Medicine and Health Sciences Commons^™

Hyperkalemia And Electrocardiogram Manifestations In End-Stage Renal Disease, Zubaid Rafique, Bryan Hoang, Heba Mesbah, Ryan Pappal, Frank W Peacock, Raul Juarez-Vela, Lukasz Szarpak, Dick C Kuo

2020-Current year OA Pubs

Hyperkalemia is one of the more common acute life-threatening metabolic emergencies. The aim of our study is to determine the correlation and accuracy of abnormal ECG parameters as a function of serum potassium concentration in the end-stage renal disease (ESRD) population. We performed a retrospective chart review of emergency department patients presenting with ESRD and receiving emergent hemodialysis treatment. A total of 96 patients, each with five independent ED visits, provided 480 sets of ECGs and electrolytes. Of these, four ECGs were excluded for inability to interpret, leaving a total of 476 patient encounters that met all inclusion criteria. Linear …

Distinct Tumor Necrosis Factor Alpha Receptors Dictate Stem Cell Fitness Versus Lineage Output In Dnmt3a-Mutant Clonal Hematopoiesis, Jennifer M Sanmiguel, Elizabeth Eudy, Matthew A Loberg, Kira A Young, Jayna J Mistry, Kristina D Mujica, Logan S Schwartz, Timothy M Stearns, Grant A Challen, Jennifer J Trowbridge

2020-Current year OA Pubs

UNLABELLED: Clonal hematopoiesis resulting from the enhanced fitness of mutant hematopoietic stem cells (HSC) associates with both favorable and unfavorable health outcomes related to the types of mature mutant blood cells produced, but how this lineage output is regulated is unclear. Using a mouse model of a clonal hematopoiesis-associated mutation, DNMT3AR882/+ (Dnmt3aR878H/+), we found that aging-induced TNFα signaling promoted the selective advantage of mutant HSCs and stimulated the production of mutant B lymphoid cells. The genetic loss of the TNFα receptor TNFR1 ablated the selective advantage of mutant HSCs without altering their lineage output, whereas the loss of TNFR2 resulted …

Identification Of Novel Antifungal Skeleton Of Hydroxyethyl Naphthalimides With Synergistic Potential For Chemical And Dynamic Treatments, Pengli Zhang, Vijai Kumar Reddy Tangadanchu, Chenghe Zhou

2020-Current year OA Pubs

The invasion of pathogenic fungi poses nonnegligible threats to the human health and agricultural industry. This work exploited a family of hydroxyethyl naphthalimides as novel antifungal species with synergistic potential of chemical and dynamic treatment to combat the fungal resistance. These prepared naphthalimides showed better antifungal potency than fluconazole towards some tested fungi including

Equity Implications Of Hospital Penalties During 4 Years Of The Comprehensive Care For Joint Replacement Model, 2016 To 2019, Sukruth A Shashikumar, Andrew M Ryan, Karen E Joynt Maddox

2020-Current year OA Pubs

No abstract provided.

Macrophage Depletion Blocks Congenital Sarm1-Dependent Neuropathy, Caitlin B Dingwall, Amy Strickland, Sabrina W Yum, Aldrin Ky Yim, Jian Zhu, Peter L. Wang, Yurie Yamada, Robert E. Schmidt, Yo Sasaki, A. Joseph Bloom, Aaron Diantonio, Jeffrey Milbrandt

2020-Current year OA Pubs

Axon loss contributes to many common neurodegenerative disorders. In healthy axons, the axon survival factor NMNAT2 inhibits SARM1, the central executioner of programmed axon degeneration. We identified 2 rare NMNAT2 missense variants in 2 brothers afflicted with a progressive neuropathy syndrome. The polymorphisms resulted in amino acid substitutions V98M and R232Q, which reduced NMNAT2 NAD+-synthetase activity. We generated a mouse model to mirror the human syndrome and found that Nmnat2V98M/R232Q compound-heterozygous CRISPR mice survived to adulthood but developed progressive motor dysfunction, peripheral axon loss, and macrophage infiltration. These disease phenotypes were all SARM1-dependent. Remarkably, macrophage depletion therapy blocked and reversed …

Derivation And Validation Of A Clinical Prediction Rule For Upper Limb Functional Outcomes After Traumatic Cervical Spinal Cord Injury, Saad Javeed, Jacob K Greenberg, Justin K Zhang, Christopher F Dibble, Jawad M Khalifeh, Ying Liu, Thomas J Wilson, Lynda J Yang, Yikyung Park, Wilson Z Ray

2020-Current year OA Pubs

IMPORTANCE: Traumatic cervical spinal cord injury (SCI) can result in debilitating paralysis. Following cervical SCI, accurate early prediction of upper limb recovery can serve an important role in guiding the appropriateness and timing of reconstructive therapies.

OBJECTIVE: To develop a clinical prediction rule to prognosticate upper limb functional recovery after cervical SCI.

DESIGN, SETTING, AND PARTICIPANTS: This prognostic study was a retrospective review of a longitudinal cohort study including patients enrolled in the National SCI model systems (SCIMS) database in US. Eligible patients were 15 years or older with tetraplegia (neurological level of injury C1-C8, American Spinal Cord Injury Association …

Changes In Racial Equity Associated With Participation In The Bundled Payments For Care Improvement Advanced Program, Gmerice Hammond, E John Orav, Jie Zheng, Arnold M Epstein, Karen E Joynt Maddox

2020-Current year OA Pubs

IMPORTANCE: The Medicare alternative payment models are designed to incentivize cost reduction and quality improvement, but there are no requirements established for evaluating the outcomes of the Medicare populations.

OBJECTIVE: To examine whether participation in the Medicare Bundled Payments for Care Improvement Advanced (BPCI-A) program was associated with narrowing or widening of Black and White racial inequities in outcomes and access.

DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort alternative payment models on equity and quality for disadvantaged populations were studied between April 6, 2021, and August 28, 2022, in US hospitals. Black and White Medicare beneficiaries admitted for any of the …

Circulating Tumour Dna Characterisation Of Invasive Lobular Carcinoma In Patients With Metastatic Breast Cancer, Andrew A Davis, Katherine Clifton, Whitney L. Hensing, Nusayba A. Bagegni, Foluso O. Ademuyiwa, Ron Bose, Cynthia X. Ma, Et Al.

2020-Current year OA Pubs

BACKGROUND: Limited data exist to characterise molecular differences in circulating tumour DNA (ctDNA) for patients with invasive lobular carcinoma (ILC). We analysed metastatic breast cancer patients with ctDNA testing to assess genomic differences among patients with ILC, invasive ductal carcinoma (IDC), and mixed histology.

METHODS: We retrospectively analysed 980 clinically annotated patients (121 ILC, 792 IDC, and 67 mixed histology) from three academic centers with ctDNA evaluation by Guardant360™. Single nucleotide variations (SNVs), copy number variations (CNVs), and oncogenic pathways were compared across histologies.

FINDINGS: ILC was significantly associated with HR+ HER2 negative and HER2 low. SNVs were higher in …

Infections In The First Year Of Life And Development Of Beta Cell Autoimmunity And Clinical Type 1 Diabetes In High-Risk Individuals: The Trigr Cohort, Olga Kordonouri, David Cuthbertson, Malin Belteky, Bärbel Aschemeier-Fuchs, Neil H White, Elisabeth Cummings, Mikael Knip, Johnny Ludvigsson

2020-Current year OA Pubs

AIMS/HYPOTHESIS: Accumulated data suggest that infections in early life contribute to the development of type 1 diabetes. Using data from the Trial to Reduce IDDM in the Genetically at Risk (TRIGR), we set out to assess whether children who later developed diabetes-related autoantibodies and/or clinical type 1 diabetes had different exposure to infections early in life compared with those who did not.

METHODS: A cohort of 2159 children with an affected first-degree relative and HLA-conferred susceptibility to type 1 diabetes were recruited between 2002 and 2007 and followed until 2017. Infections were registered prospectively. The relationship between infections in the …

Association Of Leukocyte Telomere Length With Perceived Physical Fatigability, Rain Katz, Emma L Gay, Allison L Kuipers, Joseph H Lee, Lawrence S Honig, Kaare Christensen, Mary F Feitosa, Mary K Wojczynski, Nancy W Glynn, Llfs Research Group

2020-Current year OA Pubs

BACKGROUND: Leukocyte telomere length (LTL) is a potential genomic marker of biological aging, but its relation to fatigability, a prognostic indicator of phenotypic aging (e.g., functional decline) is unknown. We hypothesized shorter LTL would predict greater perceived physical fatigability, but that this association would be attenuated by adjusting for chronological age.

METHODS: Two generations of participants (N = 1997; 309 probands, 1688 offspring) were from the Long Life Family Study (age = 73.7 ± 10.4, range 60-108, 54.4 % women), a longitudinal cohort study of aging. LTL was assayed at baseline. Perceived physical fatigability was measured 8.0 ± 1.1 years …

The Multifaceted Mechanisms Of Malignant Glioblastoma Progression And Clinical Implications, Rui Sun, Albert H Kim

2020-Current year OA Pubs

With the application of high throughput sequencing technologies at single-cell resolution, studies of the tumor microenvironment in glioblastoma, one of the most aggressive and invasive of all cancers, have revealed immense cellular and tissue heterogeneity. A unique extracellular scaffold system adapts to and supports progressive infiltration and migration of tumor cells, which is characterized by altered composition, effector delivery, and mechanical properties. The spatiotemporal interactions between malignant and immune cells generate an immunosuppressive microenvironment, contributing to the failure of effective anti-tumor immune attack. Among the heterogeneous tumor cell subpopulations of glioblastoma, glioma stem cells (GSCs), which exhibit tumorigenic properties and …

Nosocomial Outbreak Of Vancomycin-Resistant Enterococcus Faecium (Vre) St796, Switzerland, 2017 To 2020, Vanja Piezzi, Nasstasja Wassilew, Andrew Atkinson, Stéphanie D'Incau, Tanja Kaspar, Helena Mb Seth-Smith, Carlo Casanova, Pascal Bittel, Philipp Jent, Rami Sommerstein, Niccolò Buetti, Jonas Marschall

2020-Current year OA Pubs

A large clonal outbreak caused by vancomycin-resistant

G Protein Gamma Subunit, A Hidden Master Regulator Of Gpcr Signaling, Dinesh Kankanamge, Mithila Tennakoon, Ajith Karunarathne, N Gautam

2020-Current year OA Pubs

Heterotrimeric G proteins (αβγ subunits) that are activated by G protein-coupled receptors (GPCRs) mediate the biological responses of eukaryotic cells to extracellular signals. The α subunits and the tightly bound βγ subunit complex of G proteins have been extensively studied and shown to control the activity of effector molecules. In contrast, the potential roles of the large family of γ subunits have been less studied. In this review, we focus on present knowledge about these proteins. Induced loss of individual γ subunit types in animal and plant models result in strikingly distinct phenotypes indicating that γ subtypes play important and …

Comparing Antigenaemia- And Microfilaraemia As Criteria For Stopping Decisions In Lymphatic Filariasis Elimination Programmes In Africa, Wilma A. Stolk, Luc E. Coffeng, Fatorma K. Bolay, Obiora A. Eneanya, Peter U. Fischer, T. Déirdre Hollingsworth, Benjamin G. Koudou, Aboulaye Méité, Edwin Michael, Joaquin M. Prada, Rocio M. Caja Rivera, Swarnali Sharma, Panayiota Touloupou, Gary J. Weil, Sake J. De Vlas

2020-Current year OA Pubs

BACKGROUND: Mass drug administration (MDA) is the main strategy towards lymphatic filariasis (LF) elimination. Progress is monitored by assessing microfilaraemia (Mf) or circulating filarial antigenaemia (CFA) prevalence, the latter being more practical for field surveys. The current criterion for stopping MDA requires <2% CFA prevalence in 6- to 7-year olds, but this criterion is not evidence-based. We used mathematical modelling to investigate the validity of different thresholds regarding testing method and age group for African MDA programmes using ivermectin plus albendazole.

METHODOLGY/PRINCIPAL FINDINGS: We verified that our model captures observed patterns in Mf and CFA prevalence during annual MDA, assuming that CFA tests are positive if at least one adult worm is present. We then assessed how well elimination can be predicted from CFA prevalence in 6-7-year-old children or from Mf or CFA prevalence in the 5+ or 15+ …

Mouse Tissue Harvest-Induced Hypoxia Rapidly Alters The In Vivo Metabolome, Between-Genotype Metabolite Level Differences, And 13c-Tracing Enrichments, Adam J Rauckhorst, Nicholas Borcherding, Daniel J Pape, Alora S Kraus, Diego A Scerbo, Eric B Taylor

2020-Current year OA Pubs

OBJECTIVE: Metabolomics as an approach to solve biological problems is exponentially increasing in use. Thus, this a pivotal time for the adoption of best practices. It is well known that disrupted tissue oxygen supply rapidly alters cellular energy charge. However, the speed and extent to which delayed mouse tissue freezing after dissection alters the broad metabolome is not well described. Furthermore, how tissue genotype may modulate such metabolomic drift and the degree to which traced

METHODS: By combined liquid chromatography (LC)- and gas chromatography (GC)-mass spectrometry (MS), we measured how levels of 255 mouse liver metabolites changed following 30-second, 1-minute, …

Changes In Practice/Outcomes Of Pediatric/Congenital Catheterization In Response To The First Wave Of Covid, Brian Quinn, Andrew C Glatz, Et Al.

2020-Current year OA Pubs

BACKGROUND: The COVID-19 pandemic has posed tremendous stress on the health care system. Its effects on pediatric/congenital catheterization program practice and performance have not been described.

OBJECTIVES: The purpose of this study was to evaluate how case volumes, risk-profile, and outcomes of pediatric/congenital catheterization procedures changed in response to the first wave of COVID-19 and after that wave.

METHODS: A multicenter retrospective observational study was performed using Congenital Cardiac Catheterization Project on Outcomes Registry (C3PO) data to study changes in volume, case mix, and outcomes (high-severity adverse events [HSAEs]) during the first wave of COVID (March 1, 2020, to May …

Cortical Bone Relationships Are Maintained Regardless Of Sex And Diet In A Large Population Of Lgxsm Advanced Intercross Mice, Nicole Migotsky, Michael D Brodt, James M Cheverud, Matthew J Silva

2020-Current year OA Pubs

INTRODUCTION: Knowledge of bone structure-function relationships in mice has been based on relatively small sample sets that limit generalizability. We sought to investigate structure-function relationships of long bones from a large population of genetically diverse mice. Therefore, we analyzed previously published data from the femur and radius of male and female mice from the F34 generation of the Large-by-Small advanced intercross line (LGXSM AI), which have over a two-fold continuous spread of bone and body sizes (Silva et al. 2019 JBMR).

METHODS: Morphological traits, mechanical properties, and estimated material properties were collected from the femur and radius from 1113 LGXSM …

Leflunomide-Induced And Paraneoplastic Ulcers In A Rheumatoid Arthritis Patient, Michael R Vittori, Jonathan Z Tang, William H Mccoy Iv

2020-Current year OA Pubs

No abstract provided.

Delayed Diagnosis And Recovery Of Fulminant Immune Checkpoint Inhibitor-Associated Myocarditis On Va-Ecmo Support, Tarun Ramayya, Joshua D Mitchell, Justin C Hartupee, Kory Lavine, Clare H Ridley, Kunal D Kotkar, Jesus Jimenez, Chieh-Yu Lin, Jose A Alvarez-Cardona, Ronald K Krone, Courtney M Campbell

2020-Current year OA Pubs

No abstract provided.

Practice Patterns Of Induction Therapy In Severe Anti-Neutrophil Cytoplasmic Autoantibody-Associated Vasculitis, Faten Aqeel, Lillian Xu, Ojaswi Tomar, Jessica Duchen, Tingting Li, Duvuru Geetha

2020-Current year OA Pubs

No abstract provided.

Defining Terms Commonly Used In Sarcopenia Research: A Glossary Proposed By The Global Leadership In Sarcopenia (Glis) Steering Committee, Peggy M Cawthon, Ellen Binder, Et Al.

2020-Current year OA Pubs

METHODS: The aim of this paper is to define terms commonly related to sarcopenia to enable standardization of these terms in research and clinical settings. The Global Leadership Initiative in Sarcopenia (GLIS) aims to bring together leading investigators in sarcopenia research to develop a single definition that can be utilized worldwide; work on a global definition of sarcopenia is ongoing. The first step of GLIS is to develop the common terminology, or a glossary, that will facilitate agreement on a global definition of sarcopenia as well as interpretation of clinical and research findings.

RESULTS: Several terms that are commonly used …

Outcomes In Participants With Failure Of Initial Antibacterial Therapy For Hospital-Acquired/Ventilator-Associated Bacterial Pneumonia Prior To Enrollment In The Randomized, Controlled Phase 3 Aspect-Np Trial Of Ceftolozane/Tazobactam Versus Meropenem, Marin H Kollef, Jean-François Timsit, Ignacio Martin-Loeches, Richard G Wunderink, Jennifer A Huntington, Erin H Jensen, Brian Yu, Christopher J Bruno

2020-Current year OA Pubs

BACKGROUND: Ceftolozane/tazobactam, a combination antibacterial agent comprising an anti-pseudomonal cephalosporin and β-lactamase inhibitor, is approved for the treatment of hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP) in adults. Participants in the ASPECT-NP trial received ceftolozane/tazobactam (3 g [2 g ceftolozane/1 g tazobactam] every 8 h) or meropenem (1 g every 8 h). Participants failing prior antibacterial therapy for the current HABP/VABP episode at study entry had lower 28-day all-cause mortality (ACM) rates with ceftolozane/tazobactam versus meropenem treatment. Here, we report a post hoc analysis examining this result.

METHODS: The phase 3, randomized, controlled, double-blind, multicenter, noninferiority trial compared ceftolozane/tazobactam versus meropenem for treatment …

Basal Bodies Bend In Response To Ciliary Forces, Anthony D Junker, Louis G Woodhams, Adam W J Soh, Eileen T O'Toole, Philip V Bayly, Chad G Pearson

2020-Current year OA Pubs

Motile cilia beat with an asymmetric waveform consisting of a power stroke that generates a propulsive force and a recovery stroke that returns the cilium back to the start. Cilia are anchored to the cell cortex by basal bodies (BBs) that are directly coupled to the ciliary doublet microtubules (MTs). We find that, consistent with ciliary forces imposing on BBs, bending patterns in BB triplet MTs are responsive to ciliary beating. BB bending varies as environmental conditions change the ciliary waveform. Bending occurs where striated fibers (SFs) attach to BBs and mutants with short SFs that fail to connect to …

Public Interest In Hyaluronic Acid Injections For Knee Osteoarthritis In The United States And Europe: An International Google Trends Analysis, Samuel A Cohen, Robert H Brophy, Antonia F Chen, Karl C Roberts, Robert H Quinn, Kevin G Shea

2020-Current year OA Pubs

BACKGROUND: Hyaluronic acid injections remain a common nonsurgical alternative for the treatment of knee osteoarthritis despite limited clinical evidence and varying global recommendations regarding its use. We used the Google Trends tool to provide a quantitative analysis of public interest in hyaluronic acid injections for knee osteoarthritis in the United States and Europe.

METHODS: We customized Google Trends parameters to obtain search data from January 2009 to December 2019 in both the United States and Europe. Combinations of "arthritis", "osteoarthritis", "hyaluronic acid", "knee arthritis", "knee osteoarthritis", and "knee injection" were entered into the Google Trends tool, and trend analyses were …

The Genetic Risk Factor Cel-Hyb1 Causes Proteotoxicity And Chronic Pancreatitis In Mice, Karianne Fjeld, Steven J Wilhelm, Jianguo Lin, Xunjun Xiao, Mark E Lowe, Et Al.

2020-Current year OA Pubs

BACKGROUND & AIMS: The CEL gene encodes the digestive enzyme carboxyl ester lipase. CEL-HYB1, a hybrid allele of CEL and its adjacent pseudogene CELP, is a genetic variant suggested to increase the risk of chronic pancreatitis (CP). Our aim was to develop a mouse model for CEL-HYB1 that enables studies of pancreatic disease mechanisms.

METHODS: We established a knock-in mouse strain where the variable number of tandem repeat (VNTR) region of the endogenous mouse Cel gene was substituted with the mutated VNTR of the human CEL-HYB1 allele. Heterozygous and homozygous Cel-HYB1 mice and littermate wildtype controls were characterized with respect …

X-Linked Hypophosphatemia Caused By The Prevailing North American Phex Variant C.*231a>G; Exon 13–15 Duplication Is Often Misdiagnosed As Ankylosing Spondylitis And Manifests In Both Men And Women, Kathryn Mccrystal Dahir, Margo Black, Gary S Gottesman, Erik A Imel, Steven Mumm, Cindy M Nichols, Michael P Whyte

2020-Current year OA Pubs

Inactivating mutations of the gene coding for phosphate-regulating endopeptidase homolog X-linked (PHEX) cause X-linked hypophosphatemia (XLH). A novel

The Clinical Spectrum Of Sma-Pme And In Vitro Normalization Of Its Cellular Ceramide Profile, Michelle M Lee, Toni S Pearson, Et Al.

2020-Current year OA Pubs

OBJECTIVE: The objectives of this study were to define the clinical and biochemical spectrum of spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) and to determine if aberrant cellular ceramide accumulation could be normalized by enzyme replacement.

METHODS: Clinical features of 6 patients with SMA-PME were assessed by retrospective chart review, and a literature review of 24 previously published cases was performed. Leukocyte enzyme activity of acid ceramidase was assessed with a fluorescence-based assay. Skin fibroblast ceramide content and was assessed by high performance liquid chromatography, electrospray ionization tandem mass spectroscopy. Enzyme replacement was assessed using recombinant human acid ceramidase …

Vascular Endothelial-Cadherin As A Marker Of Endothelial Injury In Preclinical Alzheimer Disease, Rawan Tarawneh, Rachel S Kasper, Jessie Sanford, Chia-Ling Phuah, Jason Hassenstab, Carlos Cruchaga

2020-Current year OA Pubs

OBJECTIVE: Endothelial dysfunction is an early and prevalent pathology in Alzheimer disease (AD). We here investigate the value of vascular endothelial-cadherin (VEC) as a cerebrospinal fluid (CSF) marker of endothelial injury in preclinical AD.

METHODS: Cognitively normal participants (Clinical Dementia Rating [CDR] 0) from the Knight Washington University-ADRC were included in this study (n = 700). Preclinical Alzheimer's Cognitive Composite (PACC) scores, CSF VEC, tau, p-tau181, Aβ42/Aβ40, neurofilament light-chain (NFL) levels, and magnetic resonance imaging (MRI) assessments of white matter injury (WMI) were obtained from all participants. A subset of participants underwent brain amyloid imaging using positron emission tomography (amyloid-PET) …

Diptoindonesin G Is A Middle Domain Hsp90 Modulator For Cancer Treatment, Kristine Donahue, Haibo Xie, Miyang Li, Ang Gao, Min Ma, Yidan Wang, Rose Tipton, Nicole Semanik, Tina Primeau, Shunqiang Li, Lingjun Li, Weiping Tang, Wei Xu

2020-Current year OA Pubs

HSP90 inhibitors can target many oncoproteins simultaneously, but none have made it through clinical trials due to dose-limiting toxicity and induction of heat shock response, leading to clinical resistance. We identified diptoindonesin G (dip G) as an HSP90 modulator that can promote degradation of HSP90 clients by binding to the middle domain of HSP90 (K

A Novel, Likely Pathogenic Variant In Ubtf-Related Neurodegeneration With Brain Atrophy Is Associated With A Severe Divergent Neurodevelopmental Phenotype, Rory J Tinker, Tiffany Guess, David C Rinker, Jonathan H Sheehan, Daniel Lubarsky, Binu Porath, Mackenzie Mosera, Ping Mayo, Emily Solem, Laura A Lee, Asha Sharam, Jennifer Brault

2020-Current year OA Pubs

BACKGROUND: A de novo, pathogenic, missense variant in UBTF, c.628G>A p.Glu210Lys, has been described as the cause of an emerging neurodegenerative disorder, Childhood-Onset Neurodegeneration with Brain Atrophy (CONDBA). The p.Glu210Lys alteration yields a positively charged stretch of three lysine residues. Functional studies confirmed this change results in a stronger interaction with negatively charged DNA and gain-of-function activity when compared to the wild-type sequence. The CONDBA phenotype reported in association with p.Glu210Lys consists of normal early-neurodevelopment followed by progressive motor, cognitive, and behavioral regression in early-to-middle childhood.

METHODS AND RESULTS: The current proband presented at 9 months of age with …