Medicine and Health Sciences Commons^™

Uropathogenic Escherichia Coli Infection-Induced Epithelial Trained Immunity Impacts Urinary Tract Disease Outcome, Seongmi K Russell, Jessica K Harrison, Benjamin S Olson, Hyung Joo Lee, Valerie P O'Brien, Xiaoyun Xing, Lu Yu, Elisha D O Roberson, Rajdeep Bomjan, Changxu Fan, Marina Sha, Marco Colonna, Ting Wang, Thomas J Hannan, Scott J Hultgren, Et Al.

2020-Current year OA Pubs

Previous urinary tract infections (UTIs) can predispose one to future infections; however, the underlying mechanisms affecting recurrence are poorly understood. We previously found that UTIs in mice cause differential bladder epithelial (urothelial) remodelling, depending on disease outcome, that impacts susceptibility to recurrent UTI. Here we compared urothelial stem cell (USC) lines isolated from mice with a history of either resolved or chronic uropathogenic Escherichia coli (UPEC) infection, elucidating evidence of molecular imprinting that involved epigenetic changes, including differences in chromatin accessibility, DNA methylation and histone modification. Epigenetic marks in USCs from chronically infected mice enhanced caspase-1-mediated cell death upon UPEC …

Il-15 Enhances Hiv-1 Infection By Promoting Survival And Proliferation Of Ccr5+Cd4+ T Cells, Yuhao Li, Hongbo Gao, Kolin M. Clark, Liang Shan

2020-Current year OA Pubs

HIV-1 usually utilizes CCR5 as its coreceptor and rarely switches to a CXCR4-tropic virus until the late stage of infection. CCR5+CD4+ T cells are the major virus-producing cells in viremic individuals as well as SIV-infected nonhuman primates. The differentiation of CCR5+CD4+ T cells is associated with the availability of IL-15, which increases during acute HIV-1 infection. Here, we report that CCR5 was expressed by CD4+ T cells exhibiting effector or effector memory phenotypes with high expression levels of the IL-2/IL-15 receptor common β and γ chains. IL-15, but not IL-7, improved the survival of CCR5+CD4+ T cells, drove their expansion, …

Automatic Detection Of Circulating Tumor Cells And Cancer Associated Fibroblasts Using Deep Learning, Cheng Shen, Siddarth Rawal, Rebecca Brown, Haowen Zhou, Ashutosh Agarwal, Mark A Watson, Richard J Cote, Changhuei Yang

2020-Current year OA Pubs

Circulating tumor cells (CTCs) and cancer-associated fibroblasts (CAFs) from whole blood are emerging as important biomarkers that potentially aid in cancer diagnosis and prognosis. The microfilter technology provides an efficient capture platform for them but is confounded by two challenges. First, uneven microfilter surfaces makes it hard for commercial scanners to obtain images with all cells in-focus. Second, current analysis is labor-intensive with long turnaround time and user-to-user variability. Here we addressed the first challenge through developing a customized imaging system and data pre-processing algorithms. Utilizing cultured cancer and CAF cells captured by microfilters, we showed that images from our …

Factor Xa Cleaves Sars-Cov-2 Spike Protein To Block Viral Entry And Infection, Wenjuan Dong, Sean P J Whelan, Et Al.

2020-Current year OA Pubs

Serine proteases (SP), including furin, trypsin, and TMPRSS2 cleave the SARS-CoV-2 spike (S) protein, enabling the virus to enter cells. Here, we show that factor (F) Xa, an SP involved in blood coagulation, is upregulated in COVID-19 patients. In contrast to other SPs, FXa exerts antiviral activity. Mechanistically, FXa cleaves S protein, preventing its binding to ACE2, and thus blocking viral entry and infection. However, FXa is less effective against variants carrying the D614G mutation common in all pandemic variants. The anticoagulant rivaroxaban, a direct FXa inhibitor, inhibits FXa-mediated S protein cleavage and facilitates viral entry, whereas the indirect FXa …

Sphingomyelin 16:0 Is A Therapeutic Target For Neuronal Death In Acid Sphingomyelinase Deficiency, Ángel Gaudioso, Xuntian Jiang, Josefina Casas, Edward H Schuchman, María Dolores Ledesma

2020-Current year OA Pubs

Acid sphingomyelinase deficiency (ASMD) is a lysosomal storage disorder caused by mutations in the SMPD1 gene encoding for the acid sphingomyelinase (ASM). While intravenous infusion of recombinant ASM is an effective treatment for the peripheral disease, the neurological complications of ASMD remain unaddressed. It has been shown that aberrantly high level of total brain sphingomyelin (SM) is a key pathological event leading to neurodegeneration. Using mice lacking ASM (ASMko), which mimic the disease, we here demonstrate that among the SM species, SM16:0 shows the highest accumulation and toxicity in ASMko neurons. By targeting lysosomes, SM16:0 causes permeabilization and exocytosis of …

Cross-Sectional Study To Assess Depression Among Healthcare Workers In Lusaka, Zambia During The Covid-19 Pandemic, Sandra Simbeza, Jacob Mutale, Musunge Mulabe, Lazarus Jere, Chama Bukankala, Kombatende Sikombe, Izukanji Sikazwe, Carolyn Bolton-Moore, Aaloke Mody, Elvin H. Geng, Anjali Sharma, Laura K. Beres, Jake M. Pry

2020-Current year OA Pubs

OBJECTIVES: We sought to assess depression among healthcare workers (HCWs) in the context of COVID-19 in Lusaka Province, Zambia.

DESIGN: This cross-sectional study is nested within a larger study, the Person-Centred Public Health for HIV Treatment in Zambia (PCPH), a cluster-randomised trial to assess HIV care and outcomes.

SETTING: The research was conducted in 24 government-run health facilities from 11 August to 15 October 2020 during the first wave of the COVID-19 pandemic in Lusaka, Zambia.

PARTICIPANTS: We used convenience sampling to recruit HCW participants who were previously enrolled in the PCPH study, had more than 6 months' experience working …

Statins Enhance The Efficacy Of Her2-Targeting Radioligand Therapy In Drug-Resistant Gastric Cancers, Yi Rao, Zachary Samuels, Lukas M Carter, Sebastien Monette, Sandeep Surendra Panikar, Patricia M R Pereira, Jason S Lewis

2020-Current year OA Pubs

Human epidermal growth factor receptor 2 (HER2) is overexpressed in various cancer types. HER2-targeting trastuzumab plus chemotherapy is used as first-line therapy for HER2-positive recurrent or primary metastatic gastric cancer, but intrinsic and acquired trastuzumab resistance inevitably develop over time. To overcome gastric cancer resistance to HER2-targeted therapies, we have conjugated trastuzumab with a beta-emitting therapeutic isotope, lutetium-177, to deliver radiation locally to gastric tumors with minimal toxicity. Because trastuzumab-based targeted radioligand therapy (RLT) requires only the extramembrane domain binding of membrane-bound HER2 receptors, HER2-targeting RLT can bypass any resistance mechanisms that occur downstream of HER2 binding. Leveraging our previous …

A Dna Damage-Induced Phosphorylation Circuit Enhances Mec1atr Ddc2atrip Recruitment To Replication Protein A, Luke A Yates, Elias A Tannous, R Marc Morgan, Peter M Burgers, Xiaodong Zhang

2020-Current year OA Pubs

The cell cycle checkpoint kinase Mec1

Advanced Care Planning For Hospitalized Patients Following Clinician Notification Of Patient Mortality By A Machine Learning Algorithm, Stephen Chi, Seunghwan Kim, Matthew Reuter, Katharine Ponzillo, Debra Parker Oliver, Randi Foraker, Kevin Heard, Jingxia Liu, Kyle Pitzer, Patrick White, Nathan Moore

2020-Current year OA Pubs

IMPORTANCE: Goal-concordant care is an ongoing challenge in hospital settings. Identification of high mortality risk within 30 days may call attention to the need to have serious illness conversations, including the documentation of patient goals of care.

OBJECTIVE: To examine goals of care discussions (GOCDs) in a community hospital setting with patients identified as having a high risk of mortality by a machine learning mortality prediction algorithm.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study took place at community hospitals within 1 health care system. Participants included adult patients with a high risk of 30-day mortality who were admitted to 1 …

Estimated Clinical Outcomes And Cost-Effectiveness Associated With Provision Of Addiction Treatment In Us Primary Care Clinics, Raagini Jawa, Yjuliana Tin, Samantha Nall, Susan L Calcaterra, Alexandra Savinkina, Laura R Marks, Simeon D Kimmel, Benjamin P Linas, Joshua A Barocas

2020-Current year OA Pubs

IMPORTANCE: US primary care practitioners (PCPs) are the largest clinical workforce, but few provide addiction care. Primary care is a practical place to expand addiction services, including buprenorphine and harm reduction kits, yet the clinical outcomes and health care sector costs are unknown.

OBJECTIVE: To estimate the long-term clinical outcomes, costs, and cost-effectiveness of integrated buprenorphine and harm reduction kits in primary care for people who inject opioids.

DESIGN, SETTING, AND PARTICIPANTS: In this modeling study, the Reducing Infections Related to Drug Use Cost-Effectiveness (REDUCE) microsimulation model, which tracks serious injection-related infections, overdose, hospitalization, and death, was used to examine …

On-The-Go Adaptation Of Implementation Approaches And Strategies In Health: Emerging Perspectives And Research Opportunities, Elvin H Geng, Aaloke Mody, Byron J Powell

2020-Current year OA Pubs

In many cases, implementation approaches (composed of one or more strategies) may need to change over time to work optimally. We use a literature review to inform a mechanistic analysis of such on-the-go adaptations. We suggest that such adaptations of implementation strategies consist of three necessary steps. The first component is the initial effect of the implementation approach on intended implementation, service delivery, or clinical outcomes. Second, these initial effects must in turn be used to modify, alter, intensify, or otherwise change the implementation approach. Third, the modified approach itself has effects. Conceiving of adaptation as all three steps implies …

Associations Of Combined Physical Activity And Body Mass Index Groups With Colorectal Cancer Survival Outcomes, Caroline Himbert, Matthew G Mutch, Corey Bernadt, Adetunji T Toriola, Et Al.

2020-Current year OA Pubs

BACKGROUND: Physical activity and BMI have been individually associated with cancer survivorship but have not yet been studied in combinations in colorectal cancer patients. Here, we investigate individual and combined associations of physical activity and BMI groups with colorectal cancer survival outcomes.

METHODS: Self-reported physical activity levels (MET hrs/wk) were assessed using an adapted version of the International Physical Activity Questionnaire (IPAQ) at baseline in 931 patients with stage I-III colorectal cancer and classified into 'highly active' and'not-highly active'(≥ / < 18 MET hrs/wk). BMI (kg/m

RESULTS: 'Not-highly active' compared to 'highly active' and 'overweight'/ 'obese' compared to 'normal weight' patients had a 40-50% increased risk …

Rapid Profiling Of Dna Replication Dynamics Using Mass Spectrometry-Based Analysis Of Nascent Dna, Mohamed E Ashour, Andrea K Byrum, Alice Meroni, Jun Xia, Saurabh Singh, Roberto Galletto, Susan M Rosenberg, Alessandro Vindigni, Nima Mosammaparast

2020-Current year OA Pubs

The primary method for probing DNA replication dynamics is DNA fiber analysis, which utilizes thymidine analog incorporation into nascent DNA, followed by immunofluorescent microscopy of DNA fibers. Besides being time-consuming and prone to experimenter bias, it is not suitable for studying DNA replication dynamics in mitochondria or bacteria, nor is it adaptable for higher-throughput analysis. Here, we present mass spectrometry-based analysis of nascent DNA (MS-BAND) as a rapid, unbiased, quantitative alternative to DNA fiber analysis. In this method, incorporation of thymidine analogs is quantified from DNA using triple quadrupole tandem mass spectrometry. MS-BAND accurately detects DNA replication alterations in both …

Monocyte Depletion Enhances Neutrophil Influx And Proneural To Mesenchymal Transition In Glioblastoma, Zhihong Chen, David H Gutmann, Et Al.

2020-Current year OA Pubs

Myeloid cells comprise the majority of immune cells in tumors, contributing to tumor growth and therapeutic resistance. Incomplete understanding of myeloid cells response to tumor driver mutation and therapeutic intervention impedes effective therapeutic design. Here, by leveraging CRISPR/Cas9-based genome editing, we generate a mouse model that is deficient of all monocyte chemoattractant proteins. Using this strain, we effectively abolish monocyte infiltration in genetically engineered murine models of de novo glioblastoma (GBM) and hepatocellular carcinoma (HCC), which show differential enrichment patterns for monocytes and neutrophils. Eliminating monocyte chemoattraction in monocyte enriched PDGFB-driven GBM invokes a compensatory neutrophil influx, while having no …

Evaluation Of Birth By Cesarean Delivery And Development Of Early-Onset Colorectal Cancer, Yin Cao, Long H Nguyen, Stefani Tica, Ebunoluwa Otegbeye, Xiaoyu Zong, Bjorn Roelstraete, Andrew T Chan, Barbara B Warner, Olof Stephansson, Jonas F Ludvigsson

2020-Current year OA Pubs

IMPORTANCE: The incidence of early-onset colorectal cancer (CRC), diagnosed younger than 50 years of age, has increased worldwide. Gut dysbiosis throughout the life course is hypothesized as a leading mechanism, yet epidemiologic data are limited.

OBJECTIVE: To prospectively examine the association between birth by cesarean delivery and early-onset CRC among offspring.

DESIGN, SETTING, AND PARTICIPANTS: In this population-based, nationwide case-control study in Sweden, adults diagnosed with CRC between 18 and 49 years of age from 1991 to 2017 were identified through the Epidemiology Strengthened by Histopathology Reports in Sweden (ESPRESSO) cohort. Up to 5 general population control individuals without CRC …

Priorities To Promote Participant Engagement In The Participant Engagement And Cancer Genome Sequencing (Pe-Cgs) Network, Anne Lr Schuster, Graham A Colditz, Li Ding, Bettina F Drake, Ryan C Fields, Et Al.

2020-Current year OA Pubs

BACKGROUND: Engaging diverse populations in cancer genomics research is of critical importance and is a fundamental goal of the NCI Participant Engagement and Cancer Genome Sequencing (PE-CGS) Network. Established as part of the Cancer Moonshot, PE-CGS is a consortium of stakeholders including clinicians, scientists, genetic counselors, and representatives of potential study participants and their communities. Participant engagement is an ongoing, bidirectional, and mutually beneficial interaction between study participants and researchers. PE-CGS sought to set priorities in participant engagement for conducting the network's research.

METHODS: PE-CGS deliberatively engaged its stakeholders in the following four-phase process to set the network's research priorities …

The Value And Impacts Of Academic Public Health Departments, Paul C Erwin, Julie H Grubaugh, Stephanie Mazzucca-Ragan, Ross C Brownson

2020-Current year OA Pubs

The academic health department (AHD) is a partnership between an academic institution and a governmental health agency. These partnerships are meant to provide mutual benefits that include opportunities for student field placements and internships, practice-informed curriculum, and practice-based research. The term academic health department dates back only to 2000, although there are several examples of academic-practice partnerships prior to that date. In addition to AHDs that have been established over the past two decades, other forms of academic-practice engagement provide similar mutual benefits, such as prevention research centers and public health training centers. Current research on AHDs explores how these …

Impact Of The Covid-19 Pandemic On Chronic Disease Management And Patient Reported Outcomes In Patients With Pulmonary Hypertension: The Pulmonary Hypertension Association Registry, Megan Mayer, Murali M Chakinala, Et Al.

2020-Current year OA Pubs

To better understand the impact of the COVID-19 pandemic on the care of patients with pulmonary hypertension, we conducted a retrospective cohort study evaluating health insurance status, healthcare access, disease severity, and patient reported outcomes in this population. Using the Pulmonary Hypertension Association Registry (PHAR), we defined and extracted a longitudinal cohort of pulmonary arterial hypertension (PAH) patients from the PHAR's inception in 2015 until March 2022. We used generalized estimating equations to model the impact of the COVID-19 pandemic on patient outcomes, adjusting for demographic confounders. We assessed whether insurance status modified these effects via covariate interactions. PAH patients …

Multidimensional Poverty Is Associated With Dementia Among Adults In Afghanistan, Jean-Francois Trani, Yiqi Zhu, Soobin Park, Dauod Khuram, Rahim Azami, Monib Rahim Fazal, Ganesh M Babulal

2020-Current year OA Pubs

BACKGROUND: Multidimensional poverty is associated with dementia, but no evidence is available for countries in conflict.

METHODS: A cross-sectional study was conducted in two provinces of Afghanistan between February 15th 2022 and April 20th 2022 among adults age 50 and older. Multidimensional poverty included six dimensions of well-being and 16 indicators of deprivation. The Rowland Universal Dementia Assessment Scale measured dementia. Poverty between adults with and without dementia was examined, adjusting for sex. Associations between dementia and poverty were investigated using multivariate regression model.

FINDINGS: Of the 478 adults included, 89 (52.7%) had mild, and 25 (14.8%) had moderate to …

Baseline Characteristics Of The North American Prodromal Synucleinopathy Cohort, Jonathan E Elliott, Jennifer Mcleland, Susan R Criswell, Yo-El S Ju, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Rapid eye movement (REM) sleep behavior disorder (RBD) is widely considered a prodromal synucleinopathy, as most with RBD develop overt synucleinopathy within ~10 years. Accordingly, RBD offers an opportunity to test potential treatments at the earliest stages of synucleinopathy. The North American Prodromal Synucleinopathy (NAPS) Consortium has created a multisite RBD participant, primarily clinic-based cohort to better understand characteristics at diagnosis, and in future work, identify predictors of phenoconversion, develop synucleinopathy biomarkers, and enable early stage clinical trial enrollment.

METHODS: Participants ≥18 years of age with overnight polysomnogram-confirmed RBD without Parkinson's disease, dementia, multiple system atrophy, or narcolepsy were …

Lrp6 High Bone Mass Characterized In Two Generations Harboring A Unique Mutation Of Low-Density Lipoprotein Receptor-Related Protein 6, Michael P Whyte, Steven Mumm, Jonathan C Baker, Fan Zhang, Homer Sedighi, Shenghui Duan, Tim Cundy

2020-Current year OA Pubs

Osteoblast Wnt/

Area Deprivation Index And Segregation On The Risk Of Hiv: A U.S. Veteran Case-Control Study, Abiodun O Oluyomi, Angela L Mazul, Yongquan Dong, Donna L White, Christine M Hartman, Peter Richardson, Wenyaw Chan, Jose M Garcia, Jennifer R Kramer, Elizabeth Chiao

2020-Current year OA Pubs

BACKGROUND: Preventing HIV infection remains a critically important tool in the continuing fight against HIV/AIDS. The primary aim is to evaluate the effect and interactions between a composite area-level social determinants of health measure and an area-level measure of residential segregation on the risk of HIV/AIDS in U.S. Veterans.

METHODS: Using the individual-level patient data from the U.S. Department of Veterans Affairs, we constructed a case-control study of veterans living with HIV/AIDS (VLWH) and age-, sex assigned at birth- and index date-matched controls. We geocoded patient's residential address to ascertain their neighborhood and linked their information to two measures of …

Delayed Ipsilateral Intestinal Perforation After Endoscopic Gastrojejunostomy: A Perspective On Underlying Mechanisms, Juan Reyes Genere, Zoilo K Suarez, Vladimir Kushnir

2020-Current year OA Pubs

The endoscopic management for malignant gastric outlet obstruction has expanded with the advent of endoscopic ultrasound-guided gastrojejunostomy. Delayed perforation after endoscopic ultrasound-guided gastrojejunostomy is an important yet rarely reported adverse event, and it is unclear why some patients may suffer this complication. We present a case of intestinal perforation occurring one month after endoscopic ultrasound-guided gastrojejunostomy and discuss potential mechanisms which may contribute to this outcome.

Potential Uses Of Ai For Perioperative Nursing Handoffs: A Qualitative Study, Christopher Ryan King, Ayanna Shambe, Joanna Abraham

2020-Current year OA Pubs

OBJECTIVE: Situational awareness and anticipatory guidance for nurses receiving a patient after surgery are keys to patient safety. Little work has defined the role of artificial intelligence (AI) to support these functions during nursing handoff communication or patient assessment. We used interviews to better understand how AI could work in this context.

MATERIALS AND METHODS: Eleven nurses participated in semistructured interviews. Mixed inductive-deductive thematic analysis was used to extract major themes and subthemes around roles for AI supporting postoperative nursing.

RESULTS: Five themes were generated from the interviews: (1) nurse understanding of patient condition guides care decisions, (2) handoffs are …

Corticosteroids Increase The Risk Of Invasive Fungal Infections More Than Tumor Necrosis Factor-Alpha Inhibitors In Patients With Inflammatory Bowel Disease, Martin H Gregory, Andrej Spec, Dustin Stwalley, Anas Gremida, Carlos Mejia-Chew, Katelin B Nickel, Matthew A Ciorba, Richard P Rood, Margaret A Olsen, Parakkal Deepak

2020-Current year OA Pubs

BACKGROUND: Invasive fungal infections are a devastating complication of inflammatory bowel disease (IBD) treatment. We aimed to determine the incidence of fungal infections in IBD patients and examine the risk with tumor necrosis factor-alpha inhibitors (anti-TNF) compared with corticosteroids.

METHODS: In a retrospective cohort study using the IBM MarketScan Commercial Database we identified US patients with IBD and at least 6 months enrollment from 2006 to 2018. The primary outcome was a composite of invasive fungal infections, identified by ICD-9/10-CM codes plus antifungal treatment. Tuberculosis (TB) infections were a secondary outcome, with infections presented as cases/100 000 person-years (PY). A …

Insights Into The Pathogenesis Of Hereditary Angioedema Using Genetic Sequencing And Recombinant Protein Expression Analyses, Zhen Ren, Shuangxia Zhao, Tiandao Li, H James Wedner, John P Atkinson

2020-Current year OA Pubs

BACKGROUND: The pathogenesis of hereditary angioedema (HAE) type I and type II is linked to defective C1 esterase inhibitor (C1-INH) encoded by the SERPING1 gene. There are substantial variabilities in the clinical presentations of patients with HAE that are not directly correlated to the serum levels of C1-INH. The impact of SERPING1 variants on C1-INH expression, structure, and function is incompletely understood.

OBJECTIVE: To investigate the influence of SERPING1 variants on the C1-INH expression, structure, and function of 20 patients with HAE from 14 families with no prior genetic diagnosis.

METHODS: Patients underwent whole-exome sequencing (WES). If no variants were …

Logistical, Technical, And Radiation Safety Aspects Of Establishing A Radiopharmaceutical Therapy Program: A Case In Lutetium-177 Prostate-Specific Membrane Antigen (Psma) Therapy, Jacqueline E Zoberi, Jose Garcia-Ramirez, David Luechtefeld, Nichole M Maughan, Maxwell Amurao, Reiko Oyama, Brian C Baumann, Hiram A Gay, Jeff M Michalski

2020-Current year OA Pubs

Prostate-specific membrane antigen (PSMA) is a cell surface protein highly expressed in nearly all prostate cancers, with restricted expression in some normal tissues. The differential expression of PSMA from tumor to non-tumor tissue has resulted in the investigation of numerous targeting strategies for therapy of patients with metastatic prostate cancer. In March of 2022, the FDA granted approval for the use of lutetium-177 PSMA-617 (Lu-177-PSMA-617) for patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibition and taxane-based chemotherapy. Therefore, the use of Lu-177-PSMA-617 is expected to increase and become more widespread. Herein, …

Presentation And Prognosis Of Excessive Asymptomatic Atrial Ectopy In Children And Adolescents With Structurally And Functionally Normal Hearts, Thomas R Joyce, James J Joyce, Marye J Gleva, Sunita J Ferns

2020-Current year OA Pubs

Excessive premature atrial complexes (PACs) in pediatric patients with a structurally normal heart are presumed to be benign and self-resolving, but no studies have confirmed this. Adults with excessive PACs, however, are at increased risk for future sustained atrial arrhythmias and cardiovascular morbidity and mortality. Therefore, we sought to evaluate the clinical course of frequent PACs in asymptomatic children. Patients < 21 years old with numerous asymptomatic PACs (>50/24 hours) were retrospectively selected over a 10-year period. Demographics, clinical characteristics, and results of cardiovascular testing were tabulated. Two groups were defined: those with a significant (>20%) reduction in burden of atrial ectopy versus those with an insignificant …

Regulation Of Astrocyte Lipid Metabolism And Apoe Secretion By The Microglial Oxysterol, 25-Hydroxycholesterol, Anil G Cashikar, Danira Toral-Rios, David Timm, Johnathan Romero, Michael Strickland, Justin M Long, Xianlin Han, David M Holtzman, Steven M Paul

2020-Current year OA Pubs

Neuroinflammation, a major hallmark of Alzheimer's disease and several other neurological and psychiatric disorders, is often associated with dysregulated cholesterol metabolism. Relative to homeostatic microglia, activated microglia express higher levels of Ch25h, an enzyme that hydroxylates cholesterol to produce 25-hydroxycholesterol (25HC). 25HC is an oxysterol with interesting immune roles stemming from its ability to regulate cholesterol metabolism. Since astrocytes synthesize cholesterol in the brain and transport it to other cells via ApoE-containing lipoproteins, we hypothesized that secreted 25HC from microglia may influence lipid metabolism as well as extracellular ApoE derived from astrocytes. Here, we show that astrocytes take up externally …

Understanding Misimplementation In U.S. State Health Departments: An Agent-Based Model, Matt Kasman, Ross A Hammond, Rob Purcell, Louise Farah Saliba, Stephanie Mazzucca-Ragan, Margaret Padek, Peg Allen, Douglas A Luke, Sarah Moreland-Russell, Paul C Erwin, Ross C Brownson

2020-Current year OA Pubs

INTRODUCTION: The research goal of this study is to explore why misimplementation occurs in public health agencies and how it can be reduced. Misimplementation is ending effective activities prematurely or continuing ineffective ones, which contributes to wasted resources and suboptimal health outcomes.

METHODS: The study team created an agent-based model that represents how information flow, filtered through organizational structure, capacity, culture, and leadership priorities, shapes continuation decisions. This agent-based model used survey data and interviews with state health department personnel across the U.S. between 2014 and 2020; model design and analyses were conducted with substantial input from stakeholders between 2019 …