Medical Specialties Commons^™

Insights Into Cell-Specific Functions Of Microtubules In Skeletal Muscle Development And Homeostasis, Lathan Lucas, Thomas A Cooper

Faculty, Staff and Students Publications

The contractile cells of skeletal muscles, called myofibers, are elongated multinucleated syncytia formed and maintained by the fusion of proliferative myoblasts. Human myofibers can be hundreds of microns in diameter and millimeters in length. Myofibers are non-mitotic, obviating the need for microtubules in cell division. However, microtubules have been adapted to the unique needs of these cells and are critical for myofiber development and function. Microtubules in mature myofibers are highly dynamic, and studies in several experimental systems have demonstrated the requirements for microtubules in the unique features of muscle biology including myoblast fusion, peripheral localization of nuclei, assembly of …

Gasdermin D Deficiency In Vascular Smooth Muscle Cells Ameliorates Abdominal Aortic Aneurysm Through Reducing Putrescine Synthesis, Jianing Gao, Yanghui Chen, Huiqing Wang, Xin Li, Ke Li, Yangkai Xu, Xianwei Xie, Yansong Guo, Nana Yang, Xinhua Zhang, Dong Ma, Hong S. Lu, Ying H. Shen, Yong Liu, Jifeng Zhang, Y. Eugene Chen, Alan Daugherty, Dao Wen Wang, Lemin Zheng

Saha Cardiovascular Research Center Faculty Publications

Abdominal aortic aneurysm (AAA) is a common vascular disease associated with significant phenotypic alterations in vascular smooth muscle cells (VSMCs). Gasdermin D (GSDMD) is a pore-forming effector of pyroptosis. In this study, the role of VSMC-specific GSDMD in the phenotypic alteration of VSMCs and AAA formation is determined. Single-cell transcriptome analyses reveal Gsdmd upregulation in aortic VSMCs in angiotensin (Ang) II-induced AAA. VSMC-specific Gsdmd deletion ameliorates Ang II-induced AAA in apolipoprotein E (ApoE)−/− mice. Using untargeted metabolomic analysis, it is found that putrescine is significantly reduced in the plasma and aortic tissues of VSMC-specific GSDMD deficient mice. High putrescine levels …

Hemoglobin Concentration Impacts Viscoelastic Hemostatic Assays In Icu Admitted Patients, David J Roh, Tiffany R Chang, Aditya Kumar, Devin Burke, Glenda Torres, Katherine Xu, Winni Yang, Azzurra Cottarelli, Ernest Moore, Angela Sauaia, Kirk Hansen, Angela Velazquez, Amelia Boehme, Athina Vrosgou, Shivani Ghoshal, Soojin Park, Sachin Agarwal, Jan Claassen, E Sander Connolly, Gebhard Wagener, Richard O Francis, Eldad Hod

Faculty, Staff and Student Publications

Objectives: Low hemoglobin concentration impairs clinical hemostasis across several diseases. It is unclear whether hemoglobin impacts laboratory functional coagulation assessments. We evaluated the relationship of hemoglobin concentration on viscoelastic hemostatic assays in intracerebral hemorrhage (ICH) and perioperative patients admitted to an ICU.

Design: Observational cohort study and separate in vitro laboratory study.

Setting: Multicenter tertiary referral ICUs.

Patients: Two acute ICH cohorts receiving distinct testing modalities: rotational thromboelastometry (ROTEM) and thromboelastography (TEG), and a third surgical ICU cohort receiving ROTEM were evaluated to assess the generalizability of findings across disease processes and testing platforms. A separate in vitro ROTEM laboratory …

Automated Field-In-Field Whole Brain Radiotherapy Planning, Kai Huang, Soleil Hernandez, Chenyang Wang, Callistus Nguyen, Tina Marie Briere, Carlos Cardenas, Laurence Court, Yao Xiao

Faculty, Staff and Student Publications

PURPOSE: We developed and tested an automatic field-in-field (FIF) solution for whole-brain radiotherapy (WBRT) planning that creates a homogeneous dose distribution by minimizing hotspots, resulting in clinically acceptable plans.

METHODS: A configurable auto-planning algorithm was developed to automatically generate FIF WBRT plans independent of the treatment planning system. Configurable parameters include the definition of hotspots, target volume, maximum number of subfields, and minimum number of monitor units per field. This algorithm iteratively identifies a hotspot, creates two opposing subfields, calculates the dose, and optimizes the beam weight based on user-configured constraints of dose-volume histogram coverage and least-squared cost functions. The …

Spatial Molecular And Cellular Determinants Of Stat3 Activation In Liver Fibrosis Progression In Non-Alcoholic Fatty Liver Disease, Jingjing Jiao, Jessica I Sanchez, Omar A Saldarriaga, Luisa M Solis, David J Tweardy, Dipen M Maru, Heather L Stevenson, Laura Beretta

Faculty, Staff and Student Publications

BACKGROUND & AIMS: The prevalence of non-alcoholic fatty liver disease (NAFLD) and its severe form, non-alcoholic steatohepatitis (NASH), is increasing. Individuals with NASH often develop liver fibrosis and advanced liver fibrosis is the main determinant of mortality in individuals with NASH. We and others have reported that STAT3 contributes to liver fibrosis and hepatocellular carcinoma in mice.

METHODS: Here, we explored whether STAT3 activation in hepatocyte and non-hepatocyte areas, measured by phospho-STAT3 (pSTAT3), is associated with liver fibrosis progression in 133 patients with NAFLD. We further characterized the molecular and cellular determinants of STAT3 activation by integrating spatial distribution and …

Machine Learning And Acute Stroke Imaging, Sunil A Sheth, Luca Giancardo, Marco Colasurdo, Visish M Srinivasan, Arash Niktabe, Peter Kan

Faculty, Staff and Student Publications

BACKGROUND: In recent years, machine learning (ML) has had notable success in providing automated analyses of neuroimaging studies, and its role is likely to increase in the future. Thus, it is paramount for clinicians to understand these approaches, gain facility with interpreting ML results, and learn how to assess algorithm performance.

OBJECTIVE: To provide an overview of ML, present its role in acute stroke imaging, discuss methods to evaluate algorithms, and then provide an assessment of existing approaches.

METHODS: In this review, we give an overview of ML techniques commonly used in medical imaging analysis and methods to evaluate performance. …

A Multicenter Study Of Clinical Impact Of Variant Of Uncertain Significance Reclassification In Breast, Ovarian And Colorectal Cancer Susceptibility Genes, Sukh Makhnoon, Brooke Levin, Megan Ensinger, Kristin Mattie, Robert J Volk, Zhongming Zhao, Tito Mendoza, Sanjay Shete, Laila Samiian, Generosa Grana, Andrew Grainger, Banu Arun, Brian H Shirts, Susan K Peterson

Faculty, Staff and Student Publications

BACKGROUND: Clinical interpretation of genetic test results is complicated by variants of uncertain significance (VUS) that have an unknown impact on health but can be clarified through reclassification. There is little empirical evidence regarding VUS reclassification in oncology care settings, including the prevalence and outcomes of reclassification, and racial/ethnic differences.

METHODS: This was a retrospective analysis of persons with and without a personal history of cancer carrying VUS (with or without an accompanying pathogenic or likely pathogenic [P/LP] variant) in breast, ovarian, and colorectal cancer predisposition genes seen at four cancer care settings (in Texas, Florida, Ohio, and New Jersey) …

Impact Of Us Preventive Services Task Force Lung Cancer Screening Update On Drivers Of Disparities In Screening Eligibility, Kristin G Maki, Rajesh Talluri, Iakovos Toumazis, Sanjay Shete, Robert J Volk

Faculty, Staff and Student Publications

BACKGROUND: In 2021, the U.S. Preventive Services Task Force (USPSTF) updated its recommendation to expand lung cancer screening (LCS) eligibility and mitigate disparities. Although this increased the number of non-White individuals who are eligible for LCS, the update's impact on drivers of disparities is less clear. This analysis focuses on racial disparities among Black individuals because members of this group disproportionately share late-stage lung cancer diagnoses, despite typically having a lower intensity smoking history compared to non-Hispanic White individuals.

METHODS: We used data from the National Health Interview Survey to examine the impact of the 2021 eligibility criteria on racial …

Aapm Btsc Report 377: Physicist Brachytherapy Training In 2021-A Survey Of Therapeutic Medical Physics Residency Program Directors, Manik Aima, Samantha J Simiele, Susan L Richardson, Christopher S Melhus

Faculty, Staff and Student Publications

BACKGROUND: Brachytherapy (BT) was the first radiotherapeutic technique used to treat human disease and remains an essential modality in radiation oncology. A decline in the utilization of BT as a treatment modality has been observed and reported, which may impact training opportunities for medical physics residents. A survey of therapeutic medical physics residency program directors was performed as part of an assessment of the current state of BT training during residency.

METHODS: In March 2021, a survey consisting of 23 questions was designed by a working unit of the Brachytherapy Subcommittee of the American Association of Physicists in Medicine (AAPM) …

Panoptosis Is A Prominent Feature Of Desmoplakin Cardiomyopathy, Melis Olcum, Leila Rouhi, Siyang Fan, Maya M Gonzales, Hyun-Hwan Jeong, Zhongming Zhao, Priyatansh Gurha, Ali J Marian

Faculty, Staff and Student Publications

INTRODUCTION: Arrhythmogenic cardiomyopathy (ACM) is hereditary cardiomyopathy caused by pathogenic variants (mutations) in genes encoding the intercalated disc (ID), particularly desmosome proteins. ACM caused by mutations in the

AIM: The aim of this article was to gain insight into the pathogenesis of DSP cardiomyopathy.

METHODS AND RESULTS: The

CONCLUSION: The findings identify PANoptosis as a prominent phenotypic feature of DSP cardiomyopathy and set the stage for delineating the specific molecular mechanisms involved in its pathogenesis. The model also provides the opportunity to test the effects of pharmacological and genetic interventions on myocardial fibrosis and cell death.

Acoustic Voice And Speech Biomarkers Of Treatment Status During Hospitalization For Acute Decompensated Heart Failure, Olivia M Murton, G William Dec, Robert E Hillman, Maulik D Majmudar, Johannes Steiner, John V Guttag, Daryush D Mehta

Faculty, Staff and Student Publications

This study investigates acoustic voice and speech features as biomarkers for acute decompensated heart failure (ADHF), a serious escalation of heart failure symptoms including breathlessness and fatigue. ADHF-related systemic fluid accumulation in the lungs and laryngeal tissues is hypothesized to affect phonation and respiration for speech. A set of daily spoken recordings from 52 patients undergoing inpatient ADHF treatment was analyzed to identify voice and speech biomarkers for ADHF and to examine the trajectory of biomarkers during treatment. Results indicated that speakers produce more stable phonation, a more creaky voice, faster speech rates, and longer phrases after ADHF treatment compared …

Structural Basis For Transcription Factor Zbtb7a Recognition Of Dna And Effects Of Zbtb7a Somatic Mutations That Occur In Human Acute Myeloid Leukemia, Ren Ren, John R Horton, Qin Chen, Jie Yang, Bin Liu, Yun Huang, Robert M Blumenthal, Xing Zhang, Xiaodong Cheng

Faculty, Staff and Student Publications

ZBTB7A belongs to a small family of transcription factors having three members in humans (7A, 7B, and 7C). They share a BTB/POZ protein interaction domain at the amino end and a zinc-finger DNA-binding domain at the carboxyl end. They control the transcription of a wide range of genes, having varied functions in hematopoiesis, oncogenesis, and metabolism (in particular glycolysis). ZBTB7A-binding profiles at gene promoters contain a consensus G(a/c)CCC motif, followed by a CCCC sequence in some instances. Structural and mutational investigations suggest that DNA-specific contacts with the four-finger tandem array of ZBTB7A are formed sequentially, initiated from ZF1-ZF2 binding to …

The Orf7a Protein Of Sars-Cov-2 Initiates Autophagy And Limits Autophagosome-Lysosome Fusion Via Degradation Of Snap29 To Promote Virus Replication, Peili Hou, Xuefeng Wang, Hongmei Wang, Tiecheng Wang, Zhangping Yu, Chunqing Xu, Yudong Zhao, Wenqi Wang, Yong Zhao, Fengyun Chu, Huasong Chang, Hongchao Zhu, Jiahui Lu, Fuzhen Zhang, Xue Liang, Xingyu Li, Song Wang, Yuwei Gao, Hongbin He

Faculty, Staff and Student Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is closely related to various cellular aspects associated with autophagy. However, how SARS-CoV-2 mediates the subversion of the macroautophagy/autophagy pathway remains largely unclear. In this study, we demonstrate that overexpression of the SARS-CoV-2 ORF7a protein activates LC3-II and leads to the accumulation of autophagosomes in multiple cell lines, while knockdown of the viral ORF7a gene via shRNAs targeting ORF7a sgRNA during SARS-CoV-2 infection decreased autophagy levels. Mechanistically, the ORF7a protein initiates autophagy via the AKT-MTOR-ULK1-mediated pathway, but ORF7a limits the progression of autophagic flux by activating CASP3 (caspase 3) to cleave the …

Biosynthesis Of Chlorophyll And Other Isoprenoids In The Plastid Of Red Grape Berry Skins, António Teixeira, Henrique Noronha, Sarah Frusciante, Gianfranco Diretto, Hernâni Gerós

Faculty, Staff and Student Publications

Despite current knowledge showing that fruits like tomato and grape berries accumulate different components of the light reactions and Calvin cycle, the role of green tissues in fruits is not yet fully understood. In mature tomato fruits, chlorophylls are degraded and replaced by carotenoids through the conversion of chloroplasts in chromoplasts, while in red grape berries, chloroplasts persist at maturity and chlorophylls are masked by anthocyanins. To study isoprenoid and lipid metabolism in grape skin chloroplasts, metabolites of enriched organelle fractions were analyzed by high-performance liquid chromatography-high-resolution mass spectrometry (HPLC-HRMS) and the expression of key genes was evaluated by real-time …

Biomarkers For Dementia In Latin American Countries: Gaps And Opportunities, Mario A Parra, Paulina Orellana, Tomas Leon, Cabello G Victoria, Fernando Henriquez, Rodrigo Gomez, Constanza Avalos, Andres Damian, Andrea Slachevsky, Agustin Ibañez, Henrik Zetterberg, Betty M Tijms, Jennifer S Yokoyama, Stefanie D Piña-Escudero, J Nicholas Cochran, Diana L Matallana, Daisy Acosta, Ricardo Allegri, Bianca P Arias-Suárez, Bernardo Barra, Maria Isabel Behrens, Sonia M D Brucki, Geraldo Busatto, Paulo Caramelli, Sheila Castro-Suarez, Valeria Contreras, Nilton Custodio, Sergio Dansilio, Myriam De La Cruz-Puebla, Leonardo Cruz De Souza, Monica M Diaz, Lissette Duque, Gonzalo A Farías, Sergio T Ferreira, Nahuel Magrath Guimet, Ana Kmaid, David Lira, Francisco Lopera, Beatriz Mar Meza, Eliane C Miotto, Ricardo Nitrini, Alberto Nuñez, Santiago O'Neill, John Ochoa, Maritza Pintado-Caipa, Elisa De Paula França Resende, Shannon Risacher, Luz Angela Rojas, Valentina Sabaj, Lucas Schilling, Allis F Sellek, Ana Sosa, Leonel T Takada, Antonio L Teixeira, Martha Unaucho-Pilalumbo, Claudia Duran-Aniotz

Faculty, Staff and Student Publications

Limited knowledge on dementia biomarkers in Latin American and Caribbean (LAC) countries remains a serious barrier. Here, we reported a survey to explore the ongoing work, needs, interests, potential barriers, and opportunities for future studies related to biomarkers. The results show that neuroimaging is the most used biomarker (73%), followed by genetic studies (40%), peripheral fluids biomarkers (31%), and cerebrospinal fluid biomarkers (29%). Regarding barriers in LAC, lack of funding appears to undermine the implementation of biomarkers in clinical or research settings, followed by insufficient infrastructure and training. The survey revealed that despite the above barriers, the region holds a …

Inhibition Of Myeloperoxidase Enhances Immune Checkpoint Therapy For Melanoma, Tracy W Liu, Seth T Gammon, Ping Yang, Wencai Ma, Jing Wang, David Piwnica-Worms

Faculty, Staff and Student Publications

BACKGROUND: The presence of a highly immunosuppressive tumor microenvironment has limited the success of immune checkpoint therapy (ICT). Immune suppressing myeloid cells with increased production of reactive oxygen species are critical drivers of this immunosuppressive tumor microenvironment. Strategies to limit these immune suppressing myeloid cells are needed to enhance response to ICT.

METHODS: To evaluate the contribution of myeloperoxidase (MPO), a myeloid lineage-restricted enzyme and a major source of reactive oxygen species, to mediating ICT response, we compared treatment outcome and immune composition in wild-type, MPO-deficient (

RESULTS: Tumor growth and survival studies demonstrated that either host deficiency (

CONCLUSION: …

Innately Expressed Estrogen-Related Receptors In The Skeletal Muscle Are Indispensable For Exercise Fitness, Danesh H Sopariwala, Andrea S Rios, Guangsheng Pei, Anirban Roy, Meiricris Tomaz Da Silva, Hao Thi Thu Nguyen, Addison Saley, Rachel Van Drunen, Anastasia Kralli, Kristin Mahan, Zhongming Zhao, Ashok Kumar, Vihang A Narkar

Faculty, Staff and Student Publications

Transcriptional determinants in the skeletal muscle that govern exercise capacity, while poorly defined, could provide molecular insights into how exercise improves fitness. Here, we have elucidated the role of nuclear receptors, estrogen-related receptor alpha and gamma (ERRα/γ) in regulating myofibrillar composition, contractility, and exercise capacity in skeletal muscle. We used muscle-specific single or double (DKO) ERRα/γ knockout mice to investigate the effect of ERRα/γ deletion on muscle and exercise parameters. Individual knockout of ERRα/γ did not have a significant impact on the skeletal muscle. On the other hand, DKO mice exhibit pale muscles compared to wild-type (WT) littermates. RNA-seq analysis …

Bilirubin Nanoparticle Treatment In Obese Mice Inhibits Hepatic Ceramide Production And Remodels Liver Fat Content, Zachary A. Kipp, Genesee J. Martinez, Evelyn A. Bates, Agil B. Maharramov, Robert M. Flight, Hunter N. B. Moseley, Andrew J. Morris, David E. Stec, Terry D. Hinds Jr.

Markey Cancer Center Faculty Publications

Studies have indicated that increasing plasma bilirubin levels might be useful for preventing and treating hepatic lipid accumulation that occurs with metabolic diseases such as obesity and diabetes. We have previously demonstrated that mice with hyperbilirubinemia had significantly less lipid accumulation in a diet-induced non-alcoholic fatty liver disease (NAFLD) model. However, bilirubin’s effects on individual lipid species are currently unknown. Therefore, we used liquid chromatography-mass spectroscopy (LC-MS) to determine the hepatic lipid composition of obese mice with NAFLD treated with bilirubin nanoparticles or vehicle control. We placed the mice on a high-fat diet (HFD) for 24 weeks and then treated …

Clic And Membrane Wound Repair Pathways Enable Pandemic Norovirus Entry And Infection, B. Vijayalakshmi Ayyar, Khalil Ettayebi, Wilhelm Salmen, Umesh C. Karandikar, Frederick H. Neill, Victoria R. Tenge, Sue E. Crawford, Erhard Bieberich, B. V. Venkataram Prasad, Robert L. Atmar, Mary K. Estes

Markey Cancer Center Faculty Publications

Globally, most cases of gastroenteritis are caused by pandemic GII.4 human norovirus (HuNoV) strains with no approved therapies or vaccines available. The cellular pathways that these strains exploit for cell entry and internalization are unknown. Here, using nontransformed human jejunal enteroids (HIEs) that recapitulate the physiology of the gastrointestinal tract, we show that infectious GII.4 virions and virus-like particles are endocytosed using a unique combination of endosomal acidification-dependent clathrin-independent carriers (CLIC), acid sphingomyelinase (ASM)-mediated lysosomal exocytosis, and membrane wound repair pathways. We found that besides the known interaction of the viral capsid Protruding (P) domain with host glycans, the Shell …

Contouring Quality Assurance Methodology Based On Multiple Geometric Features Against Deep Learning Auto-Segmentation, Jingwei Duan, Mark E. Bernard, James Castle, Xue Feng, Chi Wang, Mark C. Kenamond, Quan Chen

Markey Cancer Center Faculty Publications

Background: Contouring error is one of the top failure modes in radiation treatment. Multiple efforts have been made to develop tools to automatically detect segmentation errors.Deep learning-based auto-segmentation (DLAS) has been used as a baseline for flagging manual segmentation errors, but those efforts are limited to using only one or two contour comparison metrics.

Purpose: The purpose of this research is to develop an improved contouring quality assurance system to identify and flag manual contouring errors.

Methods and materials: DLAS contours were used as a reference to compare with manually segmented contours. A total of 27 geometric agreement metrics were …

Critical Role Of The Sulfiredoxin-Peroxiredoxin Iv Axis In Urethane-Induced Non-Small Cell Lung Cancer, Yanning Hao, Hong Jiang, Pratik Thapa, Na Ding, Aziza Alshahrani, Junichi Fujii, Michel B. Toledano, Qiou Wei

Markey Cancer Center Faculty Publications

Non-small cell lung cancer (NSCLC), the most common type of lung cancer, etiologically associates with tobacco smoking which mechanistically contributes to oxidative stress to facilitate the occurrence of mutations, oncogenic transformation and aberrantly activated signaling pathways. Our previous reports suggested an essential role of Sulfiredoxin (Srx) in promoting the development of lung cancer in humans, and was causally related to Peroxiredoxin IV (Prx4), the major downstream substrate and mediator of Srx-enhanced signaling. To further explore the role of the Srx-Prx4 axis in de novo lung tumorigenesis, we established Prx4−/− and Srx−/−/Prx4−/− mice in pure FVB/N background. Together with wild-type litter …

Ifn-Γ Production By Brain-Resident Cells Activates Cerebral Mrna Expression Of A Wide Spectrum Of Molecules Critical For Both Innate And T Cell-Mediated Protective Immunity To Control Reactivation Of Chronic Infection With Toxoplasma Gondii, Yasuhiro Suzuki, Jenny Lutshumba, Kuey Chu Chen, Mohamed H. Abdelaziz, Qila Sa, Eri Ochiai

Markey Cancer Center Faculty Publications

We previously demonstrated that brain-resident cells produce IFN-g in response to reactivation of cerebral infection with Toxoplasma gondii. To obtain an overall landscape view of the effects of IFN-g from brain-resident cells on the cerebral protective immunity, in the present study we employed NanoString nCounter assay and quantified mRNA levels for 734 genes in myeloid immunity in the brains of T and B cell-deficient, bone marrow chimeric mice with and without IFN-g production by brain-resident cells in response to reactivation of cerebral T. gondii infection. Our study revealed that IFN-g produced by brain-resident cells amplified mRNA expression for the molecules …

Recombinant Protein Vaccines Formulated With Enantio-Specific Cationic Lipid R-Dotap Induce Protective Cellular And Antibody-Mediated Immune Responses In Mice, Siva Gandhapudi, Hua Shi, Martin Ward, John Peyton Bush, Margarita G. Avdiushko, Karuna Sundarapandiyan, Lauren V. Wood, Mania Dorrani, Afsheen Fatima, Joe Dervan, Frank Bedu-Addo, Greg Conn, Ted M. Ross, Jerold Woodward

Markey Cancer Center Faculty Publications

Adjuvants are essential components of subunit vaccines added to enhance immune responses to antigens through immunomodulation. Very few adjuvants have been approved for human use by regulatory agencies due to safety concerns. Current subunit vaccine adjuvants approved for human use are very effective in promoting humoral immune responses but are less effective at promoting T-cell immunity. In this study, we evaluated a novel pure enantio-specific cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (R-DOTAP) as an immunomodulator for subunit vaccines capable of inducing both humoral- and cellular-mediated immunity. Using recombinant protein antigens derived from SARS-CoV2 spike or novel computationally optimized broadly reactive influenza antigen (COBRA) …

Production And Characterization Of Monoclonal Antibodies To Xenopus Proteins, Brett Horr, Ryan Kurtz, Ankit Pandey, Benjamin G. Hoffstrom, Elizabeth Schock, Carole Labonne, Dominique Alfandari

Markey Cancer Center Faculty Publications

Monoclonal antibodies are powerful and versatile tools that enable the study of proteins in diverse contexts. They are often utilized to assist with identification of subcellular localization and characterization of the function of target proteins of interest. However, because there can be considerable sequence diversity between orthologous proteins in Xenopus and mammals, antibodies produced against mouse or human proteins often do not recognize Xenopus counterparts. To address this issue, we refined existing mouse monoclonal antibody production protocols to generate antibodies against Xenopus proteins of interest. Here, we describe several approaches for the generation of useful mouse anti-Xenopus antibodies to multiple …

How Much Did It Cost To Develop And Implement An Ehealth Intervention For A Minority Children Population That Overlapped With The Covid-19 Pandemic?, Alexandra Monashefsky, Dar Alon, Tom Baranowski, Tiago V Barreira, Kelly A Chiu, Amy Fleischman, Melanie C Green, Shirley Huang, Ronald C Samuels, Caio Victor Sousa, Debbe Thompson, Amy S Lu

Children’s Nutrition Research Center Staff Publications

Background: eHealth interventions using active video games (AVGs) offer an alternative method to help children exercise, especially during a pandemic where options are limited. There is limited data on costs associated with developing and implementing such interventions.

Objectives: We quantified the costs of delivering an eHealth RCT intervention among minority children during COVID-19.

Methods: We categorized the total trial cost into five subcategories: intervention material development, advertising and recruitment, intervention delivery, personnel salaries, and COVID-19-related equipment costs.

Results: The total RCT cost was $1,927,807 (Direct: $1,227,903; Indirect: $699,904) with three visits required for each participant. The average cost per participant …

Randomized Controlled Trial Of A Novel Lifestyle Intervention Used With Or Without Meal Replacements In Work Sites, Sai Krupa Das, Rachel E Silver, Taylor A Vail, Meghan K Chin, Caroline M Blanchard, Stephanie L Dickinson, Xiwei Chen, Lisa Ceglia, Edward Saltzman, David B Allison, Susan B Roberts

Children’s Nutrition Research Center Staff Publications

Objective: Lifestyle interventions have had limited effectiveness in work sites when evaluated in randomized trials. This study assessed the effectiveness of a novel lifestyle intervention for weight loss (Healthy Weight for Living [HWL]) implemented with or without meal replacements (MR) in work sites. HWL used a new behavioral approach emphasizing reducing hunger and building healthy food preferences, and, unlike traditional lifestyle interventions, it did not require calorie counting.

Methods: Twelve work sites were randomized to an 18-month intervention (n = 8; randomization within work sites to HWL, HWL + MR) or 6-month wait-listed control (n = 4). Participants were employees …

Diabetes Of Unclear Type In An Adolescent Boy With Multiple Islet-Cell Autoantibody Positivity Successfully Managed With Glucagon-Like Peptide-1 Receptor Agonist Alone: A Case Report, Olivia Z B Ginnard, Maria J Redondo, Sarah K Lyons

Children’s Nutrition Research Center Staff Publications

Diabetes classification has traditionally considered type 1 and type 2 diabetes as 2 separate entities with different pathogenic mechanisms. However, clinicians and researchers see increasingly more exceptions to this conventional paradigm, leading to a concept of mixed phenotypes in diabetes classification. Herein we report the case of an adolescent with unclear diabetes type due to the presence of obesity, robust endogenous insulin production, multiple islet autoantibody positivity and severe hyperglycemia at diabetes diagnosis that has been successfully treated with liraglutide therapy alone. Our case report highlights the difficulty of diabetes classification and subsequent need for personalized medicine with regard to …

How Much Did It Cost To Develop And Implement An Ehealth Intervention For A Minority Children Population That Overlapped With The Covid-19 Pandemic?, Alexandra Monashefsky, Dar Alon, Tom Baranowski, Tiago V Barreira, Kelly A Chiu, Amy Fleischman, Melanie C Green, Shirley Huang, Ronald C Samuels, Caio Victor Sousa, Debbe Thompson, Amy S Lu

Children’s Nutrition Research Center Staff Publications

Background: eHealth interventions using active video games (AVGs) offer an alternative method to help children exercise, especially during a pandemic where options are limited. There is limited data on costs associated with developing and implementing such interventions.

Objectives: We quantified the costs of delivering an eHealth RCT intervention among minority children during COVID-19.

Methods: We categorized the total trial cost into five subcategories: intervention material development, advertising and recruitment, intervention delivery, personnel salaries, and COVID-19-related equipment costs.

Results: The total RCT cost was $1,927,807 (Direct: $1,227,903; Indirect: $699,904) with three visits required for each participant. The average cost per participant …

Genetic Effect On Body Mass Index And Cardiovascular Disease Across Generations, Chloé Sarnowski, Matthew P Conomos, Ramachandran S Vasan, James B Meigs, Josée Dupuis, Ching-Ti Liu, Aaron Leong

Faculty, Staff and Student Publications

BACKGROUND: Whether genetics contribute to the rising prevalence of obesity or its cardiovascular consequences in today's obesogenic environment remains unclear. We sought to determine whether the effects of a higher aggregate genetic burden of obesity risk on body mass index (BMI) or cardiovascular disease (CVD) differed by birth year.

METHODS: We split the FHS (Framingham Heart Study) into 4 equally sized birth cohorts (birth year before 1932, 1932 to 1946, 1947 to 1959, and after 1960). We modeled a genetic predisposition to obesity using an additive genetic risk score (GRS) of 941 BMI-associated variants and tested for GRS-birth year interaction …

Ampk Regulates Homeostasis Of Invasion And Viability In Trophoblasts By Redirecting Glucose Metabolism: Implications For Pre-Eclampsia, Ping Xu, Yangxi Zheng, Jiujiang Liao, Mingyu Hu, Yike Yang, Baozhen Zhang, Mark D Kilby, Huijia Fu, Yamin Liu, Fumei Zhang, Liling Xiong, Xiyao Liu, Huili Jin, Yue Wu, Jiayu Huang, Tingli Han, Li Wen, Rufei Gao, Yong Fu, Xiujun Fan, Hongbo Qi, Philip N Baker, Chao Tong

Faculty, Staff and Student Publications

Pre-eclampsia (PE) is deemed an ischemia-induced metabolic disorder of the placenta due to defective invasion of trophoblasts during placentation; thus, the driving role of metabolism in PE pathogenesis is largely ignored. Since trophoblasts undergo substantial glycolysis, this study aimed to investigate its function and regulatory mechanism by AMPK in PE development. Metabolomics analysis of PE placentas was performed by gas chromatography-mass spectrometry (GC-MS). Trophoblast-specific AMPKα1-deficient mouse placentas were generated to assess morphology. A mouse PE model was established by Reduced Uterine Perfusion Pressure, and placental AMPK was modulated by nanoparticle-delivered A769662. Trophoblast glucose uptake was measured by 2-NBDG and 2-deoxy-d-[