Digital Commons Network^™

Neonatal Mouse Gut Metabolites Influence Cryptosporidium Parvum Infection In Intestinal Epithelial Cells, Kelli L Vandussen, Lisa J Funkhouser-Jones, Marianna E Akey, Deborah A Schaefer, Kevin Ackman, Michael W Riggs, Thaddeus S Stappenbeck, L David Sibley

Open Access Publications

The protozoan parasite

Large-Scale Characterization Of Drug Responses Of Clinically Relevant Proteins In Cancer Cell Lines, Wei Zhao, Jun Li, Mei-Ju M Chen, Yikai Luo, Zhenlin Ju, Nicole K Nesser, Katie Johnson-Camacho, Christopher T Boniface, Yancey Lawrence, Nupur T Pande, Michael A Davies, Meenhard Herlyn, Taru Muranen, Ioannis K Zervantonakis, Erika Von Euw, Andre Schultz, Shwetha V Kumar, Anil Korkut, Paul T Spellman, Rehan Akbani, Dennis J Slamon, Joe W Gray, Joan S Brugge, Yiling Lu, Gordon B Mills, Han Liang

Faculty, Staff and Students Publications

Perturbation biology is a powerful approach to modeling quantitative cellular behaviors and understanding detailed disease mechanisms. However, large-scale protein response resources of cancer cell lines to perturbations are not available, resulting in a critical knowledge gap. Here we generated and compiled perturbed expression profiles of ∼210 clinically relevant proteins in >12,000 cancer cell line samples in response to ∼170 drug compounds using reverse-phase protein arrays. We show that integrating perturbed protein response signals provides mechanistic insights into drug resistance, increases the predictive power for drug sensitivity, and helps identify effective drug combinations. We build a systematic map of "protein-drug" connectivity …

Conversational Ontology Operator: Patient-Centric Vaccine Dialogue Management Engine For Spoken Conversational Agents, Muhammad Amith, Rebecca Z Lin, Licong Cui, Dennis Wang, Anna Zhu, Grace Xiong, Hua Xu, Kirk Roberts, Cui Tao

2020-Current year OA Pubs

BACKGROUND: Previously, we introduced our Patient Health Information Dialogue Ontology (PHIDO) that manages the dialogue and contextual information of the session between an agent and a health consumer. In this study, we take the next step and introduce the Conversational Ontology Operator (COO), the software engine harnessing PHIDO. We also developed a question-answering subsystem called Frankenstein Ontology Question-Answering for User-centric Systems (FOQUS) to support the dialogue interaction.

METHODS: We tested both the dialogue engine and the question-answering system using application-based competency questions and questions furnished from our previous Wizard of OZ simulation trials.

RESULTS: Our results revealed that the dialogue …

Evaluating The Implementation Of The Switch® School Wellness Intervention And Capacity-Building Process Through Multiple Methods, Gabriella M Mcloughlin, Priscila Candal, Spyridoula Vazou, Joey A Lee, David A Dzewaltowski, Richard R Rosenkranz, Lorraine Lanningham-Foster, Douglas A Gentile, Laura Liechty, Senlin Chen, Gregory J Welk

2020-Current year OA Pubs

BACKGROUND: School wellness programming is important for promoting healthy lifestyles and academic achievement in youth; however, research is needed on methods that can help schools implement and sustain such programs on their own. The purpose of this study was to investigate factors within and outside the school environment that influenced school capacity for implementation and potential sustainability of wellness programming.

METHODS: As part of the School Wellness Integration Targeting Child Health (SWITCH®) intervention, elementary school wellness teams (N = 30) were guided through a capacity-building process focused on promoting the adoption of healthy lifestyle behaviors in students. Data on implementation …

Impact Of A 2-Year Trial Of Nutritional Ketosis On Indices Of Cardiovascular Disease Risk In Patients With Type 2 Diabetes, Shaminie J Athinarayanan, Sarah J Hallberg, Amy L Mckenzie, Katharina Lechner, Sarah King, James P Mccarter, Jeff S Volek, Stephen D Phinney, Ronald M Krauss

Open Access Publications

BACKGROUND: We have previously reported that in patients with type 2 diabetes (T2D) consumption of a very low carbohydrate diet capable of inducing nutritional ketosis over 2 years (continuous care intervention, CCI) resulted in improved body weight, glycemic control, and multiple risk factors for cardiovascular disease (CVD) with the exception of an increase in low density lipoprotein cholesterol (LDL-C). In the present study, we report the impact of this intervention on markers of risk for atherosclerotic cardiovascular disease (CVD), with a focus on lipoprotein subfraction particle concentrations as well as carotid-artery intima-media thickness (CIMT).

METHODS: Analyses were performed in patients …

Approaches To Aggressive B-Cell Lymphomas In Less Fit Patients, Nancy L Bartlett

2020-Current year OA Pubs

Treating unfit patients with aggressive B-cell lymphoma poses the dilemma of balancing potential cure while minimizing toxicity because of frailty and comorbidities. Age greater than 80 years and common comorbidities such as cardiovascular disease and poorly controlled diabetes mellitus often preclude the use of full-dose anthracyclines and steroids, the backbones of standard regimens for aggressive B-cell lymphomas. Assessing patient fitness remains subjective, with no consensus on best practice or how to integrate assessment tools into decision making. Incorporation of prephase steroids for all unfit patients may markedly improve performance status with consideration of standard dose therapy, especially in patients less …

Stem Cell And Niche Regulation In Human Short Bowel Syndrome, Vered A Gazit, Elzbieta A Swietlicki, Miranda U Liang, Adam Surti, Raechel Mcdaniel, Mackenzie Geisman, David M Alvarado, Matthew A Ciorba, Grant Bochicchio, Obeid Ilahi, John Kirby, William J Symons, Nicholas O Davidson, Marc S. Levin, Deborah C Rubin

Open Access Publications

Loss of functional small bowel surface area following surgical resection for disorders such as Crohn's disease, intestinal ischemic injury, radiation enteritis, and in children, necrotizing enterocolitis, atresia, and gastroschisis, may result in short bowel syndrome, with attendant high morbidity, mortality, and health care costs in the United States. Following resection, the remaining small bowel epithelium mounts an adaptive response, resulting in increased crypt cell proliferation, increased villus height, increased crypt depth, and enhanced nutrient and electrolyte absorption. Although these morphologic and functional changes are well described in animal models, the adaptive response in humans is less well understood. Clinically the …

Medicine And Surgery Residents' Perspectives On The Impact Of Covid-19 On Graduate Medical Education., Tanvi Rana, Christopher Hackett, Timothy Quezada, Abhishek Chaturvedi, Veli Bakalov, Jody Leonardo, Sandeep Rana

COVID-19 Papers, Posters, and Presentations

The COVID-19 crisis has had an unprecedented impact on resident education and well-being: social distancing guidelines have limited patient volumes and forced virtual learning, while personal protective equipment (PPE) shortages, school/daycare closures, and visa restrictions have served as additional stressors. Our study aimed to analyze the effects of COVID-19 crisis-related stressors on residents' professional and personal lives. In April 2020, we administered a survey to residents at a large academic hospital system in order to assess the impact of the pandemic on residency training after >6 weeks of a modified schedule. The primary outcome was to determine which factors or …

Pomalidomide, Dexamethasone, And Daratumumab In Relapsed Refractory Multiple Myeloma After Lenalidomide Treatment., David S Siegel, Gary J Schiller, Christy Samaras, Michael Sebag, Jesus Berdeja, Siddhartha Ganguly, Jeffrey Matous, Kevin Song, Christopher S Seet, Giampaolo Talamo, Mirelis Acosta-Rivera, Michael Bar, Donald Quick, Bertrand Anz, Gustavo Fonseca, Donna Reece, William E Pierceall, Weiyuan Chung, Faiza Zafar, Amit Agarwal, Nizar J Bahlis

Articles, Abstracts, and Reports

Patients with multiple myeloma who have relapsed after or become refractory to lenalidomide in early treatment lines represent a clinically important population in need of effective therapies. The safety and efficacy of pomalidomide, low-dose dexamethasone, and daratumumab was evaluated in lenalidomide-pretreated patients with relapsed or refractory multiple myeloma (RRMM) after one to two prior treatment lines in the phase 2 MM-014 study. Patients received pomalidomide 4 mg daily from days 1-21 and dexamethasone 40 mg weekly (28-day cycles). Daratumumab 16 mg/kg was administered per label. Primary endpoint was overall response rate (ORR); secondary endpoints included progression-free survival (PFS) and safety. …

A Randomized, Placebo-Controlled Trial Evaluating Effects Of Lebrikizumab On Airway Eosinophilic Inflammation And Remodelling In Uncontrolled Asthma (Clavier), Cary D Austin, Kaharu Sumino, Et Al.

2020-Current year OA Pubs

BACKGROUND: The anti-interleukin 13 (IL-13) monoclonal antibody lebrikizumab improves lung function in patients with moderate-to-severe uncontrolled asthma, but its effects on airway inflammation and remodelling are unknown. CLAVIER was designed to assess lebrikizumab's effect on eosinophilic inflammation and remodelling.

OBJECTIVE: To report safety and efficacy results from enrolled participants with available data from CLAVIER.

METHODS: We performed bronchoscopy on patients with uncontrolled asthma before and after 12 weeks of randomized double-blinded treatment with lebrikizumab (n = 31) or placebo (n = 33). The pre-specified primary end-point was relative change in airway subepithelial eosinophils per mm

RESULTS: There was a baseline …

Positive Information Facilitates Response Inhibition In Older Adults Only When Emotion Is Task-Relevant, Samantha E Williams, Eric J Lenze, Jill D Waring

Open Access Publications

Emotional information is integral to everyday life and impacts a variety of cognitive abilities including response inhibition, a critical skill for maintaining appropriate and flexible behaviour. However, reported effects of emotion on response inhibition are inconsistent in younger adults, and very limited in older adults. Effects of aging are especially relevant because emotion regulation improves with aging despite declining inhibitory control over neutral information. Across three studies, we assessed the impact of emotional facial expressions on response inhibition in younger and older adults while manipulating attention to task stimuli. Emotional faces (versus neutral faces) altered response inhibition only when task …

Epilepsy Risk Prediction Model For Patients With Tuberous Sclerosis Complex, Laura S Farach, Melissa A Richard, Philip J Lupo, Mustafa Sahin, Darcy A Krueger, Joyce Y Wu, Elizabeth M Bebin, Kit Sing Au, Hope Northrup, Tacern Study Group

Faculty, Staff and Student Publications

BACKGROUND: Individuals with tuberous sclerosis complex are at increased risk of epilepsy. Early seizure control improves developmental outcomes, making identifying at-risk patients critically important. Despite several identified risk factors, it remains difficult to predict. The purpose of the study was to evaluate the combined risk prediction of previously identified risk factors for epilepsy in individuals with tuberous sclerosis complex.

METHODS: The study group (n = 333) consisted of individuals with tuberous sclerosis complex who were enrolled in the Tuberous Sclerosis Complex Autism Center of Excellence Research Network and UT TSC Biobank. The outcome was defined as having an epilepsy diagnosis. …

Lipid Management In Patients With Endocrine Disorders: An Endocrine Society Clinical Practice Guideline., Connie B Newman, Michael J Blaha, Jeffrey B. Boord, Bertrand Cariou, Alan Chait, Henry G Fein, Henry N Ginsberg, Ira J Goldberg, M Hassan Murad, Savitha Subramanian, Lisa R Tannock

Hospital Medicine

OBJECTIVE: This guideline will provide the practicing endocrinologist with an approach to the assessment and treatment of dyslipidemia in patients with endocrine diseases, with the objective of preventing cardiovascular (CV) events and triglyceride-induced pancreatitis. The guideline reviews data on dyslipidemia and atherosclerotic cardiovascular disease (ASCVD) risk in patients with endocrine disorders and discusses the evidence for the correction of dyslipidemia by treatment of the endocrine disease. The guideline also addresses whether treatment of the endocrine disease reduces ASCVD risk.

CONCLUSION: This guideline focuses on lipid and lipoprotein abnormalities associated with endocrine diseases, including diabetes mellitus, and whether treatment of the …

International Council For Standardization In Haematology (Icsh) Recommendations For Laboratory Measurement Of Adamts13, Ian Mackie, Ilaria Mancini, Joshua Muia, Johanna Kremer Hovinga, Sukesh Nair, Sam Machin, Ross Baker

2020-Current year OA Pubs

This guidance document was prepared on behalf of the International Council for Standardization in Haematology (ICSH), by the ADAMTS13 Assay Working Group, which comprises an international group of both clinical and laboratory experts. The document provides recommendations on best practice for the performance of ADAMTS13 assays in clinical laboratories. ADAMTS13 assays support the differential diagnosis of thrombotic microangiopathies and have utility in the management of thrombotic thrombocytopenic purpura (TTP). There are three types of assay: activity, antigen and autoantibody/inhibitor assays. Methods for activity assays differ in terms of sensitivity, specificity, precision and turnaround time. The most widely used assays involve …

Evolution Of The Epigenetic Landscape In Childhood B Acute Lymphoblastic Leukemia And Its Role In Drug Resistance, Shella Saint Fleur-Lominy, Nikki A. Evensen, Teena Bhatla, Gunjan Sethia, Sonali Narang, Jun H. Choi, Xiaotu Ma, Jun J. Yang, Stephen Kelly, Elizabeth Raetz, Richard C. Harvey, Cheryl Willman, Mignon L. Loh, Stephen P. Hunger, Patrick A. Brown, Kylie M. Getz, Cem Meydan, Christopher E. Mason, Aristotelis Tsirigos, William Carroll

Pathology Research and Scholarship

Although B-cell acute lymphoblastic leukemia (B-ALL) is the most common malignancy in children and while highly curable, it remains a leading cause of cancer-related mortality. The outgrowth of tumor subclones carrying mutations in genes responsible for resistance to therapy has led to a Darwinian model of clonal selection. Previous work has indicated that alterations in the epigenome might contribute to clonal selection, yet the extent to which the chromatin state is altered under the selective pressures of therapy is unknown. To address this, we performed chromatin immunoprecipitation, gene expression analysis, and enhanced reduced representation bisulfite sequencing on a cohort of …

Inflammatory Myopathies: Update On Diagnosis, Pathogenesis And Therapies, And Covid-19-Related Implications., Marinos C. Dalakas

Department of Neurology Faculty Papers

The inflammatory myopathies constitute a heterogeneous group of acquired myopathies that have in common the presence of endomysial inflammation. Based on steadily evolved clinical, histological and immunopathological features and some autoantibody associations, these disorders can now be classified in five characteristic subsets: Dermatomyositis (DM) Polymyositis (PM), Necrotizing Autoimmune Myositis (NAM), Anti-synthetase syndrome-overlap myositis (Anti-SS-OM), and Inclusion-Body-Myositis (IBM). Each inflammatory myopathy subset has distinct immunopathogenesis, prognosis and response to immunotherapies, necessitating the need to correctly identify each subtype from the outset to avoid disease mimics and proceed to early therapy initiation. The review presents the main clinicopathologic characteristics of each subset …

Antibody Profiling Of Patients With Prostate Cancer Reveals Differences In Antibody Signatures Among Disease Stages, Hemanth K Potluri, Tun Lee Ng, Michael A Newton, Jin Zhang, Christopher A Maher, Peter S Nelson, Douglas G Mcneel

2020-Current year OA Pubs

BACKGROUND: Previous studies of prostate cancer autoantibodies have largely focused on diagnostic applications. So far, there have been no reports attempting to more comprehensively profile the landscape of prostate cancer-associated antibodies. Specifically, it is unknown whether the quantity of antibodies or the types of proteins recognized change with disease progression.

METHODS: A peptide microarray spanning the amino acid sequences of the gene products of 1611 prostate cancer-associated genes was synthesized. Serum samples from healthy male volunteers (n=15) and patients with prostate cancer (n=85) were used to probe the array. These samples included patients with various clinical stages of disease: newly …

Spinal Cord Injury Provider Knowledge And Attitudes Toward Bacteriuria Management And Antibiotic Stewardship, Felicia Skelton, Sarah May, Larissa Grigoryan, Ivy Poon, Sally Ann Holmes, Lindsey Martin, Barbara W Trautner

Faculty, Staff and Students Publications

INTRODUCTION: Bacteriuria, either asymptomatic or urinary tract infection, is common in persons with spinal cord injury or disorder (SCI/D). In the Veterans Health Administration (VHA), conflicting clinical practice guidelines make appropriate bacteriuria management and antibiotic stewardship challenging.

OBJECTIVE: To explore SCI/D provider knowledge, attitudes, and teamwork around bacteriuria management during the VHA SCI/D annual examination.

DESIGN: Mixed methods.

SETTING: VHA SCI/D centers.

PARTICIPANTS: SCI/D staff providers and physical medicine and rehabilitation resident physicians.

MAIN OUTCOME MEASUREMENTS: Knowledge, safety, and teamwork scores on bacteriuria management using a validated questionnaire. Themes on barriers and facilitators to bacteriuria management during the SCI/D annual …

The Cancer Patient And Cardiology, José Luis Zamorano, Christer Gottfridsson, Riccardo Asteggiano, Dan Atar, Lina Badimon, Jeroen J Bax, Daniela Cardinale, Antonella Cardone, Elizabeth A M Feijen, Péter Ferdinandy, Teresa López-Fernández, Chris P Gale, John H Maduro, Javid Moslehi, Torbjørn Omland, Juan Carlos Plana Gomez, Jessica Scott, Thomas M Suter, Giorgio Minotti

Faculty, Staff and Students Publications

Advances in cancer treatments have improved clinical outcomes, leading to an increasing population of cancer survivors. However, this success is associated with high rates of short- and long-term cardiovascular (CV) toxicities. The number and variety of cancer drugs and CV toxicity types make long-term care a complex undertaking. This requires a multidisciplinary approach that includes expertise in oncology, cardiology and other related specialties, and has led to the development of the cardio-oncology subspecialty. This paper aims to provide an overview of the main adverse events, risk assessment and risk mitigation strategies, early diagnosis, medical and complementary strategies for prevention and …

Sequence Analysis In Bos Taurus Reveals Pervasiveness Of X-Y Arms Races In Mammalian Lineages, Jennifer F Hughes, Colin Kremitzki, Catrina Fronick, Tina A Graves-Lindsay, Lucinda Fulton, Wesley C Warren, Richard K Wilson, Et Al.

2020-Current year OA Pubs

Studies of Y Chromosome evolution have focused primarily on gene decay, a consequence of suppression of crossing-over with the X Chromosome. Here, we provide evidence that suppression of X-Y crossing-over unleashed a second dynamic: selfish X-Y arms races that reshaped the sex chromosomes in mammals as different as cattle, mice, and men. Using super-resolution sequencing, we explore the Y Chromosome of

Differences In Gynecologic Tumor Development In Amhr2-Cre Mice With Krasg12d Or Krasg12v Mutations, Eucharist H S Kun, Yvonne T M Tsang, Sophia Lin, Sophia Pan, Tejas Medapalli, Anais Malpica, Joanne S Richards, David M Gershenson, Kwong-Kwok Wong

Faculty, Staff and Students Publications

How different KRAS variants impact tumor initiation and progression in vivo has not been thoroughly examined. We hypothesize that the ability of either KRASG12D or KRASG12V mutations to initiate tumor formation is context dependent. Amhr2-Cre mice express Cre recombinase in tissues that develop into the fallopian tubes, uterus, and ovaries. We used these mice to conditionally express either the KRASG12V/+ or KRASG12D/+ mutation. Mice with the genotype Amhr2-Cre Pten(fl/fl) KrasG12D/+(G12D mice) had abnormal follicle structures and developed low-grade serous ovarian carcinomas with 100% penetrance within 18 weeks. In contrast, mice with …

A Genomic Signature For Accurate Classification And Prediction Of Clinical Outcomes In Cancer Patients Treated With Immune Checkpoint Blockade Immunotherapy, Mei Lu, Kuan-Han Wu, Sheri Trudeau, Margaret Jiang, Joe Zhao, Elliott Fan

Public Health Sciences Articles

Tumor mutational burden (TMB) is associated with clinical response to immunotherapy, but application has been limited to a subset of cancer patients. We hypothesized that advanced machine-learning and proper modeling could identify mutations that classify patients most likely to derive clinical benefits. Training data: Two sets of public whole-exome sequencing (WES) data for metastatic melanoma. Validation data: One set of public non-small cell lung cancer (NSCLC) data. Least Absolute Shrinkage and Selection Operator (LASSO) machine-learning and proper modeling were used to identify a set of mutations (biomarker) with maximum predictive accuracy (measured by AUROC). Kaplan-Meier and log-rank methods were used …

Altered Capicua Expression Drives Regional Purkinje Neuron Vulnerability Through Ion Channel Gene Dysregulation In Spinocerebellar Ataxia Type 1, Ravi Chopra, David D Bushart, John P Cooper, Dhananjay Yellajoshyula, Logan M Morrison, Haoran Huang, Hillary P Handler, Luke J Man, Warunee Dansithong, Daniel R Scoles, Stefan M Pulst, Harry T Orr, Vikram G Shakkottai

2020-Current year OA Pubs

Selective neuronal vulnerability in neurodegenerative disease is poorly understood. Using the ATXN1[82Q] model of spinocerebellar ataxia type 1 (SCA1), we explored the hypothesis that regional differences in Purkinje neuron degeneration could provide novel insights into selective vulnerability. ATXN1[82Q] Purkinje neurons from the anterior cerebellum were found to degenerate earlier than those from the nodular zone, and this early degeneration was associated with selective dysregulation of ion channel transcripts and altered Purkinje neuron spiking. Efforts to understand the basis for selective dysregulation of channel transcripts revealed modestly increased expression of the ATXN1 co-repressor Capicua (Cic) in anterior cerebellar Purkinje neurons. Importantly, …

Social And Leisure Activities Predict Transitions In Cognitive Functioning In Older Mexican Adults: A Latent Transition Analysis Of The Mexican Health And Aging Study, Heather Mary Brown, Stephen A Murray, Hope Northrup, Kit Sing Au, Lee A Niswander

Faculty, Staff and Student Publications

Disruptions in neural tube (NT) closure result in neural tube defects (NTDs). To understand the molecular processes required for mammalian NT closure, we investigated the role of Snx3, a sorting nexin gene. Snx3−/− mutant mouse embryos display a fully-penetrant cranial NTD. In vivo, we observed decreased canonical WNT target gene expression in the cranial neural epithelium of the Snx3−/− embryos and a defect in convergent extension of the neural epithelium. Snx3−/− cells show decreased WNT secretion, and live cell imaging reveals aberrant recycling of the WNT ligand-binding protein WLS and mis-trafficking to the lysosome for degradation. The importance …

Anemocheck-Lrs: An Optimized, Color-Based Point-Of-Care Test To Identify Severe Anemia In Limited-Resource Settings, Marina S Perez-Plazola, Erika A Tyburski, Luke R Smart, Thad A Howard, Amanda Pfeiffer, Russell E Ware, Wilbur A Lam, Patrick T Mcgann

2020-Current year OA Pubs

BACKGROUND: Severe anemia is common and frequently fatal for hospitalized patients in limited-resource settings. Lack of access to low-cost, accurate, and rapid diagnosis of anemia impedes the delivery of life-saving care and appropriate use of the limited blood supply. The WHO Haemoglobin Colour Scale (HCS) is a simple low-cost test but frequently inaccurate. AnemoCheck-LRS (limited-resource settings) is a rapid, inexpensive, color-based point-of-care (POC) test optimized to diagnose severe anemia.

METHODS: Deidentified whole blood samples were diluted with plasma to create variable hemoglobin (Hb) concentrations, with most in the severe (≤ 7 g/dL) or profound (≤ 5 g/dL) anemia range. Each …

Evolution Of Brain-Wide Activity In The Awake Behaving Mouse After Acute Fear By Longitudinal Manganese-Enhanced Mri, Taylor W. Uselman, Daniel R. Barto, Russell E. Jacobs, Elaine L. Bearer

Pathology Research and Scholarship

Life threatening fear after a single exposure evolves in a subset of vulnerable individuals to anxiety, which may persist for their lifetime. Yet neither the whole brain's response to innate acute fear nor how brain activity evolves over time is known. Sustained neuronal activity may be a factor in the development of a persistent fear response. We couple two experimental protocols to provoke acute fear leading to prolonged fear: Predator stress (PS), a naturalistic approach to induce fear in rodents; and Serotonin transporter knockout mouse (SERT-KO) that responds to PS with sustained defensive behavior. Behavior was monitored before, during and …

A Praziquantel Treatment Study Of Immune And Transcriptome Profiles In Schistosoma Haematobium-Infected Gabonese Schoolchildren, Lucja A Labuda, Ayola A Adegnika, Bruce A Rosa, John Martin, Ulysse Ateba-Ngoa, Abena Serwaa Amoah, Honorine Mbenkep Lima, Lynn Meurs, Moustapha Mbow, Mikhael D Manurung, Jeannot F Zinsou, Hermelijn H Smits, Peter G Kremsner, Makedonka Mitreva, Maria Yazdanbakhsh

2020-Current year OA Pubs

BACKGROUND: Although Schistosoma haematobium infection has been reported to be associated with alterations in immune function, in particular immune hyporesponsiveness, there have been only few studies that have used the approach of removing infection by drug treatment to establish this and to understand the underlying molecular mechanisms.

METHODS: Schistosoma haematobium-infected schoolchildren were studied before and after praziquantel treatment and compared with uninfected controls. Cellular responses were characterized by cytokine production and flow cytometry, and in a subset of children RNA sequencing (RNA-Seq) transcriptome profiling was performed.

RESULTS: Removal of S haematobium infection resulted in increased schistosome-specific cytokine responses that were …

Structural Basis Of Ion Transport And Inhibition In Ferroportin, Yaping Pan, Zhenning Ren, Shuai Gao, Jiemin Shen, Lie Wang, Zhichun Xu, Ye Yu, Preetham Bachina, Hanzhi Zhang, Xiao Fan, Arthur Laganowsky, Nieng Yan, Ming Zhou

Faculty, Staff and Students Publications

Ferroportin is an iron exporter essential for releasing cellular iron into circulation. Ferroportin is inhibited by a peptide hormone, hepcidin. In humans, mutations in ferroportin lead to ferroportin diseases that are often associated with accumulation of iron in macrophages and symptoms of iron deficiency anemia. Here we present the structures of the ferroportin from the primate Philippine tarsier (TsFpn) in the presence and absence of hepcidin solved by cryo-electron microscopy. TsFpn is composed of two domains resembling a clamshell and the structure defines two metal ion binding sites, one in each domain. Both structures are in an outward-facing conformation, and …

Fetal And Early Postnatal Lead Exposure Measured In Teeth Associates With Infant Gut Microbiota, Alexandra R. Sitarik, Manish Arora, Christine Austin, Lawrence F. Bielak, Shoshannah Eggers, Christine C. Johnson, Susan V Lynch, Sung Kyun Park, Kuan-Han H. Wu, Germaine Jm Yong, Andrea E. Cassidy-Bushrow

Public Health Sciences Articles

BACKGROUND: Lead (Pb) is an environmentally ubiquitous heavy metal associated with a wide range of adverse health effects in children. Both lead exposure and the early life microbiome- which plays a critical role in human development-have been linked to similar health outcomes, but it is unclear if the adverse effects of lead are partially driven by early life gut microbiota dysbiosis. The objective of this study was to examine the association between in utero and postnatal lead levels (measured in deciduous baby teeth) and early life bacterial and fungal gut microbiota in the first year of life.

METHODS: Data from …

Organizational Readiness Assessment In Acute And Long-Term Care Has Important Implications For Antibiotic Stewardship For Asymptomatic Bacteriuria, Melanie C Goebel, Barbara W Trautner, Yiqun Wang, John N Van, Laura M Dillon, Payal K Patel, Dimitri M Drekonja, Christopher J Graber, Bhavarth S Shukla, Paola Lichtenberger, Christian D Helfrich, Anne Sales, Larissa Grigoryan

Faculty, Staff and Students Publications

BACKGROUND: Prior to implementing an antibiotic stewardship intervention for asymptomatic bacteriuria (ASB), we assessed institutional barriers to change using the Organizational Readiness to Change Assessment.

METHODS: Surveys were self-administered on paper in inpatient medicine and long-term care units at 4 Veterans Affairs facilities. Participants included providers, nurses, and pharmacists. The survey included 7 subscales: evidence (perceived strength of evidence) and six context subscales (favorability of organizational context). Responses were scored on a 5-point Likert-type scale.

RESULTS: One hundred four surveys were completed (response rate = 69.3%). Overall, the evidence subscale had the highest score; the resources subscale (mean 2.8) was …