Standardizing Dietary Recall: A Necessity for the Expanded Food and Nutrition Education Program.

This report explores the 24-hour dietary recall (24HDR) form used for the Expanded Food and Nutrition Education Program (EFNEP). Dietary supplement use, amount of money spent on food, time being physically active, portion size consumed, foods reported by meals, and preparation of the meal were common components collected among 61 EFNEP programs. Components not included were instructions for the peer educator, use of food models/measuring cups, examples of foods/beverages, time food/beverages were consumed, color coding, and a prompt to review what was written. A standardized 24-hour dietary recall form with training protocols is recommended to uphold the integrity of data collection.

Mean Arterial Pressure and Neonatal Outcomes in Pregnancies Complicated by Mild Chronic Hypertension.

OBJECTIVE: To estimate the association between mean arterial pressure during pregnancy and neonatal outcomes in participants with chronic hypertension using data from the CHAP (Chronic Hypertension and Pregnancy) trial. METHODS: A secondary analysis of the CHAP trial, an open-label, multicenter randomized trial of antihypertensive treatment in pregnancy, was conducted. The CHAP trial enrolled participants with mild chronic hypertension (blood pressure [BP] 140-159/90-104 mm Hg) and singleton pregnancies less than 23 weeks of gestation, randomizing them to active treatment (maintained on antihypertensive therapy with a goal BP below 140/90 mm Hg) or standard treatment (control; antihypertensives withheld unless BP reached 160 mm Hg systolic BP or higher or 105 mm Hg diastolic BP or higher). We used logistic regression to measure the strength of association between mean arterial pressure (average and highest across study visits) and to select neonatal outcomes. Unadjusted and adjusted odds ratios (per 1-unit increase in millimeters of mercury) of the primary neonatal composite outcome (bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, or intraventricular hemorrhage grade 3 or 4) and individual secondary outcomes (neonatal intensive care unit admission [NICU], low birth weight [LBW] below 2,500 g, and small for gestational age [SGA]) were calculated. RESULTS: A total of 2,284 participants were included: 1,155 active and 1,129 control. Adjusted models controlling for randomization group demonstrated that increasing average mean arterial pressure per millimeter of mercury was associated with an increase in each neonatal outcome examined except NEC, specifically neonatal composite (adjusted odds ratio [aOR] 1.12, 95% CI, 1.09-1.16), NICU admission (aOR 1.07, 95% CI, 1.06-1.08), LBW (aOR 1.12, 95% CI, 1.11-1.14), SGA below the fifth percentile (aOR 1.03, 95% CI, 1.01-1.06), and SGA below the 10th percentile (aOR 1.02, 95% CI, 1.01-1.04). Models using the highest mean arterial pressure as opposed to average mean arterial pressure also demonstrated consistent associations. CONCLUSION: Increasing mean arterial pressure was positively associated with most adverse neonatal outcomes except NEC. Given that the relationship between mean arterial pressure and adverse pregnancy outcomes may not be consistent at all mean arterial pressure levels, future work should attempt to further elucidate whether there is an absolute threshold or relative change in mean arterial pressure at which fetal benefits are optimized along with maternal benefits. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT02299414.

24-Hour Dietary Recall in the Expanded Food and Nutrition Education Program: Perspective of the Program Coordinator.

The purpose of this study was to determine how the 24-hour dietary recall (24HDR) is administered and how the Expanded Food and Nutrition Education Program (EFNEP) peer educators and other staff are trained on the data collection and entry process, from the EFNEP coordinators' perspectives. This cross-sectional, quantitative study utilized an online survey to collect information from EFNEP coordinators representing 61 of 76 EFNEP programs. While 56% of the programs collected the 24HDR data starting with the first thing eaten the previous day, 49% of them started collecting data at the time of class, going backwards. Most programs, i.e., 72%, reported using a multiple-pass method; however, only one-third of them reported using the standard five-pass method. Almost all programs, i.e., 97%, reported one peer educator collecting data from a group of 2-12 clients. All programs reported collecting the 24HDR data in a group setting, with about one-third of the programs also collecting data one-on-one. Most programs, i.e., 57%, reported spending ≤4 h on the initial training of staff in how to collect 24HDR data, and 54% of them reported that the peer educators entered the data themselves. This study found that the methods used to collect answers, train the staff, and enter the 24HDR data varied across EFNEP programs and that there is a need to standardize or revise the collection of 24HDR data.

Conducting 24-Hour Dietary Recalls in Group Settings with Adults Having Low-Income: Perspectives of EFNEP Peer Educators.

The Expanded Food and Nutrition Education Program (EFNEP) is a federally funded program that teaches nutrition education to adults and youth with low-income. EFNEP is funded throughout the United States including federal territories. The purpose of EFNEP is to provide nutrition education. Evaluation for adult programs includes pre/post surveys and pre/post 24-h diet recalls (24HDR). A validated standard of dietary measures, 24HDR are useful when collected as designed: one-on-one by a trained professional. In EFNEP, 24HDR are collected in group settings by EFNEP peer educators who often have not received a college degree or any formal education in nutrition. The purpose of this study was to explore attitudes and behaviors of EFNEP peer educators regarding how they collect diet recalls in a group setting, their perceptions of how adult participants feel about the recalls, and the benefits and challenges of using recalls. Online interviews were conducted with EFNEP peer educators across the U.S. Peer educators recognized the importance of collecting the recall data but identified several challenges such as time, resources, and participant reluctance to complete the recall. Program evaluation through methods like the 24HDR is important to measure outcomes and inform program improvements but also needs to include how evaluation can benefit participants and minimize data collection burden. Future research needs to examine the validity of collecting recalls in a group setting compared to other measures of diet quality.

Analysis of Plasmablasts From Children With Kawasaki Disease Reveals Evidence of a Convergent Antibody Response to a Specific Protein Epitope.

BACKGROUND: Kawasaki disease (KD) is a febrile illness of young childhood that can result in coronary artery aneurysms and death. Coronavirus disease 2019 (COVID-19) mitigation strategies resulted in a marked decrease in KD cases worldwide, supporting a transmissible respiratory agent as the cause. We previously reported a peptide epitope recognized by monoclonal antibodies (MAbs) derived from clonally expanded peripheral blood plasmablasts from 3 of 11 KD children, suggesting a common disease trigger in a subset of patients with KD. METHODS: We performed amino acid substitution scans to develop modified peptides with improved recognition by KD MAbs. We prepared additional MAbs from KD peripheral blood plasmablasts and assessed MAb characteristics that were associated with binding to the modified peptides. RESULTS: We report a modified peptide epitope that is recognized by 20 MAbs from 11 of 12 KD patients. These MAbs predominantly use heavy chain VH3-74; two-thirds of VH3-74 plasmablasts from these patients recognize the epitope. The MAbs were nonidentical between patients but share a common complementarity-determining region 3 (CDR3) motif. CONCLUSIONS: These results demonstrate a convergent VH3-74 plasmablast response to a specific protein antigen in children with KD, supporting one predominant causative agent in the etiopathogenesis of the illness.

Short-Term Efficacy of a Childhood Obesity Prevention Program Designed to Pair Feeding Content With Nutrition Education.

Background: Family-based programs show considerable promise in preventing overweight and obesity in young children. However, dissemination is difficult because significant participant and staff involvement is required. This study examined the short-term efficacy of adding parental feeding content to a widely-used nutrition education curriculum for families in low-resourced communities comparing the influence of two delivery methods (in-class and online) on parents' feeding knowledge, practices, and styles. Methods: In this cluster randomized controlled trial, parents of 2- to 8-year-old children enrolled in the EFNEP (Expanded Food and Nutrition Education Program) in Colorado and Washington were randomly assigned to: in-class nutrition education only, in-class nutrition education with in-class feeding content, or in-class nutrition education with online feeding content. Data from the 382 participants who completed both pretest and posttest assessments are reported in this study. Results: Multilevel analyses showed empirical support for the influence of the program on parents' feeding knowledge, practices, and styles. Online and in-class methods were equally effective in delivering feeding content in low-resourced communities. Consistent effects were seen across the two delivery methods for encouraging children to try new foods (p < 0.05), use of child-centered feeding practices (i.e., greater responsiveness, p < 0.05), child involvement in food preparation (p < 0.05), and understanding the number of presentations often necessary for child acceptance of a new food (p < 0.001). Location and language differences were seen across some constructs. Conclusions: This study demonstrates the efficacy of in-class and online approaches to feeding highlighting the program's positive effects on promoting healthy feeding behaviors for parents of children in low-resourced families. ClinicalTrials.gov Identifier: NCT03170700.

The Impact of a Prenatal Education Program for Opioid-Dependent Mothers on Breastfeeding Rates of Infants at Risk for Neonatal Abstinence Syndrome.

INTRODUCTION: This study aimed to determine the effect of a prenatal education program for opioid-dependent women on breastfeeding frequency, newborn hospital length of stay, and cost of care for neonates at risk of developing neonatal abstinence syndrome. METHODS: From January 1, 2015 to January 1, 2020, opioid-dependent obstetric patients were educated on non-pharmacological preventative measures for neonatal abstinence syndrome (NAS), with focused counseling on breastfeeding. Data were collected and compared to a control group of opioid-dependent pregnant women who received standard care before initiation of the education program. RESULTS: Sample size calculation revealed that to detect doubling of the breastfeeding rate from 25% to 50% with 80% power and α error of 0.05, 66 participants were required in each group. CONCLUSION: There were 75 women with opioid use disorder who had prenatal NAS education (study group) and 108 women with opioid use disorder who underwent standard care before NAS education (control group). Prenatal NAS education participants significantly increased breastfeeding initiation rates compared to the control group. Newborn length of stay significantly decreased after initiation of prenatal NAS education compared to the 36 months before NAS education program.

Stratification of risk of progression to colectomy in ulcerative colitis via measured and predicted gene expression.

An important goal of clinical genomics is to be able to estimate the risk of adverse disease outcomes. Between 5% and 10% of individuals with ulcerative colitis (UC) require colectomy within 5 years of diagnosis, but polygenic risk scores (PRSs) utilizing findings from genome-wide association studies (GWASs) are unable to provide meaningful prediction of this adverse status. By contrast, in Crohn disease, gene expression profiling of GWAS-significant genes does provide some stratification of risk of progression to complicated disease in the form of a transcriptional risk score (TRS). Here, we demonstrate that a measured TRS based on bulk rectal gene expression in the PROTECT inception cohort study has a positive predictive value approaching 50% for colectomy. Single-cell profiling demonstrates that the genes are active in multiple diverse cell types from both the epithelial and immune compartments. Expression quantitative trait locus (QTL) analysis identifies genes with differential effects at baseline and week 52 follow-up, but for the most part, differential expression associated with colectomy risk is independent of local genetic regulation. Nevertheless, a predicted polygenic transcriptional risk score (PPTRS) derived by summation of transcriptome-wide association study (TWAS) effects identifies UC-affected individuals at 5-fold elevated risk of colectomy with data from the UK Biobank population cohort studies, independently replicated in an NIDDK-IBDGC dataset. Prediction of gene expression from relatively small transcriptome datasets can thus be used in conjunction with TWASs for stratification of risk of disease complications.

Masitinib is a broad coronavirus 3CL inhibitor that blocks replication of SARS-CoV-2.

There is an urgent need for antiviral agents that treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We screened a library of 1900 clinically safe drugs against OC43, a human beta coronavirus that causes the common cold, and evaluated the top hits against SARS-CoV-2. Twenty drugs significantly inhibited replication of both viruses in cultured human cells. Eight of these drugs inhibited the activity of the SARS-CoV-2 main protease, 3CLpro, with the most potent being masitinib, an orally bioavailable tyrosine kinase inhibitor. X-ray crystallography and biochemistry show that masitinib acts as a competitive inhibitor of 3CLpro. Mice infected with SARS-CoV-2 and then treated with masitinib showed >200-fold reduction in viral titers in the lungs and nose, as well as reduced lung inflammation. Masitinib was also effective in vitro against all tested variants of concern (B.1.1.7, B.1.351, and P.1).

Detecting SARS-CoV-2 3CLpro expression and activity using a polyclonal antiserum and a luciferase-based biosensor.

The need to stem the current outbreak of SARS-CoV-2 responsible for COVID-19 is driving the search for inhibitors that will block coronavirus replication and pathogenesis. The coronavirus 3C-like protease (3CLpro) encoded in the replicase polyprotein is an attractive target for antiviral drug development because protease activity is required for generating a functional replication complex. Reagents that can be used to screen for protease inhibitors and for identifying the replicase products of SARS-CoV-2 are urgently needed. Here we describe a luminescence-based biosensor assay for evaluating small molecule inhibitors of SARS-CoV-2 3CLpro/main protease. We also document that a polyclonal rabbit antiserum developed against SARS-CoV 3CLpro cross reacts with the highly conserved 3CLpro of SARS-CoV-2. These reagents will facilitate the pre-clinical evaluation of SARS-CoV-2 protease inhibitors.

Positive Change in Healthy Eating Scores Among Adults With Low Income After Expanded Food and Nutrition Education Program Participation.

OBJECTIVE: Using 24-hour dietary recalls, compare Healthy Eating Index (HEI)-2005 scores of Expanded Food and Nutrition Education Program participants before and after 8-12 weekly lessons. DESIGN: Analysis of preexisting 24-hour dietary recalls information collected from October, 2012 through September, 2014. PARTICIPANTS: Participants with complete pre-post dietary data (n = 122,961); subset of those with complete demographic data (n = 97,522). MAIN OUTCOME MEASURES: Change in HEI-2005 scores (total and components). STATISTICAL ANALYSIS: Linear regression model fit separately for total HEI and 12 components. The response variable was changed in the HEI-2005 score; predictor variables included age, education, sex, and race/ethnicity. RESULTS: The mean total HEI scores were 51.1 (SD, 13.7) at entry and 56.5 (SD, 13.7) at exit, with a change of 5.4 (SD, 16.2). Nine of 12 component scores increased. Changes were greater as age increased, with increasing education, and in women. Hispanics had the greatest improvement (mean ± SE) in total HEI score (8.3 ± 0.1). CONCLUSIONS AND IMPLICATIONS: Although diet quality remained poor, participation in the Expanded Food and Nutrition Education Program resulted in improvement in dietary quality. The degree of improvements varied among demographic groups, but all groups improved.

Drug repurposing screen identifies masitinib as a 3CLpro inhibitor that blocks replication of SARS-CoV-2 in vitro.

There is an urgent need for anti-viral agents that treat SARS-CoV-2 infection. The shortest path to clinical use is repurposing of drugs that have an established safety profile in humans. Here, we first screened a library of 1,900 clinically safe drugs for inhibiting replication of OC43, a human beta-coronavirus that causes the common-cold and is a relative of SARS-CoV-2, and identified 108 effective drugs. We further evaluated the top 26 hits and determined their ability to inhibit SARS-CoV-2, as well as other pathogenic RNA viruses. 20 of the 26 drugs significantly inhibited SARS-CoV-2 replication in human lung cells (A549 epithelial cell line), with EC50 values ranging from 0.1 to 8 micromolar. We investigated the mechanism of action for these and found that masitinib, a drug originally developed as a tyrosine-kinase inhibitor for cancer treatment, strongly inhibited the activity of the SARS-CoV-2 main protease 3CLpro. X-ray crystallography revealed that masitinib directly binds to the active site of 3CLpro, thereby blocking its enzymatic activity. Mastinib also inhibited the related viral protease of picornaviruses and blocked picornaviruses replication. Thus, our results show that masitinib has broad anti-viral activity against two distinct beta-coronaviruses and multiple picornaviruses that cause human disease and is a strong candidate for clinical trials to treat SARS-CoV-2 infection.

Secreted phosphoglucose isomerase is a novel biomarker of nonalcoholic fatty liver in mice and humans.

The current gold standard for diagnosis of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) is through a liver biopsy, and there is an urgent need to develop non-invasive methods for early detection. We previously demonstrated metabolic remodeling in the mouse fatty liver, which is marked by increased hepatic expression and activities of phosphoglucose isomerase (PGI) and several other glycolytic enzymes. Since PGI is actively transported out of the cell, acting as a multifunctional cytokine referred to as autocrine motility factor (AMF), we explored the possibility that PGI secreted from the fatty liver may be targeted for early detection of the silent disease. We report here that mice with NASH exhibited significantly elevated serum PGI enzyme activities compared to normal control (P < 0.005). We further confirmed the finding using serum/plasma samples (n = 73) collected from a cohort of NASH patients who were diagnosed according to Kleiner's criteria, showing a normal mean PGI of 19.5 ± 8.8 IU/L and patient mean PGI of 105.6 ± 79.9 IU/L (P < 0.005). In addition, elevated blood PGI in NASH patients coincided with increased blood L-lactate. Cell culture experiments were then conducted to delineate the PGI-lactate axis, which revealed that treatment of HepG2 cells with recombinant PGI protein stimulated glycolysis and lactate output, suggesting that the disease-induced PGI likely contributed to the increased lactate in NASH patients. Taken together, the preclinical and clinical data validate secreted PGI as a useful biomarker of the fatty liver that can be easily screened at the point of care.

Cystic Fibrosis-related Liver Disease: The Next Challenge.

Up to 40% of individuals with cystic fibrosis have cystic fibrosis-related liver disease (CFLD); however, only 5% to 10% will have clinically evident disease. With the introduction of powerful cystic fibrosis transmembrane conductance regulator (CFTR) enhancers, effective treatment for cystic fibrosis is available. The role of CFTR enhancers in liver disease is unknown at this time. The traditionally accepted theory of the pathogenesis of CFLD is being questioned. A different pathogenesis may lead to new ways to treat CFLD. The way that CFLD is diagnosed and monitored is evolving as new imaging technology become available.

Mucosal Inflammatory and Wound Healing Gene Programs Reveal Targets for Stricturing Behavior in Pediatric Crohn's Disease.

BACKGROUND AND AIMS: Ileal strictures are the major indication for resective surgery in Crohn's disease (CD). We aimed to define ileal gene programs present at diagnosis linked with future stricturing behavior during five year follow-up, and to identify potential small molecules to reverse these gene signatures. METHODS: Antimicrobial serologies and pre-treatment ileal gene expression were assessed in a representative subset of 249 CD patients within the RISK multicenter pediatric CD inception cohort study, including 113 that are unique to this report. These data were used to define genes associated with stricturing behavior and for model testing to predict stricturing behavior. A bioinformatics approach to define small molecules which may reverse the stricturing gene signature was applied. RESULTS: 19 of the 249 patients developed isolated B2 stricturing behavior during follow-up, while 218 remained B1 inflammatory. Using deeper RNA sequencing than in our prior report, we have now defined an inflammatory gene signature including an oncostatin M co-expression signature, tightly associated with extra-cellular matrix (ECM) gene expression in those who developed stricturing complications. We further computationally prioritize small molecules targeting macrophage and fibroblast activation and angiogenesis which may reverse the stricturing gene signature. A model containing ASCA and CBir1 serologies and a refined eight ECM gene set was significantly associated with stricturing development by year five after diagnosis (AUC (95th CI) = 0.82 (0.7-0.94)). CONCLUSION: An ileal gene program for macrophage and fibroblast activation is linked to stricturing complications in treatment naïve pediatric CD, and may inform novel small molecule therapeutic approaches.

Analysis of Using the Total White Blood Cell Count to Define Severe New-onset Ulcerative Colitis in Children.

OBJECTIVES: The aim of this study was to assess common laboratory tests in identifying severe ulcerative colitis in children at diagnosis. METHODS: A cohort of 427 children 4 to 17 years of age newly diagnosed with ulcerative colitis (UC) was prospectively enrolled. Boosted classification trees were used to characterize predictive ability of disease attributes based on clinical disease severity using Pediatric Ulcerative Colitis Activity Index (PUCAI), severe (65+) versus not severe (<65) and total Mayo score, severe (10-12) versus not severe (<10); mucosal disease by Mayo endoscopic subscore, severe (3) versus not severe (<3); and extensive disease versus not extensive (left-sided and proctosigmoiditis). RESULTS: Mean age was 12.7 years; 49.6% (n = 212) were girls, and 83% (n = 351) were Caucasian. Severe total Mayo score was present in 28% (n = 120), mean PUCAI score was 49.8 ±â€Š20.1, and 33% (n = 142) had severe mucosal disease with extensive involvement in 82% (n = 353). Classification and regression trees identified white blood cell count, erythrocyte sedimentation rate, and platelet count (PLT) as the set of 3 best blood laboratory tests to predict disease extent and severity. For mucosal severity, albumin (Alb) replaced PLT. Classification models for PUCAI and total Mayo provided sensitivity of at least 0.65 using standard clinical cut-points with misclassification rates of approximately 30%. CONCLUSIONS: A combination of the white blood cell count, erythrocyte sedimentation rate, and either PLT or albumin is the best predictive subset of standard laboratory tests to identify severe from nonsevere clinical or mucosal disease at diagnosis in relation to objective clinical scores.

Gut Microbiota and Liver Injury (II): Chronic Liver Injury.

Chronic liver injury mainly comprises viral hepatitis, fatty liver disease, autoimmune hepatitis, cirrhosis and liver cancer. It is well established that gut microbiota serves as the key upstream modulator for chronic liver injury progression. Indeed, the term "gut-liver axis" was mostly applied for chronic liver injury. In the current chapter, we will summarize the relationship between gut microbiota and chronic liver injury, including the interaction between them based on latest clinic and basic research.

Structure-Guided Mutagenesis Alters Deubiquitinating Activity and Attenuates Pathogenesis of a Murine Coronavirus.

Coronaviruses express a multifunctional papain-like protease, termed papain-like protease 2 (PLP2). PLP2 acts as a protease that cleaves the viral replicase polyprotein and as a deubiquitinating (DUB) enzyme which removes ubiquitin (Ub) moieties from ubiquitin-conjugated proteins. Previous in vitro studies implicated PLP2/DUB activity as a negative regulator of the host interferon (IFN) response, but the role of DUB activity during virus infection was unknown. Here, we used X-ray structure-guided mutagenesis and functional studies to identify amino acid substitutions within the ubiquitin-binding surface of PLP2 that reduced DUB activity without affecting polyprotein processing activity. We engineered a DUB mutation (Asp1772 to Ala) into a murine coronavirus and evaluated the replication and pathogenesis of the DUB mutant virus (DUBmut) in cultured macrophages and in mice. We found that the DUBmut virus replicates similarly to the wild-type (WT) virus in cultured cells, but the DUBmut virus activates an IFN response at earlier times compared to the wild-type virus infection in macrophages, consistent with DUB activity negatively regulating the IFN response. We compared the pathogenesis of the DUBmut virus to that of the wild-type virus and found that the DUBmut-infected mice had a statistically significant reduction (P < 0.05) in viral titer in liver and spleen at day 5 postinfection (d p.i.), although both wild-type and DUBmut virus infections resulted in similar liver pathology. Overall, this study demonstrates that structure-guided mutagenesis aids the identification of critical determinants of the PLP2-ubiquitin complex and that PLP2/DUB activity plays a role as an interferon antagonist in coronavirus pathogenesis.IMPORTANCE Coronaviruses employ a genetic economy by encoding multifunctional proteins that function in viral replication and also modify the host environment to disarm the innate immune response. The coronavirus papain-like protease 2 (PLP2) domain possesses protease activity, which cleaves the viral replicase polyprotein, and also DUB activity (deconjugating ubiquitin/ubiquitin-like molecules from modified substrates) using identical catalytic residues. To separate the DUB activity from the protease activity, we employed a structure-guided mutagenesis approach and identified residues that are important for ubiquitin binding. We found that mutating the ubiquitin-binding residues results in a PLP2 that has reduced DUB activity but retains protease activity. We engineered a recombinant murine coronavirus to express the DUB mutant and showed that the DUB mutant virus activated an earlier type I interferon response in macrophages and exhibited reduced replication in mice. The results of this study demonstrate that PLP2/DUB is an interferon antagonist and a virulence trait of coronaviruses.

Coronavirus Endoribonuclease and Deubiquitinating Interferon Antagonists Differentially Modulate the Host Response during Replication in Macrophages.

Coronaviruses (CoVs) encode multiple interferon (IFN) antagonists that modulate the host response to virus replication. Here, we evaluated the host transcriptional response to infection with murine coronaviruses encoding independent mutations in one of two different viral antagonists, the deubiquitinase (DUB) within nonstructural protein 3 or the endoribonuclease (EndoU) within nonstructural protein 15. We used transcriptomics approaches to compare the scope and kinetics of the host response to the wild-type (WT), DUBmut, and EndoUmut viruses in infected macrophages. We found that the EndoUmut virus activates a focused response that predominantly involves type I interferons and interferon-related genes, whereas the WT and DUBmut viruses more broadly stimulate upregulation of over 2,800 genes, including networks associated with activating the unfolded protein response (UPR) and the proinflammatory response associated with viral pathogenesis. This study highlights the role of viral interferon antagonists in shaping the kinetics and magnitude of the host response during virus infection and demonstrates that inactivating a dominant viral antagonist, the coronavirus endoribonuclease, dramatically alters the host response in macrophages.IMPORTANCE Macrophages are an important cell type during coronavirus infections because they "notice" the infection and respond by inducing type I interferons, which limits virus replication. In turn, coronaviruses encode proteins that mitigate the cell's ability to signal an interferon response. Here, we evaluated the host macrophage response to two independent mutant coronaviruses, one with reduced deubiquitinating activity (DUBmut) and the other containing an inactivated endoribonuclease (EndoUmut). We observed a rapid, robust, and focused response to the EndoUmut virus, which was characterized by enhanced expression of interferon and interferon-related genes. In contrast, wild-type virus and the DUBmut virus elicited a more limited interferon response and ultimately activated over 2,800 genes, including players in the unfolded protein response and proinflammatory pathways associated with progression of significant disease. This study reveals that EndoU activity substantially contributes to the ability of coronaviruses to evade the host innate response and to replicate in macrophages.

Celiac Disease Nutritional Status and Poor Adherence to Follow-up.

Introduction. Celiac disease, an autoimmune enteropathy, occurs in susceptible individuals and is treatable with a gluten-free diet. These may not be supplemented with vitamins. Objective. To assess the nutritional health of children who have biopsy-proven celiac disease. Methods. Charts were reviewed between July 1, 2007, and June 30, 2017. Results. A total of 252 children ages 0 to 21 years had biopsy-proven celiac disease, mean age 11 ± 4.1 years. Body mass index Z-score was 0.2 ± 1.2 at diagnosis. Except for vitamin D, few had deficiencies at diagnosis. At 1-year follow-up, there was no significant change in anthropomorphics or vitamin status. Adherence to follow-up was poor; at 5 years after diagnosis, 39% adhered to follow-up. Conclusion. Despite a rigorous, proactive protocol for contacting and following children with celiac disease, adherence to follow-up was poor. New strategies, such as follow-up through the primary care provider, are needed.