Digital Commons Network^™

A D2 To D1 Shift In Dopaminergic Inputs To Midbrain 5-Ht Neurons Causes Anorexia In Mice, Xing Cai, Hailan Liu, Bing Feng, Meng Yu, Yang He, Hesong Liu, Chen Liang, Yongjie Yang, Longlong Tu, Nan Zhang, Lina Wang, Na Yin, Junying Han, Zili Yan, Chunmei Wang, Pingwen Xu, Qi Wu, Qingchun Tong, Yanlin He, Yong Xu

Faculty, Staff and Students Publications

Midbrain dopamine (DA) and serotonin (5-HT) neurons regulate motivated behaviors, including feeding, but less is known about how these circuits may interact. In this study, we found that DA neurons in the mouse ventral tegmental area bidirectionally regulate the activity of 5-HT neurons in the dorsal raphe nucleus (DRN), with weaker stimulation causing DRD2-dependent inhibition and overeating, while stronger stimulation causing DRD1-dependent activation and anorexia. Furthermore, in the activity-based anorexia (ABA) paradigm, which is a mouse model mimicking some clinical features of human anorexia nervosa (AN), we observed a DRD2 to DRD1 shift of DA neurotransmission on 5-HT

Enpp1 Variants In Patients With Gaci And Pxe Expand The Clinical And Genetic Heterogeneity Of Heritable Disorders Of Ectopic Calcification., Douglas Ralph, Yvonne Nitschke, Michael A Levine, Matthew Caffet, Tamara Wurst, Amir Hossein Saeidian, Leila Youssefian, Hassan Vahidnezhad, Sharon F Terry, Frank Rutsch, Jouni Uitto, Qiaoli Li

Department of Medicine Faculty Papers

Pseudoxanthoma elasticum (PXE) and generalized arterial calcification of infancy (GACI) are clinically distinct genetic entities of ectopic calcification associated with differentially reduced circulating levels of inorganic pyrophosphate (PPi), a potent endogenous inhibitor of calcification. Variants in ENPP1, the gene mutated in GACI, have not been associated with classic PXE. Here we report the clinical, laboratory, and molecular evaluations of ten GACI and two PXE patients from five and two unrelated families registered in GACI Global and PXE International databases, respectively. All patients were found to carry biallelic variants in ENPP1. Among ten ENPP1 variants, one homozygous variant demonstrated uniparental disomy …

Home-Grown School Feeding: Implementation Lessons From A Pilot In A Poor Ethnic Minority Community In Vietnam, Sabina Di Prima, Dai Nguyen Dinh, Demi D. Reurings, E Pamela Wright Phd, Ms, Med, Rn, Cen, Dirk Essink, Jacqueline E. Broerse

Publications

BACKGROUND:

Undernutrition threatens the health and future of preschool children in disadvantaged remote communities. Home-grown school feeding (HGSF) in nursery schools could positively impact children's nutrition while creating multiple benefits for the whole community. However, evidence is lacking on implementation of HGSF within multi-sectoral programs in remote areas.

OBJECTIVE:

This study assessed an HGSF pilot intervention, part of a nutrition-sensitive agriculture (NSA) program, in a mountain ethnic minority community in Vietnam. It aimed to identify the changes brought about by the intervention, in particular diversity of children's food, food sources, barriers and facilitators to change, and future challenges and strategies. …

Long Noncoding Rna Zfp36l2-As Functions As A Metabolic Modulator To Regulate Muscle Development., Bolin Cai, Manting Ma, Jing Zhang, Shaofen Kong, Zhen Zhou, Zhenhui Li, Bahareldin Ali Abdalla, Haiping Xu, Xiquan Zhang, Raman Akinyanju Lawal, Qinghua Nie

Faculty Research 2022

Skeletal muscle is the largest metabolic organ in the body, and its metabolic flexibility is essential for maintaining systemic energy homeostasis. Metabolic inflexibility in muscles is a dominant cause of various metabolic disorders, impeding muscle development. In our previous study, we found lncRNA ZFP36L2-AS (for "ZFP36L2-antisense transcript") is specifically enriched in skeletal muscle. Here, we report that ZFP36L2-AS is upregulated during myogenic differentiation, and highly expressed in breast and leg muscle. In vitro, ZFP36L2-AS inhibits myoblast proliferation but promotes myoblast differentiation. In vivo, ZFP36L2-AS facilitates intramuscular fat deposition, as well as activates fast-twitch muscle phenotype and induces muscle atrophy. Mechanistically, …

Meal Timing, Meal Frequency And Metabolic Syndrome, Fatema Alkhulaifi, Charles Darkoh

Faculty, Staff and Student Publications

Individuals with metabolic syndrome have increased risk for developing health conditions, including cardiovascular diseases and stroke. Modifiable risk factors, such as exercise and diet, are key components in the prevention and control of metabolic syndrome. Specifically, dietary patterns and habits are extremely successful in controlling more than one of the metabolic syndrome risk factors. Meal timing and frequency have been associated with type 2 diabetes, cardiovascular diseases, and other chronic conditions. However, there is limited evidence linking metabolic syndrome to meal timing and meal frequency. This review summarizes and discusses how meal timing and frequency impact metabolic outcomes in adults.

Gastrointestinal Kohlmeier-Degos Disease: A Narrative Review, Samantha S. Sattler, Cynthia M. Magro, Lee Shapiro, Jamie F. Merves, Rebecca Levy, Jesse Veenstra, Puraj P. Patel

Dermatology Articles

INTRODUCTION: Kohlmeier-Degos (K-D) disease is a rare obliterative vasculopathy that can present as a benign cutaneous form or with potentially malignant systemic involvement. The gastrointestinal tract is most frequently involved in systemic disease and mortality is often related to bowel perforations. Herein, we provide information to providers and patients regarding gastrointestinal K-D symptomology, pathology, treatment, and diagnosis, with a focus on the importance of timely diagnostic laparoscopy. We present three new cases of gastrointestinal K-D to highlight varying disease presentations and outcomes.

BODY: Based on reviewed reports, perforation is preceded by at least one gastrointestinal symptom: abdominal pain/cramping, anorexia/weight loss, …

Hyperactivation Is Sufficient To Release Porcine Sperm From Immobilized Oviduct Glycans, Momal Sharif, Vincent Hickl, Gabriel Juarez, Xingjian Di, Karl Kerns, Peter Sutovsky, Nicolai Bovin, David J Miller

Faculty, Staff and Students Publications

Fertilizing sperm are retained by adhesion to specific glycans on the epithelium of the oviduct forming a reservoir before sperm are released from the reservoir so fertilization can ensue. Capacitated sperm lose affinity for the oviduct epithelium but the components of capacitation that are important for sperm release are uncertain. One important correlate of capacitation is the development of hyperactivated motility. Hyperactivation is characterized by asymmetrical flagellar beating with high beat amplitude. We tested whether the development of full-type asymmetrical motility was sufficient to release sperm from immobilized oviduct glycans. Sperm hyperactivation was induced by four different compounds, a cell-permeable …

Applying Systems Thinking To Identify Enablers And Challenges To Scale-Up Interventions For Hypertension And Diabetes In Low-Income And Middle-Income Countries: Protocol For A Longitudinal Mixed-Methods Study, Anusha Ramani-Chander, Mark D Huffman, Et Al

Open Access Publications

INTRODUCTION: There is an urgent need to reduce the burden of non-communicable diseases (NCDs), particularly in low-and middle-income countries, where the greatest burden lies. Yet, there is little research concerning the specific issues involved in scaling up NCD interventions targeting low-resource settings. We propose to examine this gap in up to 27 collaborative projects, which were funded by the Global Alliance for Chronic Diseases (GACD) 2019 Scale Up Call, reflecting a total funding investment of approximately US$50 million. These projects represent diverse countries, contexts and adopt varied approaches and study designs to scale-up complex, evidence-based interventions to improve hypertension and …

Emergency Department Antimicrobial Use In A Low-Resource Setting: Results From A Retrospective Observational Study At A Referral Hospital In Liberia, Sojung Yi, Anu Ramachandran, Lane Epps, Alex Mayah, Taylor W Burkholder, Michael Senyu Jaung, Ahson Haider, Paul Whesseh, John Shakpeh, Kayla Enriquez, Corey Bills

Faculty, Staff and Students Publications

OBJECTIVE: Data on antimicrobial use in low-income and middle-income countries (LMICs) remain limited. In Liberia, the absence of local data impedes surveillance and may lead to suboptimal treatment, injudicious use and resistance against antimicrobials. This study aims to examine antimicrobial prescribing patterns for patients in the emergency department (ED) of a large Liberian public hospital. Secondarily, this prescribing was compared with WHO prescribing indicators.

DESIGN: Retrospective observational study.

SETTING: An adult ED of a large public hospital in Monrovia, Liberia.

PARTICIPANTS: A total of 1082 adult patients (>18 years of age) were recorded in the ED, from 1 January …

Measuring Case Severity: A Novel Tool For Benchmarking And Clinical Documentation Improvement, Jie Xiang, Paul W. Durance, Louisa C. Griffes, Yalei Chen, Rishi R. Bakshi

Public Health Sciences Articles

BACKGROUND: Severity of illness (SOI) is an All Patients Refined Diagnosis Related Groups (APR DRG) modifier based on comorbidity capture. Tracking SOI helps hospitals improve performance and resource distribution. Furthermore, benchmarking SOI plays a key role in Quality Improvement (QI) efforts such as Clinical Documentation Improvement (CDI) programs. The current SOI system highly relies on the 3 M APR DRG grouper that is updated annually, making it difficult to track severity longitudinally and benchmark against hospitals with different patient populations. Here, we describe an alternative SOI scoring system that is grouper-independent and that can be tracked longitudinally.

METHODS: Admission data …

Evaluation Of An Adapted Version Of The Diabetes Prevention Program For Low- And Middle-Income Countries: A Cluster Randomized Trial To Evaluate "Lifestyle Africa" In South Africa., Delwyn Catley, Thandi Puoane, Lungiswa Tsolekile, Ken Resnicow, Kandace K. Fleming, Emily A. Hurley, Joshua M. Smyth, Frank T. Materia, Estelle V. Lambert, Mara Z. Vitolins, Naomi S. Levitt, Kathy Goggin

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Low- and middle-income countries (LMICs) are experiencing major increases in diabetes and cardiovascular conditions linked to overweight and obesity. Lifestyle interventions such as the United States National Diabetes Prevention Program (DPP) developed in high-income countries require adaptation and cultural tailoring for LMICs. The objective of this study was to evaluate the efficacy of "Lifestyle Africa," an adapted version of the DPP tailored for an underresourced community in South Africa compared to usual care.

METHODS AND FINDINGS: Participants were residents of a predominantly Xhosa-speaking urban township of Cape Town, South Africa characterized by high rates of poverty. Participants with body …

Associations Of Steps Per Day And Step Intensity With The Risk Of Diabetes: The Hispanic Community Health Study / Study Of Latinos (Hchs/Sol)., Carmen C. Cuthbertson, Christopher C. Moore, Daniela Sotres-Alvarez, Gerardo Heiss, Carmen R. Isasi, Yasmin Mossavar-Rahmani, Jordan A. Carlson, Linda C. Gallo, Maria M. Llabre, Olga L. Garcia-Bedoya, David Goldsztajn Farelo, Kelly R. Evenson

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Higher levels of moderate-to-vigorous physical activity have been associated with a lower risk of diabetes, but less is known about how daily step counts (steps/day) are associated with diabetes risk. Therefore, we examined the association of steps/day and step intensity with incident diabetes.

METHODS: We included 6634 adults from the population-based prospective cohort Hispanic Community Health Study/Study of Latinos (HCHS/SOL) (2008-2017). Cox proportional hazard models that accounted for complex survey design and sampling weights were used to estimate the association of baseline accelerometer-assessed steps/day and step intensity with 6-year risk of incident diabetes as hazard ratios (HR) and 95% …

Vulvovaginal Candidiasis: A Review Of The Evidence For The 2021 Centers For Disease Control And Prevention Of Sexually Transmitted Infections Treatment Guidelines., Paul Nyirjesy, Carolyn Brookhart, Gweneth Lazenby, Jane Schwebke, Jack D Sobel

Department of Obstetrics and Gynecology Faculty Papers

BACKGROUND: Vulvovaginal candidiasis (VVC) is a common cause of vulvovaginal itching and discharge. This article discusses the latest CDC STI Treatment Guidelines for VVC.

METHODS: A literature search of relevant topics was performed, and a team of experts was convened to discuss (1) diagnosis/testing modalities; treatment of (2) uncomplicated VVC , (3) complicated VVC, and (4) VVC caused by non-albicans yeast; (5) alternative treatment regimens; (6) susceptibility testing of yeast; Special Populations: (7) pregnancy and (8) HIV and VVC.

RESULTS: Yeast culture remains the gold standard for diagnoses. Newer molecular assays have been developed for the diagnosis of VVC and …

Human Pancreatic Microenvironment Promotes Β-Cell Differentiation Via Non-Canonical Wnt5a/Jnk And Bmp Signaling, Jolanta Chmielowiec, Wojciech J Szlachcic, Diane Yang, Marissa A Scavuzzo, Katrina Wamble, Alejandro Sarrion-Perdigones, Omaima M Sabek, Koen J T Venken, Malgorzata Borowiak

Faculty, Staff and Students Publications

In vitro derivation of pancreatic β-cells from human pluripotent stem cells holds promise as diabetes treatment. Despite recent progress, efforts to generate physiologically competent β-cells are still hindered by incomplete understanding of the microenvironment's role in β-cell development and maturation. Here, we analyze the human mesenchymal and endothelial primary cells from weeks 9-20 fetal pancreas and identify a time point-specific microenvironment that permits β-cell differentiation. Further, we uncover unique factors that guide in vitro development of endocrine progenitors, with WNT5A markedly improving human β-cell differentiation. WNT5A initially acts through the non-canonical (JNK/c-JUN) WNT signaling and cooperates with Gremlin1 to inhibit …

Prep Patient Attitudes, Beliefs And Perceived Barriers Surrounding Hpv Vaccination: A Qualitative Study Of Semistructured Interviews With Prep Patients In Primary Care Clinics In Kansas And Missouri., Zoe C Sullivan-Blum, Margaret Brophy, Ryan Didde, Radha Nagireddy, Hannah Swagerty, Sumiko Weir, Kevin J. Sykes, Craig Dietz, Marcus Alt, Megha Ramaswamy, Paul Rotert

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: Men who have sex with men who use pre-exposure prophylaxis (PrEP) have not traditionally been targets for human papillomavirus (HPV) vaccine programmes, despite their high risk for HPV-related cancers and HPV vaccine being approved by the U.S. Food and Drug Administration (FDA) for people up to age 45. The objective of this study was to assess attitudes and barriers towards HPV vaccine for adult PrEP users in the primary care context.

METHODS: Semistructured phone interviews of 16 primary care patients taking PrEP in the Kansas City metropolitan area were conducted, with interviews assessing HPV vaccination status, and attitudes, beliefs …

Methylation Quantitative Trait Loci Are Largely Consistent Across Disease States In Crohn’S Disease, Suresh Venkateswaran, Hari K Somineni, Varun Kilaru, Seyma Katrinli, Jarod Prince, David T Okou, Jeffrey S Hyams, Lee A Denson, Richard Kellermayer, Greg Gibson, David J Cutler, Alicia K Smith, Subra Kugathasan, Karen N Conneely

Faculty, Staff and Students Publications

Recently, we identified 1,189 CpG sites whose DNA methylation level in blood associated with Crohn's disease. Here, we examined associations between DNA methylation and genetic variants to identify methylation quantitative trait loci across disease states in (1) 402 blood samples from 164 newly diagnosed pediatric Crohn's disease patients taken at 2 time points (diagnosis and follow-up), and 74 non-inflammatory bowel disease controls, (2) 780 blood samples from a non-Crohn's disease adult population, and (3) 40 ileal biopsies (17 Crohn's disease cases and 23 non-inflammatory bowel disease controls) from group (1). Genome-wide DNAm profiling and genotyping were performed using the Illumina …

Baroreflex Sensitivity In Facioscapulohumeral Muscular Dystrophy, Miguel Anselmo, Shandon Coffman, Mia Larson, Kathryn Vera, Emma Lee, Mary Mcconville, Michael Kyba, Manda L Keller-Ross

Department of Medicine Faculty Papers

Facioscapulohumeral muscular dystrophy (FSHD), a common form of muscular dystrophy, is caused by a genetic mutation that alters DUX4 gene expression. This mutation contributes to significant skeletal muscle loss. Although it is suggested that cardiac muscle may be spared, people with FSHD have demonstrated autonomic dysregulation. It is unknown if baroreflex function, an important regulator of blood pressure (BP), is impaired in people with FSHD. We examined if baroreflex sensitivity (BRS) is blunted in patients with FSHD. Thirty minutes of resting BP, heart rate, and cardiovagal BRS were measured in 13 patients with FSHD (age: 50 ± 13 years, avg …

Longitudinal Analysis Of The Impact Of Oral Contraceptive Use On The Gut Microbiome, Xinwei Hua, Yueming Cao, David M Morgan, Kaia Miller, Samantha M Chin, Danielle Bellavance, Hamed Khalili

Department of Medicine Faculty Papers

Introduction. Evidence has linked exogenous and endogenous sex hormones with the human microbiome.Hypothesis/Gap statement. The longitudinal effects of oral contraceptives (OC) on the human gut microbiome have not previously been studied.Aim. We sought to examine the longitudinal impact of OC use on the taxonomic composition and metabolic functions of the gut microbiota and endogenous sex steroid hormones after initiation of OC use.Methodology. We recruited ten healthy women who provided blood and stool samples prior to OC use, 1 month and 6 months after starting OC. We measured serum levels of sex hormones, including estradiol, progesterone, sex hormone-binding …

Pediatric Growth Patterns In Youth-Onset Type 2 Diabetes Mellitus: Implications For Physiologically-Based Pharmacokinetic Models., Chelsea M. Hosey, Kelsee Halpin, Valentina Shakhnovich, Chengpeng Bi, Brooke Sweeney, Yun Yan, J Steven Leeder

Manuscripts, Articles, Book Chapters and Other Papers

An accurate understanding of the changes in height and weight of children with age is critical to the development of models predicting drug concentrations in children (i.e., physiologically-based pharmacokinetic models). However, curves describing the growth of a typical population of children may not accurately characterize growth of children with various conditions, such as obesity. Therefore, to develop height and weight versus age growth curves for youth who were diagnosed with type 2 diabetes, we extracted data from electronic medical records. Robust nonlinear models were parameterized to the equations describing height and weight versus age as defined by the Centers for …

Metabolic Inflexibility In Youth With Obesity: Is It A Feature Of Obesity Or Distinctive Of Youth Who Are Metabolically Unhealthy?, Nour Y Gebara, Joon Young Kim, Fida Bacha, Sojung Lee, Silva Arslanian

Faculty, Staff and Students Publications

Individuals with obesity have metabolic inflexibility with diminished fasting fat oxidation and blunted increase in respiratory quotient (RQ) in insulin-stimulated states. However, it is unclear if metabolic inflexibility is a characteristic of obesity per se or is unique to youth who have metabolically unhealthy obesity (MUO) compared with metabolically healthy obesity (MHO). We investigated metabolic flexibility in youth with MUO, MHO and normal weight (NW) and compared their metabolic characteristics. Youth (n = 188) were divided, based on cut-off points for in vivo insulin sensitivity (IS) of adolescents with NW, into 137 with MUO and 51 with MHO. Fasting hepatic …

Examining 24-Hour Activity And Sleep Behaviors And Related Determinants In Latino Adolescents And Young Adults With Obesity, Erica G Soltero, Neeku Navabi, Kiley B Vander Wyst, Edith Hernandez, Felipe G Castro, Stephanie L Ayers, Jenny Mendez, Gabriel Q Shaibi

Children’s Nutrition Research Center Staff Publications

Background.

Few studies have examined 24-hour activity and sleep behaviors and their contribution to type 2 diabetes (T2D) in Latino adolescents and young adults with obesity.

Aim.

This study included quantitative data on T2D risk and 24-hour activity and sleep behaviors and qualitative data on individual, social, and environmental behavioral determinants.

Method.

A 7 day, 24-hour, wrist-worn accelerometer protocol assessed moderate-to-vigorous physical activity (PA), sedentary behaviors (SB), sleep, and sleep regularity, in adolescents (N = 38; 12–16 years) and young adults (N = 22; 18–22 years). T2D-related outcomes included adiposity (BMI, BF%, waist circumference), fasting, and 2-hour glucose. …

Food Assistance Use Among Food Bank Clients Affected By Type 2 Diabetes, Eliza Short, Jayati Sharma, Debbe I Thompson, Douglas Taren, Rhonda Gonzalez, Melanie Hingle

Children’s Nutrition Research Center Staff Publications

Objective: To understand the perspectives of food bank clients affected by type 2 diabetes (T2DM).

Design: Semi-structured in-depth interviews conducted with food bank clients.

Setting: Arizona regional food bank.

Participants: Twenty English- and Spanish-speaking food bank clients with T2DM or living with a person with T2DM, aged 45-83 years, majority female, Hispanic, and food insecure.

Phenomenon of interest: Food bank use and preferences, and how these related to T2DM management.

Analysis: A hybrid thematic analysis combining inductive and deductive reasoning.

Results: Three organizing themes emerged from the analysis. First, food assistance was influenced by food preferences and the ability to …

Trans Fatty Acid Biomarkers And Incident Type 2 Diabetes: Pooled Analysis Of 12 Prospective Cohort Studies In The Fatty Acids And Outcomes Research Consortium (Force), Heidi T M Lai, Fumiaki Imamura, Andres V Ardisson Korat, Rachel A Murphy, Nathan Tintle, Julie K Bassett, Jiaying Chen, Janine Kröger, Kuo-Liong Chien, Mackenzie Senn, Alexis C Wood, Nita G Forouhi, Matthias B Schulze, William S Harris, Ramachandran S Vasan, Frank Hu, Graham G Giles, Allison Hodge, Luc Djousse, Ingeborg A Brouwer, Frank Qian, Qi Sun, Jason H Y Wu, Matti Marklund, Rozenn N Lemaitre, David S Siscovick, Amanda M Fretts, Aladdin H Shadyab, Joann E Manson, Barbara V Howard, Jennifer G Robinson, Robert B Wallace, Nick J Wareham, Yii-Der Ida Chen, Jerome I Rotter, Michael Y Tsai, Renata Micha, Dariush Mozaffarian, Fatty Acids And Outcomes Research Consortium (Force)

Children’s Nutrition Research Center Staff Publications

Objective: Trans fatty acids (TFAs) have harmful biologic effects that could increase the risk of type 2 diabetes (T2D), but evidence remains uncertain. We aimed to investigate the prospective associations of TFA biomarkers and T2D by conducting an individual participant-level pooled analysis.

Research design and methods: We included data from an international consortium of 12 prospective cohorts and nested case-control studies from six nations. TFA biomarkers were measured in blood collected between 1990 and 2008 from 25,126 participants aged ≥18 years without prevalent diabetes. Each cohort conducted de novo harmonized analyses using a prespecified protocol, and findings were pooled using …

Identification Of Genetic Loci Simultaneously Associated With Multiple Cardiometabolic Traits, Alexis C Wood, Amit Arora, Michelle Newell, Victoria L Bland, Jin Zhou, Nicola Pirastu, Jose M Ordovas, Yann C Klimentidis

Children’s Nutrition Research Center Staff Publications

Background and aims: Cardiometabolic disorders (CMD) arise from a constellation of features such as increased adiposity, hyperlipidemia, hypertension and compromised glucose control. Many genetic loci have shown associations with individual CMD-related traits, but no investigations have focused on simultaneously identifying loci showing associations across all domains. We therefore sought to identify loci associated with risk across seven continuous CMD-related traits.

Methods and results: We conducted separate genome-wide association studies (GWAS) for systolic and diastolic blood pressure (SBP/DBP), hemoglobin A1c (HbA1c), low- and high- density lipoprotein cholesterol (LDL-C/HDL-C), waist-to-hip-ratio (WHR), and triglycerides (TGs) in the UK Biobank (N = 356,574-456,823). Multiple …

Metabolic Inflexibility In Youth With Obesity: Is It A Feature Of Obesity Or Distinctive Of Youth Who Are Metabolically Unhealthy?, Nour Y Gebara, Joon Young Kim, Fida Bacha, Sojung Lee, Silva Arslanian

Children’s Nutrition Research Center Staff Publications

Background:

Individuals with obesity have metabolic inflexibility with diminished fasting fat oxidation and blunted increase in respiratory quotient (RQ) in insulin-stimulated states. However, it is unclear if metabolic inflexibility is a characteristic of obesity per se or is unique to youth who have metabolically unhealthy obesity (MUO) compared with metabolically healthy obesity (MHO).

Objective:

We investigated metabolic flexibility in youth with MUO, MHO and normal weight (NW) and compared their metabolic characteristics.

Patients/Design:

Youth (n=188) were divided, based on cut-off points for in vivo insulin sensitivity (IS) of adolescents with NW, into 137 with MUO and 51 with MHO. Fasting …

Peppermint Oil Effects On The Gut Microbiome In Children With Functional Abdominal Pain., Santosh Thapa, Ruth Ann Luna, Bruno P. Chumpitazi, Numan Oezguen, Susan M. Abdel-Rahman, Uttam Garg, Salma Musaad, James Versalovic, Gregory L. Kearns, Robert J. Shulman

Manuscripts, Articles, Book Chapters and Other Papers

Peppermint oil (PMO) is effective in the treatment of functional abdominal pain disorders, but its mechanism of action is unclear. Evidence suggests PMO has microbicidal activity. We investigated the effect of three different doses of PMO on gut microbiome composition. Thirty children (7-12 years of age) with functional abdominal pain provided a baseline stool sample prior to randomization to 180, 360, or 540 mg of enteric coated PMO (10 participants per dose). They took their respective dose of PMO (180 mg once, 180 mg twice, or 180 mg thrice daily) for 1 week, after which the stool collection was repeated. …

Inhibiting Type I Arginine Methyltransferase Activity Promotes T Cell-Mediated Antitumor Immune Responses, Andrew Fedoriw, Leilei Shi, Shane O'Brien, Kimberly N Smitheman, Yunfei Wang, Jiakai Hou, Christian Sherk, Satyajit Rajapurkar, Jenny Laraio, Leila J Williams, Chunyu Xu, Guangchun Han, Qin Feng, Mark T Bedford, Linghua Wang, Olena Barbash, Ryan G Kruger, Patrick Hwu, Helai P Mohammad, Weiyi Peng

Faculty, Staff and Student Publications

Protein arginine methyltransferases (PRMT) are a widely expressed class of enzymes responsible for catalyzing arginine methylation on numerous protein substrates. Among them, type I PRMTs are responsible for generating asymmetric dimethylarginine. By controlling multiple basic cellular processes, such as DNA damage responses, transcriptional regulation, and mRNA splicing, type I PRMTs contribute to cancer initiation and progression. A type I PRMT inhibitor, GSK3368715, has been developed and has entered clinical trials for solid and hematologic malignancies. Although type I PRMTs have been reported to play roles in modulating immune cell function, the immunologic role of tumor-intrinsic pathways controlled by type I …

Prevalence Of Metabolic Syndrome Among The Adult Population In Western China And The Association With Socioeconomic And Individual Factors: Four Cross-Sectional Studies, Xinyin Xu, Jing Zeng, Wei Yang, Ting Dong, Xin Zhang, Shuwen Cheng, Xiaobo Zhou, Maigeng Zhou, Ling Niu, Guanghui Yi, You Li, Lishi Zhang, Yin Deng, Xianping Wu

Faculty, Staff and Student Publications

Objectives: This study explored the prevalence of and individual influencing factors for metabolic syndrome (MS) as well as associated socioeconomic factors and regional aggregation.

Design: Four cross-sectional surveys were analysed for trends in MS and associations with socioeconomic and individual factors through multilevel logistic regression analyses. The risk associated with nutrient intake was also assessed through a dietary survey in 2015.

Setting: From 2010 to 2018, 8-15 counties/districts of West China were included.

Participants: A total of 28 274 adults were included in the prevalence analysis. A total of 23 708 adults were used to analyse the related factors.

Results: …

Development And Characterization Of Anti-Galectin-9 Antibodies That Protect T Cells From Galectin-9-Induced Cell Death, Riyao Yang, Linlin Sun, Ching-Fei Li, Yu-Han Wang, Weiya Xia, Boning Liu, Yu-Yi Chu, Laura Bover, Long Vien, Mien-Chie Hung

Faculty, Staff and Student Publications

Antibodies that target immune checkpoint proteins such as programmed cell death protein 1, programmed death ligand 1, and cytotoxic T-lymphocyte-associated antigen 4 in human cancers have achieved impressive clinical success; however, a significant proportion of patients fail to respond to these treatments. Galectin-9 (Gal-9), a β-galactoside-binding protein, has been shown to induce T-cell death and facilitate immunosuppression in the tumor microenvironment by binding to immunomodulatory receptors such as T-cell immunoglobulin and mucin domain-containing molecule 3 and the innate immune receptor dectin-1, suggesting that it may have potential as a target for cancer immunotherapy. Here, we report the development of two …

Combination Of Sulindac And Eflornithine Delays The Need For Lower Gastrointestinal Surgery In Patients With Familial Adenomatous Polyposis: Post Hoc Analysis Of A Randomized Clinical Trial, Francesc Balaguer, Paul E Wise, Et Al

Open Access Publications

BACKGROUND: Colectomy and proctocolectomy are the initial standard of care for patients with familial adenomatous polyposis. Pharmacotherapy to prevent the progression of polyposis and surgeries in the lower GI tract would be beneficial to patients with this disease.

OBJECTIVE: This analysis aimed to evaluate the impact of eflornithine-sulindac combination versus monotherapy in delaying time to disease progression in the lower GI tract of patients with familial adenomatous polyposis.

DESIGN: This is a post hoc analysis of a randomized phase 3 trial.

SETTING: This study was conducted in 21 hospitals in 7 countries treating patients with familial adenomatous polyposis.

PATIENTS: Adults …