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3. Microbiome Signatures Associated With Steatohepatitis and Moderate to Severe Fibrosis in Children With Nonalcoholic Fatty Liver Disease

Author

Schwimmer, Jeffrey B, Johnson, Jethro S, Angeles, Jorge E, Behling, Cynthia, Belt, Patricia H, Borecki, Ingrid, Bross, Craig, Durelle, Janis, Goyal, Nidhi P, Hamilton, Gavin, Holtz, Mary L, Lavine, Joel E, Mitreva, Makedonka, Newton, Kimberly P, Pan, Amy, Simpson, Pippa M, Sirlin, Claude B, Sodergren, Erica, Tyagi, Rahul, Yates, Katherine P, Weinstock, George M, and Salzman, Nita H

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Nutrition and Dietetics, Clinical Research, Biotechnology, Genetics, Liver Disease, Chronic Liver Disease and Cirrhosis, Digestive Diseases, Pediatric, Hepatitis, Aetiology, 2.1 Biological and endogenous factors, Oral and gastrointestinal, Adolescent, Bacteria, Case-Control Studies, Child, Cross-Sectional Studies, DNA, Bacterial, Dysbiosis, Feces, Female, Gastrointestinal Microbiome, Host-Pathogen Interactions, Humans, Intestines, Liver Cirrhosis, Male, Metagenome, Non-alcoholic Fatty Liver Disease, Prospective Studies, RNA, Ribosomal, 16S, Ribotyping, Severity of Illness Index, Intestinal Microbiota, Lipopolysaccharide, Flagellin, Neurosciences, Paediatrics and Reproductive Medicine, Gastroenterology & Hepatology, Clinical sciences, Nutrition and dietetics
Abstract

Background & aimsThe intestinal microbiome might affect the development and severity of nonalcoholic fatty liver disease (NAFLD). We analyzed microbiomes of children with and without NAFLD.MethodsWe performed a prospective, observational, cross-sectional study of 87 children (age range, 8-17 years) with biopsy-proven NAFLD and 37 children with obesity without NAFLD (controls). Fecal samples were collected and microbiome composition and functions were assessed using 16S ribosomal RNA amplicon sequencing and metagenomic shotgun sequencing. Microbial taxa were identified using zero-inflated negative binomial modeling. Genes contributing to bacterial pathways were identified using gene set enrichment analysis.ResultsFecal microbiomes of children with NAFLD had lower α-diversity than those of control children (3.32 vs 3.52, P = .016). Fecal microbiomes from children with nonalcoholic steatohepatitis (NASH) had the lowest α-diversity (control, 3.52; NAFLD, 3.36; borderline NASH, 3.37; NASH, 2.97; P = .001). High abundance of Prevotella copri was associated with more severe fibrosis (P = .036). Genes for lipopolysaccharide biosynthesis were enriched in microbiomes from children with NASH (P < .001). Classification and regression tree model with level of alanine aminotransferase and relative abundance of the lipopolysaccharide pathway gene encoding 3-deoxy-d-manno-octulosonate 8-phosphate-phosphatase identified patients with NASH with an area under the receiver operating characteristic curve value of 0.92. Genes involved in flagellar assembly were enriched in the fecal microbiomes of patients with moderate to severe fibrosis (P < .001). Classification and regression tree models based on level of alanine aminotransferase and abundance of genes encoding flagellar biosynthesis protein had good accuracy for identifying case children with moderate to severe fibrosis (area under the receiver operating characteristic curve, 0.87).ConclusionsIn an analysis of fecal microbiomes of children with NAFLD, we associated NAFLD and NASH with intestinal dysbiosis. NAFLD and its severity were associated with greater abundance of genes encoding inflammatory bacterial products. Alterations to the intestinal microbiome might contribute to the pathogenesis of NAFLD and be used as markers of disease or severity.

Published
2019

6. MYH6 Variants Are Associated with Atrial Dysfunction in Neonates with Hypoplastic Left Heart Syndrome.

Author

Quintanilla Anfinson, Melissa, Creighton, Sara, Simpson, Pippa M., James, Jeanne M., Lim, Phoebe, Frommelt, Peter C., Tomita-Mitchell, Aoy, and Mitchell, Michael E.

Subjects
GLOBAL longitudinal strain, HYPOPLASTIC left heart syndrome, SPECKLE tracking echocardiography, CONGENITAL heart disease, STRAIN rate
Abstract

Background: MYH6 variants are the most well-known genetic risk factor (10%) for hypoplastic left heart syndrome (HLHS) and are associated with decreased cardiac transplant-free survival. MYH6 encodes for α-myosin heavy chain (α-MHC), a contractile protein expressed in the neonatal atria. We therefore assessed atrial function in HLHS patients with MYH6 variants. Methods: We performed a retrospective, blinded assessment of pre-stage I atrial function using 2D speckle-tracking echocardiography (2D-STE). Variant carriers were control-matched based on AV valve anatomy, sex, and birth year. Studies were obtained postnatally from awake patients prior to surgical intervention. Right atrial (RA) and right ventricular (RV) strain and strain rate (SR) were measured from the apical four-chamber view. Results: A total of 19 HLHS patients with MYH6 variants had echocardiograms available; 18 were matched to two controls each, and one had a single control. RA active strain (ASct) was decreased in variant carriers (−1.41%, IQR −2.13, −0.25) vs. controls (−3.53%, IQR −5.53, −1.28; p = 0.008). No significant differences were identified in RV strain between the groups. RA reservoir strain (ASr) and conduit strain (AScd) positively correlated with heart rate (HR) in MYH6 variant carriers only (ASr R = 0.499, p = 0.029; AScd R = 0.469, p = 0.043). RV global longitudinal strain (GLS) as well as RV systolic strain (VSs) and strain rate (VSRs) correlated with HR in controls only (GLS R = 0.325, p = 0.050; VSs R = 0.419, p = 0.010; VSRs R = 0.410, p = 0.012). Conclusions: We identified functional consequences associated with MYH6 variants, a known risk factor for poor outcomes in HLHS. MYH6 variant carriers exhibit impaired RA contractility despite there being no differences in RV function between variant carriers and controls. MYH6 variants are also associated with an ineffective RA reservoir and conduit function at high heart rates, despite preserved RV diastolic function. RA dysfunction and reduced atrial "kick" may therefore be a significant contributor to RV failure and worse clinical outcomes in HLHS patients with MYH6 variants. [ABSTRACT FROM AUTHOR]

Published
2024
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14. Evaluating threshold for donor fraction cell‐free DNA using clinically available assay for rejection in pediatric and adult heart transplantation

Author

Deshpande, Shriprasad R., primary, Zangwill, Steven D., additional, Richmond, Marc E., additional, Kindel, Steven J., additional, Schroder, Jacob N., additional, Gaglianello, Nunzio, additional, Bichell, David P., additional, Wigger, Mark A., additional, Knecht, Kenneth R., additional, Thrush, Phillip T., additional, Mahle, William T., additional, North, Paula E., additional, Simpson, Pippa M., additional, Zhang, Liyun, additional, Dasgupta, Mahua, additional, Tomita‐Mitchell, Aoy, additional, and Mitchell, Michael E., additional

Published
2024
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36. Collagen‐Specific HSP47 + Myofibroblasts and CD163 + Macrophages Identify Profibrotic Phenotypes in Deceased Hearts With SARS‐CoV‐2 Infections

Author

Puzyrenko, Andrii, primary, Jacobs, Elizabeth R., additional, Padilla, Nathan, additional, Devine, Adam, additional, Aljadah, Michael, additional, Gantner, Benjamin N., additional, Pan, Amy Y., additional, Lai, Shuping, additional, Dai, Qiang, additional, Rubenstein, Jason C., additional, North, Paula E., additional, Simpson, Pippa M., additional, Willoughby, Rodney E., additional, O'Meara, Caitlin C., additional, Flinn, Michael A., additional, Lough, John W., additional, Ibrahim, El‐Sayed H., additional, Zheng, Ze, additional, Sun, Yunguang, additional, Felix, Juan, additional, Hunt, Bryan C., additional, Ross, Gracious, additional, Rui, Hallgeir, additional, and Benjamin, Ivor J., additional

Published
2023
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46. Food Shopping Perceptions, Behaviors, and Ability to Purchase Healthful Food Items in the Lower Mississippi Delta

Author

McGee, Bernestine B., Johnson, Glenda S., Yadrick, M. Kathleen, Richardson, Valerie, Simpson, Pippa M., Gossett, Jeffrey M., Thornton, Alma, Johnson, Crystal, and Bogle, Margaret L.

Abstract

Objective: To examine the agreement between perceptions, behaviors, and ability to purchase healthful food in the Lower Mississippi Delta (LMD). Design: A regional food store survey of healthful food options in supermarkets, small/medium stores, and convenience stores. Focus group discussions were conducted on shopping perceptions and behaviors. Setting: Counties in Arkansas, Louisiana, and Mississippi. Participants: Eighty-one LMD residents, 18-60+ years of age. Main Outcome Measure: Perceptions of healthful food and ability to acquire these food items across store types. Analysis: Focus group data were analyzed using thematic coding. Summary food store statistics were weighted, and estimates were constructed using SUDAAN 9. Data triangulation was achieved by comparing focus group findings with food availability data. Results: A majority (greater than 85%) of supermarkets had selected vegetables, breads, and cereals perceived as healthful, whereas availability was limited in small to medium grocery stores and convenience stores. Skim milk, perceived as healthful, was limited in all store types. Conclusions and Implications: Limited availability and perceived costs of healthful food in the LMD influenced purchasing behaviors. Attitudes and perceptions should be incorporated into intervention development to improve food choices in conjunction with increasing the availability of healthful food in the LMD. (Contains 2 figures and 5 tables.)

Published
2011
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50. Sibling Family Practices: Guidelines for Healthy Boundaries

Author

Johnson, Toni Cavanagh, Huang, Bevan Emma, and Simpson, Pippa M.

Abstract

A questionnaire was given to 500 mental health and child welfare professionals asking for maximum acceptable ages for siblings to engage jointly in certain family practices related to hygiene, affection, and privacy. A large proportion of respondents felt it was never acceptable for siblings to take showers together (40%), kiss on the mouth (37%), or toilet together (32%). Some significant differences occurred based on the gender of the older sibling within sets of same gender or mixed gender pairs, with older brothers being acceptable up to lower ages than older sisters. The effects of child abuse, age, race, and the amount of education on the respondents' answers are investigated. The limitations of the age guidelines are discussed. (Contains 2 tables.)

Published
2009
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