Digital Commons Network^™

Integrating Nonindividual Patient Features In Machine Learning Models Of Hospital-Onset Bacteremia, M Cristina Vazquez-Guillamet, Jingwen Zhang, Alice Bewley, Andrew Atkinson, Heidi Holtz, Ziqian Wang, Nicole Brougham, Chenyang Lu, Marin H Kollef, Philip Payne, David Warren, Victoria J Fraser

2020-Current year OA Pubs

IMPORTANCE: Hospital-onset bacteremia and fungemia (HOB) are common and potentially preventable complications of hospital care.

OBJECTIVE: To assess whether nonindividual patient features, which summarize interactions with other patients and health care workers (HCWs), can contribute to predictive and causal machine learning models for HOB.

DESIGN, SETTING, AND PARTICIPANTS: This prognostic study included adult patients admitted to Barnes-Jewish Hospital, an academic hospital in St Louis, Missouri, in 2021. Analyses were developed between October 2023 and August 2024 and in April 2025.

EXPOSURE: Individual patient features were extracted from electronic health records and used to engineer nonpatient features, including interactions with HCWs …

Soft Tissue Stabilization Of Midcarpal Instability In Ehlers-Danlos Patients Using A Cadaveric Tendon Graft, Mohammed Muneer, Fadi Bouri, Kjell Van Royen, Saif Badran, Jorge I. Quintero, Tuna Ozyurekoglu

2020-Current year OA Pubs

Ehlers-Danlos syndrome (EDS) is a group of hereditary disorders that affects collagen synthesis. In the wrist, pain and midcarpal laxity may affect up to 70% of EDS patients. The mainstay treatment of midcarpal instability in patients with ligamentous injury but not EDS includes orthotics, physiotherapy, and activity modification. These methods of conservative treatment may be unsuccessful in controlling instability in the longer term. Using autologous tendon for reconstructing midcarpal instability in patients with EDS carries the risk of loosening over time due to intrinsic abnormalities in collagen metabolism. In this article, we present a novel surgical technique using a cadaveric …

The Loss Of Opa1 Accelerates Intervertebral Disc Degeneration And Osteoarthritis In Aged Mice, Vedavathi Madhu, Miriam Hernandaz-Meadows, Ashley Coleman, Kimheak Sao, Kameron Inguito, Owen Haslam, Paige K Boneski, Hiromi Sesaki, Ruteja A Barve, John A Collins, Makarand V Risbud

2020-Current year OA Pubs

Recent studies have highlighted the importance of mitochondria in NP cells and articular chondrocyte health. Since the understanding of mechanisms governing mitochondrial dynamics in these tissues is lacking, we investigated the role of OPA1, a mitochondrial fusion protein, in their homeostasis. OPA1 knockdown in NP cells altered mitochondrial size and cristae shape and increased the oxygen consumption rate. OPA1 governed the morphology of multiple organelles, including peroxisomes, early endosomes and cis-Golgi and loss resulted in the dysregulation of autophagy. Metabolic profiling and

Participation In Activities Among People With Long-Term Spinal Cord Injury In Sweden And The Usa - An Explorative Study Using Secondary Data Analysis, Jessica L Dashner, Ulrica Antepohl

2020-Current year OA Pubs

STUDY DESIGN: Secondary data analysis.

OBJECTIVE: To explore differences in participation, secondary health complications, and the use of assistive devices and personal assistance among people with long-term SCI in Sweden and the USA.

SETTING: Community dwelling individuals with SCI in Sweden and USA.

METHODS: Secondary analysis of data collected via PARTS-Mv3 among individuals living with SCI in Sweden (n = 73) and in the USA (n = 45). Descriptive analyses provided information regarding the participants, their participation in activities, and secondary health complications, together with the use of assistive devices and personal assistance.

RESULTS: Both samples included more males than …

Robust Photogrammetric Scalp Morphology Estimation For Functional Optical Neuroimaging, Abigail L Magee, Calamity Svoboda, Tessa G George, Alvin A Agato, Edward J Richter, Joseph P Culver, Adam T Eggebrecht

2020-Current year OA Pubs

SIGNIFICANCE: Optical functional neuroimaging relies upon accurate anatomical models to provide optimal data registration and image reconstruction.

AIM: We establish and validate a robust photogrammetric algorithm for scalp morphology that utilizes 3-dimensional (3D) imaging with a photogrammetric cap to provide individualized scalp morphology estimation through hair in the absence of magnetic resonance imaging (MRI).

APPROACH: The scalp morphology estimation uses a flexible, neoprene cap and 3D-printed photogrammetric modules with fiducials. We create a sparse scalp sampling and align the MNI152 atlas to generate the scalp morphology estimation. We used the international 10 to 20 electroencephalogram positions for alignment and calculated …

Reference Range Determination For The Sflt-1/Plgf Ratio In A Diverse Cohort Of Pregnant Women In The United States, Antonio F Saad, David M Haas, Eugene Chang, Scott A Shainker, Miriah Denbo, Michelle Silasi, George Saade, Sarosh Rana, Tetsuya Kawakita, Luis D Pacheco, Jennifer Powers Carson, Angela Dietl, Deirdre Allegranza, Ge Guo, David Stamilio

2020-Current year OA Pubs

BACKGROUND: The serum soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) ratio is an established tool for predicting preeclampsia in many countries but is not widely adopted in the United States. This study aimed to determine reference ranges for the Elecsys® sFlt-1/PlGF ratio and the sFlt-1 and PlGF immunoassays (Roche Diagnostics International Ltd) in a diverse US population of healthy pregnant women.

METHODS: This was a prospective, noninterventional sample and data collection study performed between November 2022 and November 2023 at 9 collection sites and one measurement site in the United States. Evaluable women were ≥18 years old, …

Increasing Birth-Dose Hepatitis B Vaccination In Nigeria: Qualitative Analysis Of Data From A Crowdsourcing Open Call, Sonam J Shah, Maria Afadapa, Nkiruka Obodoechina, Olufunto A Olusanya, Temitope Ojo, Dawit Alemu, Juliet Iwelunmor, Et Al.

2020-Current year OA Pubs

BACKGROUND: Despite World Health Organization and Nigerian recommendations for hepatitis B birth-dose (HepB-BD) vaccination, only one-third of Nigerian newborns receive timely HepB-BD vaccination, This study identified facilitators to increasing HepB-BD vaccination based on data from a crowdsourcing open call in Nigeria.

METHODS: Our team conducted an open call across Nigeria for teams to submit ideas on how to increase HepB-BD vaccination. Independent judges evaluated the submissions based on predefined criteria. We analyzed textual data from the top 29 entries using iterative coding and thematic analysis within a socioecological model to identify priority facilitators.

RESULTS: The open call received 362 total …

Optimized Legionella Expression Strain For Affinity Purification Of His-Tagged Membrane Proteins Eliminates Major Multimeric Contaminant, Sukhithasri Vijayrajratnam, Jonasz B Patkowski, Joshua Khorsandi, Wandy L Beatty, Shanmugapriya Kannaiah, Ahmet Hasanovic, Tamara J O'Connor, Tiago R D Costa, Joseph P Vogel

2020-Current year OA Pubs

Polyhistidine tags are frequently used for isolating proteins through

Kpna2 Promotes Osteosarcoma Progression By Regulating The Alternative Splicing Of Ddx3x Mediated By Ybx1, Li Cao, Ke Jia, B A Van Tine, Yihan Yu, Yizhong Peng, Xuanzuo Chen, Qing Pan, Wenbo Yang, Zhicai Zhang, Zengwu Shao, Wei Wu

2020-Current year OA Pubs

Osteosarcoma (OS) is a rapidly progressive primary malignant bone tumor that occurs in children and adolescents aged between 15 and 19 years and adults aged over 60 years. As alternative splicing (AS) changes caused by abnormal splicing factors contribute to tumor progression, gene expression and AS analyses were performed on 44 osteosarcoma patients to create a genome-wide co-expression network of RNA-binding proteins (RBPs), AS events, and AS genes. A gain- or loss-of-function osteosarcoma cell model was established, and an interactive network analysis and enrichment analysis were performed. Karyopherin Subunit Alpha 2 (KPNA2) negatively correlated with patient survival. KPNA2 transports splicing …

Incident Depression After Breast Cancer Among Older Asian, Native Hawaiian, And Pacific Islander Women, Alzina Koric, Chun-Pin Esther Chang, Yuan-Chin Amy Lee, Mei Wei, Catherine Lee, Jing Wang, Mia Hashibe

2020-Current year OA Pubs

BACKGROUND: Longitudinal studies examining mental health outcomes among older (≥66 years) Asian, Native Hawaiian, and Pacific Islander (ANHPI) women diagnosed with breast cancer are limited. We evaluated incident depression after breast cancer among specific groups of older ANHPI compared with older non-Hispanic White (NHW) women. Predictors of depression and the risk of death following early onset of depression after breast cancer were also evaluated.

METHODS: A cohort of 26 776 older ANHPI women in the United States diagnosed with breast cancer between 2000 and 2017 was identified from the SEER-Medicare linked claims. There were 6694 older ANHPI and 20 082 …

Landscape Of Cancer Associated Epcam Mutations: Molecular Modeling, Predictive Insights And Impact On Patient Survival, Priyanka S Dhotare, Audrey C Bochi-Layec, Timothy P Fleming, William E Gillanders, Ross M Bremner, Kailas D Sonawane, Narendra V Sankpal

2020-Current year OA Pubs

BACKGROUND: EpCAM (epithelial cell adhesion molecule) is a key regulator of epithelial cell-cell adhesion, signal transduction, tissue regeneration, and serves as a stem cell marker. It is frequently overexpressed in epithelial cancers and is linked to tumor progression, survival, and metastasis. However, the functional impact of EpCAM mutations in cancer remains poorly understood.

METHODS: To investigate the role of EpCAM mutations, we performed a comprehensive analysis of cancer cohorts from multiple genomic datasets, identifying novel somatic EpCAM mutations across diverse epithelial cancers. Using bioinformatics tools (SIFT, PolyPhen-2, Mutation Assessor) and molecular modeling, we assessed the potential impact of these mutations. …

Factors Associated With Self-Report Symptom Screening Adherence In Pediatric Cancer Patients, L Lee Dupuis, Allison A King, Lisa M Klesges, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Objective was to describe the association between baseline characteristics and the number of Symptom Screening in Pediatrics Tool (SSPedi) assessments completed over an 8-week period.

METHODS: This was a sub-analysis of a cluster randomized controlled trial among 10 sites that were randomized to the intervention group. Participants were English- or Spanish-speaking pediatric patients 8-18 years of age newly diagnosed with cancer. Participants were prompted to complete SSPedi three times weekly for 8 weeks. The outcome was the number of SSPedi assessments completed during the 8-week period. Factors associated with the number of assessments were determined using mixed effects Poisson …

Mayo Normative Studies: Regression-Based Normative Data For Remote Self-Administration Of The Stricker Learning Span, Symbols Test, And Mayo Test Drive Screening Battery Composite And Validation In Individuals With Mild Cognitive Impairment And Dementia, Nikki H Stricker, Jason Hassenstab, Et Al.

2020-Current year OA Pubs

No abstract provided.

Projection-Tags Enable Multiplex Projection Tracing And Multi-Modal Profiling Of Projection Neurons, Lite Yang, Fang Liu, Hannah Hahm, Takao Okuda, Xiaoyue Li, Yufen Zhang, Vani Kalyanaraman, Monique R Heitmeier, Vijay K Samineni

2020-Current year OA Pubs

Single-cell multiomic techniques have sparked immense interest in developing a comprehensive multi-modal map of diverse neuronal cell types and their brain-wide projections. However, investigating the complex wiring diagram, spatial organization, transcriptional, and epigenetic landscapes of brain-wide projection neurons is hampered by the lack of efficient and easily adoptable tools. Here we introduce Projection-TAGs, a retrograde AAV platform that allows multiplex tagging of projection neurons using RNA barcodes. By using Projection-TAGs, we performed multiplex projection tracing of the cortex and high-throughput single-cell profiling of the transcriptional and epigenetic landscapes of the cortical projection neurons in female mice. Projection-TAGs can be leveraged …

Medications To Reduce Breast Cancer Risk: A Network Meta-Analysis Of Randomized Controlled Trials, Ghazaleh Pourali, Minglu Liu, Supriya S Sherpa, Angela Hardi, Chongliang Luo, Adetunji T Toriola

2020-Current year OA Pubs

BACKGROUND: Given the rising incidence of breast cancer, especially in premenopausal women, there is an urgent need to identify additional risk-reducing medications to accelerate prevention, as only a few are currently approved. We, therefore, performed network meta-analysis (NMA) to identify and compare the efficacy of medications for primary breast cancer prevention.

METHODS: We performed a literature search completed on November 16, 2023, in Embase, Ovid-Medline, Scopus, and Cochrane Library for randomized controlled trials (RCTs) evaluating risk-reducing medications in women without a history of invasive breast cancer. Two reviewers independently screened and extracted data based on predefined criteria, following the Preferred …

High-Frequency, At-Home Monitoring Of Drug Safety And Tolerability In Clinical Trials: Results From Studies Of Fluvoxamine For Covid-19 Treatment, Eric J Lenze, Madeline Nykamp, J Philip Miller, Angela Stevens, Julia Schweiger, Torie Gettinger, Michael Yingling, Yi Zhang, Ginger E Nicol, Charles F Zorumski, Angela M Reiersen

2020-Current year OA Pubs

Clinical trials are increasingly using remote monitoring techniques at the patient's home. We conducted a secondary analysis of remote safety and tolerability monitoring from two fully-remote clinical trials that tested fluvoxamine for the acute treatment of COVID-19. Both trials assessed pulse and blood pressure daily, and one study assessed symptoms daily via Ecological Momentary Assessment. On average, patients provided data on vital signs on 93% of the study days and provided data on side effects on 81% of the study days. With respect to safety, patients taking fluvoxamine had reduced pulse rate compared to placebo, with the greatest difference-5 points-at …

Cardiac Transplantation Does Not Improve Exercise Tolerance, Muscle Mass, Or Substrate Metabolism In Barth Syndrome, W Todd Cade, Kathryn L Bohnert, Linda R Peterson, Lisa De Las Fuentes, Emily Poehlein, Cynthia L Green, Christina A Pacak, Barry J Byrne, Dominic N Reeds, Adil Bashir, Brian Feingold, Carolyn Taylor

2020-Current year OA Pubs

Barth syndrome (BTHS) is a rare X-linked recessive disorder characterized by mutations in the TAFAZZIN gene, leading to mitochondrial dysfunction, cardioskeletal myopathy, neutropenia, exercise intolerance, and growth delay. While cardiac transplantation can improve heart function in BTHS patients, the metabolic effects of this procedure remain poorly understood. This study aimed to compare skeletal muscle morphology, substrate metabolism, energetics, and exercise tolerance in individuals with BTHS who had undergone cardiac transplantation (BTHS-T) versus BTHS patients without transplantation (BTHS-noT) and healthy controls. Six (

Clinical Evaluation Of The Healgen Rapid Covid-19 Antigen Test As A Point-Of-Care Diagnostic Tool, Stephen A Young, Hua Zhang, Jose Rodriguez, David Mishkin, Ward Paine, Li Seyfried, Latisha Hargrove, Dennis L Broyles, Chermaen Lindberg, Anurag Purushothaman, Stacey House

2020-Current year OA Pubs

BACKGROUND: Development of readily available Rapid COVID-19 Antigen tests essential for promptly identifying SARS-CoV2 infection and preventing its spread.

METHODS: This study evaluated the clinical performance of the Healgen Rapid COVID-19 antigen test as a point-of-care diagnostic tool with 806 evaluable subjects who were within 6 days post-symptom onset. The results from the Healgen test were compared to the results from Emergency Use Authorization (EUA) approved SARS-CoV-2 RT-PCR tests.

RESULTS: Out of the 806 evaluable subjects, 140 tested positive and 640 tested negative for SARS-CoV-2 with the Healgen COVID-19 test, showing good agreement with the EUA RT-PCR results. There were …

The Impact Of Diabetes And Metabolic Syndrome Burden On Pain, Neuropathy Severity And Fiber Type, Long Davalos, Brian C Callaghan, Lavanya Muthukumar, Simone Thomas, Evan L Reynolds, A Gordon Smith, J Robinson Singleton, Ahmet Höke, Senda Ajroud-Driss, Mazen M Dimachkie, Stefanie Geisler, David M Simpson, Pnrr Study Group, Amro M Stino

2020-Current year OA Pubs

OBJECTIVE: Determine the association between diabetes and metabolic syndrome (MetS) burden (number of MetS criteria fulfilled) and pain, neuropathy severity, and fiber type involvement in individuals with established polyneuropathy.

METHODS: The Peripheral Neuropathy Research Registry was queried for individuals with type 1 and type 2 diabetes (DPN) and non-diabetic peripheral neuropathy (cryptogenic sensory polyneuropathy and prediabetes) using cross-sectional observational data. Associations between diabetes or MetS burden and pain presence (yes/no), neuropathy severity (Total Neuropathy Score reduced), and fiber type involvement (pinprick, vibration, and proprioception examination-small, large, mixed) using logistic, linear, and multinomial regression models were determined.

RESULTS: A total of …

Reduced Risk Of Cesarean Delivery With Oxytocin Discontinuation In Active Labor: A Systematic Review And Meta-Analysis, Julia Whitley, Julia Burd, Michelle Doering, Jeannie Kelly, Antonina Frolova, Nandini Raghuraman

2020-Current year OA Pubs

OBJECTIVE: Our objective was to determine if oxytocin discontinuation in the active phase of labor impacts the rate of cesarean delivery compared to continuation of oxytocin.

DATA SOURCES: This study was a systematic review and meta-analysis of randomized controlled trials. A research librarian performed a database search using a combination of standardized terms and keywords related to oxytocin discontinuation and stages of labor from database inception until February 2024. This protocol was registered in The International Prospective Register of Systematic Reviews (PROSPERO).

STUDY ELIGIBILITY CRITERIA: Randomized controlled trials of pregnant patients who received oxytocin for induction or augmentation of labor, …

Polygenic Prediction Of Body Mass Index And Obesity Through The Life Course And Across Ancestries, Roelof A J Smit, Lihua Wang, Mary F. Feitosa, Michael A. Province, Dabeeru C. Rao, Adam E. Locke, Et Al.

2020-Current year OA Pubs

No abstract provided.

Molecular Mechanisms Of Inverse Agonism Via Κ-Opioid Receptor-G Protein Complexes, Aaliyah S Tyson, Saif Khan, Zenia Motiwala, Gye Won Han, Zixin Zhang, Mohsen Ranjbar, Daniel Styrpejko, Nokomis Ramos-Gonzalez, Stone Woo, Kelly Villers, Delainey Landaker, Terry Kenakin, Ryan Shenvi, Susruta Majumdar, Cornelius Gati

2020-Current year OA Pubs

Opioid receptors, a subfamily of G protein-coupled receptors (GPCRs), are key therapeutic targets. In the canonical GPCR activation model, agonist binding is required for receptor-G protein complex formation, while antagonists prevent G protein coupling. However, many GPCRs exhibit basal activity, allowing G protein association without an agonist. The pharmacological impact of agonist-free receptor-G protein complexes is poorly understood. Here we present biochemical evidence that certain κ-opioid receptor (KOR) inverse agonists can act via KOR-G

Comparison Of Clinical Features And Outcomes Of Chinese Patients With Takotsubo Syndrome And Acute Myocardial Infarction- Results From The First Chinese Takotsubo Syndrome Registry, Yuxi Huang, Kan Liu, Et Al.

2020-Current year OA Pubs

BACKGROUND: Takotsubo syndrome (TTS) differs significantly from acute myocardial infarction (AMI) in clinical features and pathological mechanisms, but evidence in Asian populations remains limited. The aim of this study is to compare clinical features and outcomes between patients with TTS and AMI in the first Chinese registry of TTS (ChiTTS Registry, ChiCTR1900026725).

METHODS: In this multicenter 6-year retrospective cohort study (February 2016-June 2022), a total of 116 consecutive TTS patients diagnosed according to the international Takotsubo diagnostic criteria and 232 age- and sex-matched AMI patients (1:2 ratio) meeting the 2023 European Society of Cardiology guidelines criteria were enrolled from 10 …

Determining Falls Risk In People With Parkinson's Disease Using Wearable Sensors: A Systematic Review, Maeve Bradley, Sarah O'Loughlin, Eoghan Donlon, Amy Gallagher, Clodagh O'Keeffe, John Inocentes, Federica Ruggieri, Richard B Reilly, Richard Walsh, Tim Lynch, Daniel G Di Luca, Conor Fearon

2020-Current year OA Pubs

A prior history of falls remains the strongest predictor of future falls in individuals with Parkinson's disease (PD). There are limited biomarkers available to identify falls risk before falls begin to occur. The aim of this review is to investigate if features associated with falls risk may be detected by wearable sensors in patients with PD. A systematic search of the MEDLINE, EMBASE, Cochrane, and Cinahl databases was performed. Key quality criteria include sample size adequacy, data collection procedures, and the clarity of statistical analyses. The data from each included study were extracted into defined data extraction spreadsheets. Results were …

Evolution And Predictors Of Right Ventricular Failure In Fontan Patients: A Case-Control Study, Hannah S Kim, Ginnie Abarbanell, Kathleen Simpson, Aaron M Abarbanell, Pirooz Eghtesady, Philip T Levy, Gautam K Singh

2020-Current year OA Pubs

No abstract provided.

Low Frequency, High Complexity: Assessing Skill Decay In Transesophageal Echocardiography Post-Simulation Training, Enyo Ablordeppey, Emily Terian, Collyn T Murray, Laura Wallace, Wendy Huang, Erica Blustein, Alexander Croft, Ernesto Romo, Mansi Agarwal, Daniel Theodoro

2020-Current year OA Pubs

INTRODUCTION: Resuscitative transesophageal echo (rTEE) is a promising adjunct to cardiac arrest resuscitation. However, it is a high-acuity diagnostic tool that is rarely used in this setting and its safety establishment is limited because of low occurrence. High-acuity, low occurrence skills such as rTEE during cardiac arrest inevitably decay. In this study we examined the content and percentage of rTEE skill decay following simulation-based education (SBE).

METHODS: Resuscitative TEE-naïve emergency physicians (EP) were trained using a combination of clinical exposure, web-based didactics, and monthly hands-on sessions with a high-fidelity rTEE simulator for four months. The COVID-19 pandemic created a natural …

Cannabis Use In Women And Sexual Dysfunction, Becky K. Lynn, Julia D. López, Morgan E. Link, E C. Campian

2020-Current year OA Pubs

No abstract provided.

What Drives Clinic Follow-Up After Traumatic Spinal Injury? An Observational Cohort Study From Tanzania, Chibuikem A Ikwuegbuenyi, Julie Woodfield, Romani Roman Sabas, Sean Inzerillo, Noah Willett, Magalie Cadieux, Scott L Zuckerman, Francois Waterkeyn, Halinder S Mangat, Hamisi K Shabani, Roger Härtl

2020-Current year OA Pubs

OBJECTIVES: To evaluate factors associated with clinic follow-up after traumatic spinal injury (TSI) in Tanzania, focusing on demographic, injury-related and hospital variables. We hypothesised that socioeconomic and injury-specific factors would predict follow-up adherence.

DESIGN: Retrospective observational cohort study.

SETTING: Tertiary government referral centre for neurosurgery and orthopaedics in Dar es Salaam, Tanzania.

PARTICIPANTS: 443 adults with TSI admitted between September 2016 and October 2021. Inclusion criteria included survival to discharge and availability of the discharge date. Patients with missing data were excluded.

PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes were any clinic follow-up and 1-year follow-up post-discharge. Secondary outcome was …

Metabolic Control Of Glycosylation Forms For Establishing Glycan-Dependent Protein Interaction Networks, Xingyu Liu, Li Yi, Zongtao Lin, Siyu Chen, Shunyang Wang, Ying Sheng, Carlito B Lebrilla, Benjamin A Garcia, Yixuan Xie

2020-Current year OA Pubs

Protein-protein interactions (PPIs) are crucial for comprehending the molecular mechanisms and signaling pathways underlying diverse biological processes and disease progression. However, investigating PPIs involving membrane proteins is challenging due to the complexity and heterogeneity of glycosylation. To tackle this challenge, we developed an approach termed glycan-dependent affinity purification coupled with mass spectrometry (GAP-MS), specifically designed to characterize changes in glycoprotein PPIs under varying glycosylation conditions. GAP-MS integrates metabolic control of glycan profiles in cultured cells using small molecules referred to as glycan modifiers with affinity purification followed by mass spectrometry analysis (AP-MS). Here, GAP-MS was applied to characterize and compare …

Apolipoprotein M Attenuates Age-Related Macular Degeneration Phenotypes Via Sphingosine-1-Phosphate Signaling And Lysosomal Lipid Catabolism, Tae Jun Lee, Andrea Santeford, Kristen M Pitts, Carla Valenzuela Ripoll, Ryo Terao, Zhen Guo, Mualla Ozcan, Dagmar Kratky, Christina Christoffersen, Ali Javaheri, Rajendra S Apte

2020-Current year OA Pubs

Age-related macular degeneration (AMD) is a leading cause of blindness in people over 50. AMD and cardiovascular disease share risk factors including age, impaired lipid metabolism, and extracellular lipid deposition. Because of its importance in age-related diseases, we hypothesize that apolipoprotein M (ApoM), a lipocalin that binds sphingosine-1-phosphate (S1P), might restore lipid homeostasis and retinal function in AMD. In support, we find that human patients with AMD demonstrate significantly reduced ApoM compared to controls. In mice with impaired retinal cholesterol efflux, ApoM improves retinal pigment epithelium (RPE) function and lipotoxicity in an S1P- and S1P receptor 3-dependent manner. Ultrastructural evidence …