Digital Commons Network^™

Assessing Potentiation Of The (Α4)3(Β2)2 Nicotinic Acetylcholine Receptor By The Allosteric Agonist Cmpi, Farah Deba, Kemburli Munoz, Eloisa Peredia, Gustav Akk, Ayman K Hamouda

Open Access Publications

The extracellular domain of the nicotinic acetylcholine receptor isoforms formed by three α4 and two β2 subunits ((α4)3(β2)2 nAChR) harbors two high-affinity "canonical" acetylcholine (ACh)-binding sites located in the two α4:β2 intersubunit interfaces and a low-affinity "noncanonical" ACh-binding site located in the α4:α4 intersubunit interface. In this study, we used ACh, cytisine, and nicotine (which bind at both the α4:α4 and α4:β2 interfaces), TC-2559 (which binds at the α4:β2 but not at the α4:α4 interface), and 3-(2-chlorophenyl)-5-(5-methyl-1-(piperidin-4-yl)-1H-pyrrazol-4-yl)isoxazole (CMPI, which binds at the α4:α4 but not at the α4:β2 interface), to investigate the binding and gating properties of CMPI at the …

Low Knowledge Of Hiv Prep Within A Midwestern Us Cohort Of Persons Who Inject Drugs, Sena Sayood, Laura R. Marks, Rupa Patel, Nathanial S. Nolan, Stephen Y. Liang, Michael J. Durkin

Open Access Publications

We interviewed persons who inject drugs (PWID) to understand perceptions of pre-exposure prophylaxis (PrEP) to prevent HIV infection. Knowledge of PrEP was poor. Patients felt that PrEP was for sexual intercourse rather than injection drug use, and PWID managed on medications for opioid use disorder felt that they had no need for PrEP.

Prospective Nasal Screening For Methicillin-Resistant Staphylococcus Aureus In Critically Ill Patients With Suspected Pneumonia, Nicholas Raush, Kevin D. Betthauser, Karen Shen, Tamara Krekel, Marin H. Kollef

Open Access Publications

We carried out a prospective de-escalation study based on methicillin-resistant

Understanding And Application Of Daptomycin-Susceptible Dose-Dependent Category For Enterococcus: A Mixed-Methods Study, Jennifer L. Adema, Laurel N. Lake, Ryan W. Stevens, Breann M. Hogan, Audrey N. Schuetz, Aaron J. Tande, Kristin C. Mara, Allison R. Eberly, Christina G. Rivera

Open Access Publications

Background: In 2018, the Clinical Microbiology Laboratory at our institution adopted updated daptomycin

Methods: This mixed-methods study combined a clinician survey with a retrospective pre-post prescribing analysis. An 8-question survey was distributed to infectious diseases (ID) and internal medicine (IM) clinicians. A retrospective chart review of hospitalized adults with infections due to

Results: Survey response rates were 40 of 98 (41%) for IM and 22 of 34 (65%) for ID clinicians. ID clinicians scored significantly higher than IM clinicians in knowledge of SDD. Chart review of 474 patients (225 pre- vs 249 post-SDD) showed that daptomycin dosage following susceptibility testing …

Outcomes Of Sars-Cov-2-Positive Youths Tested In Emergency Departments: The Global Pern-Covid-19 Study, Anna L. Funk, Fahd A. Ahmad, Et Al

Open Access Publications

Importance: Severe outcomes among youths with SARS-CoV-2 infections are poorly characterized.

Objective: To estimate the proportion of children with severe outcomes within 14 days of testing positive for SARS-CoV-2 in an emergency department (ED).

Design, Setting, and Participants: This prospective cohort study with 14-day follow-up enrolled participants between March 2020 and June 2021. Participants were youths aged younger than 18 years who were tested for SARS-CoV-2 infection at one of 41 EDs across 10 countries including Argentina, Australia, Canada, Costa Rica, Italy, New Zealand, Paraguay, Singapore, Spain, and the United States. Statistical analysis was performed from September to October 2021. …

Cost-Effectiveness Of Total Neoadjuvant Therapy With Short-Course Radiotherapy For Resectable Locally Advanced Rectal Cancer, Re-I Chin, Ebunoluwa E. Otegbeye, Kylie H. Kang, Su-Hsin Chang, Scott Mchenry, Amit Roy, William C. Chapman, Lauren E. Henke, Shahed N. Badiyan, Katrina Pedersen, Benjamin R. Tan, Sean C. Glasgow, Matthew G. Mutch, Pamela P. Samson, Hyun Kim

Open Access Publications

Importance: Short-course radiotherapy and total neoadjuvant therapy (SCRT-TNT) followed by total mesorectal excision (TME) has emerged as a new treatment paradigm for patients with locally advanced rectal adenocarcinoma. However, the economic implication of this treatment strategy has not been compared with that of conventional long-course chemoradiotherapy (LCCRT) followed by TME with adjuvant chemotherapy.

Objective: To perform a cost-effectiveness analysis of SCRT-TNT vs LCCRT in conjunction with TME for patients with locally advanced rectal cancer.

Design, Setting, and Participants: A decision analytical model with a 5-year time horizon was constructed for patients with biopsy-proven, newly diagnosed, primary locally advanced rectal adenocarcinoma …

Multi-Omics Investigation Of Clostridioides Difficile-Colonized Patients Reveals Pathogen And Commensal Correlates Of C. Difficile Pathogenesis, Skye R.S. Fishbein, John I. Robinson, Tiffany Hink, Kimberly A. Reske, Erin P. Newcomer, Carey-Ann D. Burnham, Jeffrey P. Henderson, Erik R. Dubberke, Gautam Dantas

Open Access Publications

No abstract provided.

An Evidence-Based Definition Of Anemia For Singleton, Uncomplicated Pregnancies, Amanda C. Zofkie, W. Holt Garner, Rachel C. Schell, Alexandra S. Ragsdale, Donald D. Mcintire, Scott W. Roberts, Catherine Y. Spong

Open Access Publications

BACKGROUND: The definition for anemia in pregnancy is outdated, derived from Scandinavian studies in the 1970's to 1980's. To identity women at risk of blood transfusion, a common cause of Severe Maternal Morbidity, a standard definition of anemia in pregnancy in a modern, healthy United States cohort is needed.

OBJECTIVE: To define anemia in pregnancy in a United States population including a large county vs. private hospital population using uncomplicated patients.

MATERIALS AND METHODS: Inclusion criteria were healthy women with the first prenatal visit before 20 weeks. Exclusion criteria included preterm birth, preeclampsia, hypertension, diabetes, short interval pregnancy (<18 months), multiple gestation, abruption, and fetal demise. All women had iron fortification (Ferrous sulfate 325 mg daily) recommended. The presentation to care and pre-delivery hematocrits were obtained, and the percentiles determined. A total of 2000 patients were included, 1000 from the public county hospital and 1000 from the private hospital. Each cohort had 250 patients in each 2011, 2013, 2015, and 2018. The cohorts were compared for differences in the fifth percentile for each antepartum epoch. Student's t-test and chi-squared statistical tests were used for analysis, p-value of ≤0.05 was considered significant.

RESULTS: …

Fish In The Sea: Number, Characteristics, And Partner Preferences Of Unmarried Japanese Adults - Analysis Of A National Survey, Cyrus Ghaznavi, Haruka Sakamoto, Shuhei Nomura, Anna Kubota, Daisuke Yoneoka, Kenji Shibuya, Peter Ueda

Open Access Publications

BACKGROUND: A large proportion of adults in Japan remain unmarried even though they intend to marry during their lifetime. To provide data for policy makers and those searching for partners in the Japanese marriage market, we estimated the number and characteristics of unmarried women and men with marriage intention and assessed their partner preferences. Based on the findings, we hypothesized regarding potential mismatches between the individuals available in the marriage market and the type of partners they are looking for.

METHODS: We used data from the National Fertility Survey (2015), a nationally representative survey in Japan, and included 20,344 participants …

Understanding Contributors To Racial And Ethnic Inequities In Covid-19 Incidence And Mortality Rates, Karen E. Joynt Maddox, Mat Reidhead, Joshua Grotzinger, Timothy Mcbride, Aaloke Mody, Elna Nagasako, Will Ross, Joseph T. Steensma, Abigail R. Barker

Open Access Publications

BACKGROUND: Racial inequities in Coronavirus 2019 (COVID-19) have been reported over the course of the pandemic, with Black, Hispanic/Latinx, and Native American individuals suffering higher case rates and more fatalities than their White counterparts.

METHODS: We used a unique statewide dataset of confirmed COVID-19 cases across Missouri, linked with historical statewide hospital data. We examined differences by race and ethnicity in raw population-based case and mortality rates. We used patient-level regression analyses to calculate the odds of mortality based on race and ethnicity, controlling for comorbidities and other risk factors.

RESULTS: As of September 10, 2020 there were 73,635 confirmed …

High Temporal Resolution Measurements Of Movement Reveal Novel Early-Life Physiological Decline In C. Elegans, Drew Benjamin Sinha, Zachary Scott Pincus

Open Access Publications

Age-related physiological changes are most notable and best-studied late in life, while the nature of aging in early- or middle-aged individuals has not been explored as thoroughly. In C. elegans, many studies of movement vs. age generally focus on three distinct phases: sustained, youthful movement; onset of rapidly progressing impairment; and gross immobility. We investigated whether this first period of early-life adult movement is a sustained "healthy" level of high function followed by a discrete "movement catastrophe"-or whether there are early-life changes in movement that precede future physiological declines. To determine how movement varies during early adult life, we followed …

Estimated Population Access To Acute Stroke And Telestroke Centers In The Us, 2019, Kori S. Zachrison, Rebecca E. Cash, Opeolu Adeoye, Krislyn M. Boggs, Lee H. Schwamm, Ateev Mehrotra, Carlos A. Camargo

Open Access Publications

No abstract provided.

Advances And Gaps In Sars-Cov-2 Infection Models, César Muñoz-Fontela, Michael S. Diamond, Et Al

Open Access Publications

The global response to Coronavirus Disease 2019 (COVID-19) is now facing new challenges such as vaccine inequity and the emergence of SARS-CoV-2 variants of concern (VOCs). Preclinical models of disease, in particular animal models, are essential to investigate VOC pathogenesis, vaccine correlates of protection and postexposure therapies. Here, we provide an update from the World Health Organization (WHO) COVID-19 modeling expert group (WHO-COM) assembled by WHO, regarding advances in preclinical models. In particular, we discuss how animal model research is playing a key role to evaluate VOC virulence, transmission and immune escape, and how animal models are being refined to …

Gastric Organoids: Progress And Remaining Challenges, Min-Jiao Pang, Joseph R Burclaff, Ramon Jin, Mahliyah Adkins-Threats, Luciana H Osaki, Yunan Han, Jason C Mills, Zhi-Feng Miao, Zhen-Ning Wang

Open Access Publications

The stomach is a complex and physiologically necessary organ, yet large differences in physiology between mouse and human stomachs have impeded translation of physiological discoveries and drug screens performed using murine gastric tissues. Gastric cancer (GC) is a global health threat, with a high mortality rate and limited treatment options. The heterogeneous nature of GC makes it poorly suited for current "one size fits all" standard treatments. In this review, we discuss the rapidly evolving field of gastric organoids, with a focus on studies expanding cultures from primary human tissues and describing the benefits of mouse organoid models. We introduce …

Integrating The Ohif Viewer Into Xnat: Achievements, Challenges And Prospects For Quantitative Imaging Studies, Simon J. Doran, Woonchan Cho, Dan Marcus, Et Al

Open Access Publications

No abstract provided.

Disruption Of Thymic Central Tolerance By Infection With Murine Roseolovirus Induces Autoimmune Gastritis, Tarin M. Bigley, Liping Yang, Liang-I Kang, Jose B. Saenz, Francisco Victorino, Wayne M. Yokoyama

Open Access Publications

Infections with herpesviruses, including human roseoloviruses, have been proposed to cause autoimmune disease, but defining a causal relationship and mechanism has been difficult due to the ubiquitous nature of infection and development of autoimmunity long after acute infection. Murine roseolovirus (MRV) is highly related to human roseoloviruses. Herein we show that neonatal MRV infection induced autoimmune gastritis (AIG) in adult mice in the absence of ongoing infection. MRV-induced AIG was dependent on replication during the neonatal period and was CD4+ T cell and IL-17 dependent. Moreover, neonatal MRV infection was associated with development of a wide array of autoantibodies in …

Sonobiopsy For Minimally Invasive, Spatiotemporally-Controlled, And Sensitive Detection Of Glioblastoma-Derived Circulating Tumor Dna, Christopher Pacia, Jinyun Yuan, Yimei Yue, Lu Xu, Arash Nazeri, Rupen Desai, H. Michael Gach, Xiaowei Wang, Michael Talcott, Aadel Chaudhuri, Gavin Dunn, Eric Leuthardt, Hong Chen

Open Access Publications

No abstract provided.

Neutrophil Dream Promotes Neutrophil Recruitment In Vascular Inflammation, Jing Li, Tripti Kumari, Andrew Barazia, Vishwanath Jha, Si-Yeon Jeong, Amber Olson, Mijeong Kim, Bum-Kyu Lee, Vijayprakash Manickam, Zhimin Song, Regina Clemens, Babak Razani, Jonghwan Kim, Mary C Dinauer, Jaehyung Cho

Open Access Publications

The interaction between neutrophils and endothelial cells is critical for the pathogenesis of vascular inflammation. However, the regulation of neutrophil adhesive function remains not fully understood. Intravital microscopy demonstrates that neutrophil DREAM promotes neutrophil recruitment to sites of inflammation induced by TNF-α but not MIP-2 or fMLP. We observe that neutrophil DREAM represses expression of A20, a negative regulator of NF-κB activity, and enhances expression of pro-inflammatory molecules and phosphorylation of IκB kinase (IKK) after TNF-α stimulation. Studies using genetic and pharmacologic approaches reveal that DREAM deficiency and IKKβ inhibition significantly diminish the ligand-binding activity of β2 integrins in TNF-α-stimulated …

Clinical And Kidney Structural Characteristics Of Living Kidney Donors With Nephrolithiasis And Their Long-Term Outcomes, Matthew R D'Costa, Massini A Merzkani, Aleksandar Denic, Aidan F Mullan, Joseph J Larson, Walter K Kremers, Walter D Park, Mariam P Alexander, Harini A Chakkera, Sandra J Taler, Stephen J Erickson, Mark D Stegall, Naim Issa, Andrew D Rule

Open Access Publications

Background: Nephrolithiasis in living kidney donors is concerning due to the potential impact on long-term postdonation kidney function.

Methods: We performed a cohort study of living kidney donors from 2 centers with a baseline computed tomography scan and implantation renal biopsy. Donors (>5 y since donation) completed a follow-up survey or underwent chart review to assess eGFR and incident hypertension. Stone formers were classified as symptomatic if they had a past symptomatic episode or asymptomatic if only incidental radiographic kidney stones were identified during donor evaluation. We compared baseline clinical, imaging, and biopsy characteristics by stone former status including …

Sarm1 Activation Produces Cadpr To Increase Intra-Axonal Ca++ And Promote Axon Degeneration In Pipn, Yihang Li, Maria F. Pazyra-Murphy, Daina Avizonis, Mariana De Sá Tavares Russo, Sophia Tang, Chiung-Ya Chen, Yi-Ping Hsueh, Johann S. Bergholz, Tao Jiang, Jean J. Zhao, Jian Zhu, Kwang Woo Ko, Jeffrey Milbrandt, Aaron Diantonio, Rosalind A. Segal

Open Access Publications

Cancer patients frequently develop chemotherapy-induced peripheral neuropathy (CIPN), a painful and long-lasting disorder with profound somatosensory deficits. There are no effective therapies to prevent or treat this disorder. Pathologically, CIPN is characterized by a "dying-back" axonopathy that begins at intra-epidermal nerve terminals of sensory neurons and progresses in a retrograde fashion. Calcium dysregulation constitutes a critical event in CIPN, but it is not known how chemotherapies such as paclitaxel alter intra-axonal calcium and cause degeneration. Here, we demonstrate that paclitaxel triggers Sarm1-dependent cADPR production in distal axons, promoting intra-axonal calcium flux from both intracellular and extracellular calcium stores. Genetic or …

The 2021 Faseb Science Research Conference On Nad Metabolism And Signaling, Vera Gorbunova, Shin-Ichiro Imai, Et Al

Open Access Publications

No abstract provided.

Epigenetic Regulation Of Human T‐Cell Leukemia Virus Gene Expression, Lee Ratner

Open Access Publications

No abstract provided.

Dopamine D4 Receptor Is A Regulator Of Morphine-Induced Plasticity In The Rat Dorsal Striatum, Alicia Rivera, Diana Suarez-Boomgard, Cristina Miguelez, Alejandra Valderrama-Carvajal, Jerome Baufreton, Kirill Shumilov, Anne Taupignon, Belen Gago, M.Angeles Real

Open Access Publications

No abstract provided.

Utility Of Using Electrocardiogram Measures Of Heart Rate Variability As A Measure Of Cardiovascular Autonomic Neuropathy In Type 1 Diabetes Patients, Rodica Pop-Busui, Jye-Yu C Backlund, Ionut Bebu, Barbara H Braffett, Gayle Lorenzi, Neil H White, John M Lachin, Elsayed Z Soliman, Dcct/Edic Research Group

Open Access Publications

AIMS/INTRODUCTION: Cardiovascular autonomic neuropathy (CAN) is a predictor of cardiovascular disease and mortality. Cardiovascular reflex tests (CARTs) are the gold standard for the diagnosis of CAN, but might not be feasible in large research cohorts or in clinical care. We investigated whether measures of heart rate variability obtained from standard electrocardiogram (ECG) recordings provide a reliable measure of CAN.

MATERIALS AND METHODS: Standardized CARTs (R-R response to paced breathing, Valsalva, postural changes) and digitized 12-lead resting ECGs were obtained concomitantly in Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications participants (n = 311). Standard deviation of normally conducted …

Differences In Shoulder Internal Rotation Strength Between Baseball Players With Ulnar Collateral Ligament Reconstruction And Healthy Controls, Sean Kennedy, Philip Sheedy, Brooks Klein, Mason Gist, Joseph Hannon, John Conway, Kalyssa Creed, J. Craig Garrison

Open Access Publications

Background: Studies have indicated decreased shoulder internal rotation (IR) and external rotation (ER) strength in the throwing limb of baseball players after ulnar collateral ligament injury. There is limited evidence on the recovery of shoulder rotation strength after primary ulnar collateral ligament reconstruction (UCLR).

Hypothesis: At the time of return to throwing, baseball players who underwent UCLR would demonstrate decreased IR and ER shoulder strength in the throwing arm as compared with healthy baseball players.

Study Design: Cross-sectional study; Level of evidence, 3.

Methods: Male competitive high school and collegiate baseball athletes participated in this study. Athletes who underwent UCLR …

Task Modulation Of Single-Neuron Activity In The Human Amygdala And Hippocampus, Runnan Cao, Alexander Todorov, Nicholas Brandmeir, Shuo Wang

Open Access Publications

The human amygdala and hippocampus are critically involved in various processes in face perception. However, it remains unclear how task demands or evaluative contexts modulate processes underlying face perception. In this study, we employed two task instructions when participants viewed the same faces and recorded single-neuron activity from the human amygdala and hippocampus. We comprehensively analyzed task modulation for three key aspects of face processing and we found that neurons in the amygdala and hippocampus (1) encoded high-level social traits such as perceived facial trustworthiness and dominance and this response was modulated by task instructions; (2) encoded low-level facial features …

Mitigating The Effects Of Covid-19 On Hiv Treatment And Care In Lusaka, Zambia: A Before-After Cohort Study Using Mixed Effects Regression, Jake Pry, Kombatende Sikombe, Aaloke Mody, Shilpa Iyer, Jacob Mutale, Natalie Vlahakis, Theodora Savory, Mwanza Wa Mwanza, Keith Mweebo, Annie Mwila, Consity Mwale, Mpande Mukumbwa-Mwenechanya, Andrew Kerkhoff, Izukanji Sikazwe, Carolyn Bolton Moore, Daniel Mwamba, Elvin Geng, Michael Herce

Open Access Publications

INTRODUCTION: The Zambian Ministry of Health (MoH) issued COVID-19 mitigation guidance for HIV care immediately after the first COVID-19 case was confirmed in Zambia on 18 March 2020. The Centre for Infectious Disease Research in Zambia implemented MoH guidance by: 1) extending antiretroviral therapy (ART) refill duration to 6 multi-month dispensation (6MMD) and 2) task-shifting communication and mobilisation of those in HIV care to collect their next ART refill early. We assessed the impact of COVID-19 mitigation guidance on HIV care 3 months before and after guidance implementation.

METHODS: We reviewed all ART pharmacy visit data in the national HIV …

Severe Ocrelizumab-Induced Enterocolitis Treated Successfully With Ustekinumab, Janaki Shah, Ahmad Al-Taaee, Parakkal Deepak, Anas Gremida

Open Access Publications

No abstract provided.

Transition From Cmyc To L-Myc During Dendritic Cell Development Coordinated By Rising Levels Of Irf8, David A. Anderson, Feiya Ou, Sunkyung Kim, Theresa L. Murphy, Kenneth M. Murphy

Open Access Publications

During dendritic cell (DC) development, Myc expression in progenitors is replaced by Mycl in mature DCs, but when and how this transition occurs is unknown. We evaluated DC development using reporters for MYC, MYCL, and cell cycle proteins Geminin and CDT1 in wild-type and various mutant mice. For classical type 1 dendritic cells (cDC1s) and plasmacytoid DCs (pDCs), the transition occurred upon their initial specification from common dendritic cell progenitors (CDPs) or common lymphoid progenitors (CLPs), respectively. This transition required high levels of IRF8 and interaction with PU.1, suggesting the use of EICEs within Mycl enhancers. In pDCs, maximal MYCL …

M6a Modifications Regulate Intestinal Immunity And Rotavirus Infection, Anmin Wang, Gaopeng Hou, Siyuan Ding, Et Al

Open Access Publications

N6-methyladenosine (m6A) is an abundant mRNA modification and affects many biological processes. However, how m6A levels are regulated during physiological or pathological processes such as virus infections, and the in vivo function of m6A in the intestinal immune defense against virus infections are largely unknown. Here, we uncover a novel antiviral function of m6A modification during rotavirus (RV) infection in small bowel intestinal epithelial cells (IECs). We found that rotavirus infection induced global m6A modifications on mRNA transcripts by down-regulating the m6a eraser ALKBH5. Mice lacking the m6A writer enzymes METTL3 in IECs (