Digital Commons Network^™

Unbiased High-Content Screening Reveals Aβ- And Tau-Independent Synaptotoxic Activities In Human Brain Homogenates From Alzheimer's Patients And High-Pathology Controls, Hao Jiang, Thomas J. Esparza, Terrance T. Kummer, David L. Brody

Open Access Publications

Alzheimer's disease (AD) is tightly correlated with synapse loss in vulnerable brain regions. It is assumed that specific molecular entities such as Aβ and tau cause synapse loss in AD, yet unbiased screens for synaptotoxic activities have not been performed. Here, we performed size exclusion chromatography on soluble human brain homogenates from AD cases, high pathology non-demented controls, and low pathology age-matched controls using our novel high content primary cultured neuron-based screening assay. Both presynaptic and postsynaptic toxicities were elevated in homogenates from AD cases and high pathology non-demented controls to a similar extent, with more modest synaptotoxic activities in …

Diffusion Basis Spectrum Imaging Measures Anti-Inflammatory And Neuroprotective Effects Of Fingolimod On Murine Optic Neuritis, Ruimeng Yang, Tsen-Hsuan Lin, Jie Zhan, Shengsheng Lai, Chunyu Song, Peng Sun, Zezhong Ye, Michael Wallendorf, Ajit George, Anne H Cross, Sheng-Kwei Song

Open Access Publications

OBJECTIVE: To prospectively determine whether diffusion basis spectrum imaging (DBSI) detects, differentiates and quantitates coexisting inflammation, demyelination, axonal injury and axon loss in mice with optic neuritis (ON) due to experimental autoimmune encephalomyelitis (EAE), and to determine if DBSI accurately measures effects of fingolimod on underlying pathology.

METHODS: EAE was induced in 7-week-old C57BL/6 female mice. Visual acuity (VA) was assessed daily to detect onset of ON after which daily oral-treatment with either fingolimod (1 mg/kg) or saline was given for ten weeks. In vivo DBSI scans of optic nerves were performed at baseline, 2-, 6- and 10-weeks post treatment. …

The Kanyakla Study: Randomized Controlled Trial Of A Microclinic Social Network Intervention For Promoting Engagement And Retention In Hiv Care In Rural Western Kenya, Matthew D. Hickey, Elvin H. Geng, Et Al

Open Access Publications

BACKGROUND: Existing social relationships are a potential source of "social capital" that can enhance support for sustained retention in HIV care. A previous pilot study of a social network-based 'microclinic' intervention, including group health education and facilitated HIV status disclosure, reduced disengagement from HIV care. We conducted a pragmatic randomized trial to evaluate microclinic effectiveness.

METHODS: In nine rural health facilities in western Kenya, we randomized HIV-positive adults with a recent missed clinic visit to either participation in a microclinic or usual care (NCT02474992). We collected visit data at all clinics where participants accessed care and evaluated intervention effect on …

Inflammatory Myoglandular Polyps Presenting With Diarrhea, Cassandra D. L. Fritz, Pooja Navale, Matthew Mutch, Vladimir Kushnir

Open Access Publications

No abstract provided.

Live Imaging Reveals The Cellular Events Downstream Of Sarm1 Activation, Kwang Woo Ko, Laura Devault, Yo Sasaki, Jeffrey Milbrandt, Aaron Diantonio

Open Access Publications

SARM1 is an inducible NAD

Intestinal Goblet Cells Sample And Deliver Lumenal Antigens By Regulated Endocytic Uptake And Transcytosis, Jenny K. Gustafsson, Jazmyne E. Davis, Tracy Rappai, Keely G. Mcdonald, Devesha H. Kulkarni, Kathryn A. Knoop, Simon P. Hogan, James A.J. Fitzpatrick, Wayne I. Lencer, Rodney D. Newberry

Open Access Publications

Intestinal goblet cells maintain the protective epithelial barrier through mucus secretion and yet sample lumenal substances for immune processing through formation of goblet cell associated antigen passages (GAPs). The cellular biology of GAPs and how these divergent processes are balanced and regulated by goblet cells remains unknown. Using high-resolution light and electron microscopy, we found that in mice, GAPs were formed by an acetylcholine (ACh)-dependent endocytic event remarkable for delivery of fluid-phase cargo retrograde into the trans-golgi network and across the cell by transcytosis - in addition to the expected transport of fluid-phase cargo by endosomes to multi-vesicular bodies and …

Patterns Of Extrapulmonary Metastases In Sarcoma Surveillance, Zachery Hong, Patrick England, Lee Rhea, Angela Hirbe, Douglas Mcdonald, Cara A Cipriano

Open Access Publications

Soft tissue sarcomas (STS) most commonly metastasize to the lungs. Current surveillance guidelines variably recommend abdominal and pelvic imaging, but there is little evidence to support this. We sought to determine the proportion of initial pulmonary versus extrapulmonary metastases, the time to development of each, and factors to identify patients that would benefit from abdominopelvic surveillance. We retrospectively reviewed 382 patients who underwent surgical treatment for STS at a single institution. Of the 33% (126/382) of patients who developed metastases, 72% (90/126) were pulmonary, 22% (28/126) were extrapulmonary, and 6% (8/126) developed both simultaneously. Initial extrapulmonary metastases occurred later (log …

Processing Pipeline For Image Reconstructed Fnirs Analysis Using Both Mri Templates And Individual Anatomy, Samuel Forbes, Sobanawartiny Wijeakumar, Adam Eggebrecht, Vincent Magnotta, John Spencer

Open Access Publications

No abstract provided.

Bacterial Meta-Analysis Of Chicken Cecal Microbiota, Luis Alberto Chica Cardenas, Viviana Clavijo, Martha Vives, Alejandro Reyes

Open Access Publications

Poultry production is an industry that generates 90,000 metric tons of chicken meat worldwide. Thus, optimizing chicken growth and sustainable production is of great importance. A central factor determining not only production parameters, but also stability of the immune system and chicken health, is the diversity and variability of the microbiota present throughout the gastrointestinal tract. To date, several studies have investigated the relationship between bacterial communities and the gut microbiome, with limited data to compare. This study aims to create a bacterial meta-analysis based on studies using amplicon sequencing with Illumina sequencing technologies in order to build a baseline …

Anesthesia For Gi Endoscopy In The Era Of Covid-19, Basavana Goudra, Preet Mohinder Singh

Open Access Publications

As a result of COVID-19, the last few weeks have necessitated a reevaluation of the sedation paradigm for gastrointestinal (GI) endoscopic procedures. Routine screening and some surveillance procedures have taken a backseat and likely to remain so until a vaccine or effective treatment becomes available. Anesthesia providers and endoscopists are required to adapt to this new reality rapidly. The general aim of sedation remains the same-patient comfort, reduced hypoxia, prevention of aspiration along with rapid recovery, and discharge. The present review focuses on necessary modification to reduce the risk of virus contagion for both patients (from health-care providers) and vice …

Assessment Of Antibiotic De-Escalation By Spectrum Score In Patients With Nosocomial Pneumonia: A Single-Center, Retrospective Cohort Study, Dan Ilges, David J. Ritchie, Tamara Krekel, Elizabeth A. Neuner, Nicholas Hampton, Marin H. Kollef, Scott Micek

Open Access Publications

Background: Hospital-acquired and ventilator-associated pneumonia (HAP/VAP) cause significant mortality. Guidelines recommend empiric broad-spectrum antibiotics followed by de-escalation (DE). This study sought to assess the impact of DE on treatment failure.

Methods: This single-center retrospective cohort study screened all adult patients with a discharge diagnosis code for pneumonia from 2016 to 2019. Patients were enrolled if they met predefined criteria for HAP/VAP ≥48 hours after admission. Date of pneumonia diagnosis was defined as day 0. Spectrum scores were calculated, and DE was defined as a score reduction on day 3 versus day 1. Patients with DE were compared to patients with …

Outcomes Of Mechanical Thrombectomy For Patients With Stroke Presenting With Low Alberta Stroke Program Early Computed Tomography Score In The Early And Extended Window, Eyad Almallouhi, Joshua Osbun, Et Al

Open Access Publications

Importance: Limited data are available about the outcomes of mechanical thrombectomy (MT) for real-world patients with stroke presenting with a large core infarct.

Objective: To investigate the safety and effectiveness of MT for patients with large vessel occlusion and an Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of 2 to 5.

Design, Setting, and Participants: This retrospective cohort study used data from the Stroke Thrombectomy and Aneurysm Registry (STAR), which combines the prospectively maintained databases of 28 thrombectomy-capable stroke centers in the US, Europe, and Asia. The study included 2345 patients presenting with an occlusion in the internal carotid …

Pet Study Of Sphingosine-1-Phosphate Receptor 1 Expression In Response To S. Aureus Infection, Hao Jiang, Jiwei Gu, Haiyang Zhao, Sumit Joshi, Joel Perlmutter, Robert Gropler, Robyn Klein, Tammie Benzinger, Zhude Tu

Open Access Publications

Sphingosine-1-phosphate receptor 1 (S1PR1) plays a crucial role in infectious diseases. Targeting S1PR1 provides protection against pathogens, such as influenza viruses. This study is aimed at investigating S1PR1 in response to bacterial infection by assessing S1PR1 expression in

Reproducibility Of Hospital Rankings Based On Centers For Medicare & Medicaid Services Hospital Compare Measures As A Function Of Measure Reliability, Laurent G. Glance, David R. Nerenz, Karen E. Joynt Maddox, Bruce L. Hall, Andrew W. Dick

Open Access Publications

Importance: Unreliable performance measures can mask poor-quality care and distort financial incentives in value-based purchasing.

Objective: To examine the association between test-retest reliability and the reproducibility of hospital rankings.

Design, Setting, and Participants: In a cross-sectional design, Centers for Medicare & Medicaid Services Hospital Compare data were analyzed for the 2017 (based on 2014-2017 data) and 2018 (based on 2015-2018 data) reporting periods. The study was conducted from December 13, 2020, to September 30, 2021. This analysis was based on 28 measures, including mortality (acute myocardial infarction, congestive heart failure, pneumonia, and coronary artery bypass grafting), readmissions (acute myocardial infarction, …

Infectious Disease Providers’ Knowledge Of And Engagement In Quality Improvement, Kathleen R. Sheridan, Michael A. Lane, Thomas J. Kim, Joshua C. Eby

Open Access Publications

No abstract provided.

Risk Factors And Medical Resource Utilization Of Respiratory Syncytial Virus, Human Metapneumovirus, And Influenza-Related Hospitalizations In Adults—A Global Study During The 2017–2019 Epidemic Seasons (Hospitalized Acute Respiratory Tract Infection [Harti] Study), Ann R. Falsey, Edward E. Walsh, Yannick Vandenijck, Xiaohui Ren, Sofia Keim, Diye Kang, Pascale Peeters, James Witek, Gabriela Ispas

Open Access Publications

No abstract provided.

Value Of Packaged Testing For Sexually Transmitted Infections For Persons Who Inject Drugs Hospitalized With Serious Injection-Related Infections, Laura R. Marks, Hilary Reno, Stephen Y. Liang, Evan S. Schwarz, David B. Liss, Linda Jiang, Nathanial S. Nolan, Michael J. Durkin

Open Access Publications

Background: Persons who inject drugs (PWID) are frequently admitted for serious injection-related infections (SIRIs). PWID are also at risk for sexually transmitted infections (STIs).

Methods: We conducted a multicenter quality improvement project at 3 hospitals in Missouri. PWID with SIRI who received an infectious diseases consultation were prospectively identified and placed into an electronic database as part of a Centers for Disease Control and Prevention-funded quality improvement project. Baseline data were collected from 8/1/2019 to 1/30/2020. During the intervention period (2/1/2020-2/28/2021), infectious diseases physicians caring for patients received 2 interventions: (1) email reminders of best practice screening for HIV, viral …

Evaluation Of The 3-Minute Diagnostic Confusion Assessment Method For Identification Of Postoperative Delirium In Older Patients, Jordan Oberhaus, Wei Wang, Angela M. Mickle, Jennifer Becker, Catherine Tedeschi, Hannah R. Maybrier, Ravi T. Upadhyayula, Maxwell R. Muench, Nan Lin, Eva M. Schmitt, Sharon K. Inouye, Michael S. Avidan

Open Access Publications

Importance: Delirium is a common postoperative complication in older patients that often goes undetected and might lead to worse outcomes. The 3-Minute Diagnostic Confusion Assessment Method (3D-CAM) might be a practical tool for routine clinical diagnosis of delirium.

Objective: To assess the 3D-CAM for detecting postoperative delirium compared with the long-form CAM used for research purposes.

Design, Setting, and Participants: This cohort study of older patients enrolled in ongoing clinical trials between 2015 and 2018 was conducted at a single tertiary US hospital. Included participants were aged 60 years or older undergoing major elective surgical procedures that required at least …

Comparison Of Response To Definitive Radiotherapy For Localized Prostate Cancer In Black And White Men: A Meta-Analysis, Ting Martin Ma, Jeff M. Michalski, Et Al

Open Access Publications

Importance: Black men have a 2-fold increased risk of dying from prostate cancer compared with White men. However, race-specific differences in response to initial treatment remain unknown.

Objective: To compare overall and treatment-specific outcomes of Black and White men with localized prostate cancer receiving definitive radiotherapy (RT).

Data Sources: A systematic search was performed of relevant published randomized clinical trials conducted by the NRG Oncology/Radiation Therapy Oncology Group between January 1, 1990, and December 31, 2010. This meta-analysis was performed from July 1, 2019, to July 1, 2021.

Study Selection: Randomized clinical trials of definitive RT for patients with localized …

A Proinflammatory Stimulus Disrupts Hippocampal Plasticity And Learning Via Microglial Activation And 25-Hydroxycholesterol, Yukitoshi Izumi, Anil G. Cashikar, Kathiresan Krishnan, Steven M. Paul, Douglas F. Covey, Steven J. Mennerick, Charles F. Zorumski

Open Access Publications

Inflammatory cells, including macrophages and microglia, synthesize and release the oxysterol 25-hydroxycholesterol (25HC), which has antiviral and immunomodulatory properties. Here, we examined the effects of lipopolysaccharide (LPS), an activator of innate immunity, on 25HC production in microglia, and the effects of LPS and 25HC on CA1 hippocampal synaptic plasticity and learning. In primary microglia, LPS markedly increases the expression of cholesterol 25-hydroxylase (Ch25h), the key enzyme involved in 25HC synthesis, and increases the levels of secreted 25HC. Wild-type microglia produced higher levels of 25HC than

A Randomized, Placebo-Controlled Trial Assessing The Effect Of Visbiome Es Probiotic In People With Hiv On Antiretroviral Therapy, Rachel M. Presti, Et Al

Open Access Publications

Background: A5350, a phase II, randomized, double-blind study, evaluated the safety and tolerability of the probiotic Visbiome Extra Strength (ES) over 24 weeks and measured effects on inflammation and intestinal barrier function.

Methods: The primary outcome was change in soluble CD14 (sCD14) levels; secondary outcomes included safety and tolerability, markers of inflammation and cellular activation, and microbiome. In a substudy, gut permeability was assessed by paired colonic biopsies measuring the area of lamina propria occupied by CD4+ cells, interleukin (IL)-17+ cells, and myeloperoxidase (MPO). Changes between arms were compared with the 2-sample

Results: Overall, 93 participants enrolled: 86% male, median …

Inhibitor Of Growth Protein 3 Epigenetically Silences Endogenous Retroviral Elements And Prevents Innate Immune Activation, Yanhua Song, Gaopeng Hou, Jonathan Diep, Yaw Shin Ooi, Natalia S. Akopyants, Stephen M. Beverley, Jan E. Carette, Harry B. Greenberg, Siyuan Ding

Open Access Publications

Endogenous retroviruses (ERVs) are subject to transcriptional repression in adult tissues, in part to prevent autoimmune responses. However, little is known about the epigenetic silencing of ERV expression. Here, we describe a new role for inhibitor of growth family member 3 (ING3), to add to an emerging group of ERV transcriptional regulators. Our results show that ING3 binds to several ERV promoters (for instance MER21C) and establishes an EZH2-mediated H3K27 trimethylation modification. Loss of ING3 leads to decreases of H3K27 trimethylation enrichment at ERVs, induction of MDA5-MAVS-interferon signaling, and functional inhibition of several virus infections. These data demonstrate an important …

Coronavirus Disease 2019-Associated Invasive Fungal Infection, John W. Baddley, George R. Thompson, Sharon C.-A. Chen, P. Lewis White, Melissa D. Johnson, M. Hong Nguyen, Ilan S. Schwartz, Andrej Spec, Luis Ostrosky-Zeichner, Brendan R. Jackson, Thomas F. Patterson, Peter G. Pappas

Open Access Publications

Coronavirus disease 2019 (COVID-19) can become complicated by secondary invasive fungal infections (IFIs), stemming primarily from severe lung damage and immunologic deficits associated with the virus or immunomodulatory therapy. Other risk factors include poorly controlled diabetes, structural lung disease and/or other comorbidities, and fungal colonization. Opportunistic IFI following severe respiratory viral illness has been increasingly recognized, most notably with severe influenza. There have been many reports of fungal infections associated with COVID-19, initially predominated by pulmonary aspergillosis, but with recent emergence of mucormycosis, candidiasis, and endemic mycoses. These infections can be challenging to diagnose and are associated with poor outcomes. …

An Absence Of Equipoise: Examining Surgeons' Decision Talk During Encounters With Women Considering Breast Cancer Surgery, Mary C. Politi, Catherine H. Saunders, Victoria F. Grabinski, Renata W. Yen, Amy E. Cyr, Marie-Anne Durand, Glyn Elwyn

Open Access Publications

Shared decision-making is recommended for decisions with multiple reasonable options, yet clinicians often subtly or explicitly guide choices. Using purposive sampling, we performed a secondary analysis of 142 audio-recorded encounters between 13 surgeons and women eligible for breast-conserving surgery with radiation or mastectomy. We trained 9 surgeons in shared decision-making and provided them one of two conversation aids; 4 surgeons practiced as usual. Based on a published taxonomy of treatment recommendations (pronouncements, suggestions, proposals, offers, assertions), we examined how surgeons framed choices with patients. Many surgeons made assertions providing information and advice (usual care 71% vs. intervention 66%; p = …

Human B Cell Lineages Associated With Germinal Centers Following Influenza Vaccination Are Measurably Evolving, Kenneth B. Hoehn, Jackson S. Turner, Frederick I. Miller, Ruoyi Jiang, Oliver G. Pybus, Ali H. Ellebedy, Steven H. Kleinstein

Open Access Publications

The poor efficacy of seasonal influenza virus vaccines is often attributed to pre-existing immunity interfering with the persistence and maturation of vaccine-induced B cell responses. We previously showed that a subset of vaccine-induced B cell lineages are recruited into germinal centers (GCs) following vaccination, suggesting that affinity maturation of these lineages against vaccine antigens can occur. However, it remains to be determined whether seasonal influenza vaccination stimulates additional evolution of vaccine-specific lineages, and previous work has found no significant increase in somatic hypermutation among influenza-binding lineages sampled from the blood following seasonal vaccination in humans. Here, we investigate this issue …

Toxoplasma Bradyzoites Exhibit Physiological Plasticity Of Calcium And Energy Stores Controlling Motility And Egress, Yong Fu, Kevin M. Brown, Nathaniel G. Jones, Silvia N.J. Moreno, L. David Sibley

Open Access Publications

No abstract provided.

Cell Death And Transcriptional Responses Induced In Larvae Of The Nematode Haemonchus Contortus By Toxins/Toxicants With Broad Phylogenetic Efficacy, Douglas P Jasmer, Bruce A Rosa, Makedonka Mitreva

Open Access Publications

Establishing methods to investigate treatments that induce cell death in parasitic nematodes will promote experimental approaches to elucidate mechanisms and to identify prospective anthelmintics capable of inducing this outcome. Here, we extended recent progress on a method to monitor cell death and to identify small molecule inhibitors in

A Comprehensive Review Of Tic Disorders In Children, Keisuke Ueda, Kevin J. Black

Open Access Publications

Tics are characterized by sudden, rapid, recurrent, nonrhythmic movement or vocalization, and are the most common movement disorders in children. Their onset is usually in childhood and tics often will diminish within one year. However, some of the tics can persist and cause various problems such as social embarrassment, physical discomfort, or emotional impairments, which could interfere with daily activities and school performance. Furthermore, tic disorders are frequently associated with comorbid neuropsychiatric symptoms, which can become more problematic than tic symptoms. Unfortunately, misunderstanding and misconceptions of tic disorders still exist among the general population. Understanding tic disorders and their comorbidities …

Vaccines For Protecting Infants From Bacterial Causes Of Diarrheal Disease, Richard Walker, Robert W Kaminski, Chad Porter, Robert K M Choy, Jessica A White, James M Fleckenstein, Fred Cassels, Louis Bourgeois

Open Access Publications

The global diarrheal disease burden for

Aapm Medical Physics Practice Guideline 3.B.: Levels Of Supervision For Medical Physicists In Clinical Training, Douglas Pfeiffer, Hania Al-Hallaq, Per Halvorsen, Kristi Hendrickson, Zheng Feng Lu, Melissa Carol Martin, Beth Schueler, Jillian Shuman, Jacqueline E Zoberi

Open Access Publications

The American Association of Physicists in Medicine (AAPM) is a nonprofit professional society whose primary purposes are to advance the science, education and professional practice of medical physics. The AAPM has more than 8,000 members and is the principal organization of medical physicists in the United States. The AAPM will periodically define new practice guidelines for medical physics practice to help advance the science of medical physics and to improve the quality of service to patients throughout the United States. Existing medical physics practice guidelines will be reviewed for the purpose of revision or renewal, as appropriate, on their fifth …