Digital Commons Network^™

Functional Or Structural Impairment Of Flow-Mediated Epicardial Vasodilation May Precede Coronary Microvascular Dysfunction, Ines Valenta, Salwa Mikhail, Ashwin Singh Parihar, Sudhir Jain, Thomas H Schindler

2020-Current year OA Pubs

BACKGROUND: The aim was to investigate whether functional and/or structural impairment of flow-mediated epicardial vasodilation (IEV) may precede coronary microvascular dysfunction (CMD) in a cardiometabolic risk population.

METHODS:

RESULTS: The prevalence of diffuse coronary artery calcification was highest in G1 with 51 %, followed by G3 with 46 % and G2 with 34 %. The extent of CCS was mild-to-moderate and did not differ significantly among groups (p = 0.222). Overall, IEV was present in 60 %, while there was a comparable prevalence of IEV between G2 and G3 (27 % and 33 %, p = 0.27). The hyperemic MBF …

Endogenous And Fluorescent Sterols Reveal The Molecular Basis For Ligand Selectivity Of Human Sterol Transporters, Laura Depta, Hogan P Bryce-Rogers, Nienke J Dekker, Anna Wiehl Bønke, Nicolò Camporese, Mingxing Qian, Yuanjian Xu, Douglas F Covey, Luca Laraia

2020-Current year OA Pubs

Sterol transport proteins (STPs) play a pivotal role in cholesterol homeostasis and therefore are essential for healthy human physiology. Despite recent advances in dissecting functions of STPs in the human cell, there is still a significant knowledge gap regarding their specific biological functions and a lack of suitable selective probes for their study. Here, we profile fluorescent steroid-based probes across ten STPs, uncovering substantial differences in their selectivity, aiding the retrospective and prospective interpretation of biological results generated with those probes. These results guided the establishment of an STP screening panel combining diverse biophysical assays, enabling the evaluation of 42 …

Neuroimaging Findings In Nondemented Frail Individuals: A Systematic Review, Hamid Harandi, Soheil Mohammadi, Ali Jahanshahi, Mahsa Dolatshahi, Sogol Alikarami, Rasa Zafari, Cyrus A Raji

2020-Current year OA Pubs

BACKGROUND: Frailty is a chronic condition characterised by the progressive decline of multiple physiological functions. There is a critical need to investigate neuroimaging findings in nondemented frail individuals to better understand the underlying mechanisms and implications of frailty on brain health. This paper is aimed at reviewing neuroimaging studies assessing brain changes in nondemented frail individuals to understand the neuropsychological basis of frailty.

METHODS: A systematic review was conducted on studies focusing on neuroimaging modalities in frailty, including MRI, fMRI, DTI and PET. The review was based on PRISMA instructions and a two-step screening process. The studies evaluating neuroimaging findings …

Tofersen Treatment Leads To Sustained Stabilization Of Disease In Sod1 Als In A "Real-World" Setting, Sean E Smith, Kelly Mccoy-Gross, Amber Malcolm, Jeri Oranski, Jesse W Markway, Timothy M Miller, Robert C Bucelli

2020-Current year OA Pubs

OBJECTIVE: Patients with amyotrophic lateral sclerosis (ALS) caused by superoxide dismutase 1 (SOD1) gene mutations (SOD1 ALS) treated with tofersen have shown slowing of disease progression, and disease stabilization with recovery of function in some patients. We report our clinical experience with treating patients with SOD1 ALS and the effects of tofersen on outcome measures.

METHODS: This was a single-center observational study of patients with SOD1 ALS receiving treatment with tofersen. The effects of tofersen treatment on neurofilament levels, muscle strength, and clinical outcome measures were assessed. Several patients had outpatient neuromuscular rehabilitation in addition to tofersen treatment and we …

Prospective Observational Study Of Fkrp-Related Limb-Girdle Muscular Dystrophy R9: A Grasp Consortium Study, Lindsay N Alfano, Stephanie Hunn, Conrad C Weihl, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Limb-girdle muscular dystrophy R9 (LGMDR9, formerly known as LGMD2I), caused by variants in the fukutin-related protein (FKRP) gene leads to progressive muscle weakness of the shoulder and pelvic limb-girdles and loss of motor function over time. Clinical management and future trial design are improved by determining which standardized clinical outcome assessments (COA) of function are most appropriate to capture disease presentation and progression, informing endpoint selection and enrollment criteria. The purpose of our study was to evaluate the cross-sectional validity and reliability of clinical outcome assessments in patients with FKRP-related LGMDR9 participating in the Genetic Resolution and Assessments Solving …

Identification And Characterization Of Factor Xi Autoantibodies In 2 Patients With Systemic Lupus Erythematosus: Insights Into Mechanisms Of Acquired Factor Xi Deficiency, Priyanka Srivastava, Amy Zhou, Christine Fuja, Charles S Eby, Gail Baxter, Anton Matafonov, Serena Fedorov, Miriam Brown, Michael Pettit, Benjamin F Tillman, David Gailani, Jeremy W Jacobs

2020-Current year OA Pubs

BACKGROUND: Factor (F)XI is a zymogen that contributes to thrombin generation through activation of FIX. Patients with a complete absence of FXI are prone to developing alloantibody inhibitors after replacement therapy. Acquired FXI autoantibodies are less common, and data regarding their mechanisms of action are lacking.

OBJECTIVES: We describe 2 patients with severe acquired FXI deficiency and identify the FXI domains to which the autoantibodies bind.

METHODS: FXI and prekallikrein (PK) are homologs with similar structures. We prepared recombinant human FXI and PK, as well as chimeric molecules in which individual domains within FXI or PK are replaced with the …

Two Cardinal Features Of Als, Reduced Stmn2 And Pathogenic Tdp-43, Synergize To Accelerate Motor Decline In Mice, Kelsey L Krus, Ana Morales Benitez, Amy Strickland, Jeffrey Milbrandt, A Joseph Bloom, Aaron Diantonio

2020-Current year OA Pubs

Pathological TDP-43 loss from the nucleus and cytoplasmic aggregation occurs in almost all cases of ALS and half of frontotemporal dementia patients. Stathmin2 (Stmn2) is a key target of TDP-43 regulation and aberrantly spliced Stmn2 mRNA is found in patients with ALS, frontotemporal dementia, and Alzheimer's Disease. STMN2 participates in the axon injury response and its depletion in vivo partially replicates ALS-like symptoms including progressive motor deficits and distal NMJ denervation. The interaction between STMN2 loss and TDP-43 dysfunction has not been studied in mice because TDP-43 regulates human but not murine Stmn2 splicing. Therefore, we generated trans-heterozygous mice that …

Virtual Reality Training For Pediatric Sedation Challenges: A Cross-Sectional Study, Nadia Shaikh, Fiona S. Gruzmark, Francesca Rios, Curie Subramanian, Keith Hanson, Teresa Riech

2020-Current year OA Pubs

Background Teaching the management of pediatric sedation-related airway concerns is challenging due to the time-sensitive interventions required and their infrequent occurrence. Recognizing this educational gap in the sedation experience, virtual reality (VR) was utilized to prepare learners and provide an immersive training experience in a controlled environment. Methods We describe simulation-based training using a VR environment, Enduvo Inc., an innovative software for medical trainees. This two-hour course creates a problem-based learning experience, allowing learners to apply their knowledge and develop a framework for managing these stressful and less commonly encountered situations. Results From 2019 to 2022, 35 learners participated in …

Postpolypectomy Syndrome Without The Use Of Hot Snare, Ryan D. Plunkett, Neel Matiwala, Matthew Schroeder, Amna Qureshi, Michael Presti

2020-Current year OA Pubs

The mechanism of postpolypectomy syndrome (PPS) has been largely attributed to transmural injury related to electrocoagulation. This syndrome classically presents with fever, leukocytosis, localized peritoneal inflammation, and abdominal pain following colonoscopy with polypectomy, resolving with conservative management. However, this case describes a patient who presented with these symptoms after undergoing resection of 11 polyps via cold snare and biopsy forceps. Histology did not show deep colonic injury from the polypectomy, and no electrocoagulation was used, making this case inconsistent with the accepted explanation of postpolypectomy syndrome.

The Role Of Desflurane In The Functional Outcomes Among Spinal Cord Injury Patients Undergoing Upper Extremity Nerve Transfer Procedures, Muhammad I Kaleem, Arbi B. Abdallah, Saad Javeed, Sahasraara Hemanth, Daniel M. Hafez, Jacob K. Greenberg, Wilson Z. Ray, Umeshkumar Athiraman

2020-Current year OA Pubs

Background and objective While several experimental studies have demonstrated the neuroprotective role of volatile anesthetics after spinal cord injury (SCI), the impact of volatile anesthetics on improving neurologic outcomes in spinal cord-injured patients is not known. Hence, this study aimed to examine the impact of volatile anesthetics on functional outcomes of chronic cervical SCI patients undergoing peripheral nerve transfer procedures. Methods We conducted a retrospective analysis involving adult patients with cervical SCI and upper extremity paralysis undergoing nerve transfer procedures between September 1, 2015, and January 31, 2019. The principal outcome measured was the motor strength of the reinnervated muscle …

Perinatal Arterial Ischemic Stroke Diagnosed In Infants Receiving Therapeutic Hypothermia For Hypoxic-Ischemic Encephalopathy, Fernando F Gonzalez, Sarah E Monsell, Marie-Coralie Cornet, Hannah Glass, Jessica Wisnowski, Amit Mathur, Robert Mckinstry, Yi Li, Tai-Wei Wu, Dennis E Mayock, Patrick J Heagerty, Sandra E Juul, Yvonne W Wu

2020-Current year OA Pubs

BACKGROUND: Both perinatal arterial ischemic stroke (PAIS) and hypoxic-ischemic encephalopathy (HIE) can present with neonatal encephalopathy. We hypothesized that among infants undergoing therapeutic hypothermia, presence of PAIS is associated with a higher risk of seizures and a lower risk of persistent encephalopathy after rewarming.

METHODS: We studied 473 infants with moderate or severe HIE enrolled in the HEAL Trial who received a brain MRI. We defined PAIS as focal ischemic infarct(s) within an arterial distribution, and HIE pattern of brain injury as central gray, peripheral watershed, or global injury. We compared the risk of seizures (clinically suspected or electrographic), and …

Analysis Of Predefined Safety Events Across Spesolimab Trials In Dermatological And Non-Dermatological Conditions, Kenneth B Gordon, Yayoi Tada, Milan J Anadkat, Siew Eng Choon, Boni Elewski, Jonathan N Barker, Arash Mostaghimi, Kilian Eyerich, Ming Tang, Thomas Haeufel, Christian Thoma, Diamant Thaçi

2020-Current year OA Pubs

INTRODUCTION: Spesolimab, a selective, humanised monoclonal antibody targeting the interleukin-36 receptor, is approved for the treatment of generalised pustular psoriasis (GPP). As a result of the limited patient numbers in GPP trials of spesolimab, analysing safety events across dermatological and non-dermatological diseases helps to further characterise the known safety profile of spesolimab. Here, we analyse predefined safety events from nine randomised, placebo-controlled spesolimab trials across dermatological (including GPP) and gastrointestinal conditions.

METHODS: Predefined safety events were based on the known safety profile of spesolimab across all diseases investigated to date and potential risks of biological therapeutics, and included serious/severe/opportunistic infections, …

Illustrated Capsules From The Advanced Course In Platelet Research, Christian Andrea Di Buduo, Fan He, Stephen Oh, Jorge Di Paola, Et Al.

2020-Current year OA Pubs

This series of illustrated capsules summarizes the presentations made by the speakers at the first International Advanced Course in Platelet Research held in Murcia (Spain) from 27 to 28 September, 2024. This is the first course to receive a Fundamental Research Workshop Grant from the International Society on Thrombosis and Haemostasis (ISTH) and was also supported administratively and scientifically by the Spanish Society of Thrombosis and Haemostasis (SETH). This unique course focused on new methodologies applied in platelet research and how these are increasing our understanding of platelet formation, their multifunctionality in different physiological and pathological contexts, and contributing to …

Cross-Sectional Comparison Of Structural Mri Markers Of Impairment In A Diverse Cohort Of Older Adults, Julie K Wisch, Kalen Petersen, Peter R Millar, Omar Abdelmoity, Ganesh M Babulal, Karin L Meeker, Meredith N Braskie, Kristine Yaffe, Arthur W Toga, Sid O'Bryant, Beau M Ances, Habs‐Hd Study Team

2020-Current year OA Pubs

Neurodegeneration is presumed to be the pathological process measure most proximal to clinical symptom onset in Alzheimer Disease (AD). Structural MRI is routinely collected in research and clinical trial settings. Several quantitative MRI-based measures of atrophy have been proposed, but their low correspondence with each other has been previously documented. The purpose of this study was to identify which commonly used structural MRI measure (hippocampal volume, cortical thickness in AD signature regions, or brain age gap [BAG]) had the best correspondence with the Clinical Dementia Rating (CDR) in an ethno-racially diverse sample. 2870 individuals recruited by the Healthy and Aging …

Tuning A Secondary Dose Verification Software For A Ct-Guided Online Adaptive Delivery System, Xiaodong Zhao, Markus Baur, Phillip D H Wall, Eric Laugeman

2020-Current year OA Pubs

BACKGROUND: Quality assurance (QA) remains unstandardized for CT-guided online adaptive radiotherapy (CTgART) platforms (Ethos, Varian Medical Systems, Inc., Palo Alto, CA), as they become more clinically prevalent. A secondary dose calculation software (Mobius3D, Varian Medical Systems, Inc., Palo Alto, CA) is provided for this closed CTgART system. However, the clinical impact of tuning dosimetric leaf gap (DLG) correction values for specific delivery techniques for CTgART secondary dose calculations remains uninvestigated.

PURPOSE: Tuning the DLG correction value for different delivery techniques of the independent secondary dose verification software for adaptive online QA.

METHODS: A total of 31 volumetric arc therapy (VMAT) …

A Roadmap To Cysteine Specific Labeling Of Membrane Proteins For Single-Molecule Photobleaching Studies, Melanie Ernst, Robyn Mahoney-Kruszka, Nathan B Zelt, Janice L Robertson

2020-Current year OA Pubs

Single-molecule photobleaching analysis is a useful approach for quantifying reactive membrane protein oligomerization in membranes. It provides a binary readout of a fluorophore attached to a protein subunit at dilute conditions. However, quantification of protein stoichiometry from this data requires information about the subunit labeling yields and whether there is non-specific background labeling. Any increases in subunit-specific labeling improves the ability to determine oligomeric states with confidence. A common strategy for site-specific labeling is by conjugation of a fluorophore bearing a thiol-reactive maleimide group to a substituted cysteine. Yet, cysteine reactivity can be difficult to predict as it depends on …

Sex-Specific Divergences In The Types And Timing Of Infiltrating Immune Cells During The Intervertebral Disc Acute Injury Response And Their Associations With Degeneration, Sade W Clayton, Remy E Walk, Laura Mpofu, Garrett W D Easson, Simon Y Tang

2020-Current year OA Pubs

OBJECTIVE: Inadequate repair of the intervertebral disc (IVD) contributes to low back pain. Infiltrating immune cells into damaged tissues are critical mediators of repair, yet little is known about the identities, roles, and temporal regulation following IVD injury. By analyzing transcripts of immune cell markers, histopathologic analysis, immunofluorescence, and flow cytometry, we aimed to define the temporal cascade of infiltrating immune cells and their associations with IVD degeneration.

METHODS: Caudal IVDs from 12-week-old C57BL6/J mice were injured and monitored for 42 days post-injury. Transcriptional markers identifying myeloid, B, and T immune cells, and angiogenic factors were measured from the IVDs …

Cracking The Pericellular Matrix Code: Exploring How Mmp-2, -3, And -7 Influence Matrix Breakdown And Biomechanical Properties, Benjamin Tizian Baumann, Jule Nieuwstraten, Christian Konrads, Farshid Guilak, Marina Danalache

2020-Current year OA Pubs

INTRODUCTION: The intricate process of articular cartilage remodeling, pivotal for both physiological functions and osteoarthritis (OA) progression, is orchestrated through a balance of matrix synthesis and breakdown, which is mediated by matrix metalloproteinase enzymes (MMPs). At the heart of this remodeling lies the pericellular matrix (PCM), a specialized microenvironment encapsulating each chondrocyte and composed mainly of collagen type VI and perlecan. The aim of this study was to assess the impact of MMP-2, -3, and -7 on the structural integrity and biomechanical attributes of the PCM.

METHODS: Human articular cartilage explants (N = 10 patients) were incubated with activated MMP-2, …

Dataset And Analysis Of Automated And Manual Methods To Differentiate Wide Qrs Complex Tachycardias, Sarah Lococo, Anthony H Kashou, Abhishek J Deshmukh, Samuel J Asirvatham, Christopher V Desimone, Krasimira M Mikhova, Sandeep S Sodhi, Phillip S Cuculich, Rugheed Ghadban, Daniel H Cooper, Thomas M Maddox, Peter A Noseworthy, Adam M May

2020-Current year OA Pubs

The differentiation of wide complex tachycardias (WCTs) into ventricular tachycardia (VT) and supraventricular wide tachycardia (SWCT) via 12-lead ECG (electrocardiogram) interpretation is a crucial yet demanding clinical task. Decades of research have been dedicated to simplifying and improving this differentiation via manual algorithms. Despite such research, the effectiveness of such algorithms still remains limited, primarily due to reliance on user expertise. To combat this limitation, automated algorithms have been created that show promise as alternatives to manual ECG interpretation. However, direct comparison of the methods' diagnostic performances has not been undertaken. A recent publication (LoCoco et al., 2024) compared the …

Presentation And Surgical Outcomes Of Primary Hyperparathyroidism After Radioactive Iodine Therapy, Shaleen V Sathe, Blake Sparkman, Evan Bernard, Eileen R Smith, Kevin He, Alexander Chiu, Taylor C Brown

2020-Current year OA Pubs

BACKGROUND: Radioactive iodine (RAI) is a common treatment for various thyroid diseases. Previous studies have suggested susceptibility of parathyroid glands to the mutagenic effect of RAI and the development of primary hyperparathyroidism (PHPT). We tested the possible link between prior RAI treatment, disease presentation, and treatment outcomes.

METHODS: A retrospective analysis of 704 individuals who underwent parathyroidectomy for PHPT at a tertiary care center between the years 2015 and 2023 was performed. Preoperative and postoperative parameters, including demographic characteristics, biochemical markers, imaging data, and surgical and pathology findings were collected and analyzed to compare differences in patients who had previous …

Defining Neonatal Status Epilepticus: A Scoping Review From The Ilae Neonatal Task Force, Magda L Nunes, Elissa G Yozawitz, Courtney J Wusthoff, Renée A Shellhaas, Efraín Olivas-Peña, Jo M Wilmshurst, Ronit M Pressler, Chahnez C Triki, Hans Hartmann, Terrie Inder, Geraldine B Boylan, Kette Valente, Solomon L Moshe, Eli M Mizrahi, Nicholas S Abend

2020-Current year OA Pubs

OBJECTIVE: To review the available literature concerning the definition of neonatal status epilepticus (SE) and/or seizure burden.

METHODS: The International League Against Epilepsy Neonatal Task Force performed a scoping review of the definitions of neonatal SE. Following a systematic literature review, articles were screened and data were abstracted regarding: (1) article characteristics (author identification, publication year, journal name, digital object identifier, title, objective, and study design); (2) cohort characteristics (sample size, gestational age, seizure etiology); (3) definition of SE and/or seizure burden; and (4) the method used to identify and classify SE, including routine EEG (EEG), continuous EEG monitoring (cEEG), …

Occult Ventricular Fibrillation Visualized By Echocardiogram During Cardiac Arrest: A Retrospective Observational Study From The Real-Time Evaluation And Assessment For Sonography-Outcomes Network (Reason), Romolo Gaspari, Srikar Adhikari, Timothy Gleeson, Monica Kapoor, Robert Lindsay, Vicki Noble, Jason T Nomura, Anthony Weekes, Dan Theodoro

2020-Current year OA Pubs

OBJECTIVES: Cardiac arrest patients with a shockable rhythm are more likely to survive an out-of-hospital cardiac arrest (OHCA) compared with a nonshockable rhythm. An electrocardiogram (ECG) is the most common way to identify a shockable rhythm, but it can miss patients with clinically significant ventricular fibrillation (vfib). We sought to determine the percentage of nonshockable OHCA patients that demonstrated vfib on echo.

METHODS: Secondary analysis of echo images recorded from a prior study from our group, Real-Time Evaluation and Assessment for Sonography-Outcomes Network (REASON), a multicenter, observational study of OHCA patients presenting to the emergency department with nonshockable rhythms. Using …

Assessment Of Patient Satisfaction Among Patients Treated With Intravenous Vs Subcutaneous Insulin For Diabetic Ketoacidosis, Richard T Griffey, Ryan M Schneider, Margo Girardi, Gina Larossa, Julianne Yeary, Michael Lehmkuhl, Dan Suarez, Rachel Ancona, Taylor Kaser, Paulina Cruz-Bravo

2020-Current year OA Pubs

OBJECTIVES: We previously implemented the subcutaneous (SQ) insulin in diabetic ketoacidosis (DKA) (SQuID) protocol, demonstrating safe, effective treatment of low to moderate (LTM) severity DKA in a non-intensive care unit setting. SQuID replaces intravenous (IV) insulin with SQ injections and reduces glucose checks from hourly to every 2 hours. We are not aware of any data on patient satisfaction with treatment in DKA. Our objective was to compare satisfaction in patients treated with IV insulin to that in patients treated with the SQ protocol.

METHODS: We conducted a cross-sectional study in an urban academic hospital (March 2023 to March 2024) …

Antiseizure Medication Prescribing In People With Dravet Syndrome: An Analysis Of Real-Time Administrative Data, Kevin Y Xu, Binx Yezhe Lin, M Scott Perry, Fábio A Nascimento

2020-Current year OA Pubs

Since 2018, three new antiseizure medications (ASMs) received FDA approval for Dravet syndrome (DS) in the U.S: cannabidiol, stiripentol, and fenfluramine. Yet, the uptake of these ASMs in routine clinical practice is unknown. We use new ICD-10 codes for DS (implemented in 2020) to estimate ASM receipt in patients with DS. We analyzed the TriNetX Network, a real-time electronic health record-based dataset linked to prescription data encompassing all 50 states of the U.S. After identifying patients with health care encounters for DS in 2021 and 2022 (via ICD-10 codes), we examined ASM prescribing in the year following a DS claim: …

Nuclear Egfr In Breast Cancer Suppresses Nk Cell Recruitment And Cytotoxicity, Angelica Escoto, Ryan Hecksel, Chance Parkinson, Sara Crane, Benjamin Atwell, Shyanne King, Daniela Ortiz Chavez, Alison Jannuzi, Barbara Sands, Benjamin G Bitler, Todd A Fehniger, Andrew L Paek, Megha Padi, Joyce Schroeder

2020-Current year OA Pubs

Natural Killer (NK) cells can target and destroy cancer cells, yet tumor microenvironments typically suppress NK cell recruitment and cytotoxicity. The epidermal growth factor receptor (EGFR) is a potent oncogene that can activate survival, migration, and proliferation pathways, and clinical data suggests it may also play an immunomodulating role in cancers. Recent work has demonstrated a novel role for nuclear EGFR (nEGFR) in regulating transcriptional events unique from the kinase domain. Using a novel peptide therapeutic (cSNX1.3) that inhibits retrograde trafficking of EGFR and an EGFR nuclear localization mutant, we discovered that nEGFR suppresses NK cell recruitment and cytotoxicity. RNA-Seq …

The Effects Of Burst Steroid Therapy On Short-Term Decongestion In Acute Heart Failure Patients With Pro-Inflammatory Activation: A Post Hoc Analysis Of The Cortahf Randomized, Open-Label, Pilot Trial, Jan Biegus, Douglas L Mann, Et Al.

2020-Current year OA Pubs

BACKGROUND: The effect of steroids on congestion in patients with acute heart failure (AHF) is not known.

METHODS AND RESULTS: Patients with AHF, NT-proBNP levels > 1500 pg/mL and high-sensitivity C-reactive protein (hsCRP) levels > 20 mg/L were randomized to once-daily oral 40 mg prednisone for 7 days or usual care. In this post hoc analysis, congestion score was calculated on the basis of orthopnea, edema and rales (0 reflecting lack of congestion, and 9 maximal congestion) at each time point. Among 100 eligible patients randomized, those assigned to prednisone had a greater improvement in congestion score at day 31 (win odds …

Using Integrin Αvβ6-Targeted Positron Emission Tomography Imaging To Longitudinally Monitor Radiation-Induced Pulmonary Fibrosis In Vivo, William C Y Lo, Cristian W Villas Boas, Truc T Huynh, Amanda Klaas, Felicia Grogan, Lori Strong, Pamela Samson, Clifford G Robinson, Buck E Rogers, Carmen Bergom

2020-Current year OA Pubs

PURPOSE: Radiation-induced pulmonary fibrosis (RIPF) is a potentially serious and disabling late complication of radiation therapy. Monitoring RIPF progression is challenging due to the absence of early detection tools and the difficulty in distinguishing RIPF from other lung diseases using standard imaging methods. In the lungs, integrin αvβ6 is crucial in the development of RIPF, acting as a significant activator of transforming growth factor β after radiation injury. This study aimed to investigate integrin α

METHODS AND MATERIALS: We used a focal RIPF model (70 Gy delivered focally to a 3 mm spot in the lung) and a whole lung …

Evaluating The World Health Organization's Hearts Model For Hypertension And Diabetes Management: A Pilot Implementation Study In Guatemala, Irmgardt Alicia Wellmann, Luis Fernando Ayala, Taryn M Valley, Vilma Irazola, Mark D Huffman, Michele Heisler, Peter Rohloff, Rocío Donis, Eduardo Palacios, Manuel Ramírez-Zea, David Flood

2020-Current year OA Pubs

BACKGROUND: The World Health Organization HEARTS Technical Package is a widely implemented global initiative to improve the primary care management of cardiovascular disease risk factors. The study's objective is to report outcomes from a pilot implementation trial of integrated hypertension and diabetes management based on the HEARTS model in Guatemala.

METHODS: We conducted a single-arm pilot implementation trial over six months from October 2023 to May 2024 in 11 Guatemalan Ministry of Health primary care facilities in two districts. The pilot evaluated a package of five HEARTS-aligned implementation strategies to improve the pharmacological treatment of hypertension and diabetes. The primary …

Mechanisms Of Uropathogenic E. Coli Mucosal Association In The Gastrointestinal Tract, Philippe N Azimzadeh, Nathaniel C Gualbuerto, Jerome S Pinkner, Kevin O Tamadonfar, Wandy Beatty, Thomas J Hannan, Karen W Dodson, Enid C Ibarra, Seonyoung Kim, Henry L Schreiber, James W Janetka, Andrew L Kau, Mark J Miller, Scott J Hultgren, Et Al.

2020-Current year OA Pubs

Urinary tract infections (UTIs) are highly recurrent and frequently caused by Uropathogenic

Stroma-Derived Dickkopf-1 Contributes To The Suppression Of Nk Cell Cytotoxicity In Breast Cancer, Seunghyun Lee, Biancamaria Ricci, Jennifer Tran, Emily Eul, Jiayu Ye, Qihao Ren, David Clever, Julia Wang, Pamela Wong, Michael S Haas, Sheila A Stewart, Cynthia X Ma, Todd A Fehniger, Roberta Faccio

2020-Current year OA Pubs

Mechanisms related to tumor evasion from NK cell-mediated immune surveillance remain enigmatic. Dickkopf-1 (DKK1) is a Wnt/β-catenin inhibitor, whose levels correlate with breast cancer progression. We find DKK1 to be expressed by tumor cells and cancer-associated fibroblasts (CAFs) in patient samples and orthotopic breast tumors, and in bone. By using genetic approaches, we find that bone-derived DKK1 contributes to the systemic DKK1 elevation in tumor-bearing female mice, while CAFs contribute to DKK1 at primary tumor site. Systemic and bone-specific DKK1 targeting reduce tumor growth. Intriguingly, deletion of CAF-derived DKK1 also limits breast cancer progression, without affecting its levels in circulation, …