyper- and hypoactivity in numerous human diseases. Developing a detailed understanding of the link between metabolic shifts and platelet activation state is integral to improving human health. Here, we show the first application of isotopically nonstationary

Alopecia Areata After Mogamulizumab Treatment, Neel S Raval, Nora A Alexander, Karlee De Monnin, Christine C Yokoyama, Neha Mehta-Shah, Ilana S Rosman, Amy C Musiek

2020-Current year OA Pubs

No abstract provided.

Characterization Of The Genomic And Immunologic Diversity Of Malignant Brain Tumors Through Multisector Analysis, Maximilian O Schaettler, Megan M Richters, Anthony Z Wang, Zachary L Skidmore, Bryan Fisk, Albert H Kim, Michael R Chicoine, Joshua W Osbun, Eric C Leuthardt, Joshua L Dowling, Gregory J Zipfel, Ralph G Dacey, Hsiang-Chih Lu, Tanner M Johanns, Obi L Griffith, Malachi Griffith, Gavin P Dunn, Et Al.

2020-Current year OA Pubs

Despite some success in secondary brain metastases, targeted or immune-based therapies have shown limited efficacy against primary brain malignancies such as glioblastoma (GBM). Although the intratumoral heterogeneity of GBM is implicated in treatment resistance, it remains unclear whether this diversity is observed within brain metastases and to what extent cancer cell-intrinsic heterogeneity sculpts the local immune microenvironment. Here, we profiled the immunogenomic state of 93 spatially distinct regions from 30 malignant brain tumors through whole-exome, RNA, and T-cell receptor sequencing. Our analyses identified differences between primary and secondary malignancies, with gliomas displaying more spatial heterogeneity at the genomic and neoantigen …

Responding To Sexual Abuse In Health Care: Development Of A Guide For Patients, Tristan Mcintosh, Heidi Walsh, Meredith Parsons, Erin D Solomon, Jessica Mozersky, James M Dubois

2020-Current year OA Pubs

This report details the development of a stakeholder- and evidence-informed online resource guide for patients that provides information to raise awareness about sexual abuse in health care, the value of chaperones, and options for responding to sexual abuse. The guide was developed to reflect lessons learned from 10 years of researching physician wrongdoing (ie, sexual violations, improper prescribing, and unnecessary invasive procedures), a 5-year National Institutes of Health-funded mixed-methods study of 280 cases of egregious wrongdoing in medicine, and an expert working group. Focus groups were conducted with 22 patients from diverse backgrounds to obtain feedback on the acceptability of …

Evaluating The Implementation Of A Multi-Level Mhealth Study To Improve Hydroxyurea Utilization In Sickle Cell Disease, J S Hankins, A A King, A A Baumann, L M. Klesges, Et Al.

2020-Current year OA Pubs

BACKGROUND: Sickle Cell Disease (SCD) is a progressive genetic disease that causes organ damage and reduces longevity. Hydroxyurea is an underutilized evidence-based medication that reduces complications and improves survival in SCD. In a multi-site clinical trial, part of the NIH-funded Sickle Cell Disease Implementation Consortium (SCDIC), we evaluate the implementation of a multi-level and multi-component mobile health (mHealth) patient and provider intervention to target the determinants and context of low hydroxyurea use. Given the complexity of the intervention and contextual variability in its implementation, we combined different behavioral and implementation theories, models, and frameworks to facilitate the evaluation of the …

Lessons Learned From An Enterprise-Wide Clinical Datathon, Andrew J Zimolzak, Jessica A Davila, Vamshi Punugoti, Ashok Balasubramanyam, Paul E Klotman, Laura A Petersen, Ryan H Rochat, Gloria Liao, Rory R Laubscher, Lee Leiber, Christopher I Amos

Faculty, Staff and Students Publications

In 2020, Baylor College of Medicine held a datathon to inform potential users of a new data warehouse, allow users to address clinical questions, identify warehouse capabilities and limitations, foster collaborations, and engage trainees. Senior faculty selected proposals based on feasibility and impact. Selectees worked with Information Technology for 2 months and presented findings. A survey of participants showed diverse levels of experience, high perceived value of the datathon, high rates of collaboration, and significant increases in knowledge. A datathon can promote familiarity with a new data warehouse, guide data warehouse improvement, and promote collaboration.

Video Game Rehabilitation For Outpatient Stroke (Vigorous): A Multi-Site Randomized Controlled Trial Of In-Home, Self-Managed, Upper-Extremity Therapy., Lynne V Gauthier, Deborah S Nichols-Larsen, Gitendra Uswatte, Nancy Strahl, Marie Simeo, Rachel Proffitt, Kristina Kelly, Roger Crawfis, Edward Taub, David Morris, Linda Pax Lowes, Victor Mark, Alexandra Borstad

Neuroscience Articles

BACKGROUND: Integrating behavioral intervention into motor rehabilitation is essential for improving paretic arm use in daily life. Demands on therapist time limit adoption of behavioral programs like Constraint-Induced Movement (CI) therapy, however. Self-managed motor practice could free therapist time for behavioral intervention, but there remains insufficient evidence of efficacy for a self-management approach.

METHODS: This completed, parallel, five-site, pragmatic, single-blind trial established the comparative effectiveness of using in-home gaming self-management as a vehicle to redirect valuable therapist time towards behavioral intervention. Community-dwelling adults with post-stroke (>6 months) mild/moderate upper extremity hemiparesis were randomized to receive one of 4 different …

Climbing The Anki Mountain, One (Review) Step At A Time: A Written And Video-Based Guide On Using Anki In Medical School To Enhance Knowledge Acquisition And Retention, Alexander Tu, Tiffany Truong, Avi Prajapati

EMET Projects

No abstract provided.