Digital Commons Network^™

Association Of Social Determinants, Lifestyle, And Metabolic Factors With Mortality In Chinese Adults: A Nationwide 10-Year Prospective Cohort Study, Jieli Lu, Mian Li, Jiang He, Yu Xu, Ruizhi Zheng, Jie Zheng, Guijun Qin, Yingfen Qin, Yuhong Chen, Xulei Tang, Zhen Ye, Min Xu, Tiange Wang, Lixin Shi, Qing Su, Xuefeng Yu, Li Yan, Zhiyun Zhao, Qin Wan, Gang Chen, Zhengnan Gao, Guixia Wang, Feixia Shen, Xuejiang Gu, Zuojie Luo, Li Chen, Xinguo Hou, Yanan Huo, Qiang Li, Hong Qiao, Yinfei Zhang, Tianshu Zeng, Chunyan Hu, Qiuyu Cao, Xiaojing Jia, Chao Liu, Youmin Wang, Shengli Wu, Tao Yang, Huacong Deng, Hongyan Qi, Xueyan Wu, Di Zhang, Meng Dai, Donghui Li, Shenghan Lai, Lulu Chen, Jiajun Zhao, Yiming Mu, Weiguo Hu, Guang Ning, Ruying Hu, Yufang Bi, Weiqing Wang, 4c Study Group

Faculty, Staff and Student Publications

Nationwide estimates of the impact of common modifiable risk factors on mortality remain crucial. We aim to assess the influence of social determinants, lifestyle, and metabolic factors on mortality in 174,004 adults aged ≥40 years from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. We reveal that 17 modifiable factors are independently associated with mortality, accounting for 64.8% of all-cause mortality, 77.4% of cardiovascular mortality, and 44.8% of cancer mortality. Low education emerges as the leading factor for both all-cause and cancer mortality, while hypertension is predominant for cardiovascular mortality. Moreover, low gross domestic product per capita and high …

Vitamin D And Metabolic Bone Disease In Prolonged Continuous Kidney Replacement Therapy: A Prospective Observational Study., Peace Dorothy Imani, Molly Vega, Naile Tufan Pekkucuksen, Poyyapakkam Srivaths, Ayse Akcan Arikan

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Complications of prolonged continuous kidney replacement therapy (CKRT) have not been well described. Our objective was to describe mineral metabolism and bone findings in children who required prolonged CKRT.

METHODS: In this single center prospective observational study, we enrolled 37 patients who required CKRT for ≥ 28 days with regional citrate anticoagulation. Exposure was duration on CKRT and outcomes were 25-hydroxy vitamin D and osteopenia and/or fractures.

RESULTS: The prevalence of vitamin D deficiency and insufficiency was 17.2% and 69.0%, respectively. 29.7% of patients had radiographic findings of osteopenia and/or fractures. There was no association between vitamin D deficiency …

Infant And Adult Human Intestinal Enteroids Are Morphologically And Functionally Distinct, Grace O Adeniyi-Ipadeola, Julia D Hankins, Amal Kambal, Xi-Lei Zeng, Ketki Patil, Victoria Poplaski, Carolyn Bomidi, Hoa Nguyen-Phuc, Sandra L Grimm, Cristian Coarfa, Fabio Stossi, Sue E Crawford, Sarah E Blutt, Allison L Speer, Mary K Estes, Sasirekha Ramani

Faculty, Staff and Students Publications

UNLABELLED: Human intestinal enteroids (HIEs) are gaining recognition as physiologically relevant models of the intestinal epithelium. While HIEs from adults are used extensively in biomedical research, few studies have used HIEs from infants. Considering the dramatic developmental changes that occur during infancy, it is important to establish models that represent infant intestinal characteristics and physiological responses. We established jejunal HIEs from infant surgical samples and performed comparisons to jejunal HIEs from adults using RNA sequencing (RNA-Seq) and morphologic analyses. We then validated differences in key pathways through functional studies and determined whether these cultures recapitulate known features of the infant …

A Social Media Game To Increase Physical Activity Among Older Adult Women: Protocol Of A Randomized Controlled Trial To Evaluate Challenge, Michael C Robertson, Maria Chang Swartz, Karen M Basen-Engquist, Yisheng Li, Kristofer Jennings, Debbe Thompson, Tom Baranowski, Elena Volpi, Elizabeth J Lyons

Faculty, Staff and Student Publications

BACKGROUND: Older adult women often do not engage in sufficient physical activity (PA) and can encounter biological changes that exacerbate the negative effects of inadequate activity. Wearable activity monitors can facilitate PA initiation, but evidence of sustained behavior change is lacking. Supplementing wearable technologies with intervention content that evokes enjoyment, interest, meaning, and personal values associated with PA may support long term adherence. In this paper, we present the protocol of an NIA-funded study designed to evaluate the efficacy of CHALLENGE for increasing step count and motivation for PA in insufficiently active older women (Challenges for Healthy Aging: Leveraging Limits …

Patient-Reported Outcomes From The Phase Iii Himalaya Study Of Tremelimumab Plus Durvalumab In Unresectable Hepatocellular Carcinoma, Bruno Sangro, Peter R. Galle, Robin Kate Kelley, Chaiyut Charoentum, Enrico N. De Toni, Yurii Ostapenko, Jeong Heo, Ann-Lii Cheng, Andrea Wilson Woods, Charu Gupta, Jayne Abraham, Carrie L. Mccoy Phd, Rn, Anp-Bc, Nikunj Patel, Alejandra Negro, Arndt Vogel, Ghassan K. Abou-Alfa

Publications

PURPOSE:

In the phase III HIMALAYA study (ClinicalTrials.gov identifier: NCT03298451) in unresectable hepatocellular carcinoma (uHCC), the Single Tremelimumab Regular Interval Durvalumab (STRIDE) regimen significantly improved overall survival versus sorafenib, and durvalumab monotherapy was noninferior to sorafenib. Patient-reported outcomes (PROs), a secondary outcome from HIMALAYA, are reported here.

METHODS:

Participants were randomly assigned to receive STRIDE, durvalumab, or sorafenib. PROs were assessed (preplanned secondary outcome) using the European Organization for Research and Treatment of Cancer 30-item Quality of Life Questionnaire and the 18-item HCC module. Time to deterioration (TTD), change from baseline and improvement rate in global health status/quality of life …

Loss Of Transient Receptor Potential Channel 5 Causes Obesity And Postpartum Depression, Yongxiang Li, Tessa M Cacciottolo, Na Yin, Yang He, Hesong Liu, Hailan Liu, Yuxue Yang, Elana Henning, Julia M Keogh, Katherine Lawler, Edson Mendes De Oliveira, Eugene J Gardner, Katherine A Kentistou, Panayiotis Laouris, Rebecca Bounds, Ken K Ong, John R B Perry, Inês Barroso, Longlong Tu, Jonathan C Bean, Meng Yu, Kristine M Conde, Mengjie Wang, Olivia Ginnard, Xing Fang, Lydia Tong, Junying Han, Tia Darwich, Kevin W Williams, Yongjie Yang, Chunmei Wang, Shelagh Joss, Helen V Firth, Yong Xu, I Sadaf Farooqi

Duncan NRI Faculty and Staff Publications

Hypothalamic neural circuits regulate instinctive behaviors such as food seeking, the fight/flight response, socialization, and maternal care. Here, we identified microdeletions on chromosome Xq23 disrupting the brain-expressed transient receptor potential (TRP) channel 5 (TRPC5). This family of channels detects sensory stimuli and converts them into electrical signals interpretable by the brain. Male TRPC5 deletion carriers exhibited food seeking, obesity, anxiety, and autism, which were recapitulated in knockin male mice harboring a human loss-of-function TRPC5 mutation. Women carrying TRPC5 deletions had severe postpartum depression. As mothers, female knockin mice exhibited anhedonia and depression-like behavior with impaired care of offspring. Deletion of …

The Dna Methylome Of Pediatric Brain Tumors Appears Shaped By Structural Variation And Predicts Survival, Fengju Chen, Yiqun Zhang, Lanlan Shen, Chad J Creighton

Faculty, Staff and Students Publications

Structural variation heavily influences the molecular landscape of cancer, in part by impacting DNA methylation-mediated transcriptional regulation. Here, using multi-omic datasets involving >2400 pediatric brain and central nervous system tumors of diverse histologies from the Children's Brain Tumor Network, we report hundreds of genes and associated CpG islands (CGIs) for which the nearby presence of somatic structural variant (SV) breakpoints is recurrently associated with altered expression or DNA methylation, respectively, including tumor suppressor genes ATRX and CDKN2A. Altered DNA methylation near enhancers associates with nearby somatic SV breakpoints, including MYC and MYCN. A subset of genes with SV-CGI methylation associations …

Intermittent Clearance Of P21-Highly-Expressing Cells Extends Lifespan And Confers Sustained Benefits To Health And Physical Function, Binsheng Wang, Lichao Wang, Nathan S Gasek, Chia-Ling Kuo, Jia Nie, Taewan Kim, Pengyi Yan, Junyu Zhu, Blake L Torrance, Yueying Zhou, Lisa C Flores, Colton Allen, Allison M Andrade, Chun Guo, Rachel L Cohn, Evan R Jellison, Jenna M Bartley, George A Kuchel, Sheng Li, Tamar Pirtskhalava, Tamar Tchkonia, Sumit Yadav, Laura Haynes, James L Kirkland, Yuji Ikeno, Ming Xu

Faculty, Staff and Student Publications

A key challenge in aging research is to extend lifespan in tandem with slowing down functional decline so that the life with good health (healthspan) can be extended. Here, we show that monthly clearance of a small number of cells, which highly express p21Cip1 (p21high), starting from 20 months improves cardiac and metabolic function, and extends both median and maximum lifespan in mice. Importantly, by assessing health and physical function of these mice monthly until death, we show that clearance of p21high cells improves physical function at all remaining stages of life, suggesting healthspan extension. Mechanistically, …

Pkd1 Mutant Clones Within Cirrhotic Livers Inhibit Steatohepatitis Without Promoting Cancer, Min Zhu, Yunguan Wang, Tianshi Lu, Jason Guo, Lin Li, Meng-Hsiung Hsieh, Purva Gopal, Yi Han, Naoto Fujiwara, Darren P Wallace, Alan S L Yu, Xiangyi Fang, Crystal Ransom, Sara Verschleisser, David Hsiehchen, Yujin Hoshida, Amit G Singal, Adam Yopp, Tao Wang, Hao Zhu

Faculty, Staff and Student Publications

Somatic mutations in non-malignant tissues are selected for because they confer increased clonal fitness. However, it is uncertain whether these clones can benefit organ health. Here, ultra-deep targeted sequencing of 150 liver samples from 30 chronic liver disease patients revealed recurrent somatic mutations. PKD1 mutations were observed in 30% of patients, whereas they were only detected in 1.3% of hepatocellular carcinomas (HCCs). To interrogate tumor suppressor functionality, we perturbed PKD1 in two HCC cell lines and six in vivo models, in some cases showing that PKD1 loss protected against HCC, but in most cases showing no impact. However, Pkd1 haploinsufficiency …

Whole Genome Sequencing Based Analysis Of Inflammation Biomarkers In The Trans-Omics For Precision Medicine (Topmed) Consortium, Min-Zhi Jiang, Sheila M Gaynor, Xihao Li, Eric Van Buren, Adrienne Stilp, Erin Buth, Fei Fei Wang, Regina Manansala, Stephanie M Gogarten, Zilin Li, Linda M Polfus, Shabnam Salimi, Joshua C Bis, Nathan Pankratz, Lisa R Yanek, Peter Durda, Russell P Tracy, Stephen S Rich, Jerome I Rotter, Braxton D Mitchell, Joshua P Lewis, Bruce M Psaty, Katherine A Pratte, Edwin K Silverman, Robert C Kaplan, Christy Avery, Kari E North, Rasika A Mathias, Nauder Faraday, Honghuang Lin, Biqi Wang, April P Carson, Arnita F Norwood, Richard A Gibbs, Charles Kooperberg, Jessica Lundin, Ulrike Peters, Josée Dupuis, Lifang Hou, Myriam Fornage, Emelia J Benjamin, Alexander P Reiner, Russell P Bowler, Xihong Lin, Paul L Auer, Laura M Raffield, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Topmed Inflammation Working Group

Faculty, Staff and Student Publications

Inflammation biomarkers can provide valuable insight into the role of inflammatory processes in many diseases and conditions. Sequencing based analyses of such biomarkers can also serve as an exemplar of the genetic architecture of quantitative traits. To evaluate the biological insight, which can be provided by a multi-ancestry, whole-genome based association study, we performed a comprehensive analysis of 21 inflammation biomarkers from up to 38 465 individuals with whole-genome sequencing from the Trans-Omics for Precision Medicine (TOPMed) program (with varying sample size by trait, where the minimum sample size was n = 737 for MMP-1). We identified 22 distinct single-variant …

Lipid Droplet-Associated Hydrolase Mobilizes Stores Of Liver X Receptor Sterol Ligands And Protects Against Atherosclerosis, Young-Hwa Goo, Janeesh Plakkal Ayyappan, Francis D Cheeran, Sushant Bangru, Pradip K Saha, Paula Baar, Sabine Schulz, Todd A Lydic, Bernhard Spengler, Andreas H Wagner, Auinash Kalsotra, Vijay K Yechoor, Antoni Paul

Faculty, Staff and Students Publications

Foam cells in atheroma are engorged with lipid droplets (LDs) that contain esters of regulatory lipids whose metabolism remains poorly understood. LD-associated hydrolase (LDAH) has a lipase structure and high affinity for LDs of foam cells. Using knockout and transgenic mice of both sexes, here we show that LDAH inhibits atherosclerosis development and promotes stable lesion architectures. Broad and targeted lipidomic analyzes of primary macrophages and comparative lipid profiling of atheroma identified a broad impact of LDAH on esterified sterols, including natural liver X receptor (LXR) sterol ligands. Transcriptomic analyzes coupled with rescue experiments show that LDAH modulates the expression …

Renal Mass Imaging Modalities: Does Body Mass Index (Bmi) Matter?, Young Son, Mark E Quiring, Raeann M Dalton, Brian Thomas, Noah Davidson, Dayna Devincentz, Collin Payne, Sahil H Parikh, Benjamin A Fink, Thomas Mueller, Gordon Brown

Rowan-Virtua School of Osteopathic Medicine Departmental Research

PURPOSE: Accurate measurement of renal mass size is crucial in the management of renal cancer. With the burdensome cost of imaging yet its need for management, a better understanding of the variability among patients when determining mass size remains of urgent importance. Current guidelines on optimal imaging are limited, especially with respect to body mass index (BMI). The aim of this study is to discern which modalities accurately measure renal mass size and whether BMI influences such accuracy.

METHODS: A multi-institutional chart review was performed for adult patients undergoing partial or radical nephrectomy between 2018 and 2021, with 236 patients …

Autophagic Signaling Promotes Systems-Wide Remodeling In Skeletal Muscle Upon Oncometabolic Stress By D2-Hg, Yaqi Gao, Kyoungmin Kim, Heidi Vitrac, Rebecca L Salazar, Benjamin D Gould, Daniel Soedkamp, Weston Spivia, Koen Raedschelders, An Q Dinh, Anna G Guzman, Lin Tan, Stavros Azinas, David J R Taylor, Walter Schiffer, Daniel Mcnavish, Helen B Burks, Roberta A Gottlieb, Philip L Lorenzi, Blake M Hanson, Jennifer E Van Eyk, Heinrich Taegtmeyer, Anja Karlstaedt

Faculty, Staff and Student Publications

OBJECTIVES: Cachexia is a metabolic disorder and comorbidity with cancer and heart failure. The syndrome impacts more than thirty million people worldwide, accounting for 20% of all cancer deaths. In acute myeloid leukemia, somatic mutations of the metabolic enzyme isocitrate dehydrogenase 1 and 2 cause the production of the oncometabolite D2-hydroxyglutarate (D2-HG). Increased production of D2-HG is associated with heart and skeletal muscle atrophy, but the mechanistic links between metabolic and proteomic remodeling remain poorly understood. Therefore, we assessed how oncometabolic stress by D2-HG activates autophagy and drives skeletal muscle loss.

METHODS: We quantified genomic, metabolomic, and proteomic changes in …

Fetal Malrotation With Midgut Volvulus: Prenatal Diagnosis And Planning, Jai Sidpra, Sniya Sudhakar, Asthik Biswas, Flavia Massey, Valentina Turchetti, Tracy Lau, Edward Cook, Javeria Raza Alvi, Hasnaa M Elbendary, Jerry L Jewell, Antonella Riva, Alessandro Orsini, Aglaia Vignoli, Zara Federico, Jessica Rosenblum, An-Sofie Schoonjans, Matthias De Wachter, Ignacio Delgado Alvarez, Ana Felipe-Rucián, Nourelhoda A Haridy, Shahzad Haider, Mashaya Zaman, Selina Banu, Najwa Anwaar, Fatima Rahman, Shazia Maqbool, Rashmi Yadav, Vincenzo Salpietro, Reza Maroofian, Rajan Patel, Rupa Radhakrishnan, Sanjay P Prabhu, Klaske Lichtenbelt, Helen Stewart, Yoshiko Murakami, Ulrike Löbel, Felice D'Arco, Emma Wakeling, Wendy Jones, Eleanor Hay, Sanjay Bhate, Thomas S Jacques, David M Mirsky, Matthew T Whitehead, Maha S Zaki, Tipu Sultan, Pasquale Striano, Anna C Jansen, Maarten Lequin, Linda S De Vries, Mariasavina Severino, Andrew C Edmondson, Lara Menzies, Philippe M Campeau, Henry Houlden, Amy Mctague, Stephanie Efthymiou, Kshitij Mankad

Faculty, Staff and Students Publications

Inherited glycosylphosphatidylinositol deficiency disorders (IGDs) are a group of rare multisystem disorders arising from pathogenic variants in glycosylphosphatidylinositol anchor pathway (GPI-AP) genes. Despite associating 24 of at least 31 GPI-AP genes with human neurogenetic disease, prior reports are limited to single genes without consideration of the GPI-AP as a whole and with limited natural history data. In this multinational retrospective observational study, we systematically analyse the molecular spectrum, phenotypic characteristics and natural history of 83 individuals from 75 unique families with IGDs, including 70 newly reported individuals; the largest single cohort to date. Core clinical features were developmental delay or …

Individual Variation In The Distribution Of Apolipoprotein B Levels Across The Spectrum Of Ldl-C Or Non-Hdl-C Levels, Ahmed Sayed, Eric D Peterson, Salim S Virani, Allan D Sniderman, Ann Marie Navar

Faculty, Staff and Students Publications

Importance: Although apolipoprotein B (apoB) is a superior marker of lipid-related risk compared with low-density lipoprotein cholesterol (LDL-C), few data exist to translate the goals and thresholds from LDL-C to their apoB equivalent. In addition, although current American College of Cardiology/American Heart Association guidelines provide a relative indication for apoB measurement among individuals with hypertriglyceridemia, whether discordance is limited to those subgroups is unknown.

Objectives: To assess the variability in apoB level across the spectrum of LDL-C or non-high-density lipoprotein cholesterol (non-HDL-C) levels and evaluate whether discordance between apoB and LDL-C or non-HDL-C is limited to specifiable subgroups.

Design, setting, …

Associations Of Mid-To-Late-Life Inflammation With Late-Life Mobility And The Influences Of Chronic Comorbidities, Race, And Social Determinants Of Health: The Atherosclerosis Risk In Communities Study, Kirby G Parker, B Gwen Windham, Chad Blackshear, Keenan A Walker, Sara B Parker, Ron C Hoogeveen, Christie M Ballantyne, Anna Kucharska-Newton, Priya Palta, Elizabeth Selvin, Maria Vassilaki, Thomas H Mosley, Michael E Griswold

Faculty, Staff and Students Publications

Background: Relationships of midlife inflammation with late-life mobility and influences of chronic health conditions, race, and social determinants of health (SDoH) on these relationships are poorly understood.

Methods: Among 4758 community-dwelling participants (41% men, 20% Black), high-sensitivity C-reactive protein (hsCRP) was measured over 20+ years: in midlife at study visit 2 (V2: 1990-1992, 47-68 years); at V4 (1996-1998, 53-74 years); and with concurrent late-life 4-m gait speed at V5 (2011-2013, 67-88 years, mean 75 years). SDoH measures included race, the national-rank area deprivation index, education, and income. We examined associations of late-life gait speed with midlife hsCRP (V2 continuous and …

Trends In Central Nervous System-Active Polypharmacy Among People With Multiple Sclerosis, Hayden Naizer, Joseph Wozny, Trudy Millard Krause, Ethan Huson, Leorah Freeman

Faculty, Staff and Student Publications

BACKGROUND: People with multiple sclerosis (pwMS) are at risk of concurrently using multiple central nervous system (CNS)-active drugs, yet the prevalence of CNS-active polypharmacy remains unmeasured in pwMS.

OBJECTIVE: The objective is to measure the prevalence of CNS-active polypharmacy in pwMS.

METHODS: This serial, cross-sectional study measured CNS-active polypharmacy in people with MS in the United States from 2008 to 2021 using insurance claims data. CNS-active polypharmacy was defined as the concurrent prescription of ⩾3 CNS-active drugs for >30 continuous days. CNS-active drugs included antidepressants, antiepileptics, antipsychotics, benzodiazepines, nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants.

RESULTS: The …

Plasma Proteins Associated With Plant-Based Diets: Results From The Atherosclerosis Risk In Communities (Aric) Study And Framingham Heart Study (Fhs), Hyunju Kim, Jingsha Chen, Brenton Prescott, Maura E Walker, Morgan E Grams, Bing Yu, Ramachandran S Vasan, James S Floyd, Nona Sotoodehnia, Nicholas L Smith, Dan E Arking, Josef Coresh, Casey M Rebholz

Faculty, Staff and Student Publications

Background & aims: Plant-based diets are associated with a lower risk of chronic diseases. Large-scale proteomics can identify objective biomarkers of plant-based diets, and improve our understanding of the pathways that link plant-based diets to health outcomes. This study investigated the plasma proteome of four different plant-based diets [overall plant-based diet (PDI), provegetarian diet, healthful plant-based diet (hPDI), and unhealthful plant-based diet (uPDI)] in the Atherosclerosis Risk in Communities (ARIC) Study and replicated the findings in the Framingham Heart Study (FHS) Offspring cohort.

Methods: ARIC Study participants at visit 3 (1993-1995) with completed food frequency questionnaire (FFQ) data and proteomics …

Variability In Performance Of Genetic-Enhanced Dxa-Bmd Prediction Models Across Diverse Ethnic And Geographic Populations: A Risk Prediction Study, Yong Liu, Xiang-He Meng, Chong Wu, Kuan-Jui Su, Anqi Liu, Qing Tian, Lan-Juan Zhao, Chuan Qiu, Zhe Luo, Martha I Gonzalez-Ramirez, Hui Shen, Hong-Mei Xiao, Hong-Wen Deng

Faculty, Staff and Student Publications

BACKGROUND: Osteoporosis is a major global health issue, weakening bones and increasing fracture risk. Dual-energy X-ray absorptiometry (DXA) is the standard for measuring bone mineral density (BMD) and diagnosing osteoporosis, but its costliness and complexity impede widespread screening adoption. Predictive modeling using genetic and clinical data offers a cost-effective alternative for assessing osteoporosis and fracture risk. This study aims to develop BMD prediction models using data from the UK Biobank (UKBB) and test their performance across different ethnic and geographical populations.

METHODS AND FINDINGS: We developed BMD prediction models for the femoral neck (FNK) and lumbar spine (SPN) using both …

Age, Sex, And Apoe Gene-Specific Associations Between Dynapenic Obesity And Dementia In A Large Cohort, Zhao Yao, Jie Wang, Tianfang Zhang, Hongjing Ai, Zeinab Abdelrahman, Xiaohong Wu, Daming Wang, Fenfen Chen, Ziwei Zhang, Xiaosheng Wang, Zuyun Liu, Zuobing Chen

Faculty, Staff and Student Publications

Objective: To investigate the associations between dynapenic obesity and the risk of dementia, and the modifying effects of age, sex, and the APOE gene, using a large population-based cohort.

Methods: 279,884 participants aged 55 and above from the UK Biobank were included. The participants were classified into four categories based on body mass index and hand grip strength: healthy, obesity, dynapenia, and dynapenic obesity. The incident dementia was identified based on linked hospital records and death register data. Cox proportional hazards regression models were used to estimate the associations, followed by age-, sex-, and apolipoprotein E (APOE) gene-stratified analyses.

Results: …

Effect Of Semaglutide On Regression And Progression Of Glycemia In People With Overweight Or Obesity But Without Diabetes In The Select Trial, Steven E Kahn, John E Deanfield, Ole Kleist Jeppesen, Scott S Emerson, Trine Welløv Boesgaard, Helen M Colhoun, Robert F Kushner, Ildiko Lingvay, Bartolome Burguera, Grzegorz Gajos, Deborah Bade Horn, Irene M Hramiak, Ania M Jastreboff, Alexander Kokkinos, Michael Maeng, Ana Laura S A Matos, Francisco J Tinahones, A Michael Lincoff, Donna H Ryan, Select Trial Investigators

Faculty, Staff and Student Publications

OBJECTIVE: To determine whether semaglutide slows progression of glycemia in people with cardiovascular disease and overweight or obesity but without diabetes.

RESEARCH DESIGN AND METHODS: In a multicenter, double-blind trial, participants aged ≥45 years, with BMI ≥27 kg/m2, and with preexisting cardiovascular disease but without diabetes (HbA1c

RESULTS: Of 17,604 participants, 8,803 were assigned to semaglutide and 8,801 to placebo. Mean ± SD intervention exposure was 152 ± 56 weeks and follow-up 176 ± 40 weeks. In both treatment arms mean nadir HbA1c for participants was at 20 weeks. Thereafter, HbA1c increased similarly in both arms, with a mean difference …

Intermittent Mechanical Loading On Mouse Tibia Accelerates Longitudinal Bone Growth By Inducing Pthrp Expression In The Female Tibial Growth Plate., Sarah Mcgarry, Karen Kover, Daniel P. Heruth, Mark Dallas, Xinxin Jin, Shufang Wu, Francesco De Luca

Manuscripts, Articles, Book Chapters and Other Papers

It is not clear as to whether weight bearing and ambulation may affect bone growth. Our goal was to study the role of mechanical loading (one of the components of ambulation) on endochondral ossification and longitudinal bone growth. Thus, we applied cyclical, biologically relevant strains for a prolonged time period (4 weeks) to one tibia of juvenile mice, while using the contralateral one as an internal control. By the end of the 4-week loading period, the mean tibial growth of the loaded tibiae was significantly greater than that of the unloaded tibiae. The mean height and the mean area of …

A Qualitative Exploration To Inform An Oral Health Training For Disability Care Workers In Burkina Faso, Ave Põld, Dan Filwendé Kientega, Jocelyne Valérie Garé, Michael Lorenz

Faculty, Staff and Student Publications

AIM: To explore enablers and barriers to the creation of an oral health training for care workers at specialized centres for children with disabilities in Ouagadougou.

DESIGN: This was a formative study informed by the Theoretical Domains Framework using qualitative methods.

METHODS: Qualitative observations and 14 semi-structured interviews were conducted with care workers from six specialized centres for disability.

RESULTS: Carer workers emphasized that a successful oral health training must account for available resources and competencies in each specific centre. Part of the training must be dedicated to oral hygiene targeted for people with disabilities and provide knowledge about risk …

Trajectory Of C-Reactive Protein And Incident Heart Failure In Black Adults: The Jackson Heart Study, Arsalan Hamid, Wondwosen K Yimer, Adebamike A Oshunbade, Muhammad Shahzeb Khan, Daisuke Kamimura, Rodney K Kipchumba, Ambarish Pandey, Donald Clark, Robert J Mentz, Ervin R Fox, Jarett D Berry, R Brandon Stacey, Amil Shah, Adolfo Correa, Salim S Virani, Javed Butler, Michael E Hall

Faculty, Staff and Students Publications

Background: Increased hsCRP (high-sensitivity C-reactive protein), a marker of inflammation, is associated with incident cardiovascular events. We aim to determine whether the baseline or trajectory of hsCRP levels over time predicts incident heart failure (HF) hospitalization.

Methods: JHS (Jackson Heart Study) participants' (n=3920 Black adults) hsCRP levels were measured over 3 visits (from 2000 to 2013). We assessed the association of hsCRP at baseline (visit 1) with incident HF hospitalization using Cox proportional hazards models. Furthermore, we assessed the association of the trajectory of hsCRP over repeated measurements (visits 1-3) with incident HF using joint models. Hazard ratios are reflective …

Impact Of Pretreatment Body Mass Index On The Survival Of Head And Neck Cancer Patients, Zheng Yang, Jobran Mansour, Peng Sun, Peng Wei, Kristina R Dahlstrom, Mark Zafereo, Guojun Li, Neil D Gross

Faculty, Staff and Student Publications

Background: Differences in pretreatment body mass index (BMI) have been associated with survival in squamous cell carcinoma of head and neck (SCCHN). We examined effects of BMI on survival in SCCHN patients after stratifying patients by tumor human papillomavirus (HPV) status and subsite.

Methods: Totally 2204 SCCHN patients in a prospective study were included in this secondary analysis. Multivariable Cox models were used to evaluate associations between pretreatment BMI and overall survival, disease-specific survival, and disease-free survival.

Results: BMI was significantly higher among patients with HPV-positive tumors than HPV-negative tumors. BMI >25 kg/m2 was associated with improved survival, while BMI …

Cardiomyopathy, An Uncommon Phenotype Of Congenital Disorders Of Glycosylation: Recommendations For Baseline Screening And Follow-Up Evaluation, Roni Zemet, Kyle D Hope, Andrew C Edmondson, Rameen Shah, Maria Patino, Abigail M Yesso, Justin H Berger, Kyriakie Sarafoglou, Austin Larson, Christina Lam, Eva Morava, Fernando Scaglia

Faculty, Staff and Students Publications

Introduction:

Congenital disorders of glycosylation (CDG) are a continuously expanding group of monogenic disorders that disrupt glycoprotein and glycolipid biosynthesis, leading to multi-systemic manifestations. These disorders are categorized into various groups depending on which part of the glycosylation process is impaired. The cardiac manifestations in CDG can significantly differ, not only across different types but also among individuals with the same genetic cause of CDG. Cardiomyopathy is an important phenotype in CDG. The clinical manifestations and progression of cardiomyopathy in CDG patients have not been well characterized. This study aims to delineate common patterns of cardiomyopathy across a range of …

Use Of Pancreatic Endotherapy In Patients With Chronic Pancreatitis: Results From A Multicenter Cohort Study In The United States, Samuel Han, Darwin L Conwell, Jeffrey J Easler, Yunlong Yang, Dana K Andersen, William E Fisher, Evan L Fogel, Chris Forsmark, Phil A Hart, Steven J Hughes, Liang Li, Stephen J Pandol, Walter G Park, Jose Serrano, Stephen K Van Den Eeden, Santhi Swaroop Vege, Dhiraj Yadav, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Although pancreatic endotherapy (PET) is commonly used for treating adverse events of chronic pancreatitis, data on the frequency and factors associated with the use of PET are limited. Our aim was to define the use of and factors predictive for receiving PET in a well-characterized chronic pancreatitis cohort.

METHODS: This is a cross-sectional analysis of data from PROCEED, a multicenter U.S. cohort study of chronic pancreatitis. PET modalities primarily consisted of ERCP. A treatment course was defined as the number of sessions performed for a specific indication. A repeat course was defined as PET >1 year after …

Mechanisms Of Neurodevelopmental Toxicity Of Topiramate, John W Steele, Vaishnav Krishnan, Richard H Finnell

Faculty, Staff and Students Publications

Prescriptions for antiseizure medications (ASMs) have been rapidly growing over the last several decades due, in part, to an expanding list of clinical indications for which they are now prescribed. This trend has raised concern for potential adverse neurodevelopmental outcomes in ASM-exposed pregnancies. Recent large scale population studies have suggested that the use of topiramate (TOPAMAX, Janssen-Cilag), when prescribed for seizure control, migraines, and/or weight management, is associated with an increased risk for autism spectrum disorder (ASD), intellectual disability, and attention-deficit/hyperactivity disorder (ADHD) in exposed offspring. Here, we critically review epidemiologic evidence demonstrating the neurobehavioral teratogenicity of topiramate and speculate …

The Association Between Prolonged Sars-Cov-2 Symptoms And Work Outcomes, Arjun K Venkatesh, Huihui Yu, Caitlin Malicki, Michael Gottlieb, Joann G Elmore, Mandy J Hill, Ahamed H Idris, Juan Carlos C Montoy, Kelli N O'Laughlin, Kristin L. Rising, Kari A Stephens, Erica S Spatz, Robert A Weinstein

Department of Emergency Medicine Faculty Papers

While the early effects of the COVID-19 pandemic on the United States labor market are well-established, less is known about the long-term impact of SARS-CoV-2 infection and Long COVID on employment. To address this gap, we analyzed self-reported data from a prospective, national cohort study to estimate the effects of SARS-CoV-2 symptoms at three months post-infection on missed workdays and return to work. The analysis included 2,939 adults in the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE) study who tested positive for their initial SARS-CoV-2 infection at the time of enrollment, were employed before the pandemic, and completed …

Dna Methylation Patterns In Umbilical Cord Blood From Infants Of Methadone Maintained Opioid Dependent Mothers, Oluwatobi Adegboyega, Suhita Gayen Nee' Betal, Pedro Urday, Rachel Huang, Katherine Bodycot, Huda Al-Kouatly, Kolawole Solarin, Joanna Chan, Sankar Addya, Rupsa Boelig, Zubair Aghai

Department of Pediatrics Faculty Papers

Methadone maintenance treatment for opioid dependent mothers is standard of care. Infants of methadone maintained opioid dependent (MMOD) mothers have better outcomes compared to infants of opioid dependent mothers without treatment. However, when compared to non-exposed infants, infants of MMOD mothers are associated with worse outcomes. We conducted a pilot study to examine genome wide differential DNA methylation using cord blood samples from sixteen term and near-term infants of MMOD and opioid naïve mothers, excluding Infants with chorioamnionitis. A total of 152 differentially methylated loci were identified at a difference >  + 2, < - 2 and p-value < 0.05. There were 90 hypermethylated loci (59 annotated genes) and 62 hypomethylated loci (38 annotated genes) observed. The hypermethylated and hypomethylated DNA changes involved multiple genes, pathways and networks that may explain some of the changes seen in infants of MMOD mothers. Top hypermethylated and hypomethylated genes involved areas of cell growth, neurodevelopment, vision and xenobiotic metabolism functions. Our data may explain the role of key pathways and genes relevant to neonatal outcomes seen from methadone exposure in pregnancy. Functional studies on the identified pathways and genes could lead to improved understanding of the mechanisms and identify areas for intervention.