Digital Commons Network^™

Cochlear Mechanics Are Preserved After Inner Ear Delivery Of Gold Nanoparticles, Dorothy W Pan, Jinkyung Kim, Patricia M Quiñones, Anthony J Ricci, Brian E Applegate, John S Oghalai

2020-Current year OA Pubs

Novel therapeutic delivery systems and delivery methods to the inner ear are necessary to treat hearing loss and inner ear disorders. However, numerous barriers exist to therapeutic delivery into the bone-encased and immune-privileged environment of the inner ear and cochlea, which makes treating inner ear disorders challenging. Nanoparticles (NPs) are a type of therapeutic delivery system that can be engineered for multiple purposes, and posterior semicircular canal (PSCC) infusion is a method to directly deposit them into the cochlea. We sought to assess PSCC infusion of gold NPs into the cochlea, including the NPs' distribution and effect on cochlear mechanics. …

Stereotactic Cardiac Radiotherapy For Refractory Ventricular Tachycardia In Structural Heart Disease Patients: A Systematic Review, Amulya Gupta, Zeeshan Sattar, Nourhan Chaaban, Sagar Ranka, Cameron Carlson, Farhad Sami, Clifford G Robinson, Phillip S Cuculich, Seth H Sheldon, Madhu Reddy, David Akhavan, Amit Noheria

2020-Current year OA Pubs

AIMS: Among patients with structural heart disease with ventricular tachycardia (VT) refractory to medical therapy and catheter ablation, cardiac stereotactic body radiotherapy (SBRT) is a paradigm-changing treatment option. This study aims to assess the efficacy of cardiac SBRT in refractory VT by comparing the rates of VT episodes, anti-tachycardia pacing (ATP) therapies, and implantable cardioverter-defibrillator (ICD) shocks post-SBRT with pre-SBRT.

METHODS AND RESULTS: We performed a comprehensive literature search and included all clinical studies reporting outcomes on cardiac SBRT for VT. Treatment efficacy was evaluated as random-effects pooled rate-ratios of VT episodes, ATP therapies and ICD shocks post-SBRT (after 6-week …

Loss Of Chop Prevents Joint Degeneration And Pain In A Mouse Model Of Pseudoachondroplasia, Jacqueline T Hecht, Alka C Veerisetty, Mohammad G Hossain, Debabrata Patra, Michele Carrer, Frankie Chiu, Dorde Relic, Paymaan Jafar-Nejad, Karen L Posey

2020-Current year OA Pubs

Pseudoachondroplasia (PSACH), a severe dwarfing condition characterized by impaired skeletal growth and early joint degeneration, results from mutations in cartilage oligomeric matrix protein (COMP). These mutations disrupt normal protein folding, leading to the accumulation of misfolded COMP in chondrocytes. The MT-COMP mouse is a murine model of PSACH that expresses D469del human COMP in response to doxycycline and replicates the PSACH chondrocyte and clinical pathology. The basis for the mutant-COMP pathology involves endoplasmic reticulum (ER) stress signaling through the PERK/eIF2α/CHOP pathway. C/EBP homologous protein (CHOP), in conjunction with a TNFα inflammatory process, upregulates mTORC1, hindering autophagy clearance of mutant COMP …

Bile Acids In Inflammatory Bowel Disease: From Pathophysiology To Treatment, Samantha H Bai, Arun Chandnani, Siyan Cao

2020-Current year OA Pubs

Inflammatory bowel disease (IBD) is a chronic condition that affects about 7 million people worldwide, and new therapies are needed. Understanding the complex roles that bile acids (BAs) play in IBD may lead to the development of novel IBD treatments independent of direct immunosuppression. This review discusses the latest discoveries in the roles BAs play in IBD pathogenesis and explores how these discoveries offer promising new therapeutic targets to treat IBD and improve patient outcomes. Several therapies discussed include specific BA receptor (BAR) agonists, dietary therapies, supplements, probiotics, and mesenchymal stem cell therapies that have all been shown to decrease …

Retrospective Derivation Of A Causal Pathway For Diabetic Ketoacidosis In Adult Patients With Type 2 Diabetes Mellitus, Jeffrey A Kline, Nicholas A Wesner, Amina T Sharif, Richard T Griffey, Phillip D Levy, Robert D Welch, George Grunberger

2020-Current year OA Pubs

BACKGROUND: Type 2 ketone-prone diabetes mellitus (T2KPDM) is thought to occur in men of African descent, with obesity who experienced prolonged hyperglycemia; the role of medication non-adherence as a contributing cause remains unstudied.

RESEARCH DESIGN AND METHODS: This was a retrospective study of unique adults (>18 years) who sought emergency care one of four hospitals in the greater Detroit area. Patients were identified on the basis of a laboratory order for a ß-hydroxybutyrate concentration. Two research coordinators abstracted 119 data fields. Patients were divided into four phenotypes: (1) no prior DM, (2) type 2 DM without prior ketosis, (3) …

Brain Volumes, Cognitive, And Adaptive Skills In School-Age Children With Down Syndrome, Rebecca Grzadzinski, Kelly Botteron, Natasha Marrus, Robert Mckinstry, Et Al.

2020-Current year OA Pubs

BACKGROUND: Down syndrome (DS) is the most common congenital neurodevelopmental disorder, present in about 1 in every 700 live births. Despite its prevalence, literature exploring the neurobiology underlying DS and how this neurobiology is related to behavior is limited. This study fills this gap by examining cortical volumes and behavioral correlates in school-age children with DS.

METHODS: School-age children (mean = 9.7 years ± 1.1) underwent comprehensive assessments, including cognitive and adaptive assessments, as well as an MRI scan without the use of sedation. Children with DS (n = 35) were compared to available samples of typically developing (TD; n …

Number Of Prescription Medications And Overall Survival In Metastatic Castrate-Resistant Prostate Cancer, Carley R Pickett, Daniel B Eaton, Krishny Karunanandaa, Emily Cybulla, Brendan T Heiden, Su-Hsin Chang, Yan Yan, Melanie P Subramanian, Varun Puri, Martin W Schoen

2020-Current year OA Pubs

No abstract provided.

Comparative Analysis Of Outcomes In Adult Spinal Deformity Patients With Proximal Junctional Kyphosis Or Failure Initially Fused To Upper Versus Lower Thoracic Spine, Oluwatobi O Onafowokan, Munish Chandra Gupta, Et Al.

2020-Current year OA Pubs

No abstract provided.

The Biomechanics Of Fibrillin Microfibrils: Lessons From The Ciliary Zonule, Pooja Rathaur, Juan Rodriguez, John Kuchtey, Samuel Insignares, Wendell B Jones, Rachel W Kuchtey, Steven Bassnett

2020-Current year OA Pubs

Marfan syndrome is an inherited connective tissue disorder that affects the cardiovascular, musculoskeletal, and ocular systems. It is caused by pathogenic variants in the fibrillin-1 gene (

The Pace Of Biological Aging Partially Explains The Relationship Between Socioeconomic Status And Chronic Low Back Pain Outcomes, Edwin N Aroke, Jai Ganesh Nagidi, Vinodh Srinivasasainagendra, Tammie L Quinn, Fiona B A T Agbor, Kiari R Kinnie, Hemant K Tiwari, Burel R Goodin

2020-Current year OA Pubs

INTRODUCTION: Having a lower socioeconomic status (SES) is a predictor of age-related chronic conditions, including chronic low back pain (cLBP). We aimed to examine whether the pace of biological aging mediates the relationship between SES and cLBP outcomes - pain intensity, pain interference, and physical performance.

METHODS: We used the Dunedin Pace of Aging Calculated from the Epigenome (DunedinPACE) software to determine the pace of biological aging in adults ages 18 to 85 years with no cLBP (n = 74), low-impact pain (n = 56), and high-impact pain (n = 77).

RESULTS: The mean chronological age of the participants was …

Conventional Cytogenetic Analysis Of Solid Tumor Abnormalities: A 25-Year Review Of Proficiency Test Results From The College Of American Pathologists/American College Of Medical Genetics And Genomics Cytogenetics Committee, Rachel K Vanderscheldon, Yang Cao, Et Al.

2020-Current year OA Pubs

No abstract provided.

Experimental Pain Sensitivity And Parental Pain Catastrophizing, Gourav Banerjee, Joel Brown, Alana Mcmichael, Arbi Ben Abdallah, Sarah Buday, Deanna M Barch, Thomas Baranski, Simon Haroutounian, Jacob Aubuchon, Hadas Nahman-Averbuch

2020-Current year OA Pubs

BACKGROUND/OBJECTIVES: Variability in biopsychosocial factors can explain the interindividual variability in pain. One factor that can impact pain is the pain catastrophizing level. Interestingly, parental pain catastrophizing is related to the severity of the clinical pain of their children. This study explored whether parental pain catastrophizing is also associated with their children's experimental pain sensitivity.

METHODS: Forty-five healthy girls (mean age 12.07 ± 1.47 years) and one of their parents participated in this study. Parents completed the Pain Catastrophizing Scale (PCS) about their child's pain (PCS-Parent

RESULTS: No significant relationships were found between the experimental pain sensitivity measures and either …

Changes In Reproductive Health Information-Seeking Behaviors After The Dobbs Decision: Systematic Search Of The Wikimedia Database, Mackenzie Lemieux, Cyrus Zhou, Caroline Cary, Jeannie Kelly

2020-Current year OA Pubs

BACKGROUND: After the US Supreme Court overturned Roe v. Wade, confusion followed regarding the legality of abortion in different states across the country. Recent studies found increased Google searches for abortion-related terms in restricted states after the Dobbsv. Jackson Women's Health Organization decision was leaked. As patients and providers use Wikipedia (Wikimedia Foundation) as a predominant medical information source, we hypothesized that changes in reproductive health information-seeking behavior could be better understood by examining Wikipedia article traffic.

OBJECTIVE: This study aimed to examine trends in Wikipedia usage for abortion and contraception information before and after the Dobbs decision.

METHODS: Page …

Conceptualization, Measurement, And Contributors To Participation Among People Living With Parkinson’S Disease, Moon Young Kim

WUSM Theses and Dissertations – All Programs

Participation is a key outcome of rehabilitation and key to successful aging. Individuals with Parkinson’s disease (PD) often experience significant challenges in maintaining participation in meaningful activities and roles. This dissertation examines the influence of living with PD on participation by integrating findings from three studies: a systematic review, a cross-sectional study, and a longitudinal study.

The systematic review synthesized the existing quantitative research on participation in people with PD, revealing inconsistencies in the conceptualization of participation. While the evaluation tools aimed at assessing participation in PD showed acceptable coverage of domains of participation, the assessment of the aspects of …

Impact Of Site-Specific Conjugation Strategies On The Pharmacokinetics Of Antibody Conjugated Radiotherapeutics, Ábel Nagy, David Ulmert, Wahed Zedan, Claire M Storey, Julie Park, Susanne Geres, Katharina Lückerath, Kjell Sjöström, Hadis Westin, Norbert Peekhaus, Daniel Lj Thorek, Amelie Eriksson Karlström, Mohamed Altai

2020-Current year OA Pubs

Antibody radionuclide conjugates are an emerging modality for targeted imaging and potent therapy of disseminated disease. Coupling of radionuclides to monoclonal antibodies (mAbs) is typically achieved by applying non-site-specific labelling techniques. With the ambition of reducing variability, increasing labelling efficacy and stability, several site-specific conjugation strategies have been developed in recent years for toxin- and fluorophore-mAb conjugates. In this study, we studied two site-specific labelling strategies for the conjugation of the macrocyclic chelating agent, DOTA, to the anti-Leucine Rich Repeat Containing 15 (LRRC15) mAb DUNP19. Specifically, one approach utilized a DOTA-bearing peptide (FcIII) with a strong affinity for the fragment …

A Practical Clinical Approach To Navigate Pulmonary Embolism Management: A Primer And Narrative Review Of The Evolving Landscape, Kevin Benavente, Bradley Fujiuchi, Hafeez Ul Hassan Virk, Pavan K Kavali, Walter Ageno, Geoffrey D Barnes, Marc Righini, Mahboob Alam, Rachel P Rosovsky, Chayakrit Krittanawong

2020-Current year OA Pubs

Advances in imaging, pharmacological, and procedural technologies have rapidly expanded the care of pulmonary embolism. Earlier, more accurate identification and quantification has enhanced risk stratification across the spectrum of the disease process, with a number of clinical tools available to prognosticate outcomes and guide treatment. Direct oral anticoagulants have enabled a consistent and more convenient long-term therapeutic option, with a greater shift toward outpatient treatment for a select group of low-risk patients. The array of catheter-directed therapies now available has contributed to a more versatile and nuanced armamentarium of treatment options, including ultrasound-facilitated thrombolysis and mechanical thrombectomy. Research into supportive …

Estimation Of Prevalence Of Autoimmune Diseases In The United States Using Electronic Health Record Data, Aaron H. Abend, Albert M. Lai, Et Al.

2020-Current year OA Pubs

BACKGROUNDPrevious epidemiologic studies of autoimmune diseases in the US have included a limited number of diseases or used metaanalyses that rely on different data collection methods and analyses for each disease.METHODSTo estimate the prevalence of autoimmune diseases in the US, we used electronic health record data from 6 large medical systems in the US. We developed a software program using common methodology to compute the estimated prevalence of autoimmune diseases alone and in aggregate that can be readily used by other investigators to replicate or modify the analysis over time.RESULTSOur findings indicate that over 15 million people, or 4.6% of …

Out-Of-Focus Signal Rejection For In Vivo Po2 Measurements Using Two-Photon Phosphorescence Lifetime Microscopy, Qi Pian, Baoqiang Li, Ikbal Şencan-Eğilmez, Xiaojun Cheng, Jay Dubb, Xinyue Huang, Buyin Fu, Srinivasa Rao Allu, Mohammad Abbas Yaseen, Anna Devor, Sergei A Vinogradov, Sava Sakadžić

2020-Current year OA Pubs

Two-photon phosphorescence lifetime microscopy has been a key tool for studying cerebral oxygenation in mice. However, the accuracy of the partial pressure of oxygen (pO

Effects Of Dietary Medium-Chain Triglyceride Supplementation On The Serum Metabolome Of Young Adult And Senior Canines, Yuanlong Pan, Miriam Sindelar, Ethan Stancliffe, Leah P Shriver, Rondo P Middleton, Gary J Patti

2020-Current year OA Pubs

In dogs, brain aging may lead to cognitive decline and cognitive dysfunction syndrome (CDS) [...].

Imlunestrant, An Oral Selective Estrogen Receptor Degrader, As Monotherapy And In Combination With Targeted Therapy In Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Phase Ia/Ib Ember Study, Komal L Jhaveri, Cynthia X Ma, Et Al.

2020-Current year OA Pubs

PURPOSE: Imlunestrant is a next-generation oral selective estrogen receptor (ER) degrader designed to deliver continuous ER target inhibition, including in

METHODS: An i3+3 dose-escalation design was used, followed by dose expansions of imlunestrant as monotherapy or in combination with abemaciclib with or without aromatase inhibitor (AI), everolimus, or alpelisib. Imlunestrant was administered orally once daily and with the combination partner per label.

RESULTS: Overall, 262 patients with ER+/HER2- ABC were treated (phase Ia, n = 74; phase Ib, n = 188). Among patients who received imlunestrant monotherapy (n = 114), no dose-limiting toxicities or discontinuations occurred. At the RP2D (400 …

Sirtuins As Key Regulators In Pancreatic Cancer: Insights Into Signaling Mechanisms And Therapeutic Implications, Surbhi Chouhan, Anil Kumar, Naoshad Muhammad, Darksha Usmani, Tabish H Khan

2020-Current year OA Pubs

Pancreatic ductal adenocarcinoma (PDAC) stands as one of the most lethal cancers, marked by rapid progression, pronounced chemoresistance, and a complex network of genetic and epigenetic dysregulation. Within this challenging context, sirtuins, NAD

Phosphorylation Of Disordered Proteins Tunes Local And Global Intramolecular Interactions, Emery T Usher, Martin J Fossat, Alex S Holehouse

2020-Current year OA Pubs

Protein post-translational modifications, such as phosphorylation, are important regulatory signals for diverse cellular functions. In particular, intrinsically disordered protein regions (IDRs) are subject to phosphorylation as a means to modulate their interactions and functions. Toward understanding the relationship between phosphorylation in IDRs and specific functional outcomes, we must consider how phosphorylation affects the IDR conformational ensemble. Various experimental techniques are suited to interrogate the features of IDR ensembles; molecular simulations can provide complementary insights and even illuminate ensemble features that may be experimentally inaccessible. Therefore, we sought to expand the tools available to study phosphorylated IDRs by all-atom Monte Carlo …

Vps13b Is Localized At The Interface Between Golgi Cisternae And Is A Functional Partner Of Fam177a1, Berrak Ugur, Florian Schueder, Jimann Shin, Michael G Hanna, Yumei Wu, Marianna Leonzino, Maohan Su, Anthony R Mcadow, Catherine Wilson, John Postlethwait, Lilianna Solnica-Krezel, Joerg Bewersdorf, Pietro De Camilli

2020-Current year OA Pubs

Mutations in VPS13B, a member of a protein family implicated in bulk lipid transport between adjacent membranes, cause Cohen syndrome. VPS13B is known to be concentrated in the Golgi complex, but its precise location within this organelle and thus the site(s) where it achieves lipid transport remains unclear. Here, we show that VPS13B is localized at the interface between proximal and distal Golgi subcompartments and that Golgi complex reformation after Brefeldin A (BFA)-induced disruption is delayed in VPS13B KO cells. This delay is phenocopied by the loss of FAM177A1, a Golgi complex protein of unknown function reported to be a …

Heterozygous Btnl8 Variants In Individuals With Multisystem Inflammatory Syndrome In Children (Mis-C), Evangelos Bellos, Erica G Schmitt, Et Al.

2020-Current year OA Pubs

Multisystem inflammatory syndrome in children (MIS-C) is a rare condition following SARS-CoV-2 infection associated with intestinal manifestations. Genetic predisposition, including inborn errors of the OAS-RNAseL pathway, has been reported. We sequenced 154 MIS-C patients and utilized a novel statistical framework of gene burden analysis, "burdenMC," which identified an enrichment for rare predicted-deleterious variants in BTNL8 (OR = 4.2, 95% CI: 3.5-5.3, P < 10-6). BTNL8 encodes an intestinal epithelial regulator of Vγ4+γδ T cells implicated in regulating gut homeostasis. Enrichment was exclusive to MIS-C, being absent in patients with COVID-19 or bacterial disease. Using an available functional test for BTNL8, rare variants from a larger cohort of MIS-C patients (n = 835) were tested which identified eight variants in 18 patients (2.2%) with impaired engagement of Vγ4+γδ T cells. Most of these variants were in the B30.2 domain of BTNL8 implicated in sensing epithelial cell status. These findings were associated with altered intestinal permeability, suggesting a possible link between disrupted gut homeostasis and MIS-C-associated enteropathy triggered by SARS-CoV-2.

Functional Role Of Myosin-Binding Protein H In Thick Filaments Of Developing Vertebrate Fast-Twitch Skeletal Muscle, Andrew F Mead, Marilyn J Cipolla, Aaron N Johnson, Christina A Gurnett, Et Al.

2020-Current year OA Pubs

Myosin-binding protein H (MyBP-H) is a component of the vertebrate skeletal muscle sarcomere with sequence and domain homology to myosin-binding protein C (MyBP-C). Whereas skeletal muscle isoforms of MyBP-C (fMyBP-C, sMyBP-C) modulate muscle contractility via interactions with actin thin filaments and myosin motors within the muscle sarcomere "C-zone," MyBP-H has no known function. This is in part due to MyBP-H having limited expression in adult fast-twitch muscle and no known involvement in muscle disease. Quantitative proteomics reported here reveal that MyBP-H is highly expressed in prenatal rat fast-twitch muscles and larval zebrafish, suggesting a conserved role in muscle development and …

Medical And Surgical Episodes Among Hospital Participants In The Bundled Payments For Care Improvement-Advanced Program, Keenan J Robbins, Jie Zheng, R J Waken, E John Orav, Arnold M Epstein, Karen E Joynt Maddox

2020-Current year OA Pubs

IMPORTANCE: Hospital participation in the Bundled Payments for Care Improvement-Advanced (BPCI-A) initiative has been associated with modest savings and stable clinical outcomes overall, but it is unknown whether the program performs differently for medical and surgical or procedural (henceforth, surgical) episodes.

OBJECTIVE: To assess the association of BPCI-A participation with Medicare spending and clinical outcomes for medical and surgical episodes.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective difference-in-differences cohort study utilized 100% Medicare fee-for-service inpatient claims for episodes initiated between January 1, 2017, and September 30, 2019, and included 90 days of follow-up. The setting was hospitals participating in BPCI-A and …

2024 European Heart Rhythm Association/Heart Rhythm Society/Asia Pacific Heart Rhythm Society/Latin American Heart Rhythm Society Expert Consensus Statement On Catheter And Surgical Ablation Of Atrial Fibrillation, Stylianos Tzeis, Ralph J Damiano, Et Al.

2020-Current year OA Pubs

In the last three decades, ablation of atrial fibrillation (AF) has become an evidence-based safe and efficacious treatment for managing the most common cardiac arrhythmia. In 2007, the first joint expert consensus document was issued, guiding healthcare professionals involved in catheter or surgical AF ablation. Mounting research evidence and technological advances have resulted in a rapidly changing landscape in the field of catheter and surgical AF ablation, thus stressing the need for regularly updated versions of this partnership which were issued in 2012 and 2017. Seven years after the last consensus, an updated document was considered necessary to define a …

Delivery Of Hand Care To Patients With High Anxiety Burden, Caellagh D Catley, Sarah C Romans, Abby L Cheng, Ryan P Calfee

2020-Current year OA Pubs

PURPOSE: To determine whether patients presenting with Patient-Reported Outcome Measurement Information System (PROMIS) anxiety scores at >95th percentile of the US population undergo elective hand surgery at rates different from patients with less anxiety. Secondarily, we aimed to assess surgeon notation of these patients' emotional states and incidences of postoperative complications.

METHODS: This single-center retrospective cohort study analyzed data from new adult patients presenting for hand care between January 2019 and December 2020. Patients with initial PROMIS anxiety scores ≥70 were identified as the high anxiety burden (HAB) group. For each patient with HAB presenting with carpal tunnel syndrome, trigger …

Pain Interference Prior To And 1 Year After Surgery For Adult Traumatic Brachial Plexus Injury, Christopher J Dy, David M Brogan, Bryan J Loeffler, Steve K Lee, Harvey Chim, Mihir J Desai, Sami H Tuffaha, Yusha Liu, Planet Study Group

2020-Current year OA Pubs

PURPOSE: Pain after brachial plexus injury (BPI) can be severely debilitating and is poorly understood. We hypothesized that pain interference (PI) ("the extent to which pain hinders engagement in life") would be predicted by depression, anxiety, severity of pain symptoms, and poorer preoperative muscle function.

METHODS: Among patients in a prospective multicenter BPI cohort study, 37 completed Patient-Reported Outcomes Measurement Information System (PROMIS) PI questionnaires before and 1 year after surgery. At both times, participants completed anxiety and depression questionnaires and BPI-specific measures of pain symptoms, physical limitations, and emotional recovery. Surgeon-graded muscle testing, injury severity, age at the time …

Effect Of Screw Length In Volar Plating For Intra-Articular Distal Radius Fractures: A Biomechanical Study, Thomas S Hong, Daniel J Lee, Babak Jahani, Kaitlyn S Broz, Donald A Aboytes, Simon Tang, Stephen Demartini, David M Brogan

2020-Current year OA Pubs

PURPOSE: The purpose of this study was to compare the effect of varying screw lengths on load to failure and retention of the dorsal ulnar corner fragment after fixation of comminuted intra-articular distal radius fractures in a cadaveric model.

METHODS: Twenty-four fresh frozen cadaveric forearms were subjected to a standardized distal radius osteotomy to mimic an intra-articular fracture pattern. Dual X-ray absorptiometry scans were performed to ensure minimal variability in bone density. All fractures were fixed with a volar locking plate and distal locking screws. Three different lengths of distal locking screws were used in each group of eight specimens …