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Digenic Variants In The Fgf21 Signaling Pathway Associated With Severe Insulin Resistance And Pseudoacromegaly, Stephen I Stone, Daniel J Wegner, Jennifer A Wambach, F Sessions Cole, Fumihiko Urano, David M Ornitz Sep 2020

Digenic Variants In The Fgf21 Signaling Pathway Associated With Severe Insulin Resistance And Pseudoacromegaly, Stephen I Stone, Daniel J Wegner, Jennifer A Wambach, F Sessions Cole, Fumihiko Urano, David M Ornitz

Open Access Publications

Insulin-mediated pseudoacromegaly (IMPA) is a rare disease of unknown etiology. Here we report a 12-year-old female with acanthosis nigricans, hirsutism, and acromegalic features characteristic of IMPA. The subject was noted to have normal growth hormone secretion, with extremely elevated insulin levels. Studies were undertaken to determine a potential genetic etiology for IMPA. The proband and her family members underwent whole exome sequencing. Functional studies were undertaken to validate the pathogenicity of candidate variant alleles. Whole exome sequencing identified monoallelic, predicted deleterious variants in genes that mediate fibroblast growth factor 21 (FGF21) signaling,


Integrase-Rna Interactions Underscore The Critical Role Of Integrase In Hiv-1 Virion Morphogenesis, Jennifer L. Elliott, Jenna E. Eschbach, Pratibha C. Koneru, Wen Li, Maritza Puray-Chavez, Dana Townsend, Dana Q. Lawson, Alan N. Engelman, Mamuka Kvaratskhelia, Sebla B. Kutluay Sep 2020

Integrase-Rna Interactions Underscore The Critical Role Of Integrase In Hiv-1 Virion Morphogenesis, Jennifer L. Elliott, Jenna E. Eschbach, Pratibha C. Koneru, Wen Li, Maritza Puray-Chavez, Dana Townsend, Dana Q. Lawson, Alan N. Engelman, Mamuka Kvaratskhelia, Sebla B. Kutluay

Open Access Publications

A large number of human immunodeficiency virus 1 (HIV-1) integrase (IN) alterations, referred to as class II substitutions, exhibit pleiotropic effects during virus replication. However, the underlying mechanism for the class II phenotype is not known. Here we demonstrate that all tested class II IN substitutions compromised IN-RNA binding in virions by one of the three distinct mechanisms: (i) markedly reducing IN levels thus precluding the formation of IN complexes with viral RNA; (ii) adversely affecting functional IN multimerization and consequently impairing IN binding to viral RNA; and (iii) directly compromising IN-RNA interactions without substantially affecting IN levels or functional …


Incidence Of Uveitis And Macular Edema Among Patients Taking Fingolimod 0.5 Mg For Multiple Sclerosis., Scott Joseph Sonne, Bradley Thomas Smith Sep 2020

Incidence Of Uveitis And Macular Edema Among Patients Taking Fingolimod 0.5 Mg For Multiple Sclerosis., Scott Joseph Sonne, Bradley Thomas Smith

Open Access Publications

BACKGROUND: Patients with multiple sclerosis (MS) have a higher incidence of uveitis compared with the general population. Fingolimod, a first line disease modifying drug used in multiple sclerosis, may cause macular edema and thus requires ophthalmic examination. However, murine models and anecdotal reports suggest fingolimod may reduce the incidence of uveitis.

PURPOSE: To report the incidence of uveitis and macular edema among those on fingolimod 0.5 mg (Gilenya®) therapy for multiple sclerosis (MS).

METHODS: Retrospective review of patients on fingolimod who developed uveitis and/or macular edema.

RESULTS: No patients had an occurrence or history of uveitis. Four of the 188 …


Epidemiological Evidence For A Hereditary Contribution To Myasthenia Gravis: A Retrospective Cohort Study Of Patients From North America, Joshua D Green, Julaine Florence, Alan Pestronk, Charlie Wulf, Et Al Sep 2020

Epidemiological Evidence For A Hereditary Contribution To Myasthenia Gravis: A Retrospective Cohort Study Of Patients From North America, Joshua D Green, Julaine Florence, Alan Pestronk, Charlie Wulf, Et Al

Open Access Publications

OBJECTIVES: To approximate the rate of familial myasthenia gravis and the coexistence of other autoimmune disorders in the patients and their families.

DESIGN: Retrospective cohort study.

SETTING: Clinics across North America.

PARTICIPANTS: The study included 1032 patients diagnosed with acetylcholine receptor antibody (AChR)-positive myasthenia gravis.

METHODS: Phenotype information of 1032 patients diagnosed with AChR-positive myasthenia gravis was obtained from clinics at 14 centres across North America between January 2010 and January 2011. A critical review of the epidemiological literature on the familial rate of myasthenia gravis was also performed.

RESULTS: Among 1032 patients, 58 (5.6%) reported a family history of …


Etv6 Germline Mutations Cause Hdac3/Ncor2 Mislocalization And Upregulation Of Interferon Response Genes, Marlie H Fisher, Gregory D Kirkpatrick, Brett Stevens, Courtney Jones, Michael Callaghan, Madhvi Rajpurkar, Joy Fulbright, Megan A Cooper, Jesse Rowley, Christopher C Porter, Arthur Gutierrez-Hartmann, Kenneth Jones, Craig Jordan, Eric M Pietras, Jorge Di Paola Sep 2020

Etv6 Germline Mutations Cause Hdac3/Ncor2 Mislocalization And Upregulation Of Interferon Response Genes, Marlie H Fisher, Gregory D Kirkpatrick, Brett Stevens, Courtney Jones, Michael Callaghan, Madhvi Rajpurkar, Joy Fulbright, Megan A Cooper, Jesse Rowley, Christopher C Porter, Arthur Gutierrez-Hartmann, Kenneth Jones, Craig Jordan, Eric M Pietras, Jorge Di Paola

Open Access Publications

ETV6 is an ETS family transcription factor that plays a key role in hematopoiesis and megakaryocyte development. Our group and others have identified germline mutations in ETV6 resulting in autosomal dominant thrombocytopenia and predisposition to malignancy; however, molecular mechanisms defining the role of ETV6 in megakaryocyte development have not been well established. Using a combination of molecular, biochemical, and sequencing approaches in patient-derived PBMCs, we demonstrate abnormal cytoplasmic localization of ETV6 and the HDAC3/NCOR2 repressor complex that led to overexpression of HDAC3-regulated interferon response genes. This transcriptional dysregulation was also reflected in patient-derived platelet transcripts and drove aberrant proplatelet formation …


Antimicrobial Resistance Surveillance In Low- And Middle-Income Countries: Progress And Challenges In Eight South Asian And Southeast Asian Countries, Sumanth Gandra, Gerardo Alvarez-Uria, Paul Turner, Jyoti Joshi, Direk Limmathurotsakul, H. Rogier Van Doorn Sep 2020

Antimicrobial Resistance Surveillance In Low- And Middle-Income Countries: Progress And Challenges In Eight South Asian And Southeast Asian Countries, Sumanth Gandra, Gerardo Alvarez-Uria, Paul Turner, Jyoti Joshi, Direk Limmathurotsakul, H. Rogier Van Doorn

Open Access Publications

SUMMARYAntimicrobial resistance (AMR) is a serious global health threat and is predicted to cause significant health and economic impacts, particularly in low- and middle-income countries (LMICs). AMR surveillance is critical in LMICs due to high burden of bacterial infections; however, conducting AMR surveillance in resource-limited settings is constrained by poorly functioning health systems, scarce financial resources, and lack of skilled personnel. In 2015, the United Nations World Health Assembly endorsed the World Health Organization's Global Action Plan to tackle AMR; thus, several countries are striving to improve their AMR surveillance capacity, including making significant investments and establishing and expanding surveillance …


Lurasidone And Risk For Metabolic Syndrome: Results From Short- And Long-Term Clinical Studies In Patients With Schizophrenia, Michael Tocco, John W Newcomer, Yongcai Mao, Andrei Pikalov, Antony Loebel Sep 2020

Lurasidone And Risk For Metabolic Syndrome: Results From Short- And Long-Term Clinical Studies In Patients With Schizophrenia, Michael Tocco, John W Newcomer, Yongcai Mao, Andrei Pikalov, Antony Loebel

Open Access Publications

OBJECTIVE: To assess the effects of treatment with lurasidone on risk for metabolic syndrome (MetS) in patients with schizophrenia.

METHODS: Rates of metabolic syndrome during treatment with lurasidone (40-160 mg/d) were analyzed using pooled, short-term data from three randomized, double-blind, placebo-controlled studies (vs olanzapine and quetiapine XR); long-term data from two active-comparator-controlled studies (vs risperidone and quetiapine XR); and data from two open-label studies in which patients were switched from olanzapine or risperidone to lurasidone.

RESULTS: MetS was defined based on the National Cholesterol Education Program criteria. In short-term studies, the odds of meeting criteria for MetS at week 6 …


Higher Csf Strem2 And Microglia Activation Are Associated With Slower Rates Of Beta-Amyloid Accumulation, Michael Ewers, Laura Piccio, Carlos Cruchaga, Et Al Sep 2020

Higher Csf Strem2 And Microglia Activation Are Associated With Slower Rates Of Beta-Amyloid Accumulation, Michael Ewers, Laura Piccio, Carlos Cruchaga, Et Al

Open Access Publications

Microglia activation is the brain's major immune response to amyloid plaques in Alzheimer's disease (AD). Both cerebrospinal fluid (CSF) levels of soluble TREM2 (sTREM2), a biomarker of microglia activation, and microglia PET are increased in AD; however, whether an increase in these biomarkers is associated with reduced amyloid-beta (Aβ) accumulation remains unclear. To address this question, we pursued a two-pronged translational approach. Firstly, in non-demented and demented individuals, we tested CSF sTREM2 at baseline to predict (i) amyloid PET changes over ∼2 years and (ii) tau PET cross-sectionally assessed in a subset of patients. We found higher CSF sTREM2 associated …


Amygdalin Promotes Fracture Healing Through Tgf- Β/Smad Signaling In Mesenchymal Stem Cells, Jun Ying, Jie Shen, Et Al Sep 2020

Amygdalin Promotes Fracture Healing Through Tgf- Β/Smad Signaling In Mesenchymal Stem Cells, Jun Ying, Jie Shen, Et Al

Open Access Publications

No abstract provided.


A Review Of Chemotherapy And Radiotherapy Near The End Of Life In Individuals With Metastatic Non-Small Cell Lung Cancer, Benjamin C. Li, Stephanie M. Perkins, Sharon E. Phillips, Sara F. Martin, Samantha Hsieh, Eric T. Shinohara, Mark J. Stavas Sep 2020

A Review Of Chemotherapy And Radiotherapy Near The End Of Life In Individuals With Metastatic Non-Small Cell Lung Cancer, Benjamin C. Li, Stephanie M. Perkins, Sharon E. Phillips, Sara F. Martin, Samantha Hsieh, Eric T. Shinohara, Mark J. Stavas

Open Access Publications

No abstract provided.


Bypass Of Dna Interstrand Crosslinks By A Rev1-Dna Polymerase Ζ Complex, Rachel Bezalel-Buch, Young K. Cheun, Upasana Roy, Orlando D. Schärer, Peter M. Burgers Sep 2020

Bypass Of Dna Interstrand Crosslinks By A Rev1-Dna Polymerase Ζ Complex, Rachel Bezalel-Buch, Young K. Cheun, Upasana Roy, Orlando D. Schärer, Peter M. Burgers

Open Access Publications

DNA polymerase ζ (Pol ζ) and Rev1 are essential for the repair of DNA interstrand crosslink (ICL) damage. We have used yeast DNA polymerases η, ζ and Rev1 to study translesion synthesis (TLS) past a nitrogen mustard-based interstrand crosslink (ICL) with an 8-atom linker between the crosslinked bases. The Rev1-Pol ζ complex was most efficient in complete bypass synthesis, by 2-3 fold, compared to Pol ζ alone or Pol η. Rev1 protein, but not its catalytic activity, was required for efficient TLS. A dCMP residue was faithfully inserted across the ICL-G by Pol η, Pol ζ, and Rev1-Pol ζ. Rev1-Pol …


Local Complement Activation Is Associated With Primary Graft Dysfunction After Lung Transplantation, Hrishikesh S Kulkarni, Lina Ma, Kaitlyn N Speckhart, Tsuyoshi Takahashi, Derek E Byers, Mary K Porteous, Laurel Kalman, Ramsey R Hachem, Melanie Rushefski, Ja'nia Mcphatter, Marlene Cano, Daniel Kreisel, Brigitte Mittler, John P Atkinson, Andrew E Gelman, Et Al Sep 2020

Local Complement Activation Is Associated With Primary Graft Dysfunction After Lung Transplantation, Hrishikesh S Kulkarni, Lina Ma, Kaitlyn N Speckhart, Tsuyoshi Takahashi, Derek E Byers, Mary K Porteous, Laurel Kalman, Ramsey R Hachem, Melanie Rushefski, Ja'nia Mcphatter, Marlene Cano, Daniel Kreisel, Brigitte Mittler, John P Atkinson, Andrew E Gelman, Et Al

Open Access Publications

BACKGROUNDThe complement system plays a key role in host defense but is activated by ischemia/reperfusion injury (IRI). Primary graft dysfunction (PGD) is a form of acute lung injury occurring predominantly due to IRI, which worsens survival after lung transplantation (LTx). Local complement activation is associated with acute lung injury, but whether it is more reflective of allograft injury compared with systemic activation remains unclear. We proposed that local complement activation would help identify those who develop PGD after LTx. We also aimed to identify which complement activation pathways are associated with PGD.METHODSWe performed a multicenter cohort study at the University …


Co-Clinical Imaging Resource Program (Cirp): Bridging The Translational Divide To Advance Precision Medicine, Kooresh I. Shoghi, Richard Laforest, Daniel S. Marcus, Et Al Sep 2020

Co-Clinical Imaging Resource Program (Cirp): Bridging The Translational Divide To Advance Precision Medicine, Kooresh I. Shoghi, Richard Laforest, Daniel S. Marcus, Et Al

Open Access Publications

The National Institutes of Health's (National Cancer Institute) precision medicine initiative emphasizes the biological and molecular bases for cancer prevention and treatment. Importantly, it addresses the need for consistency in preclinical and clinical research. To overcome the translational gap in cancer treatment and prevention, the cancer research community has been transitioning toward using animal models that more fatefully recapitulate human tumor biology. There is a growing need to develop best practices in translational research, including imaging research, to better inform therapeutic choices and decision-making. Therefore, the National Cancer Institute has recently launched the Co-Clinical Imaging Research Resource Program (CIRP). Its …


Impact Of Annual And Semi-Annual Mass Drug Administration For Lymphatic Filariasis And Onchocerciasis On Hookworm Infection In Côte D'Ivoire, Agodio Loukouri, Aboulaye Méité, Benjamin G. Koudou, Charles W. Goss, Daphne Lew, Gary J. Weil, Eliezer K. N'Goran, Peter U. Fischer Sep 2020

Impact Of Annual And Semi-Annual Mass Drug Administration For Lymphatic Filariasis And Onchocerciasis On Hookworm Infection In Côte D'Ivoire, Agodio Loukouri, Aboulaye Méité, Benjamin G. Koudou, Charles W. Goss, Daphne Lew, Gary J. Weil, Eliezer K. N'Goran, Peter U. Fischer

Open Access Publications

Mass Drug Administration (MDA) programs to eliminate Lymphatic Filariasis (LF) in western Africa use the anthelminthics ivermectin plus albendazole. These drugs have the potential to impact also Soil-Transmitted Helminth (STH) infections, since the drugs have a broad range of anthelminthic activity. Integration of preventive chemotherapy efforts for LF, onchocerciasis and STH is recommended by the World Health Organization (WHO) in order to avoid duplication of MDA and to reduce costs. The objective of the current study was to determine whether five semi-annual rounds of community-wide MDA to eliminate LF and onchocerciasis have a greater impact on STH than three annual …


Reducing Antibiotic Prescribing And Addressing The Global Problem Of Antibiotic Resistance By Targeted Hygiene In The Home And Everyday Life Settings: A Position Paper, Jean-Yves Maillard, Sally F Bloomfield, Patrice Courvalin, Sabiha Y Essack, Sumanth Gandra, Charles P Gerba, Joseph R Rubino, Elizabeth A Scott Sep 2020

Reducing Antibiotic Prescribing And Addressing The Global Problem Of Antibiotic Resistance By Targeted Hygiene In The Home And Everyday Life Settings: A Position Paper, Jean-Yves Maillard, Sally F Bloomfield, Patrice Courvalin, Sabiha Y Essack, Sumanth Gandra, Charles P Gerba, Joseph R Rubino, Elizabeth A Scott

Open Access Publications

Antimicrobial resistance (AMR) continues to threaten global health. Although global and national AMR action plans are in place, infection prevention and control is primarily discussed in the context of health care facilities with home and everyday life settings barely addressed. As seen with the recent global SARS-CoV-2 pandemic, everyday hygiene measures can play an important role in containing the threat from infectious microorganisms. This position paper has been developed following a meeting of global experts in London, 2019. It presents evidence that home and community settings are important for infection transmission and also the acquisition and spread of AMR. It …


Adiponectin Gwas Loci Harboring Extensive Allelic Heterogeneity Exhibit Distinct Molecular Consequences, Cassandra N. Spracklen, Adam E. Locke, Et Al. Sep 2020

Adiponectin Gwas Loci Harboring Extensive Allelic Heterogeneity Exhibit Distinct Molecular Consequences, Cassandra N. Spracklen, Adam E. Locke, Et Al.

Open Access Publications

Loci identified in genome-wide association studies (GWAS) can include multiple distinct association signals. We sought to identify the molecular basis of multiple association signals for adiponectin, a hormone involved in glucose regulation secreted almost exclusively from adipose tissue, identified in the Metabolic Syndrome in Men (METSIM) study. With GWAS data for 9,262 men, four loci were significantly associated with adiponectin: ADIPOQ, CDH13, IRS1, and PBRM1. We performed stepwise conditional analyses to identify distinct association signals, a subset of which are also nearly independent (lead variant pairwise r2<0.01). Two loci exhibited allelic heterogeneity, ADIPOQ and CDH13. Of seven association signals at the ADIPOQ locus, two signals colocalized with adipose tissue expression quantitative trait loci (eQTLs) for three transcripts: trait-increasing alleles at one signal were associated with increased ADIPOQ and LINC02043, while trait-increasing alleles at the other signal were associated with decreased ADIPOQ-AS1. In reporter assays, adiponectin-increasing alleles at two signals showed corresponding directions of effect on transcriptional activity. Putative mechanisms for the seven ADIPOQ signals include a missense variant (ADIPOQ G90S), a splice variant, a promoter variant, and four enhancer variants. Of two association signals at the CDH13 locus, the first signal consisted of promoter variants, including the lead adipose tissue eQTL variant for CDH13, while a second signal included a distal intron 1 enhancer variant that showed ~2-fold allelic differences in transcriptional reporter activity. Fine-mapping and experimental validation demonstrated that multiple, distinct association signals at these loci can influence multiple transcripts through multiple molecular mechanisms.


Perceptions On Diversity In Cardiology: A Survey Of Cardiology Fellowship Training Program Directors, Anna Lisa Crowley, Julie Damp, Melanie S Sulistio, Kathryn Berlacher, Donna M Polk, Robert A Hong, Gaby Weissman, Dorothy Jackson, Chittur A Sivaram, James A Arrighi, Andrew M Kates, Claire S Duvernoy, Sandra J Lewis, Quinn Capers Iv Sep 2020

Perceptions On Diversity In Cardiology: A Survey Of Cardiology Fellowship Training Program Directors, Anna Lisa Crowley, Julie Damp, Melanie S Sulistio, Kathryn Berlacher, Donna M Polk, Robert A Hong, Gaby Weissman, Dorothy Jackson, Chittur A Sivaram, James A Arrighi, Andrew M Kates, Claire S Duvernoy, Sandra J Lewis, Quinn Capers Iv

Open Access Publications

Background The lack of diversity in the cardiovascular physician workforce is thought to be an important driver of racial and sex disparities in cardiac care. Cardiology fellowship program directors play a critical role in shaping the cardiology workforce. Methods and Results To assess program directors' perceptions about diversity and barriers to enhancing diversity, the authors conducted a survey of 513 fellowship program directors or associate directors from 193 unique adult cardiology fellowship training programs. The response rate was 21% of all individuals (110/513) representing 57% of US general adult cardiology training programs (110/193). While 69% of respondents endorsed the belief …


Antibiotic Overuse In The Primary Health Care Setting: A Secondary Data Analysis Of Standardised Patient Studies From India, China And Kenya, Giorgia Sulis, Benjamin Daniels, Ada Kwan, Sumanth Gandra, Amrita Daftary, Jishnu Das, Madhukar Pai Sep 2020

Antibiotic Overuse In The Primary Health Care Setting: A Secondary Data Analysis Of Standardised Patient Studies From India, China And Kenya, Giorgia Sulis, Benjamin Daniels, Ada Kwan, Sumanth Gandra, Amrita Daftary, Jishnu Das, Madhukar Pai

Open Access Publications

INTRODUCTION: Determining whether antibiotic prescriptions are inappropriate requires knowledge of patients' underlying conditions. In low-income and middle-income countries (LMICs), where misdiagnoses are frequent, this is challenging. Additionally, such details are often unavailable for prescription audits. Recent studies using standardised patients (SPs) offer a unique opportunity to generate unbiased prevalence estimates of antibiotic overuse, as the research design involves patients with predefined conditions.

METHODS: Secondary analyses of data from nine SP studies were performed to estimate the proportion of SP-provider interactions resulting in inappropriate antibiotic prescribing across primary care settings in three LMICs (China, India and Kenya). In all studies, SPs …


The Effect Of Exposure To Long Working Hours On Stroke: A Systematic Review And Meta-Analysis From The Who/Ilo Joint Estimates Of The Work-Related Burden Of Disease And Injury, Alexis Descatha, Bradley A Evanoff, Et Al Sep 2020

The Effect Of Exposure To Long Working Hours On Stroke: A Systematic Review And Meta-Analysis From The Who/Ilo Joint Estimates Of The Work-Related Burden Of Disease And Injury, Alexis Descatha, Bradley A Evanoff, Et Al

Open Access Publications

BACKGROUND: The World Health Organization (WHO) and the International Labour Organization (ILO) are developing joint estimates of the work-related burden of disease and injury (WHO/ILO Joint Estimates), with contributions from a large network of individual experts. Evidence from mechanistic data and prior studies suggests that exposure to long working hours may cause stroke. In this paper, we present a systematic review and meta-analysis of parameters for estimating the number of deaths and disability-adjusted life years from stroke that are attributable to exposure to long working hours, for the development of the WHO/ILO Joint Estimates.

OBJECTIVES: We aimed to systematically review …


Association Of Guideline Publication And Delays To Treatment In Pediatric Status Epilepticus, Iván Sánchez Fernández, Réjean M Guerriero, Et Al Sep 2020

Association Of Guideline Publication And Delays To Treatment In Pediatric Status Epilepticus, Iván Sánchez Fernández, Réjean M Guerriero, Et Al

Open Access Publications

OBJECTIVE: To determine whether publication of evidence on delays in time to treatment shortens time to treatment in pediatric refractory convulsive status epilepticus (rSE), we compared time to treatment before (2011-2014) and after (2015-2019) publication of evidence of delays in treatment of rSE in the Pediatric Status Epilepticus Research Group (pSERG) as assessed by patient interviews and record review.

METHODS: We performed a retrospective analysis of a prospectively collected dataset from June 2011 to September 2019 on pediatric patients (1 month-21 years of age) with rSE.

RESULTS: We studied 328 patients (56% male) with median (25th-75th percentile [p

CONCLUSION: Publication …


Genetic Variants And Functional Pathways Associated With Resilience To Alzheimer's Disease, Logan Dumitrescu, Carlos Cruchaga, Et Al Aug 2020

Genetic Variants And Functional Pathways Associated With Resilience To Alzheimer's Disease, Logan Dumitrescu, Carlos Cruchaga, Et Al

Open Access Publications

Approximately 30% of older adults exhibit the neuropathological features of Alzheimer's disease without signs of cognitive impairment. Yet, little is known about the genetic factors that allow these potentially resilient individuals to remain cognitively unimpaired in the face of substantial neuropathology. We performed a large, genome-wide association study (GWAS) of two previously validated metrics of cognitive resilience quantified using a latent variable modelling approach and representing better-than-predicted cognitive performance for a given level of neuropathology. Data were harmonized across 5108 participants from a clinical trial of Alzheimer's disease and three longitudinal cohort studies of cognitive ageing. All analyses were run …


Cefazolin Inoculum Effect And Methicillin-Susceptible Staphylococcus Aureus Osteoarticular Infections In Children, J Chase Mcneil, Lauren M Sommer, Mary Boyle, Patrick Hogan, Jesus G Vallejo, Kristina G Hultén, Anthony R Flores, Sheldon L Kaplan, Stephanie Fritz Aug 2020

Cefazolin Inoculum Effect And Methicillin-Susceptible Staphylococcus Aureus Osteoarticular Infections In Children, J Chase Mcneil, Lauren M Sommer, Mary Boyle, Patrick Hogan, Jesus G Vallejo, Kristina G Hultén, Anthony R Flores, Sheldon L Kaplan, Stephanie Fritz

Open Access Publications

Select methicillin-susceptible


Counseling On Access To Lethal Means-Emergency Department (Calm-Ed): A Quality Improvement Program For Firearm Injury Prevention, Kristen L Mueller, Sonya Naganathan, Richard T Griffey Aug 2020

Counseling On Access To Lethal Means-Emergency Department (Calm-Ed): A Quality Improvement Program For Firearm Injury Prevention, Kristen L Mueller, Sonya Naganathan, Richard T Griffey

Open Access Publications

INTRODUCTION: Suicide is the 10

METHODS: We conducted this single-center, prospective, quality improvement study (QI) in an urban, academic ED with over 90,000 annual patient visits. The study looked at adult patients who were discharged after presenting to the ED with suicidal crisis. Assessment of access to lethal means was conducted at the bedside, followed by a counseling session regarding safe storage of lethal means and follow-up via telephone call 48-72 hours after ED discharge. We collected data on patient's sociodemographics, psychiatric history, access to lethal means, lethal means storage methods, the patient's specific plans for lethal means storage after …


Cd300lf Polymorphisms Of Inbred Mouse Strains Confer Resistance To Murine Norovirus Infection In A Cell Type-Dependent Manner, Kevin Furlong, Scott B. Biering, Jayoung Choi, Craig B. Wilen, Robert C. Orchard, Christiane E. Wobus, Christopher A. Nelson, Daved H. Fremont, Megan T. Baldridge, Glenn Randall, Seungmin Hwang Aug 2020

Cd300lf Polymorphisms Of Inbred Mouse Strains Confer Resistance To Murine Norovirus Infection In A Cell Type-Dependent Manner, Kevin Furlong, Scott B. Biering, Jayoung Choi, Craig B. Wilen, Robert C. Orchard, Christiane E. Wobus, Christopher A. Nelson, Daved H. Fremont, Megan T. Baldridge, Glenn Randall, Seungmin Hwang

Open Access Publications

Human norovirus is the leading cause of gastroenteritis worldwide, yet basic questions about its life cycle remain unanswered due to an historical lack of robust experimental systems. Recent studies on the closely related murine norovirus (MNV) have identified CD300LF as an indispensable entry factor for MNV. We compared the MNV susceptibilities of cells from different mouse strains and identified polymorphisms in murine CD300LF which are critical for its function as an MNV receptor. Bone marrow-derived macrophages (BMDMs) from I/LnJ mice were resistant to infection from multiple MNV strains which readily infect BMDMs from C57BL/6J mice. The resistance of I/LnJ BMDMs …


Testing The Impact Of A Single Nucleotide Polymorphism In A Plasmodium Berghei Apiap2 Transcription Factor On Experimental Cerebral Malaria In Mice, Munir Akkaya, Abhisheka Bansal, Patrick W Sheehan, Mirna Pena, Clare K Cimperman, Chen Feng Qi, Takele Yazew, Thomas D Otto, Oliver Billker, Louis H Miller, Susan K Pierce Aug 2020

Testing The Impact Of A Single Nucleotide Polymorphism In A Plasmodium Berghei Apiap2 Transcription Factor On Experimental Cerebral Malaria In Mice, Munir Akkaya, Abhisheka Bansal, Patrick W Sheehan, Mirna Pena, Clare K Cimperman, Chen Feng Qi, Takele Yazew, Thomas D Otto, Oliver Billker, Louis H Miller, Susan K Pierce

Open Access Publications

Cerebral malaria (CM) is the deadliest form of severe Plasmodium infections. Currently, we have limited understanding of the mechanisms by which Plasmodium parasites induce CM. The mouse model of CM, experimental CM (ECM), induced by infection with the rodent parasite, Plasmodium berghei ANKA (PbANKA) has been extensively used to study the pathophysiology of CM. Recent genomic analyses revealed that the coding regions of PbANKA and the closely related Plasmodium berghei NK65 (PbNK65), that does not cause ECM, differ in only 21 single nucleotide polymorphysims (SNPs). Thus, the SNP-containing genes might contribute to the pathogenesis of ECM. Although the majority of …


Youth Participatory Research Evidence To Inform Health Policy: A Systematic Review Protocol, Janet Njelesani, Jean Hunleth Aug 2020

Youth Participatory Research Evidence To Inform Health Policy: A Systematic Review Protocol, Janet Njelesani, Jean Hunleth

Open Access Publications

INTRODUCTION: Young people's participation in health research produces knowledge that is indispensable for creating appropriate and effective policies. However, how best to disseminate youth participatory research evidence to impact health policy is not known. Therefore, the objectives of this systematic review are to describe the evidence produced through youth participatory research, including the strategies used to disseminate youth participatory research evidence to health policymakers. These are necessary to improve policymakers' use of youth participatory research evidence and, thereby, make programmes more impactful for young people.

METHODS AND ANALYSIS: The meta-narrative methodology will guide the systematic review to highlight the contrasting …


The Complement System In Covid-19: Friend And Foe?, Anuja Java, Anthony J Apicelli, M Kathryn Liszewski, Ariella Coler-Reilly, John P Atkinson, Alfred Hj Kim, Hrishikesh S Kulkarni Aug 2020

The Complement System In Covid-19: Friend And Foe?, Anuja Java, Anthony J Apicelli, M Kathryn Liszewski, Ariella Coler-Reilly, John P Atkinson, Alfred Hj Kim, Hrishikesh S Kulkarni

Open Access Publications

Coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted in a global pandemic and a disruptive health crisis. COVID-19-related morbidity and mortality have been attributed to an exaggerated immune response. The role of complement activation and its contribution to illness severity is being increasingly recognized. Here, we summarize current knowledge about the interaction of coronaviruses with the complement system. We posit that (a) coronaviruses activate multiple complement pathways; (b) severe COVID-19 clinical features often resemble complementopathies; (c) the combined effects of complement activation, dysregulated neutrophilia, endothelial injury, and hypercoagulability appear to be intertwined …


Osterix-Cre Marks Distinct Subsets Of Cd45- And Cd45+ Stromal Populations In Extra-Skeletal Tumors With Pro-Tumorigenic Characteristics, Biancamaria Ricci, Eric Tycksen, Hamza Celik, Jad I. Belle, Francesca Fontana, Roberto Civitelli, Roberta Faccio Aug 2020

Osterix-Cre Marks Distinct Subsets Of Cd45- And Cd45+ Stromal Populations In Extra-Skeletal Tumors With Pro-Tumorigenic Characteristics, Biancamaria Ricci, Eric Tycksen, Hamza Celik, Jad I. Belle, Francesca Fontana, Roberto Civitelli, Roberta Faccio

Open Access Publications

Cancer-associated fibroblasts (CAFs) are a heterogeneous population of mesenchymal cells supporting tumor progression, whose origin remains to be fully elucidated. Osterix (Osx) is a marker of osteogenic differentiation, expressed in skeletal progenitor stem cells and bone-forming osteoblasts. We report


Protocol For Economic Evaluation Alongside The Shine (Supporting Healthy Image, Nutrition And Exercise) Cluster Randomised Controlled Trial, Victoria Brown, Joanne Williams, Lisa Mcgivern, Susan Sawyer, Liliana Orellana, Wei Luo, Kylie D Hesketh, Denise E Wilfley, Marj Moodie Aug 2020

Protocol For Economic Evaluation Alongside The Shine (Supporting Healthy Image, Nutrition And Exercise) Cluster Randomised Controlled Trial, Victoria Brown, Joanne Williams, Lisa Mcgivern, Susan Sawyer, Liliana Orellana, Wei Luo, Kylie D Hesketh, Denise E Wilfley, Marj Moodie

Open Access Publications

INTRODUCTION: Limited evidence exists on the cost-effectiveness of interventions to prevent obesity and promote healthy body image in adolescents. The SHINE (Supporting Healthy Image, Nutrition and Exercise) study is a cluster randomised control trial (cRCT) aiming to deliver universal education about healthy nutrition and physical activity to adolescents, as well as targeted advice to young people with body image concerns who are at risk of developing disordered eating behaviours. This paper describes the methods for the economic evaluation of the SHINE cRCT, to determine whether the intervention is cost-effective as an obesity prevention measure.

METHODS AND ANALYSIS: A public payer …


Effectiveness Of A Digital Cognitive Behavior Therapy-Guided Self-Help Intervention For Eating Disorders In College Women: A Cluster Randomized Clinical Trial, Ellen E. Fitzsimmons-Craft, C. Barr Taylor, Andrea K. Graham, Shiri Sadeh-Sharvit, Katherine N. Balantekin, Dawn M. Eichen, Grace E. Monterubio, Neha J. Goel, Rachael E. Flatt, Anna M. Karam, Marie-Laure Firebaugh, Corinna Jacobi, Booil Jo, Mickey T. Trockel, Denise E. Wilfley Aug 2020

Effectiveness Of A Digital Cognitive Behavior Therapy-Guided Self-Help Intervention For Eating Disorders In College Women: A Cluster Randomized Clinical Trial, Ellen E. Fitzsimmons-Craft, C. Barr Taylor, Andrea K. Graham, Shiri Sadeh-Sharvit, Katherine N. Balantekin, Dawn M. Eichen, Grace E. Monterubio, Neha J. Goel, Rachael E. Flatt, Anna M. Karam, Marie-Laure Firebaugh, Corinna Jacobi, Booil Jo, Mickey T. Trockel, Denise E. Wilfley

Open Access Publications

Importance: Eating disorders (EDs) are common, serious psychiatric disorders on college campuses, yet most affected individuals do not receive treatment. Digital interventions have the potential to bridge this gap.

Objective: To determine whether a coached, digital, cognitive behavior therapy (CBT) intervention improves outcomes for college women with EDs compared with referral to usual care.

Design, Setting, and Participants: This cluster randomized trial was conducted from 2014 to 2018 at 27 US universities. Women with binge-purge EDs (with both threshold and subthreshold presentations) were recruited from enrolled universities. The 690 participants were followed up for up to 2 years after the …