Digital Commons Network^™

Revascularization Strategies For Acute And Chronic Mesenteric Ischemia: A Narrative Review, Jacob J Gries, Takashi Sakamoto, Bing Chen, Hafeez Ul Hassan Virk, Mahboob Alam, Chayakrit Krittanawong

Faculty, Staff and Students Publications

Mesenteric ischemia is a challenging condition characterized by insufficient blood perfusion to the mesentery and, consequently, intestinal tissues that continues to perplex clinicians. Despite its low prevalence, the condition’s variable clinical presentation and elusive radiographic diagnosis can delay life-saving interventions in the acute setting and deteriorate the quality of life of patients when left undiagnosed or misdiagnosed. Purpose: Review and summarize recent diagnostic updates and emergent intervention strategies for acute and chronic mesenteric ischemia. Methods: A narrative review of all relevant studies from January 2022 through September 2023. Results: A total of 11 studies from MEDLINE, supplemented with 44 studies …

Association Of Lifestyle Intervention With Risk For Cardiovascular Events Differs By Level Of Glycated Hemoglobin, Michael P Bancks, Scott J Pilla, Ashok Balasubramanyam, Hsin-Chieh Yeh, Karen C Johnson, Joseph Rigdon, Lynne E Wagenknecht, Mark A Espeland

Faculty, Staff and Students Publications

Purpose: We reevaluated the Action for Health in Diabetes (Look AHEAD) intensive lifestyle intervention (ILI) to assess whether the effect of ILI on cardiovascular disease (CVD) prevention differed by baseline glycated hemoglobin (HbA1c).

Methods: Look AHEAD randomized 5145 adults, aged 45 to 76 years with type 2 diabetes and overweight/obesity to ILI or a diabetes support and education (DSE) control group for a median of 9.6 years. ILI focused on achieving weight loss through decreased caloric intake and increased physical activity. We assessed the parent trial's primary composite CVD outcome. We evaluated additive and multiplicative heterogeneity of the intervention on …

Cpsf3 Inhibition Blocks Pancreatic Cancer Cell Proliferation Through Disruption Of Core Histone Mrna Processing, Abdulrahman A Alahmari, Aditi H Chaubey, Venkata S Jonnakuti, Arwen A Tisdale, Carla D Schwarz, Abigail C Cornwell, Kathryn E Maraszek, Emily J Paterson, Minsuh Kim, Swati Venkat, Eduardo Cortes Gomez, Jianmin Wang, Katerina V Gurova, Hari Krishna Yalamanchili, Michael E Feigin

Faculty, Staff and Students Publications

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with limited effective treatment options, potentiating the importance of uncovering novel drug targets. Here, we target cleavage and polyadenylation specificity factor 3 (CPSF3), the 3′ endonuclease that catalyzes mRNA cleavage during polyadenylation and histone mRNA processing. We find that CPSF3 is highly expressed in PDAC and is associated with poor prognosis. CPSF3 knockdown blocks PDAC cell proliferation and colony formation in vitro and tumor growth in vivo. Chemical inhibition of CPSF3 by the small molecule JTE-607 also attenuates PDAC cell proliferation and colony formation, while it has no effect on cell proliferation …

Development And Validation Of Parent-Reported Gastrointestinal Health Scale In Mecp2 Duplication Syndrome, Davut Pehlivan, Sukru Aras, Daniel G Glaze, Muharrem Ak, Bernhard Suter, Kathleen J Motil

Faculty, Staff and Students Publications

BACKGROUND/AIMS: We aimed to develop a validated patient-reported Gastrointestinal Health Scale (GHS) specific to MECP2 Duplication Syndrome (MDS) to be used in clinical trials.

METHODS: MDS parents completed a Gastrointestinal Health Questionnaire (GHQ) to investigate the most relevant and important items associated with gastrointestinal problems in MECP2-related disorders. Item reduction was executed according to EORTC guidelines. We performed reliability and validity studies for the finalized scale.

RESULTS: A total of 106 surveys were eligible for item reduction and validation processes. The initial 55 items were reduced to 38 items based on parent responses, expert opinion, and initial confirmatory factor analysis …

An Excitatory Projection From The Basal Forebrain To The Ventral Tegmental Area That Underlies Anorexia-Like Phenotypes, Jing Cai, Yanyan Jiang, Yuanzhong Xu, Zhiying Jiang, Claire Young, Hongli Li, Joshua Ortiz-Guzman, Yizhou Zhuo, Yulong Li, Yong Xu, Benjamin R Arenkiel, Qingchun Tong

Faculty, Staff and Students Publications

Maladaptation in balancing internal energy needs and external threat cues may result in eating disorders. However, brain mechanisms underlying such maladaptations remain elusive. Here, we identified that the basal forebrain (BF) sends glutamatergic projections to glutamatergic neurons in the ventral tegmental area (VTA) in mice. Glutamatergic neurons in both regions displayed correlated responses to various stressors. Notably, in vivo manipulation of BF terminals in the VTA revealed that the glutamatergic BF → VTA circuit reduces appetite, increases locomotion, and elicits avoidance. Consistently, activation of VTA glutamatergic neurons reduced body weight, blunted food motivation, and caused hyperactivity with behavioral signs of …

High-Sensitivity Cardiac Troponins I And T And Cardiovascular Outcomes: Findings From The Systolic Blood Pressure Intervention Trial (Sprint), Xiaoming Jia, Vijay Nambi, Jarett D Berry, Djhenne Dalmacy, Simon B Ascher, Addison A Taylor, Ron C Hoogeveen, James A De Lemos, Christie M Ballantyne

Faculty, Staff and Students Publications

Background: Cardiac troponins are associated with adverse cardiovascular disease (CVD) outcomes. The value of high-sensitivity cardiac troponin I (hs-cTnI) independently and in concert with troponin T (hs-cTnT) in the management of hypertension has not been well studied.

Methods: We assessed the utility of hs-cTnI independently and with hs-cTnT in identifying the highest risk individuals in the Systolic Blood Pressure Intervention Trial (SPRINT). Among 8796 eligible SPRINT participants, hs-cTnI was measured at baseline and 1 year. The association of baseline level and 1-year change in hs-cTnI with CVD events and all-cause death was evaluated using adjusted Cox regression models. We further …

Development And Validation Of The American Heart Association's Prevent Equations, Sadiya S Khan, Kunihiro Matsushita, Yingying Sang, Shoshana H Ballew, Morgan E Grams, Aditya Surapaneni, Michael J Blaha, April P Carson, Alexander R Chang, Elizabeth Ciemins, Alan S Go, Orlando M Gutierrez, Shih-Jen Hwang, Simerjot K Jassal, Csaba P Kovesdy, Donald M Lloyd-Jones, Michael G Shlipak, Latha P Palaniappan, Laurence Sperling, Salim S Virani, Katherine Tuttle, Ian J Neeland, Sheryl L Chow, Janani Rangaswami, Michael J Pencina, Chiadi E Ndumele, Josef Coresh, Chronic Kidney Disease Prognosis Consortium And The American Heart Association Cardiovascular-Kidney-Metabolic Science Advisory Group

Faculty, Staff and Students Publications

BACKGROUND: Multivariable equations are recommended by primary prevention guidelines to assess absolute risk of cardiovascular disease (CVD). However, current equations have several limitations. Therefore, we developed and validated the American Heart Association Predicting Risk of CVD EVENTs (PREVENT) equations among US adults 30 to 79 years of age without known CVD.

METHODS: The derivation sample included individual-level participant data from 25 data sets (N=3 281 919) between 1992 and 2017. The primary outcome was CVD (atherosclerotic CVD and heart failure). Predictors included traditional risk factors (smoking status, systolic blood pressure, cholesterol, antihypertensive or statin use, and diabetes) and estimated glomerular …

Metabolic Model Predictions Enable Targeted Microbiome Manipulation Through Precision Prebiotics, Georgios Marinos, Inga K Hamerich, Reena Debray, Nancy Obeng, Carola Petersen, Jan Taubenheim, Johannes Zimmermann, Dana Blackburn, Buck S Samuel, Katja Dierking, Andre Franke, Matthias Laudes, Silvio Waschina, Hinrich Schulenburg, Christoph Kaleta

Faculty, Staff and Students Publications

While numerous health-beneficial interactions between host and microbiota have been identified, there is still a lack of targeted approaches for modulating these interactions. Thus, we here identify precision prebiotics that specifically modulate the abundance of a microbiome member species of interest. In the first step, we show that defining precision prebiotics by compounds that are only taken up by the target species but no other species in a community is usually not possible due to overlapping metabolic niches. Subsequently, we use metabolic modeling to identify precision prebiotics for a two-member Caenorhabditis elegans microbiome community comprising the immune-protective target species Pseudomonas …

Long-Term Non-Progression And Risk Factors For Disease Progression Among Children Living With Hiv In Botswana And Uganda: A Retrospective Cohort Study, Samuel Kyobe, Grace Kisitu, Savannah Mwesigwa, John Farirai, Eric Katagirya, Gaone Retshabile, Lesedi Williams, Angela Mirembe, Lesego Ketumile, Misaki Wayengera, John Mukisa, Gaseene Sebetso, Thabo Diphoko, Marion Amujal, Edgar Kigozi, Fred Katabazi, Ronald Oceng, Busisiwe Mlotshwa, Koketso Morapedi, Betty Nsangi, Edward Wampande, Masego Tsimako, Chester Brown, Ishmael Kasvosve, Moses Joloba, Gabriel Anabwani, Sununguko Mpoloka, Graeme Mardon, Adeodata Kekitiinwa, Neil A Hanchard, Jacqueline Kyosiimire-Lugemwa, Mogomotsi Matshaba, Dithan Kiragga

Faculty, Staff and Students Publications

OBJECTIVES: We utilize a large retrospective study cohort derived from electronic medical records to estimate the prevalence of long-term non-progression (LTNP) and determine the factors associated with progression among children infected with HIV in Botswana and Uganda.

METHODS: Electronic medical records from large tertiary HIV clinical centers in Botswana and Uganda were queried to identify LTNP children 0-18 years enrolled between June 2003 and May 2014 and extract demographic and nutritional parameters. Multivariate subdistribution hazard analyses were used to examine demographic factors and nutritional status in progression in the pre-antiretroviral therapy era.

RESULTS: Between the two countries, 14,246 antiretroviral therapy-naïve …

The Human Vaginal Microbiota: From Clinical Medicine To Models To Mechanisms, Samantha Ottinger, Clare M Robertson, Holly Branthoover, Kathryn A Patras

Faculty, Staff and Students Publications

The composition of the vaginal microbiota is linked to numerous reproductive health problems, including increased susceptibility to infection, pregnancy complications, and impaired vaginal tissue repair; however, the mechanisms contributing to these adverse outcomes are not yet fully defined. In this review, we highlight recent clinical advancements associating vaginal microbiome composition and function with health outcomes. Subsequently, we provide a summary of emerging models employed to identify microbe-microbe interactions contributing to vaginal health, including metagenomic sequencing, multi-omics approaches, and advances in vaginal microbiota cultivation. Last, we review new in vitro, ex vivo, and in vivo models, such as organoids and humanized …

The Ddhd2-Stxbp1 Interaction Mediates Long-Term Memory Via Generation Of Saturated Free Fatty Acids, Isaac O Akefe, Saber H Saber, Benjamin Matthews, Bharat G Venkatesh, Rachel S Gormal, Daniel G Blackmore, Suzy Alexander, Emma Sieriecki, Yann Gambin, Jesus Bertran-Gonzalez, Nicolas Vitale, Yann Humeau, Arnaud Gaudin, Sevannah A Ellis, Alysee A Michaels, Mingshan Xue, Benjamin Cravatt, Merja Joensuu, Tristan P Wallis, Frédéric A Meunier

Faculty, Staff and Students Publications

The phospholipid and free fatty acid (FFA) composition of neuronal membranes plays a crucial role in learning and memory, but the mechanisms through which neuronal activity affects the brain's lipid landscape remain largely unexplored. The levels of saturated FFAs, particularly of myristic acid (C14:0), strongly increase during neuronal stimulation and memory acquisition, suggesting the involvement of phospholipase A1 (PLA1) activity in synaptic plasticity. Here, we show that genetic ablation of the PLA1 isoform DDHD2 in mice dramatically reduces saturated FFA responses to memory acquisition across the brain. Furthermore, DDHD2 loss also decreases memory performance in reward-based learning and spatial memory …

Study Design And Methods: Us Study To Protect Brain Health Through Lifestyle Intervention To Reduce Risk (Us Pointer), Laura D Baker, Heather M Snyder, Mark A Espeland, Rachel A Whitmer, Miia Kivipelto, Nancy Woolard, Jeffrey Katula, Kathryn V Papp, Jennifer Ventrelle, Sarah Graef, Marcus A Hill, Scott Rushing, Julia Spell, Laura Lovato, Deborah Felton, Benjamin J Williams, Mina Ghadimi Nouran, Rema Raman, Tiia Ngandu, Alina Solomon, Sharon Wilmoth, Maryjo L Cleveland, Jeff D Williamson, Katherine L Lambert, Sarah Tomaszewski Farias, Claire E Day, Christy C Tangney, Darren R Gitelman, Olivia Matongo, Terrianne Reynolds, Valory N Pavlik, Melissa M Yu, Ashley S Alexander, Richard Elbein, Ann Marie Mcdonald, Stephen Salloway, Rena R Wing, Susan Antkowiak, Martha Clare Morris, Maria C Carrillo

Faculty, Staff and Students Publications

INTRODUCTION: The U.S. study to protect brain health through lifestyle intervention to reduce risk (U.S. POINTER) is conducted to confirm and expand the results of the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) in Americans.

METHODS: U.S. POINTER was planned as a 2-year randomized controlled trial of two lifestyle interventions in 2000 older adults at risk for dementia due to well-established factors. The primary outcome is a global cognition composite that permits harmonization with FINGER.

RESULTS: U.S. POINTER is centrally coordinated and conducted at five clinical sites (ClinicalTrials.gov: NCT03688126). Outcomes assessments are completed at baseline and …

Host Gastric Corpus Microenvironment Facilitates Ascaris Suum Larval Hatching And Infection In A Murine Model, Yifan Wu, Grace Adeniyi-Ipadeola, Mahliyah Adkins-Threats, Matthew Seasock, Charlie Suarez-Reyes, Ricardo Fujiwara, Maria Elena Bottazzi, Lizhen Song, Jason C Mills, Jill E Weatherhead

Faculty, Staff and Students Publications

Ascariasis (roundworm) is the most common parasitic helminth infection globally and can lead to significant morbidity in children including chronic lung disease. Children become infected with Ascaris spp. via oral ingestion of eggs. It has long been assumed that Ascaris egg hatching and larval translocation across the gastrointestinal mucosa to initiate infection occurs in the small intestine. Here, we show that A. suum larvae hatched in the host stomach in a murine model. Larvae utilize acidic mammalian chitinase (AMCase; acid chitinase; Chia) from chief cells and acid pumped by parietal cells to emerge from eggs on the surface of gastric …

Using Mobile Technology For Family-Based Prevention In Families With Low Incomes: Lessons From A Randomized Controlled Trial Of A Childhood Obesity Prevention Program, Thomas G Power, Susan S Baker, Karen V Barale, M Catalina Aragón, Jane D Lanigan, Louise Parker, Karina Silva Garcia, Garry Auld, Nilda Micheli, Sheryl O Hughes

Faculty, Staff and Students Publications

Researchers are increasingly using web-based technologies to deliver family-based, prevention programming. Few studies have examined the success of such approaches for families with low incomes. The purpose of this study was to describe the level of in-class and online engagement in a childhood obesity prevention program for parents with low incomes, to examine the demographic correlates of parent engagement, and to examine dosage effects on parental feeding outcomes as a function of online exposure. All participants attended in-class nutrition education classes (Eating Smart · Being Active) as part of the Expanded Food and Nutrition Education Program (EFNEP) in Colorado and …

Leptin Reduction As A Required Component For Weight Loss, Shangang Zhao, Na Li, Wei Xiong, Guannan Li, Sijia He, Zhuzhen Zhang, Qingzhang Zhu, Nisi Jiang, Christian Ikejiofor, Yi Zhu, May-Yun Wang, Xianlin Han, Ningyang Zhang, Carolina Solis-Herrera, Christine Kusminski, Zhiqiang An, Joel K Elmquist, Philipp E Scherer

Faculty, Staff and Students Publications

Partial leptin reduction can induce significant weight loss, while weight loss contributes to partial leptin reduction. The cause-and-effect relationship between leptin reduction and weight loss remains to be further elucidated. Here, we show that FGF21 and the glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide rapidly induced a reduction in leptin. This leptin reduction contributed to the beneficial effects of GLP-1R agonism in metabolic health, as transgenically maintaining leptin levels during treatment partially curtailed the beneficial effects seen with these agonists. Moreover, a higher degree of leptin reduction during treatment, induced by including a leptin neutralizing antibody with either FGF21 or …

Genetic Architecture And Biology Of Youth-Onset Type 2 Diabetes, Soo Heon Kwak, Shylaja Srinivasan, Ling Chen, Jennifer Todd, Josep M Mercader, Elizabeth T Jensen, Jasmin Divers, Amy K Mottl, Catherine Pihoker, Rachelle G Gandica, Lori M Laffel, Elvira Isganaitis, Morey W Haymond, Lynne L Levitsky, Toni I Pollin, Jose C Florez, Jason Flannick, Progress In Diabetes Genetics In Youth (Prodigy) Consortium

Faculty, Staff and Students Publications

The prevalence of youth-onset type 2 diabetes (T2D) and childhood obesity has been rising steadily1, producing a growing public health concern1 that disproportionately affects minority groups2. The genetic basis of youth-onset T2D and its relationship to other forms of diabetes are unclear3. Here we report a detailed genetic characterization of youth-onset T2D by analysing exome sequences and common variant associations for 3,005 individuals with youth-onset T2D and 9,777 adult control participants matched for ancestry, including both males and females. We identify monogenic diabetes variants in 2.4% of individuals and three exome-wide significant ( …

Number Of Children In The Household Influences Respiratory Morbidities In Children With Bronchopulmonary Dysplasia In The Outpatient Setting, Joseph M Collaco, Katharine R Tsukahara, Michael C Tracy, Catherine A Sheils, Jessica L Rice, Lawrence M Rhein, Antonia P Popova, Leif Nelin, Audrey N Miller, Winston M Manimtim, Jonathan C Levin, Khanh Lai, Jacob A Kaslow, Lystra P Hayden, Manvi Bansal, Eric D Austin, Brianna Aoyama, Gangaram Akangire, Amit Agarwal, Natalie Villafranco, Sharon A Mcgrath-Morrow

Faculty, Staff and Students Publications

BACKGROUND: Bronchopulmonary dysplasia (BPD), a common complication of prematurity, is associated with outpatient morbidities, including respiratory exacerbations. Daycare attendance is associated with increased rates of acute and chronic morbidities in children with BPD. We sought to determine if additional children in the household conferred similar risks for children with BPD.

METHODS: The number of children in the household and clinical outcomes were obtained via validated instruments for 933 subjects recruited from 13 BPD specialty clinics in the United States. Clustered logistic regression models were used to test for associations.

RESULTS: The mean gestational age of the study population was 26.5 …

Faster Discharge With Lactated Ringers Than Normal Saline In First 72 H Of Acute Pancreatitis: A Multicenter Randomized Trial, Peter R Farrell, Angelica W Despain, Peter Farmer, Leslie M Farrell, Bryan Greenfield, Michael E Rogers, Lindsey Hornung, Esther Kim, Ryan Pearman, Beemnet Neway, Tyler Thompson, James E Heubi, Sona Sehgal, Rana Amoury, Maisam Abu-El-Haija

Faculty, Staff and Students Publications

OBJECTIVES: Data driven strategies for acute pancreatitis (AP) in pediatrics are limited; adult data suggests lactated ringers (LR) compared to normal saline (NS) resulted in favorable outcomes, but has not been studied in pediatrics. Our objective was to evaluate the efficacy of LR during the first 48 h of an AP episode compared with NS.

STUDY DESIGN: A multi-site randomized controlled clinical trial, from 2015 to 2020 (Clinical Trials.gov NCT03242473). Patients were randomized to exclusively LR or NS for the first 48 hours. Primary outcomes were C-Reactive Protein (CRP) values on admission, 24 and 48 hours. Secondary outcomes …

Adverse Metabolic Phenotypes In Parenterally Fed Neonatal Pigs Do Not Persist Into Adolescence, Sarah K Elefson, Barbara Stoll, Teresa A Davis, Marta L Fiorotto, Samer W El-Kadi, Kenneth Genovese, Thomas Thymann, Per T Sangild, Douglas G Burrin

Faculty, Staff and Students Publications

BACKGROUND: Nutrition during fetal and neonatal life is an important determinant for the risk of adult-onset diseases, especially type 2 diabetes and obesity.

OBJECTIVES: We aimed to determine whether total parenteral nutrition (TPN) compared with enteral formula feeding [enteral nutrition (EN)] in term piglets during the first 2 wk after birth would increase the long-term (5-mo) development of metabolic syndrome phenotypes with adverse glucose homeostasis, fatty liver disease, and obesity.

METHODS: Neonatal female pigs were administered TPN (n = 12) or fed enterally with a liquid enteral milk-replacer formula (EN, n = 12) for 14 d. After transitioning TPN pigs …

Pulsatile Leucine Administration During Continuous Enteral Feeding Enhances Skeletal Muscle Mechanistic Target Of Rapamycin Complex 1 Signaling And Protein Synthesis In A Preterm Piglet Model, Marko Rudar, Agus Suryawan, Hanh V Nguyen, Shaji K Chacko, Caitlin Vonderohe, Barbara Stoll, Douglas G Burrin, Marta L Fiorotto, Teresa A Davis

Faculty, Staff and Students Publications

BACKGROUND: Continuous feeding does not elicit an optimal anabolic response in skeletal muscle but is required for some preterm infants. We reported previously that intermittent intravenous pulses of leucine (Leu; 800 μmol Leu·kg–1·h–1 every 4 h) to continuously fed pigs born at term promoted mechanistic target of rapamycin complex 1 (mTORC1) activation and protein synthesis in skeletal muscle.

OBJECTIVES: The aim was to determine the extent to which intravenous Leu pulses activate mTORC1 and enhance protein synthesis in the skeletal muscle of continuously fed pigs born preterm.

METHODS: Pigs delivered 10 d preterm was advanced to full oral feeding >4 …

Circadian Dysfunction Induces Nafld-Related Human Liver Cancer In A Mouse Model, Jennifer Padilla, Noha M Osman, Beatrice Bissig-Choisat, Sandra L Grimm, Xuan Qin, Angela M Major, Li Yang, Dolores Lopez-Terrada, Cristian Coarfa, Feng Li, Karl-Dimiter Bissig, David D Moore, Loning Fu

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Chronic circadian dysfunction increases the risk of non-alcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC), but the underlying mechanisms and direct relevance to human HCC have not been established. In this study, we aimed to determine whether chronic circadian dysregulation can drive NAFLD-related carcinogenesis from human hepatocytes and human HCC progression.

METHODS: Chronic jet lag of mice with humanized livers induces spontaneous NAFLD-related HCCs from human hepatocytes. The clinical relevance of this model was analysed by biomarker, pathological/histological, genetic, RNA sequencing, metabolomic, and integrated bioinformatic analyses.

RESULTS: Circadian dysfunction induces glucose intolerance, NAFLD-associated human HCCs, and human …

Nonchromosomal Birth Defects And Risk Of Childhood Acute Leukemia: An Assessment In 15 000 Leukemia Cases And 46 000 Controls From The Childhood Cancer And Leukemia International Consortium, Philip J Lupo, Tiffany M Chambers, Beth A Mueller, Jacqueline Clavel, John D Dockerty, David R Doody, Friederike Erdmann, Sameera Ezzat, Tommaso Filippini, Johnni Hansen, Julia E Heck, Claire Infante-Rivard, Alice Y Kang, Corrado Magnani, Carlotta Malagoli, Erin L Marcotte, Catherine Metayer, Helen D Bailey, Ana M Mora, Evangelia Ntzani, Eleni Th Petridou, Maria S Pombo-De-Oliveira, Wafaa M Rashed, Eve Roman, Joachim Schüz, Catharina Wesseling, Logan G Spector, Michael E Scheurer

Faculty, Staff and Students Publications

Although recent studies have demonstrated associations between nonchromosomal birth defects and several pediatric cancers, less is known about their role on childhood leukemia susceptibility. Using data from the Childhood Cancer and Leukemia International Consortium, we evaluated associations between nonchromosomal birth defects and childhood leukemia. Pooling consortium data from 18 questionnaire-based and three registry-based case-control studies across 13 countries, we used multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between a spectrum of birth defects and leukemia. Our analyses included acute lymphoblastic leukemia (ALL, n = 13 115) and acute myeloid leukemia …

Preparing Community Health Workers To Empower Latino(A)S With Diabetes: A Real-World Implementation Study, Laura Porterfield, Zuleica Santiago Delgado, Premal G Patel, Michael L Goodman, Kendall M Campbell, Elizabeth M Vaughan

Faculty, Staff and Students Publications

Purpose: The purpose of the study was to evaluate the delivery of diabetes self-management education (DSME) to Latino(a) adults by community health workers (CHWs).

Methods: Investigators developed an evidence-based, bilingual (Spanish/English) diabetes education curriculum and trained 10 CHWs on its content. CHWs then implemented the curriculum in 6-month diabetes group visit programs for low-income Latino(a)s with type 2 diabetes in nonacademic 501(c)3 community clinics. Investigators evaluated efficacy of the training through successful implementation, measured by participant group visit acceptance and attendance.

Results: Participants (n = 70) reported high levels of program satisfaction (3.8/4.0), improvement in quality of life (9.7/10), meeting …

Circulating Microrna Expression And Nonalcoholic Fatty Liver Disease In Adolescents With Severe Obesity, Yi-Jie Li, Brittney O Baumert, Nikos Stratakis, Jesse A Goodrich, Hao-Tian Wu, Jing-Xuan He, Yin-Qi Zhao, Max T Aung, Hong-Xu Wang, Sandrah P Eckel, Douglas I Walker, Damaskini Valvi, Michele A La Merrill, Justin R Ryder, Thomas H Inge, Todd Jenkins, Stephanie Sisley, Rohit Kohli, Stavra A Xanthakos, Andrea A Baccarelli, Rob Mcconnell, David V Conti, Lida Chatzi

Faculty, Staff and Students Publications

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in children and adolescents. NAFLD ranges in severity from isolated hepatic steatosis to nonalcoholic steatohepatitis (NASH), wherein hepatocellular inflammation and/or fibrosis coexist with steatosis. Circulating microRNA (miRNA) levels have been suggested to be altered in NAFLD, but the extent to which miRNA are related to NAFLD features remains unknown. This analysis tested the hypothesis that plasma miRNAs are significantly associated with histological features of NAFLD in adolescents.

AIM: To investigate the relationship between plasma miRNA expression and NAFLD features among adolescents with NAFLD.

METHODS: This …

Role Of Polyunsaturated Fat In Modifying Cardiovascular Risk Associated With Family History Of Cardiovascular Disease: Pooled De Novo Results From 15 Observational Studies, Federica Laguzzi, Agneta Åkesson, Matti Marklund, Frank Qian, Bruna Gigante, Traci M Bartz, Julie K Bassett, Anna Birukov, Hannia Campos, Yoichiro Hirakawa, Fumiaki Imamura, Susanne Jäger, Maria Lankinen, Rachel A Murphy, Mackenzie Senn, Toshiko Tanaka, Nathan Tintle, Jyrki K Virtanen, Kazumasa Yamagishi, Matthew Allison, Ingeborg A Brouwer, Ulf De Faire, Gudny Eiriksdottir, Luigi Ferrucci, Nita G Forouhi, Johanna M Geleijnse, Allison M Hodge, Hitomi Kimura, Markku Laakso, Ulf Risérus, Anniek C Van Westing, Stefania Bandinelli, Ana Baylin, Graham G Giles, Vilmundur Gudnason, Hiroyasu Iso, Rozenn N Lemaitre, Toshiharu Ninomiya, Wendy S Post, Bruce M Psaty, Jukka T Salonen, Matthias B Schulze, Michael Y Tsai, Matti Uusitupa, Nicholas J Wareham, Seung-Won Oh, Alexis C Wood, William S Harris, David Siscovick, Dariush Mozaffarian, Karin Leander, Fatty Acids And Outcomes Research Consortium (Force)

Faculty, Staff and Students Publications

BACKGROUND: It is unknown whether dietary intake of polyunsaturated fatty acids (PUFA) modifies the cardiovascular disease (CVD) risk associated with a family history of CVD. We assessed interactions between biomarkers of low PUFA intake and a family history in relation to long-term CVD risk in a large consortium.

METHODS: Blood and tissue PUFA data from 40 885 CVD-free adults were assessed. PUFA levels ≤25th percentile were considered to reflect low intake of linoleic, alpha-linolenic, and eicosapentaenoic/docosahexaenoic acids (EPA/DHA). Family history was defined as having ≥1 first-degree relative who experienced a CVD event. Relative risks with 95% CI of CVD were …

Extreme Drought Impacts Have Been Underestimated In Grasslands And Shrublands Globally, Melinda D Smith, Kate D Wilkins, Martin C Holdrege, Peter Wilfahrt, Scott L Collins, Alan K Knapp, Osvaldo E Sala, Jeffrey S Dukes, Richard P Phillips, Laura Yahdjian, Laureano A Gherardi, Timothy Ohlert, Claus Beier, Lauchlan H Fraser, Anke Jentsch, Michael E Loik, Fernando T Maestre, Sally A Power, Qiang Yu, Andrew J Felton, Seth M Munson, Yiqi Luo, Hamed Abdoli, Mehdi Abedi, Concepción L Alados, Juan Alberti, Moshe Alon, Hui An, Brian Anacker, Maggie Anderson, Harald Auge, Seton Bachle, Khadijeh Bahalkeh, Michael Bahn, Amgaa Batbaatar, Taryn Bauerle, Karen H Beard, Kai Behn, Ilka Beil, Lucio Biancari, Irmgard Blindow, Viviana Florencia Bondaruk, Elizabeth T Borer, Edward W Bork, Carlos Martin Bruschetti, Kerry M Byrne, James F Cahill, Dianela A Calvo, Michele Carbognani, Augusto Cardoni, Cameron N Carlyle, Miguel Castillo-Garcia, Scott X Chang, Jeff Chieppa, Marcus V Cianciaruso, Ofer Cohen, Amanda L Cordeiro, Daniela F Cusack, Sven Dahlke, Pedro Daleo, Carla M D'Antonio, Lee H Dietterich, Tim S Doherty, Maren Dubbert, Anne Ebeling, Nico Eisenhauer, Felícia M Fischer, T'Ai G W Forte, Tobias Gebauer, Beatriz Gozalo, Aaron C Greenville, Karlo G Guidoni-Martins, Heather J Hannusch, Siri Vatsø Haugum, Yann Hautier, Mariet Hefting, Hugh A L Henry, Daniela Hoss, Johannes Ingrisch, Oscar Iribarne, Forest Isbell, Yari Johnson, Samuel Jordan, Eugene F Kelly, Kaitlin Kimmel, Juergen Kreyling, György Kröel-Dulay, Alicia Kröpfl, Angelika Kübert, Andrew Kulmatiski, Eric G Lamb, Klaus Steenberg Larsen, Julie Larson, Jason Lawson, Cintia V Leder, Anja Linstädter, Jielin Liu, Shirong Liu, Alexandra G Lodge, Grisel Longo, Alejandro Loydi, Junwei Luan, Frederick Curtis Lubbe, Craig Macfarlane, Kathleen Mackie-Haas, Andrey V Malyshev, Adrián Maturano-Ruiz, Thomas Merchant, Daniel B Metcalfe, Akira S Mori, Edwin Mudongo, Gregory S Newman, Uffe N Nielsen, Dale Nimmo, Yujie Niu, Paola Nobre, Rory C O'Connor, Romà Ogaya, Gastón R Oñatibia, Ildikó Orbán, Brooke Osborne, Rafael Otfinowski, Meelis Pärtel, Josep Penuelas, Pablo L Peri, Guadalupe Peter, Alessandro Petraglia, Catherine Picon-Cochard, Valério D Pillar, Juan Manuel Piñeiro-Guerra, Laura W Ploughe, Robert M Plowes, Cristy Portales-Reyes, Suzanne M Prober, Yolanda Pueyo, Sasha C Reed, Euan G Ritchie, Dana Aylén Rodríguez, William E Rogers, Christiane Roscher, Ana M Sánchez, Bráulio A Santos, María Cecilia Scarfó, Eric W Seabloom, Baoku Shi, Lara Souza, Andreas Stampfli, Rachel J Standish, Marcelo Sternberg, Wei Sun, Marie Sünnemann, Michelle Tedder, Pål Thorvaldsen, Dashuan Tian, Katja Tielbörger, Alejandro Valdecantos, Liesbeth Van Den Brink, Vigdis Vandvik, Mathew R Vankoughnett, Liv Guri Velle, Changhui Wang, Yi Wang, Glenda M Wardle, Christiane Werner, Cunzheng Wei, Georg Wiehl, Jennifer L Williams, Amelia A Wolf, Michaela Zeiter, Fawei Zhang, Juntao Zhu, Ning Zong, Xiaoan Zuo

Faculty, Staff and Students Publications

Climate change is increasing the frequency and severity of short-term (~1 y) drought events-the most common duration of drought-globally. Yet the impact of this intensification of drought on ecosystem functioning remains poorly resolved. This is due in part to the widely disparate approaches ecologists have employed to study drought, variation in the severity and duration of drought studied, and differences among ecosystems in vegetation, edaphic and climatic attributes that can mediate drought impacts. To overcome these problems and better identify the factors that modulate drought responses, we used a coordinated distributed experiment to quantify the impact of short-term drought on …

Organelle Proteomic Profiling Reveals Lysosomal Heterogeneity In Association With Longevity, Yong Yu, Shihong M Gao, Youchen Guan, Pei-Wen Hu, Qinghao Zhang, Jiaming Liu, Bentian Jing, Qian Zhao, David M Sabatini, Monther Abu-Remaileh, Sung Yun Jung, Meng C Wang

Faculty, Staff and Students Publications

Lysosomes are active sites to integrate cellular metabolism and signal transduction. A collection of proteins associated with the lysosome mediate these metabolic and signaling functions. Both lysosomal metabolism and lysosomal signaling have been linked to longevity regulation; however, how lysosomes adjust their protein composition to accommodate this regulation remains unclear. Using deep proteomic profiling, we systemically profiled lysosome-associated proteins linked with four different longevity mechanisms. We discovered the lysosomal recruitment of AMP-activated protein kinase and nucleoporin proteins and their requirements for longevity in response to increased lysosomal lipolysis. Through comparative proteomic analyses of lysosomes from different tissues and labeled with …

Dietary Folate And Cofactors Accelerate Age-Dependent P16 Epimutation To Promote Intestinal Tumorigenesis, Li Yang, Robert C Peery, Leah M Farmer, Xia Gao, Yiqun Zhang, Chad J Creighton, Lanjing Zhang, Lanlan Shen

Faculty, Staff and Students Publications

The extent to which non-genetic environmental factors, such as diet, contribute to carcinogenesis has been long debated. One potential mechanism for the effects of environmental factors is through epigenetic modifications that affect gene expression without changing the underlying DNA sequence. However, the functional cooperation between dietary factors and cancer-causing epigenetic regulation is largely unknown. Here, we use a mouse model of age-dependent p16 epimutation, in which the p16 gene activity is directly controlled by promoter DNA methylation. We show p16 epimutation is modulated by folate and cofactors in dietary supplementation, which leads to increased colon cancer risk. Importantly, our findings …

Advancements In Revascularization Strategies For Acute Mesenteric Ischemia: A Comprehensive Review, Jacob J Gries, Hafeez Ul Hassan Virk, Bing Chen, Takashi Sakamoto, Mahboob Alam, Chayakrit Krittanawong

Faculty, Staff and Students Publications

Even with modern advancements in the management of acute mesenteric ischemia over the past decade, morbidity and mortality remain high, and the best primary treatment modality is still debated amongst interventionalists. Traditionally, interventionalists have favored an open surgical approach but are now trending for endovascular interventions due to apparent reduced mortality and complications. Newer studies suggest hybrid approaches, and intestinal stroke centers may be superior to either strategy alone. This narrative review will explore the natural history of acute mesenteric ischemia with the aim of increasing interventionalist awareness of modern advancements in revascularization strategies for this devastating disease.

Disruption Of The Arabidopsis Acyl-Activating Enzyme 3 Impairs Seed Coat Mucilage Accumulation And Seed Germination, Ninghui Cheng, Paul A Nakata

Faculty, Staff and Students Publications

The Acyl-activating enzyme (AAE) 3 gene encodes an oxalyl-CoA synthetase that catalyzes the conversion of oxalate to oxalyl-CoA as the first step in the CoA-dependent pathway of oxalate catabolism. Although the role of this enzyme in oxalate catabolism has been established, its biological roles in plant growth and development are less understood. As a step toward gaining a better understanding of these biological roles, we report here a characterization of the Arabidopsis thaliana aae3 (Ataae3) seed mucilage phenotype. Ruthidium red (RR) staining of Ataae3 and wild type (WT) seeds suggested that the observed reduction in Ataae3 …