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Haptoglobin Improves Shock, Lung Injury, And Survival In Canine Pneumonia, Kenneth E. Remy, Irene Cortés-Puch, Steven B. Solomon, Junfeng Sun, Benjamin M. Pockros, Jing Feng, Juan J. Lertora, Roy R. Hantgan, Xiaohua Liu, Andreas Perlegas, H. Shaw Warren, Mark T. Gladwin, Daniel B. Kim-Shapiro, Harvey G. Klein, Charles Natanson

Open Access Publications

During the last half-century, numerous antiinflammatory agents were tested in dozens of clinical trials and have proven ineffective for treating septic shock. The observation in multiple studies that cell-free hemoglobin (CFH) levels are elevated during clinical sepsis and that the degree of increase correlates with higher mortality suggests an alternative approach. Human haptoglobin binds CFH with high affinity and, therefore, can potentially reduce iron availability and oxidative activity. CFH levels are elevated over approximately 24-48 hours in our antibiotic-treated canine model of S. aureus pneumonia that simulates the cardiovascular abnormalities of human septic shock. In this 96-hour model, resuscitative treatments, …

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No abstract provided.

Curriculum For Neurogastroenterology And Motility Training: A Report From The Joint Anms-Esnm Task Force, C P Gyawali, Et Al

Open Access Publications

Although neurogastroenterology and motility (NGM) disorders are some of the most frequent disorders encountered by practicing gastroenterologists, a structured competency-based training curriculum developed by NGM experts is lacking. The American Neurogastroenterology and Motility Society (ANMS) and the European Society of Neurogastroenterology and Motility (ESNM) jointly evaluated the components of NGM training in North America and Europe. Eleven training domains were identified within NGM, consisting of functional gastrointestinal disorders, visceral hypersensitivity and pain pathways, motor disorders within anatomic areas (esophagus, stomach, small bowel and colon, anorectum), mucosal disorders (gastro-esophageal reflux disease, other mucosal disorders), consequences of systemic disease, consequences of therapy …

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No abstract provided.

Hepatic Tristetraprolin Promotes Insulin Resistance Through Rna Destabilization Of Fgf21, Konrad T. Sawicki, Hsiang-Chun Chang, Jason S. Shapiro, Marina Bayeva, Adam De Jesus, Brian N. Finck, Jason A. Wertheim, Perry J. Blackshear, Hossein Ardehali

Open Access Publications

The role of posttranscriptional metabolic gene regulatory programs in diabetes is not well understood. Here, we show that the RNA-binding protein tristetraprolin (TTP) is reduced in the livers of diabetic mice and humans and is transcriptionally induced in response to insulin treatment in murine livers in vitro and in vivo. Liver-specific Ttp-KO (lsTtp-KO) mice challenged with high-fat diet (HFD) have improved glucose tolerance and peripheral insulin sensitivity compared with littermate controls. Analysis of secreted hepatic factors demonstrated that fibroblast growth factor 21 (FGF21) is posttranscriptionally repressed by TTP. Consistent with increased FGF21, lsTtp-KO mice fed HFD have increased brown fat …

Epigenomics And Metabolomics Reveal The Mechanism Of The Apoa2-Saturated Fat Intake Interaction Affecting Obesity, Chao-Qiang Lai, Caren E Smith, Laurence D Parnell, Yu-Chi Lee, Dolores Corella, Paul Hopkins, Bertha A Hidalgo, Stella Aslibekyan, Michael A Province, Devin Absher, Donna K Arnett, Katherine L Tucker, Jose M Ordovas

Open Access Publications

Background: The putative functional variant -265T>C (rs5082) within the APOA2 promoter has shown consistent interactions with saturated fatty acid (SFA) intake to influence the risk of obesity.

Objective: The aim of this study was to implement an integrative approach to characterize the molecular basis of this interaction.

Design: We conducted an epigenome-wide scan on 80 participants carrying either the rs5082 CC or TT genotypes and consuming either a low-SFA (<22 g/d) or high-SFA diet (≥22 g/d), matched for age, sex, BMI, and diabetes status in the Boston Puerto Rican Health Study (BPRHS). We then validated the findings in selected participants in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study (n = 379) and the Framingham Heart Study (FHS) (n = 243). Transcription and metabolomics analyses were conducted to determine the relation between epigenetic status, APOA2 mRNA expression, and blood metabolites.

Results: In the BPRHS, we identified methylation site cg04436964 as exhibiting significant differences between CC and TT participants consuming a high-SFA diet, but not among those consuming low-SFA. Similar …

Maternal Diet And Morbidity Factors Associated With Low Birth Weight In Haiti: A Case-Control Study, Abdirahim Rashid, Thomas Park, Kenneth Macneal, Lora Iannotti, Will Ross

Open Access Publications

No abstract provided.

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Research Digest - May 2018, Division Of Public Health Sciences, Department Of Surgery, Washington University School Of Medicine In St. Louis

Newsletters from the Division of Public Health Sciences

No abstract provided.

Validation Of A Novel Scoring System For Changes In Skeletal Manifestations Of Hypophosphatasia In Newborns, Infants, And Children: The Radiographic Global Impression Of Change Scale, Michael P Whyte, Kenji P Fujita, Scott Moseley, David D Thompson, William H Mcalister

Open Access Publications

Hypophosphatasia (HPP) is the heritable metabolic disease characterized by impaired skeletal mineralization due to low activity of the tissue-nonspecific isoenzyme of alkaline phosphatase. Although HPP during growth often manifests with distinctive radiographic skeletal features, no validated method was available to quantify them, including changes over time. We created the Radiographic Global Impression of Change (RGI-C) scale to assess changes in the skeletal burden of pediatric HPP. Site-specific pairs of radiographs of newborns, infants, and children with HPP from three clinical studies of asfotase alfa, an enzyme replacement therapy for HPP, were obtained at baseline and during treatment. Each pair was …

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No abstract provided.

Building Capacity For Evidence-Based Public Health: Reconciling The Pulls Of Practice And The Push Of Research, Ross C Brownson, Jonathan E Fielding, Lawrence W Green

Open Access Publications

Timely implementation of principles of evidence-based public health (EBPH) is critical for bridging the gap between discovery of new knowledge and its application. Public health organizations need sufficient capacity (the availability of resources, structures, and workforce to plan, deliver, and evaluate the preventive dose of an evidence-based intervention) to move science to practice. We review principles of EBPH, the importance of capacity building to advance evidence-based approaches, promising approaches for capacity building, and future areas for research and practice. Although there is general agreement among practitioners and scientists on the importance of EBPH, there is less clarity on the definition …

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No abstract provided.

Physiological Mechanisms Of Sustained Fumagillin-Induced Weight Loss, Jie An, Michael L Patnode, Vanessa K Ridaura, Jeffrey I Gordon, Et Al

Open Access Publications

Current obesity interventions suffer from lack of durable effects and undesirable complications. Fumagillin, an inhibitor of methionine aminopeptidase-2, causes weight loss by reducing food intake, but with effects on weight that are superior to pair-feeding. Here, we show that feeding of rats on a high-fat diet supplemented with fumagillin (HF/FG) suppresses the aggressive feeding observed in pair-fed controls (HF/PF) and alters expression of circadian genes relative to the HF/PF group. Multiple indices of reduced energy expenditure are observed in HF/FG but not HF/PF rats. HF/FG rats also exhibit changes in gut hormones linked to food intake, increased energy harvest by …

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No abstract provided.

Research Digest - March 2018, Division Of Public Health Sciences, Department Of Surgery, Washington University School Of Medicine In St. Louis

Newsletters from the Division of Public Health Sciences

No abstract provided.

Results Of Asertaa, A Randomized Prospective Crossover Pharmacogenetic Study Of Immediate-Release Versus Extended-Release Tacrolimus In African American Kidney Transplant Recipients, Jennifer Trofe-Clark, Daniel C Brennan, Patricia West-Thielke, Michael C Milone, Mary Ann Lim, Robin Neubauer, Vincenza Nigro, Roy D Bloom

Open Access Publications

BACKGROUND: Differences in tacrolimus dosing across ancestries is partly attributable to polymorphisms in CYP3A5 genes that encode tacrolimus-metabolizing cytochrome P450 3A5 enzymes. The CYP3A5*1 allele, preponderant in African Americans, is associated with rapid metabolism, subtherapeutic concentrations, and higher dose requirements for tacrolimus, all contributing to worse outcomes. Little is known about the relationship between CYP3A5 genotype and the tacrolimus pharmacokinetic area under the curve (AUC) profile in African Americans or whether pharmacogenetic differences exist between conventional twice-daily, rapidly absorbed, immediate-release tacrolimus (IR-Tac) and once-daily extended-release tacrolimus (LifeCycle Pharma Tac [LCPT]) with a delayed absorption profile.

STUDY DESIGN: Randomized prospective crossover …

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Netprophet 2.0: Mapping Transcription Factor Networks By Exploiting Scalable Data Resources, Yiming Kang, Hien-Haw Liow, Ezekiel J Maier, Michael R Brent

2010-2019 OA Pubs

MOTIVATION: Cells process information, in part, through transcription factor (TF) networks, which control the rates at which individual genes produce their products. A TF network map is a graph that indicates which TFs bind and directly regulate each gene. Previous work has described network mapping algorithms that rely exclusively on gene expression data and 'integrative' algorithms that exploit a wide range of data sources including chromatin immunoprecipitation sequencing (ChIP-seq) of many TFs, genome-wide chromatin marks, and binding specificities for many TFs determined in vitro. However, such resources are available only for a few major model systems and cannot be easily …

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No abstract provided.

Research Digest - January 2018, Division Of Public Health Sciences, Department Of Surgery, Washington University School Of Medicine In St. Louis

Newsletters from the Division of Public Health Sciences

No abstract provided.

Cardiovascular Disease Risk Factor Responses To A Type 2 Diabetes Care Model Including Nutritional Ketosis Induced By Sustained Carbohydrate Restriction At 1 Year: An Open Label, Non-Randomized, Controlled Study, Nasir H. Bhanpuri, Sarah J. Hallberg, Paul T. Williams, Amy L. Mckenzie, Kevin D. Ballard, Wayne W. Campbell, James P. Mccarter, Stephen D. Phinney, Jeff S. Volek

Open Access Publications

No abstract provided.

Fat Composition In Infant Formula Contributes To The Severity Of Necrotising Enterocolitis, Chhinder P. Sodhi, William B. Fulton, Misty Good, Mustafa Vurma, Tapas Das, Chron-Si Lai, Hongpeng Jia, Yukihiro Yamaguchi, Peng Lu, Thomas Prindle Jr, John A. Ozolek, David J. Hackam

Open Access Publications

No abstract provided.

Complementary Feeding Intervention On Stunted Guatemalan Children: A Randomised Controlled Trial, Boris Martinez, Meghan Farley Webb, Ana Gonzalez, Kate Douglas, Maria Del Pilar Grazioso, Peter Rohloff

2010-2019 OA Pubs

OBJECTIVE/BACKGROUND: Guatemala's indigenous Maya population has one of the highest rates of childhood stunting in the world. The goal of this study was to examine the impact of an intensive, individualised approach to complementary feeding education for caregivers on feeding practices and growth over usual care.

DESIGN: An individually randomised (1:1 allocation ratio), parallel-group superiority trial, with blinding of study staff collecting outcome data.

SETTING: Rural Maya communities in Guatemala.

PARTICIPANTS: 324 children aged 6-24 months with a height-for-age Z score of less than or equal to -2.5 SD were randomised, 161 to the intervention and 163 to usual care. …

Phase I Studies Of Azd1208, A Proviral Integration Moloney Virus Kinase Inhibitor In Solid And Haematological Cancers, Geoffrey L. Uy, Et Al

Open Access Publications

No abstract provided.

Multilevel Correlates Of Household Anthropometric Typologies In Colombian Mothers And Their Infants, D. C. Parra, L. F. Gomez, L. Iannotti, D. Haire-Joshu, A. K. Sebert Kuhlmann, R. C. Brownson

Open Access Publications

No abstract provided.

Burosumab Therapy In Children With X-Linked Hypophosphatemia, Thomas O. Carpenter, Michael P. Whyte, Erik A. Imel, Annemieke M. Boot, Wolfgang Hogler, Agnes Linglart, Raja Padidela, William Van't Hoff, Meng Mao, Chao-Yin Chen, Alison Skrinar, Emil Kakkis, Javier San Martin, Anthony A. Portale

Open Access Publications

No abstract provided.