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Association Between Diagnosis Code Expansion And Changes In 30-Day Risk-Adjusted Outcomes For Cardiovascular Diseases, Lauren Gilstrap, Rishi K Wadhera, Andrea M Austin, Stephen Kearing, Karen E Joynt Maddox, Robert W Yeh

Open Access Publications

BACKGROUND In January 2011, Centers for Medicare and Medicaid Services expanded the number of inpatient diagnosis codes from 9 to 25, which may influence comorbidity counts and risk-adjusted outcome rates for studies spanning January 2011. This study examines the association between (1) limiting versus not limiting diagnosis codes after 2011, (2) using inpatient-only versus inpatient and outpatient data, and (3) using logistic regression versus the Centers for Medicare and Medicaid Services risk-standardized methodology and changes in risk-adjusted outcomes. METHODS AND RESULTS Using 100% Medicare inpatient and outpatient files between January 2009 and December 2013, we created 2 cohorts of fee-for-service …

Temporal Trends Of Covid-19 Mortality And Hospitalisation Rates: An Observational Cohort Study From The Us Department Of Veterans Affairs, Miao Cai, Benjamin Bowe, Yan Xie, Ziyad Al-Aly

Open Access Publications

OBJECTIVES: To investigate the temporal trends of 30-day mortality and hospitalisation in US Veterans with COVID-19 and 30-day mortality in hospitalised veterans with COVID-19 and to decompose the contribution of changes in the underlying characteristics of affected populations to these temporal changes.

DESIGN: Observational cohort study.

SETTING: US Department of Veterans Affairs.

PARTICIPANTS: 49 238 US veterans with a positive COVID-19 test between 20 March 2020 and 19 September 2020; and 9428 US veterans hospitalised with a positive COVID-19 test during the same period.

OUTCOME MEASURES: 30-day mortality rate and hospitalisation rate.

RESULTS: Between 20 March 2020 and 19 September …

Variant Allele Fraction Of Genomic Alterations In Circulating Tumor Dna (%Ctdna) Correlates With Suv, Amin Haghighat Jahromi, Matthew Zabel, Ryosuke Okamura, Carl K Hoh, Razelle Kurzrock

Open Access Publications

The relationship between higher variant allele fraction (VAF) of genomic alterations in circulating tumor DNA (%ctDNA), an indicator of poor outcome, and maximum standardized uptake value (SUV

Year 1 Of The Bundled Payments For Care Improvement-Advanced Model, Karen E Joynt Maddox, E John Orav, Jie Zheng, Arnold M Epstein

Open Access Publications

BACKGROUND: The Center for Medicare and Medicaid Innovation launched the Medicare Bundled Payments for Care Improvement-Advanced (BPCI-A) program for hospitals in October 2018. Information is needed about the effects of the program on health care utilization and Medicare payments.

METHODS: We conducted a modified segmented regression analysis using Medicare claims and including patients with discharge dates from January 2017 through September 2019 to assess differences between BPCI-A participants and two control groups: hospitals that never joined the BPCI-A program (nonjoining hospitals) and hospitals that joined the BPCI-A program in January 2020, after the conclusion of the intervention period (late-joining hospitals). …

Effect Of Alteplase Use On Outcomes In Patients With Atrial Fibrillation: Analysis Of The Initiation Of Anticoagulation After Cardioembolic Stroke Study, Shadi Yaghi, James Giles, Angela Liu, Salah Keyrouz, Et Al

Open Access Publications

Background Intravenous alteplase improves outcome after acute ischemic stroke without a benefit in 90-day mortality. There are limited data on whether alteplase is associated with reduced mortality in patients with atrial fibrillation (AF)-related ischemic stroke whose mortality rate is relatively high. We sought to determine the association of alteplase with hemorrhagic transformation and mortality in patients with AF. Methods and Results We retrospectively analyzed consecutive patients with acute ischemic stroke between 2015 and 2018 diagnosed with AF included in the IAC (Initiation of Anticoagulation After Cardioembolic Stroke) study, which pooled data from stroke registries at 8 comprehensive stroke centers across …

Reducing Cardiovascular Maternal Mortality By Extending Medicaid For Postpartum Women, Janki P Luther, Daniel Y Johnson, Karen E Joynt Maddox, Kathryn J Lindley

Open Access Publications

Maternal mortality has been increasing in the United States over the past 3 decades, while decreasing in all other high-income countries during the same period. Cardiovascular conditions account for over one fourth of maternal deaths, with two thirds of deaths occurring in the postpartum period. There are also significant healthcare disparities that have been identified in women experiencing maternal morbidity and mortality, with Black women at 3 to 4 times the risk of death as their White counterparts and women in rural areas at heightened risk for cardiovascular morbidity and maternal morbidity. However, many maternal deaths have been shown to …

Identification Of Structures For Ion Channel Kinetic Models, Kathryn E. Mangold, Wei Wang, Eric K. Johnson, Druv Bhagavan, Jonathan D. Moreno, Jeanne M. Nerbonne, Jonathan R. Silva

Open Access Publications

Markov models of ion channel dynamics have evolved as experimental advances have improved our understanding of channel function. Past studies have examined limited sets of various topologies for Markov models of channel dynamics. We present a systematic method for identification of all possible Markov model topologies using experimental data for two types of native voltage-gated ion channel currents: mouse atrial sodium currents and human left ventricular fast transient outward potassium currents. Successful models identified with this approach have certain characteristics in common, suggesting that aspects of the model topology are determined by the experimental data. Incorporating these channel models into …

Urine Tumor Dna Detection Of Minimal Residual Disease In Muscle-Invasive Bladder Cancer Treated With Curative-Intent Radical Cystectomy: A Cohort Study, Pradeep S. Chauhan, Kevin Chen, Ramandeep K. Babbra, Wenjia Feng, Nadja Pejovic, Armaan Nallicheri, Peter K. Harris, Katherine Dienstbach, Andrew Atkocius, Lenon Maguire, Faridi Qaium, Jeffrey J. Szymanski, Brian C. Baumann, Li Ding, Dengfeng Cao, Melissa A. Reimers, Eric H. Kim, Zachary L. Smith, Vivek K. Arora, Aadel A. Chaudhuri

Open Access Publications

BACKGROUND: The standard of care treatment for muscle-invasive bladder cancer (MIBC) is radical cystectomy, which is typically preceded by neoadjuvant chemotherapy. However, the inability to assess minimal residual disease (MRD) noninvasively limits our ability to offer bladder-sparing treatment. Here, we sought to develop a liquid biopsy solution via urine tumor DNA (utDNA) analysis.

METHODS AND FINDINGS: We applied urine Cancer Personalized Profiling by Deep Sequencing (uCAPP-Seq), a targeted next-generation sequencing (NGS) method for detecting utDNA, to urine cell-free DNA (cfDNA) samples acquired between April 2019 and November 2020 on the day of curative-intent radical cystectomy from 42 patients with localized …

The Alternative Serotonin Transporter Promoter P2 Impacts Gene Function In Females With Irritable Bowel Syndrome, Sandra Mohr, Gregory Sayuk, Et Al

Open Access Publications

Irritable bowel syndrome (IBS) is a gut-brain disorder in which symptoms are shaped by serotonin acting centrally and peripherally. The serotonin transporter gene SLC6A4 has been implicated in IBS pathophysiology, but the underlying genetic mechanisms remain unclear. We sequenced the alternative P2 promoter driving intestinal SLC6A4 expression and identified single nucleotide polymorphisms (SNPs) that were associated with IBS in a discovery sample. Identified SNPs built different haplotypes, and the tagging SNP rs2020938 seems to associate with constipation-predominant IBS (IBS-C) in females. rs2020938 validation was performed in 1978 additional IBS patients and 6,038 controls from eight countries. Meta-analysis on data from …

Dietary Compliance In A Randomized Double-Blind Infant Feeding Trial During Infancy Aiming At Prevention Of Type 1 Diabetes, Suvi M Virtanen, Marilyn Tanner-Blasiar, Et Al

Open Access Publications

The international Trial to Reduce IDDM in the Genetically at Risk (TRIGR) tested the hypothesis whether extensively hydrolyzed casein-based versus regular cow's milk-based infant formula reduces the risk of type 1 diabetes. We describe dietary compliance in the trial in terms of study formula intake, feeding of nonrecommended foods, and serum cow's milk antibody concentration reflecting intake of cow's milk protein among 2,159 eligible newborn infants with a biological first-degree relative affected by type 1 diabetes and with HLA-conferred susceptibility to type 1 diabetes. The participating infants were introduced to the study formula feeding at the median age of 15 …

Air Pollution Particulate Matter Exposure And Chronic Cerebral Hypoperfusion And Measures Of White Matter Injury In A Murine Model, Qinghai Liu, Michelle Connor, Et Al

Open Access Publications

BACKGROUND: Exposure to ambient air pollution particulate matter (PM) is associated with increased risk of dementia and accelerated cognitive loss. Vascular contributions to cognitive impairment are well recognized. Chronic cerebral hypoperfusion (CCH) promotes neuroinflammation and blood-brain barrier weakening, which may augment neurotoxic effects of PM.

OBJECTIVES: This study examined interactions of nanoscale particulate matter (nPM; fine particulate matter with aerodynamic diameter

METHODS: nPM was collected using a particle sampler near a Los Angeles, California, freeway. Mice were exposed to 10 wk of reaerosolized nPM or filtered air (FA) for 150 h. CCH was induced by BCAS surgery. Mice (C57BL/6J males) …

Non-Motor Phenotypic Subgroups In Adult-Onset Idiopathic, Isolated, Focal Cervical Dystonia, Megan E Wadon, Joel S Perlmutter, Et Al

Open Access Publications

BACKGROUND: Non-motor symptoms are well established phenotypic components of adult-onset idiopathic, isolated, focal cervical dystonia (AOIFCD). However, improved understanding of their clinical heterogeneity is needed to better target therapeutic intervention. Here, we examine non-motor phenotypic features to identify possible AOIFCD subgroups.

METHODS: Participants diagnosed with AOIFCD were recruited via specialist neurology clinics (dystonia wales: n = 114, dystonia coalition: n = 183). Non-motor assessment included psychiatric symptoms, pain, sleep disturbance, and quality of life, assessed using self-completed questionnaires or face-to-face assessment. Both cohorts were analyzed independently using Cluster, and Bayesian multiple mixed model phenotype analyses to investigate the relationship between …

Decreased Antiviral Immune Response Within The Central Nervous System Of Aged Mice Is Associated With Increased Lethality Of West Nile Virus Encephalitis, Kristen E Funk, Artem D Arutyunov, Pritesh Desai, James P White, Allison L Soung, Sarah F Rosen, Michael S Diamond, Robyn S Klein

Open Access Publications

West Nile virus (WNV) is an emerging pathogen that causes disease syndromes ranging from a mild flu-like illness to encephalitis. While the incidence of WNV infection is fairly uniform across age groups, the risk of lethal encephalitis increases with advanced age. Prior studies have demonstrated age-related, functional immune deficits that limit systemic antiviral immunity and increase mortality; however, the effect of age on antiviral immune responses specifically within the central nervous system (CNS) is unknown. Here, we show that aged mice exhibit increased peripheral organ and CNS tissue viral burden, the latter of which is associated with alterations in activation …

Management Of Bone Metastasis And Cancer Treatment-Induced Bone Loss During The Covid-19 Pandemic: An International Perspective And Recommendations, J E Brown, K Weilbaecher, Et Al

Open Access Publications

Optimum management of patients with cancer during the COVID-19 pandemic has proved extremely challenging. Patients, clinicians and hospital authorities have had to balance the risks to patients of attending hospital, many of whom are especially vulnerable, with the risks of delaying or modifying cancer treatment. Those whose care has been significantly impacted include patients suffering from the effects of cancer on bone, where delivering the usual standard of care for bone support has often not been possible and clinicians have been forced to seek alternative options for adequate management. At a virtual meeting of the Cancer and Bone Society in …

Relative Risks Of Covid-19 Fatality Between The First And Second Waves Of The Pandemic In Ontario, Canada, Sylvia H Hsu, Su-Hsin Chang, Cary P Gross, Shi-Yi Wang

Open Access Publications

OBJECTIVES: To examine whether the case fatality rate (CFR) of COVID-19 decreased over time and whether the COVID-19 testing rate is a driving factor for the changes if the CFR decreased.

METHODS: Analyzing COVID-19 cases, deaths and tests in Ontario, Canada, we compared the CFR between the first wave and the second wave across 26 public health units in Ontario. We also explored whether a high testing rate was associated with a large CFR decrease.

RESULTS: The first wave CFR ranged from 0.004 to 0.146, whereas the second wave CFR ranged from 0.003 to 0.034. The pooled RR estimate of …

Cell-Free Dna Ultra-Low-Pass Whole Genome Sequencing To Distinguish Malignant Peripheral Nerve Sheath Tumor (Mpnst) From Its Benign Precursor Lesion: A Cross-Sectional Study, Jeffrey J. Szymanski, R. Taylor Sundby, Paul A. Jones, Divya Srihari, Noah Earland, Peter K. Harris, Wenjia Feng, Faridi Qaium, Haiyan Lei, David Roberts, Michele Landeau, Jamie Bell, Yi Huang, Leah Hoffman, Melissa Spencer, Matthew B. Spraker, Li Ding, Brigitte C. Widemann, Jack F. Shern, Angela C. Hirbe, Aadel A. Chaudhuri

Open Access Publications

BACKGROUND: The leading cause of mortality for patients with the neurofibromatosis type 1 (NF1) cancer predisposition syndrome is the development of malignant peripheral nerve sheath tumor (MPNST), an aggressive soft tissue sarcoma. In the setting of NF1, this cancer type frequently arises from within its common and benign precursor, plexiform neurofibroma (PN). Transformation from PN to MPNST is challenging to diagnose due to difficulties in distinguishing cross-sectional imaging results and intralesional heterogeneity resulting in biopsy sampling errors.

METHODS AND FINDINGS: This multi-institutional study from the National Cancer Institute and Washington University in St. Louis used fragment size analysis and ultra-low-pass …

Prevalence Of Spine Surgery Navigation Techniques And Availability In Africa: A Cross-Sectional Study, Ulrick Sidney Kanmounye, Yvan Zolo, Faith C Robertson, Nourou Dine Adeniran Bankole, Kantenga Dieu Merci Kabulo, Jeff M Ntalaja, Juma Magogo, Ahmed Negida, Nqobile Thango, Ignatius Esene, Brenton Pennicooke, Camilo A Molina

Open Access Publications

Background: Africa has a large burden of spine pathology but has limited and insufficient infrastructure to manage these spine disorders. Therefore, we conducted this e-survey to assess the prevalence and identify the determinants of the availability of spine surgery navigation techniques in Africa.

Materials and methods: A two-part questionnaire was disseminated amongst African neurological and orthopedic surgery consultants and trainees from January 24 to February 23, 2021. The Chi-Square, Fisher Exact, and Kruskal-Wallis tests were used to evaluate bivariable relationships, and a p-value <0.05 was considered statistically significant.

Results: We had 113 respondents from all regions of Africa. Most (86.7 %) participants who practiced or …

Normative Promis Scores In Healthy Collegiate Athletes: Establishing A Target For Return To Function In The Young Adult Athlete, Arya Minaie, David L Bernholt, Andrew M Block, Ronak M Patel, Rick W Wright, Matthew J Matava, Jeffrey J Nepple

Open Access Publications

Background: The Patient-Reported Outcomes Measurement Information System (PROMIS) computer-adaptive testing (CAT) has been shown to be a valid and reliable means of assessing patient-reported outcomes. However, normal scores and distributions for a subset of a healthy young athletic population have not been established.

Purpose: To establish normative PROMIS scores for the domains of Physical Function (PF-CAT), Mobility (M-CAT), Upper Extremity Function (UE-CAT), and Pain Interference (PI-CAT) and determine the frequency of floor and ceiling effects in a population of healthy collegiate athletes.

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

Methods: Healthy collegiate athletes (18-23 years of age) were prospectively …

Radiation Therapy For Vaginal And Perirectal Lesions In Recurrent Ovarian Cancer, E A Johns, J A Stanley, M D Toboni, J K Schwarz, F Zhang, A R Hagemann, K C Fuh, P H Thaker, C K Mccourt, D G Mutch, M A Powell, D Khabele, L M Kuroki

Open Access Publications

The role for localized radiation to treat ovarian cancer (OC) patients with locally recurrent vaginal/perirectal lesions remains unclear, though we hypothesize these patients may be salvaged locally and gain long-term survival benefit. We describe our institutional outcomes using intensity modulated radiation therapy (IMRT) +/- high-dose rate (HDR) brachytherapy to treat this population. Our primary objectives were to evaluate complete response rates of targeted lesions after radiation and calculate our 5-year in-field control (IFC) rate. Secondary objectives were to assess radiation-related toxicities, chemotherapy free-interval (CFI), as well as post-radiation progression-free (PFS) and overall survival (OS). PFS and OS were defined from …

Long-Term Complications In Youth-Onset Type 2 Diabetes, Petter Bjornstad, Kimberly L Drews, Sonia Caprio, Rose Gubitosi-Klug, David M Nathan, Bereket Tesfaldet, Jeanie Tryggestad, Neil H White, Philip Zeitler, Today Study Group

Open Access Publications

BACKGROUND: The prevalence of type 2 diabetes in youth is increasing, but little is known regarding the occurrence of related complications as these youths transition to adulthood.

METHODS: We previously conducted a multicenter clinical trial (from 2004 to 2011) to evaluate the effects of one of three treatments (metformin, metformin plus rosiglitazone, or metformin plus an intensive lifestyle intervention) on the time to loss of glycemic control in participants who had onset of type 2 diabetes in youth. After completion of the trial, participants were transitioned to metformin with or without insulin and were enrolled in an observational follow-up study …

Caregiver Health-Related Quality Of Life, Burden, And Patient Outcomes In Ambulatory Advanced Heart Failure: A Report From Revival, Nisha A Gilotra, Douglas L Mann, Et Al

Open Access Publications

Background Heart failure (HF) imposes significant burden on patients and caregivers. Longitudinal data on caregiver health-related quality of life (HRQOL) and burden in ambulatory advanced HF are limited. Methods and Results Ambulatory patients with advanced HF (n=400) and their participating caregivers (n=95) enrolled in REVIVAL (Registry Evaluation of Vital Information for VADs [Ventricular Assist Devices] in Ambulatory Life) were followed up for 24 months, or until patient death, left ventricular assist device implantation, heart transplantation, or loss to follow-up. Caregiver HRQOL (EuroQol Visual Analog Scale) and burden (Oberst Caregiving Burden Scale) did not change significantly from baseline to follow-up. At …

Eeg/Erp As A Pragmatic Method To Expand The Reach Of Infant-Toddler Neuroimaging In Hbcd: Promises And Challenges, Elizabeth S Norton, Leigha A Macneill, Emily M Harriott, Norrina Allen, Sheila Krogh-Jespersen, Christopher D Smyser, Cynthia E Rogers, Tara A Smyser, Joan Luby, Lauren Wakschlag

Open Access Publications

Though electrophysiological measures (EEG and ERP) offer complementary information to MRI and a variety of advantages for studying infants and young children, these measures have not yet been included in large cohort studies of neurodevelopment. This review summarizes the types of EEG and ERP measures that could be used in the HEALthy Brain and Cognitive Development (HBCD) study, and the promises and challenges in doing so. First, we provide brief overview of the use of EEG/ERP for studying the developing brain and discuss exemplar findings, using resting or baseline EEG measures as well as the ERP mismatch negativity (MMN) as …

Predicting The Environmental Suitability For Onchocerciasis In Africa As An Aid To Elimination Planning, Elizabeth A. Cromwell, Ziyad Al-Aly, Et Al

Open Access Publications

Recent evidence suggests that, in some foci, elimination of onchocerciasis from Africa may be feasible with mass drug administration (MDA) of ivermectin. To achieve continental elimination of transmission, mapping surveys will need to be conducted across all implementation units (IUs) for which endemicity status is currently unknown. Using boosted regression tree models with optimised hyperparameter selection, we estimated environmental suitability for onchocerciasis at the 5 × 5-km resolution across Africa. In order to classify IUs that include locations that are environmentally suitable, we used receiver operating characteristic (ROC) analysis to identify an optimal threshold for suitability concordant with locations where …

Npc1 Regulates The Distribution Of Phosphatidylinositol 4-Kinases At Golgi And Lysosomal Membranes, Candice Kutchukian, Oscar Vivas, Maria Casas, Julia G Jones, Scott A Tiscione, Sergi Simó, Daniel S Ory, Rose E Dixon, Eamonn J Dickson

Open Access Publications

Cholesterol and phosphoinositides (PI) are two critically important lipids that are found in cellular membranes and dysregulated in many disorders. Therefore, uncovering molecular pathways connecting these essential lipids may offer new therapeutic insights. We report that loss of function of lysosomal Niemann-Pick Type C1 (NPC1) cholesterol transporter, which leads to neurodegenerative NPC disease, initiates a signaling cascade that alters the cholesterol/phosphatidylinositol 4-phosphate (PtdIns4P) countertransport cycle between Golgi-endoplasmic reticulum (ER), as well as lysosome-ER membrane contact sites (MCS). Central to these disruptions is increased recruitment of phosphatidylinositol 4-kinases-PI4KIIα and PI4KIIIβ-which boosts PtdIns4P metabolism at Golgi and lysosomal membranes. Aberrantly increased PtdIns4P …

A Phase Ii Study Of Everolimus In Patients With Advanced Solid Malignancies With Tsc1, Tsc2, Nf1, Nf2 Or Stk11 Mutations, Siddhartha Devarakonda, Bruna Pellini, Luke Verghese, Haeseong Park, Daniel Morgensztern, Ramaswamy Govindan, Rama Suresh, Peter Oppelt, Maria Q. Baggstrom, Ningying Wu, Saiama N. Waqar

Open Access Publications

Background: Activation of the mTOR pathway has been implicated in the development of several malignancies and alterations in

Methods: A total of 12 patients with histologically confirmed diagnosis of advanced solid tumors (metastatic, recurrent, or unresectable) with mutations in

Results: Of 12 patients enrolled, 8 were evaluable for response at the end of 2 cycles. One complete response (CR) was observed (12.5%) and one patient (12.5%) had stable disease (SD), while six (75%) patients showed disease progression. Everolimus was overall well tolerated with anemia, decreased neutrophil and lymphocyte counts, peripheral edema and hyperglycemia representing the most common adverse events. One …

Sleep Apnea And Fetal Growth Restriction (Safer) Study: Protocol For A Pragmatic Randomised Clinical Trial Of Positive Airway Pressure As An Antenatal Therapy For Fetal Growth Restriction In Maternal Obstructive Sleep Apnoea, Alex Hincker, Jacob Nadler, Suzanne Karan, Ebony Carter, Shay Porat, Barbara Warner, Yo-El S Ju, Arbi Ben Abdallah, Elizabeth Wilson, Ellen M Lockhart, Yehuda Ginosar

Open Access Publications

INTRODUCTION: Fetal growth restriction (FGR) is a major contributor to fetal and neonatal morbidity and mortality with intrauterine, neonatal and lifelong complications. This study explores maternal obstructive sleep apnoea (OSA) as a potentially modifiable risk factor for FGR. We hypothesise that, in pregnancies complicated by FGR, treating mothers who have OSA using positive airway pressure (PAP) will improve birth weight and neonatal outcomes.

METHODS AND ANALYSIS: The Sleep Apnea and Fetal Growth Restriction study is a prospective, block-randomised, single-blinded, multicentre, pragmatic controlled trial. We enrol pregnant women aged 18-50, between 22 and 31 weeks of gestation, with established FGR based …

Does Raising The Arms Modify Head Tremor Severity In Cervical Dystonia?, Elizabeth Cisneros, Joel S Perlmutter, Et Al

Open Access Publications

Background: A defining characteristic of dystonia is its position-dependence. In cervical dystonia (CD), sensory tricks ameliorate head tremor (HT). But it remains unknown whether raising the arms alone has the same impact.

Methods: We analyzed data collected from patients enrolled by the Dystonia Coalition. For 120 patients with HT, we assessed how raising their arms without touching their head changed their HT severity.

Results: Forty-eight out of 120 patients exhibited changes in HT severity when raising their arms. These patients were more likely to exhibit decreases in HT severity (N = 35) than increases (N = 13, χ

Discussion: Raising …

Ketogenic Diet Restrains Aging-Induced Exacerbation Of Coronavirus Infection In Mice, Seungjin Ryu, Irina Shchukina, Maxim Artyomov, Et Al

Open Access Publications

Increasing age is the strongest predictor of risk of COVID-19 severity and mortality. Immunometabolic switch from glycolysis to ketolysis protects against inflammatory damage and influenza infection in adults. To investigate how age compromises defense against coronavirus infection, and whether a pro-longevity ketogenic diet (KD) impacts immune surveillance, we developed an aging model of natural murine beta coronavirus (mCoV) infection with mouse hepatitis virus strain-A59 (MHV-A59). When inoculated intranasally, mCoV is pneumotropic and recapitulates several clinical hallmarks of COVID-19 infection. Aged mCoV-A59-infected mice have increased mortality and higher systemic inflammation in the heart, adipose tissue, and hypothalamus, including neutrophilia and loss …

Sars-Cov-2 E Gene Variant Alters Analytical Sensitivity Characteristics Of Viral Detection Using A Commercial Reverse Transcription-Pcr Assay, Stephen Tahan, Bijal A Parikh, Lindsay Droit, Meghan A. Wallace, Carey-Ann D Burnham, David Wang

Open Access Publications

Diagnostic assays for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are essential for patient management, infection prevention, and the public health response for coronavirus disease 2019 (COVID-19). The efficacy and reliability of these assays are of paramount importance in both tracking and controlling the spread of the virus. Real-time reverse transcription-PCR (RT-PCR) assays rely on a fixed genetic sequence for primer and probe binding. Mutations can potentially alter the accuracy of these assays and lead to unpredictable analytical performance characteristics and false-negative results. Here, we identify a G-to-U transversion (nucleotide 26372) in the SARS-CoV-2 E gene in three specimens …

Comparison Of Microorganism Detection And Time To Positivity In Pediatric And Standard Media From Three Major Commercial Continuously Monitored Blood Culture Systems, Melanie L Yarbrough, Meghan A Wallace, Carey-Ann D Burnham

Open Access Publications

New blood culture instrumentation and medium formulations have led to improved time to positivity (TTP) for positive blood cultures. Data regarding the necessity of pediatric blood culture bottles with contemporary blood culture systems are sparse. We compared performance of three commercial blood culture systems, evaluating impact of blood volumes in standard and pediatric blood culture media across systems. Simulated blood cultures with packed red blood cells (PRBCs) and three Gram-positive, four Gram-negative, and one anaerobic organism (final concentrations ranging from 0.5 to 19 CFU/ml blood) on the Virtuo, VersaTrek, and Bactec FX instruments were evaluated with FAN Plus, Redox, and …