Medicine and Health Sciences Commons^™

The Yeh Pilus Adhesin Is Equipped With An Α-Helical Flap Motif, Which Contributes To Pectin Adherence, Kevin O Tamadonfar, Roger D Klein, Edward D B Lopatto, Maxwell I Zimmerman, Philippe N Azimzadeh, Denise A Sanick, Justin R Porter, Jesus Bazan Villicana, Jerome S Pinkner, Bo Huey Chiang, Nathaniel C Gualberto, Karen W Dodson, Michael L Patnode, George M H Et Al., Gregory R Bowman, Scott J Hultgren

2020-Current year OA Pubs

The Yeh chaperone-usher pathway (CUP) pilus adhesin is encoded in one-half of all

Renal Piezo2 Is An Essential Regulator Of Renin, Rose Z Hill, Jeffrey H Miner, Et Al.

2020-Current year OA Pubs

Renin synthesis and release is the rate-limiting step of the renin-angiotensin-aldosterone system (RAAS) that controls fluid homeostasis. A major activator of the RAAS is a decrease in perfusion pressure within the kidneys, suggesting a link between renal mechanotransduction and renin. However, the identity of the mechanosensor(s) in the kidneys and their physiological significance to the RAAS remain unclear. We find that loss of the force-gated nonselective cation channel PIEZO2 in cells of renin lineage dysregulates the RAAS by elevating renin. We observe that PIEZO2 is expressed in renin-producing juxtaglomerular granular cells and is required for their calcium dynamics in vivo. …

Characterization Of Novel Sigma Receptor Ligands Derived From Multicomponent Reactions As Efficacious Treatments For Neuropathic Pain, Ryosuke Shinouchi, Bengisu Turgutalp, Rohini S Ople, Shainnel O Eans, Ashai K Williams, Haylee R Hammond, Andras Varadi, Rebecca Notis Dardashti, Susruta Majumdar, Jay P Mclaughlin

2020-Current year OA Pubs

No abstract provided.

Costs And Cost-Effectiveness Of A Culturally Adapted Diabetes Self-Management And Education Program For Marshallese Adults, Tzeyu L Michaud, Daniel Lamprecht-Carson, Su-Hsin Chang, Clare C Brown, Jennifer A Andersen, James P Selig, Philmar Mendoza Kabua, Pearl Mcelfish

2020-Current year OA Pubs

BACKGROUND: Culturally adapted diabetes self-management education (DSME) programs are effective in improving glycemic control and diabetes outcomes among minority populations, but data on program costs and cost-effectiveness are limited. This study aimed to assess the cost and cost-effectiveness of a culturally adapted DSME (adapted DSME) compared to a standard DSME model among Marshallese adults with type 2 diabetes (T2D).

METHODS: Retrospective cost and cost-effectiveness analyses (CEA) were conducted using data from the community-based trial, conducted between May 2015 and May 2018. We applied an activity-based costing approach to quantify the implementation resources. The CEA was performed using an incremental implementation …

Antecedent Enhancer Activity Predicts Future Susceptibility To Seizures In Mice, Benjamin D Boros, Mariam A Gachechiladze, Juanru Guo, Dylan A Galloway, Shayna M Mueller, Mark Shabsovich, Allen Yen, Xuhua Chen, Alexander J Cammack, Tao Shen, Robi D Mitra, Joseph D Dougherty, Timothy M Miller

2020-Current year OA Pubs

Wide variation of responses to identical stimuli presented to genetically inbred mice suggests the hypothesis that stochastic non-genetic variation, such as in chromatin state or enhancer activity during neurodevelopment, can mediate such phenotypic differences. However, this hypothesis is largely untested since capturing pre-existing molecular states requires non-destructive, longitudinal recording. Therefore, we tested the potential of Calling Cards (CC) to record transient neuronal enhancer activity during postnatal development in mice, and thereby associate such non-genetic variation with a subsequent phenotypic presentation - degree of seizure response to the pro-convulsant pentylenetetrazol. We show that recorded differences in enhancer activity at 243 loci …

Assessing The Effects Of Ehealth Literacy And The Area Deprivation Index On Barriers To Electronic Patient Portal Use For Orthopedic Surgery: Cross-Sectional Observational Study, Audrey Lynn Litvak, Nicholas Lin, Kelly Hynes, Jason Strelzow, Jeffrey G Stepan

2020-Current year OA Pubs

BACKGROUND: As electronic patient portals (EPPs) continue to gain popularity and systems transition to online tools for scheduling, communication, and telehealth, patients without access or skills to use these tools may be overlooked.

OBJECTIVE: This study analyzed patient and neighborhood-level factors, including eHealth literacy level and the Area Deprivation Index (ADI), that may limit EPP access for orthopedic surgery.

METHODS: A cross-sectional, survey-based study was performed at a single urban tertiary academic medical center in the United States across foot and ankle, hand and upper extremity, and orthopedic trauma subspecialty clinics from June 21, 2022, to August 12, 2022. Survey …

Durability Of The Benefit Of Vagus Nerve Stimulation In Markedly Treatment-Resistant Major Depression: A Recover Trial Report, Charles R Conway, Christopher L Kriedt, Charles F Zorumski, Hunter Brown, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Greater levels of treatment resistance in major depressive disorder (MDD) are associated with lower rates of initial benefit and higher rates of relapse (lower durability).

OBJECTIVE: Characterize depressive symptoms, function, and quality of life (QoL) over 24 months of adjunctive vagus nerve stimulation (VNS) in participants with markedly treatment-resistant depression.

DESIGN: Prospective, open-label, single-arm, long-term extension study (RECOVER) conducted from September 2019 to April 2025.

SETTING: Outpatient.

PARTICIPANTS: Adults with moderate-severe MDD with ≥ 4 failed antidepressant trials in the current episode, randomized to blinded, adjunctive VNS for 12 months, who subsequently received open-label, adjunctive VNS for 12 additional …

Intravenous Thrombolysis In Patients On Direct Oral Anticoagulants: Analysis Of The Get With The Guidelines Stroke Registry, Shadi Yaghi, Opeolu Adeoye, Et Al.

2020-Current year OA Pubs

BACKGROUND: Intravenous thrombolysis for acute ischemic stroke (AIS) is a proven effective treatment. Whether thrombolysis in patients with AIS with recent direct oral anticoagulant (DOAC) use is safe and efficacious is not well established. We aimed to compare outcomes of patients with AIS and recent DOAC use who received thrombolysis to those otherwise eligible but excluded due to recent DOAC use.

METHODS: This study included patients for the GWTG (Get With The Guidelines) registry with a diagnosis of AIS within 4.5 hours from last known normal, on a DOAC, and either (1) received intravenous thrombolysis, or (2) were excluded from …

Bio-Adrenomedullin Predicts Death And Major Adverse Cardiovascular Events In Cardiac Amyloidosis: A Cross-Continental Multicenter Study, Maximilian L Müller, Fabian Knebel, Katrin Hahn, Janin Schulte, Birte Arlt, Oliver Hartmann, Kaitlin M S Moore, Seiji Takashio, Yasuhiro Izumiya, Joshua D Mitchell, Kenichi Tsujita, Ulf Landmesser, Bettina Heidecker

2020-Current year OA Pubs

BACKGROUND: Bio-ADM (bioactive adrenomedullin) is a vasoactive peptide hormone that predicts clinical outcomes in heart failure-the main driver of adverse outcomes in cardiac amyloidosis (CA). This prospective observational study sought to assess the prognostic role of bio-ADM in CA.

METHODS: Patients with CA were enrolled from amyloid centers in Germany (observation cohort), Japan, and the United States (combined validation cohort). Bio-ADM was quantified using the sphingotest bio-ADM assay. Associations of bio-ADM with all-cause death and major adverse cardiovascular events over 2 years were assessed using Kaplan-Meier and Cox regression analyses. Likelihood ratio chi-square tests for nested models evaluated whether adding …

Association Between Monoclonal Gammopathy Of Undetermined Significance And Cardiovascular Disease Risk: A Veterans Health Administration Study, Tzeyu L Michaud, Mei Wang, Daphne R Friedman, Lawrence Liu, Theodore S Thomas, Kristen M Sanfilippo, Graham A Colditz, Martin W Schoen, Su-Hsin Chang

2020-Current year OA Pubs

BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) is associated with an increased risk of cardiovascular disease (CVD). However, its potential to provide additional prognostic information beyond traditional CVD risk assessments remains unknown. This study aimed to examine the association between MGUS and incident CVD and to determine whether MGUS status offers additional prognostic value beyond the established atherosclerotic cardiovascular disease risk calculation.

METHODS: We conducted a retrospective, matched observational study using 2010 to 2021 Veterans Health Administration data. MGUS status, confirmed through a validated natural language processing algorithm, were 1:5 matched to individuals without MGUS. The outcome of interest was …

Neuronal Subtype Governs Amyloid Structure, Cellular Response, And Cognitive Outcome In Genetically Targeted App Mouse Models, Gabriella A Perez, Zoe Lai, George A Edwards Iii, Jacob M Dundee, Shannon N Leahy, Chuangye Qi, Yanyan Qi, Ye-Jin Park, Tzu-Chiao Lu, M Danish Uddin, Rong Zhao, Hui Zheng, Hongjie Li, Joanna L Jankowsky

2020-Current year OA Pubs

Pathological heterogeneity is increasingly appreciated in Alzheimer’s disease, yet we do not know how distinct aggregate conformations arise or influence cognitive outcomes. In an amyloid mouse model, we found that different brain regions formed structurally distinct Aβ deposits, prompting us to test whether neuronal subtypes shape aggregate conformation. To address this, we created transgenic mice expressing the same APP construct in either glutamatergic or GABAergic neurons. APP expression in GABAergic neurons resulted in diffuse plaques with high Aβ42/Aβ40 ratios and minimal gliosis, while glutamatergic expression produced neuritic plaques with activated glia. Despite similar Aβ levels, only mice with neuritic plaques …

The Igvf Catalog-From Genetic Variation To Function, Daofeng Li, Shane Liu, Wenjin Zhang, Juan F Macias-Velasco, Tianjie Liu, Sarah Cody, Lucinda Antonacci-Fulton, Ting Wang, Et Al.

2020-Current year OA Pubs

Genomic variation between individuals is essential for understanding how differences in the genome sequence affect molecular and cellular processes. The Impact of Genomic Variation on Function (IGVF) Consortium aims to uncover the relationships among genomic variation, genome function, and phenotypes by combining experimental techniques, such as single-cell mapping and genomic perturbation assays, with computational approaches such as machine learning-based predictive modeling. The IGVF Data and Administrative Coordinating Centers collect, analyze, and disseminate data and results from across the consortium through an open-source platform called the IGVF Catalog. This resource includes, but is not limited to, data on the effects of …

Postoperative Lymph Is A Proximal Source Of Ctdna For Detection Of Recurrence In Hpv-Independent Head And Neck Cancer, Seka Lazare, Noah Earland, Peter Harris, Ricardo Ramirez, Benjamin Wahle, Sid Puram, Doug Adkins, Wade Thorstad, Rebecca Chernock, Aadel A Chaudhuri, Et Al.

2020-Current year OA Pubs

PURPOSE: Relapse is a major cause of failure in human papillomavirus-independent head and neck squamous cell carcinoma. Clinicopathologic criteria for adjuvant treatment remain imprecise and have not changed for decades. We investigated whether ctDNA in lymphatic exudate collected via surgical drains ("lymph") 24 hours after surgery identified molecular residual disease (MRD) and compared its performance with time-matched plasma.

EXPERIMENTAL DESIGN: Using an ultra-sensitive tumor-informed sequencing approach, tumor variants were called in lymph and plasma to classify patients as ctDNA positive or ctDNA negative, trained in an initial cohort of 36 patients, and replicated in an independent cohort of 37 patients. …

Mass Spectrometry Footprinting Reveals How Kinetic Stabilizers Counteract Transthyretin Dynamics Altered By Pathogenic Mutations, Francisca Pinheiro, Ravi Kant, Saketh Chemuru, Nathalia Varejão, Adrián Velázquez-Campoy, David Reverter, Irantzu Pallarès, Michael L Gross, Salvador Ventura

2020-Current year OA Pubs

The aggregation of transthyretin (TTR) results in life-threatening transthyretin amyloidosis. Familial forms of the disease arise from point mutations that destabilize the TTR tetramer, leading to its dissociation and/or monomer unfolding and subsequent formation of amyloid fibrils. Small molecules that kinetically stabilize the native tetramer effectively inhibit this aggregation. Although over 300 X-ray crystal structures of TTR have been determined, these data refer to a static structure and do not capture the conformational effects of mutations and ligand binding. Here, we demonstrate that hydrogen-deuterium exchange (HDX) and fast photochemical oxidation of proteins (FPOP) coupled with mass spectrometry (MS) offer critical …

Polymer Conformational Entropy As The Driver Of Complex Coacervation, Tommaso Inzani, Giovanni Nava, Marco Buscaglia, Andrea Soranno, Alessandro Gori, Greta Bergamaschi, Samir Suweis, Amos Maritan, Tommaso Bellini

2020-Current year OA Pubs

Understanding the mechanisms leading to complex coacervation is a fundamental challenge in biomolecular sciences. Here, we explored the condensation transition and pretransitional behavior of an archetypal system consisting of polyuridylic acid chains (PolyU) and short cationic peptides in buffered aqueous solutions. By combining static and dynamic light scattering with confocal microscopy, we determined the location of the transition and the partitioning of PolyU and peptides between the coexisting phases as a function of the total peptides/PolyU ratio. We find that upon adding peptides in the system, the size of PolyU coils in the single-phase region is progressively reduced by peptide-mediated …

What Is The Psychological And Cognitive Impact Of Returning Alzheimer Disease Dementia Research Results To Healthy Research Participants? A Delayed-Start Randomised Clinical Trial Protocol For The Weshare Study (Washington University Study Of Having Alzheimer Disease), Sarah M Hartz, Spondita Goswami, Amy Oliver, Alissa Evans, Sacha Jackson, Erin Linnenbringer, Krista M Moulder, John C Morris, Jessica Mozersky

2020-Current year OA Pubs

INTRODUCTION: Returning research results that indicate risk of Alzheimer disease (AD) dementia-a disease for which no meaningful treatments or cure exist-to cognitively normal participants is controversial. AD is thought to begin many years before clinical signs and symptoms begin. During this time, individuals are cognitively normal but have biomarkers that indicate pathophysiological changes in the brain. With this study, we aim to evaluate the impact of returning research results on cognitively normal participants recruited from a longitudinal observational cohort on ageing at the Knight Alzheimer Disease Research Centre (Knight ADRC) at Washington University in St. Louis.

METHODS AND ANALYSIS: Our …

Environmental Enteric Dysfunction In Well-Nourished And Undernourished Women In Bangladesh, Mustafa Mahfuz, Md Shabab Hossain, Ar-Rafi Khan, Mehjabin Tishan Mahfuz, Rumana Sharmin, A H M Rezwan, Musarrat Tasnim, S M Tafsir Hasan, S M Khodeza Nahar Begum, M Masudur Rahman, Michael J Barratt, Jeffrey I Gordon, Tahmeed Ahmed

2020-Current year OA Pubs

INTRODUCTION: Environmental Enteric Dysfunction (EED) is a subacute inflammation of the small intestinal (SI) mucosa associated with undernutrition and perturbation of the SI microbiota. Its diagnosis relies on histopathological assessment of small intestinal biopsies, with a lack of validated biomarkers contributing to underdiagnosis. This study assessed the prevalence and histological features of EED in undernourished Bangladeshi women living in an urban slum in Dhaka, compared to well-nourished women from slum and non-slum areas, and examined the factors associated with histologically confirmed EED.

METHODS: This analysis included non-pregnant, non-lactating Bangladeshi women aged 18-45 years classified by location of residence and nutritional …

Omg! A Proteomic Determinant Of Neurodegenerative Resiliency, Michael R Duggan, Muhammad Ali, Menghan Liu, Ying Xu, Daniel Western, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

BACKGROUND: Biofluid proteomics can enhance our understanding of the neurodegenerative mechanisms underlying Alzheimer's disease and related dementias (ADRDs). Oligodendrocyte myelin glycoprotein (OMG) is a brain-specific protein implicated in myelination, but its potential mechanistic, biomarker, and therapeutic roles in ADRDs requires further elucidation.

METHODS: After detecting an inverse association between its abundance in peripheral circulation and cortical amyloid deposition in two community-based cohorts, the current study characterized OMG's role in ADRDs with high-throughput proteomics from sixteen independent cohorts. Data included a variety of cross-sectional and longitudinal community-based and clinical cohorts from North America, Europe, and Asia, and incorporated complementary biofluids, biospecimens, …

Clinical Performance Of A Novel Point-Of-Care High-Sensitivity Cardiac Troponin I Assay, Alan H B Wu, Stacey L House, Et Al.

2020-Current year OA Pubs

BACKGROUND: High-sensitivity cardiac troponin (hs-cTn) assays performed in the central laboratory have long turnaround times. This study evaluates the clinical performance of a novel bedside point-of-care (POC) hs-cTnI assay (i-STAT® hs-TnI) to aid in the diagnosis of myocardial infarction (MI).

METHODS: A prospective multisite cohort study involving emergency department (ED) patients with symptoms suggestive of acute coronary syndrome was conducted at 28 sites across the United States. Serial whole blood samples were collected at 0-1 h and >1-3 h from ED presentation. Primary outcome was MI or non-MI. Sensitivity, specificity, and negative predictive value (NPV) for MI were calculated with …

Accurate Chromatin Marks Peak Calling With Omnipeak, Oleg Shpynov, Maxim N Artyomov

2020-Current year OA Pubs

Chromatin immunoprecipitation sequencing (ChIP-seq) is a widely used technique for identifying transcription-factor binding and histone modifications across the genome. Peaks in ChIP-seq data vary in length depending on the biological context, from narrow transcription factor binding sites to broad histone modification domains. However, commonly used peak-calling tools are tailored to the specific types of data and struggle to consistently handle various peak lengths, datasets of varying quality, and missing control tracks-common issues in comparative or meta-analyses. These limitations are addressed with Omnipeak, a universal unsupervised peak-calling algorithm based on a constrained three-state hidden Markov model. Omnipeak accurately models global genomic …

Β2 And Β3a Regulatory Subunits Can Coassemble In The Same Bk Channels, Yu Zhou, Vivian Gonzalez-Perez, Xiao-Ming Xia, Gopal S Kallure, Sandipan Chowdhury, Christopher J Lingle

2020-Current year OA Pubs

Ca2+- and voltage-activated BK-type K+ channels are influenced profoundly by associated regulatory subunits, including β subunits (Kcnmb1-4; β1-β4). Although overlap in expression of different BK β subunits occurs in native tissues, whether they can coassemble in the same channel complex is not known. We coexpress β2 and β3a subunits together with BK α and, through a combination of macroscopic and single-channel recordings, along with quantitative pull-down of tagged subunits, test whether coassembly can occur. We evaluate two models: (1) random mixing in which β2 and β3a subunits coassemble in the same channels, and (2) segregation in which β2 and β3a …

Towards A Unified Gating Scheme For The Cnbd Ion Channel Family, Jenna L Lin, Baron Chanda

2020-Current year OA Pubs

Cyclic nucleotide-binding domain (CNBD) channels are critical components of numerous bioelectrical processes, including cardiac pacemaking, neuronal signaling, phototransduction in the eye, and stomatal regulation in plants. While members of this channel family share a conserved overall structure, they exhibit striking differences in voltage sensitivity. Hyperpolarization-activated cyclic nucleotide-gated channels are activated by membrane hyperpolarization, whereas ether-à-go-go channels open upon depolarization. Mutagenesis and chimeragenesis studies have revealed that some mutants display bipolar gating behavior-remaining closed at intermediate membrane potentials but capable of opening in response to both hyperpolarization and depolarization. Remarkably, in certain cases, just a few mutations are sufficient to reverse …

Prospective Audit And Feedback By Antibiotic Stewardship Teams To Reduce Antibiotic Overuse At Hospital Discharge: A Stepped-Wedge Cluster-Randomized Clinical Trial, Daniel J Livorsi, Michael Joshua Hendrix, Erin Rachmiel, Jahnavi Bongu, Alice Bewley, Kevin Hsueh, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Antibiotics prescribed at hospital discharge are frequently unnecessary or suboptimal. Strategies to improve prescribing are not well defined.

OBJECTIVE: To evaluate whether a discharge-focused prospective audit and feedback process decreases antibiotic overuse at hospital discharge.

DESIGN, SETTING, AND PARTICIPANTS: This stepped-wedge cluster-randomized clinical trial was conducted across participating units at 10 hospitals with antibiotic stewardship (AS) teams and supporting staff from December 5, 2022, to November 17, 2023. After a 24-week baseline period, 1 hospital crossed into the intervention arm every 2 weeks.

INTERVENTION: The intervention consisted of disseminating institutional guidelines for oral antibiotic step-down to frontline prescribers and …

Cumulative Lifespan Stress, Inflammation, And Racial Disparities In Mortality Between Black And White Adults, Isaiah D Spears, Aaron J Gorelik, Sara A Norton, Michael J Boudreaux, Megan W Wolk, Jayne Siudzinski, Sarah E Paul, Mary A Cox, Cynthia E Rogers, Thomas F Oltmanns, Patrick L Hill, Ryan Bogdan

2020-Current year OA Pubs

IMPORTANCE: In the US, Black individuals experience higher mortality risk than White individuals. Greater stress exposure and its biological sequelae are theorized to drive this heightened risk.

OBJECTIVE: To evaluate whether greater cumulative lifespan stress exposure and elevated inflammation are associated with increased mortality risk among Black compared with White US individuals.

DESIGN, SETTING, AND PARTICIPANTS: This longitudinal cohort study (St Louis Personality and Aging Network) recruited participants from 2007 to 2011 from the St Louis, Missouri, metropolitan area. Participants were required to have a mailing address to permit longitudinal follow-up and sixth grade reading level to facilitate understanding of …

White Matter Hyperintensity Burden And Decline In Driving Performance Among Older Adults, Madhur Parihar, Yasheng Chen, Byron Xu, Semere Bekena, Ramkrishna K Singh, Yiqi Zhu, Jean-Francois Trani, Jin-Moo Lee, David B Carr, Chia-Ling Phuah, Ganesh M Babulal, Driving Real-World In-Vehicle Evaluation System (Drives) Project

2020-Current year OA Pubs

IMPORTANCE: White matter hyperintensity (WMH) burden is associated with cognitive decline, but its association with driving performance among older adults and the associations of modifiable risk factors remain unclear.

OBJECTIVE: To evaluate the association of total and regional WMH burden with longitudinal naturalistic driving performance in cognitively normal older adults and evaluate moderating associations of cognitive decline and antihypertensive therapy.

DESIGN, SETTING, AND PARTICIPANTS: This prospective longitudinal cohort study enrolled community-dwelling older adults (≥65 years) in the Driving Real-World In-Vehicle Evaluation System Project. Baseline 3-T brain magnetic resonance imaging (MRI) scans and data from continuous in-vehicle driving monitoring were collected …

Impaired Complement Regulation Drives Chronic Lung Allograft Dysfunction After Lung Transplantation, Hrishikesh S. Kulkarni, Laneshia K. Tague, Fuyi Liao, Zhiyi Liu, Lorena Garnica, Nishanth R. Shankar, Xiaobo Wu, Dequan Zhou, Yan Tao, Victoria E. Davis, Cory T. Bernardt, Derek E. Byers, Chad A. Witt, Daniel Kreisel, John P. Atkinson, Andrew E. Gelman, Et Al.

2020-Current year OA Pubs

A greater understanding of chronic lung allograft dysfunction (CLAD) pathobiology, the primary cause of death after lung transplantation (LTx), is needed to improve outcomes. The complement system links innate to adaptive immune responses and is activated early after lung transplantation to form C3 convertase, a critical enzyme that cleaves the central complement component C3. We hypothesized that LTx recipients with a genetic predisposition to enhanced complement activation have worse CLAD-free survival mediated through increased adaptive alloimmunity. We interrogated a known functional C3 polymorphism (C3 R102G) that increases complement activation through impaired C3 convertase inactivation in 2 independent LTx recipient cohorts. …

A Survey-Based Assessment Of Treatment Preferences For Distal Radius Fractures In Participants Aged 65 Years And Older, Zayd Al Rawi, Elizabeth Graesser, Lindley B Wall

2020-Current year OA Pubs

PURPOSE: The management of distal radius fractures (DRF) in patients aged ≥65 years is debated because there is evidence that operative and nonsurgical treatment yield similar outcomes 1 year after injury. When more than one reasonable treatment option exists, shared decision-making between the patient and physician should be used. This study elicited preferences for the treatment of DRF using a survey of participants aged ≥65 years.

METHODS: A survey for participants ≥65 years was administered using Amazon Mechanical Turk. Participants were presented with a theoretical scenario in which they sustained a DRF, followed by two treatment options (surgery or casting) …

Development Of Colonic Polyposis In A Woman With Chronic Myeloid Leukemia Treated With Dasatinib, Guido Pelaez, Behram Suha Yildiz, Mert Candan, Mohammad Ismail, Francesca Vacca, Marianna B Ruzinova, Samuel Ballentine, Kathleen Byrnes, Armin Ghobadi

2020-Current year OA Pubs

INTRODUCTION: Chronic myeloid leukemia (CML) is a hematopoietic malignancy driven by constitutive tyrosine kinase activity. Dasatinib, a second-generation (2G) tyrosine kinase inhibitor (TKI), is a preferred treatment due to its superior, durable, and rapid response rates. While dasatinib has known gastrointestinal (GI) side effects, colonic polyposis is a rare complication, not well described in the literature.

CASE PRESENTATION: Upon routine colonoscopy, a 66-year-old woman with chronic-phase CML was incidentally discovered to have asymptomatic colonic polyposis after 11 months of dasatinib therapy. Histopathology revealed reactive inflammatory changes without evidence of dysplasia or neoplasia. The polyposis resolved completely after cessation of dasatinib. …

Treating Alzheimer's Disease In A Person Living With Hiv, David B Clifford, Tammie L S Benzinger, Jee-Young Han, Savannah Powles, Madeline Paczynski, Beau M Ances, J William Campbell

2020-Current year OA Pubs

INTRODUCTION: Human immunodeficiency virus (HIV) therapies now support survival into advanced ages by suppressing HIV replication and preserving immune function. Alzheimer's disease (AD), the most common neurologic degenerative condition, may now be treated with anti-amyloid therapies (AAT). HIV was an exclusionary criterion in clinical trials for AAT, leaving the safety and efficacy of these medications unknown in this setting.

METHODS: We report the development of AD supported by careful evaluations and biomarkers over a 10-year period in a person living with well-controlled HIV infection.

RESULTS: AD was diagnosed with consistent clinical and biomarker evidence. AAT was successfully administered without complications. …

The Association Between Major Depressive Disorder, Plasma Biomarkers Of Alzheimer's Disease, And Mild Behavioral Impairment Among Older Adults, Yiqi Zhu, Jean-Francois Trani, Ramkrishna K Singh, Semere Bekena, Jonathan Williams, Eric J Lenze, Ganesh M Babulal

2020-Current year OA Pubs

INTRODUCTION: Plasma biomarkers and mild behavioral impairment (MBI) are associated with dementia risk, but their relationships with major depressive disorder (MDD) are understudied. This study aimed to examine associations between plasma biomarkers of Alzheimer's disease (AD) and MBI among older adults with and without MDD.

METHODS: Older adults aged ≥65 were recruited from longitudinal studies of depression and AD (

RESULTS: Older adults with MDD were more likely to endorse MBI. After adjustment, Aβ42/Aβ40 and p-tau217/np-tau217 positivity were associated with MBI among those with MDD but not among those without.

DISCUSSION: Neuropsychatric symptoms (NPS) and biomarkers are AD risk factors. …