Digital Commons Network^™

Identification Of Potent Pan-Ephrin Receptor Kinase Inhibitors Using Dna-Encoded Chemistry Technology, Chandrashekhar Madasu, Zian Liao, Sydney E Parks, Kiran L Sharma, Kurt M Bohren, Qiuji Ye, Feng Li, Murugesan Palaniappan, Zhi Tan, Fei Yuan, Chad J Creighton, Suni Tang, Ramya P Masand, Xiaoming Guan, Damian W Young, Diana Monsivais, Martin M Matzuk

Faculty, Staff and Students Publications

EPH receptors (EPHs) are highly sought-after drug targets owing to their essential roles in maintaining appropriate cellular functions in both physiological and disease conditions. However, limited potency and specificity pose significant obstacles to the development of small-molecule inhibitors for EPHs. Here, using high-throughput DNA-encoded chemical library screenings, we developed potent and selective inhibitors of the EPH receptor kinase family. Our results also emphasize the therapeutic potential of our EPH inhibitors in cancer and endometriosis, a global health concern that causes chronic pain and often leads to infertility in women. This study showcases the robust pipeline of using DNA-encoded chemistry technology …

Endotrophin, A Key Marker And Driver For Fibroinflammatory Disease, Kim Henriksen, Federica Genovese, Alexander Reese-Petersen, Laurent P Audoly, Kai Sun, Morten A Karsdal, Philipp E Scherer

Faculty, Staff and Student Publications

Our overview covers several key areas related to recent results obtained for collagen type VI and endotrophin (ETP). (1) An introduction to the history of ETP, including how it was identified, how it is released, and its function and potential receptors. (2) An introduction to the collagen family, with a focus on what differentiates collagen type VI from an evolutionary standpoint. (3) An overview of collagen type VI, the 6 individual chains (COL6A1, A2, A3, A4, A5, and A6), their differences and similarities, as well as their expression profiles and function. (4) A detailed analysis of COL6A3, including the cleaved …

The Pocketperio Application Significantly Increases The Accuracy Of Diagnosing Periodontal Conditions In Didactic And Chairside Settings, Karo Parsegian, David K Okano, Sangeetha Chandrasekaran, Yoolim Kim, Tonia C Carter, Neel Shimpi, Sadaf Fadakar, Nikola Angelov

Faculty, Staff and Student Publications

The study aimed to determine the accuracy of diagnosing periodontal conditions using the developed web-based PocketPerio application and evaluate the user’s perspective on the use of PocketPerio. First, 22 third-year dental students (DS3) diagnosed ten cases without PocketPerio (control) and with PocketPerio (test) during a mock examination. Then, 105 DS3, 13 fourth-year dental students (DS4), and 32 senior second-year International Standing Program students (ISP2) used PocketPerio chairside. Statistical analysis was performed using a non-parametric paired two-tailed test of significance with the Wilcoxon matched-pairs signed rank test. The null hypothesis that PocketPerio did not increase the accuracy of periodontal diagnoses …

Rosarugosides A And D From Osa Rugosa Flower Buds: Their Potential Anti-Skin-Aging Effects Intnf-Α-Induced Human Dermal Fibroblasts, Kang Sub Kim, So-Ri Son, Yea Jung Choi, Yejin Kim, Si-Young Ahn, Dae Sik Jang, Sullim Lee

Faculty, Staff and Student Publications

This present study investigated the anti-skin-aging properties of Rosa rugosa. Initially, phenolic compounds were isolated from a hot water extract of Rosa rugosa's flower buds. Through repeated chromatography (column chromatography, MPLC, and prep HPLC), we identified nine phenolic compounds (1-9), including a previously undescribed depside, rosarugoside D (1). The chemical structure of 1 was elucidated via NMR, HR-MS, UV, and hydrolysis. Next, in order to identify bioactive compounds that are effective against TNF-α-induced NHDF cells, we measured intracellular ROS production in samples treated with each of the isolated compounds (1- …

Fatty Acid Concentrations In Preterm Infants Fed The Exclusive Human Milk Diet: A Prospective Cohort Study, Lindsay F Holzapfel, Jana P Unger, Pam Gordon, Heeju Yang, Joanne E Cluette-Brown, Laura A Gollins, Amy B Hair, Camilia R Martin

Faculty, Staff and Student Publications

OBJECTIVE: Quantify blood fatty acids and growth outcomes in preterm infants fed the exclusive human milk diet.

METHODS: A prospective cohort study of 30 infants 24-34 weeks gestation and ≤1250 g fed the exclusive human milk diet. Blood fatty acids were quantified at two time points. Comparisons were made using two-sample t-tests and Wilcoxon rank sum.

RESULTS: Donor human milk-fed (n = 12) compared to mother's own milk-fed infants (n = 18) from birth to after 28 days of life, had an increased interval change of linoleic to docosahexaenoic acid ratio (5.5 vs. -1.1 mole percent ratio, p = 0.034). …

Development And Validation Of A Rule-Based Algorithm To Identify Periodontal Diagnosis Using Structured Electronic Health Record Data, Bunmi Tokede, Ryan Brandon, Chun-Teh Lee, Guo-Hao Lin, Joel White, Alfa Yansane, Xiaoqian Jiang, Elsbeth Kalenderian, Muhammad Walji

Faculty, Staff and Student Publications

AIM: To develop and validate an automated electronic health record (EHR)-based algorithm to suggest a periodontal diagnosis based on the 2017 World Workshop on the Classification of Periodontal Diseases and Conditions.

MATERIALS AND METHODS: Using material published from the 2017 World Workshop, a tool was iteratively developed to suggest a periodontal diagnosis based on clinical data within the EHR. Pertinent clinical data included clinical attachment level (CAL), gingival margin to cemento-enamel junction distance, probing depth, furcation involvement (if present) and mobility. Chart reviews were conducted to confirm the algorithm's ability to accurately extract clinical data from the EHR, and then …

Mapping Recommendations Towards An Asian Code Against Cancer (Acac) As Part Of The World Code Against Cancer Framework: An Asian National Cancer Centers Alliance (Ancca) Initiative, Sok King Ong, Sarah K Abe, Gillian Li Gek Phua, Harindra Jayasekara, Kayo Togawa, Laureline Gatellier, Jeongseon Kim, Yawei Zhang, Siti Zuhrini Kahan, Siti Norbayah Yusof, Jong Soo Han, C S Pramesh, Manju Sengar, Abhishek Shankar, Clarito Cairo, Suleeporn Sangrajran, Erdenekhuu Nansalmaa, Tseveen Badamsuren, Tashi Dendup, Kinley Tshering, Jie He, R Soeko Werdi Nindito D, Azmi Ritana, Jeong Soo Im, Eun Young Park, Giang Nguyen Huong, Tran Thi Thanh Huong, Mohammed Biglari, Aasim Yusuf, Kishore Kumar Pradhananga, Champadeng Vongdala, Muhammad Taufiq Bin Jaafar, Nor Saleha Ibrahim Tamin, Yi Yi Myint, Kyaw Kan Kaung, Md Shafiur Rahman, Eshani Fernando, Beauta Rath, Babu Sukumaran, William Yk Hwang, Carolina Espina, Joachim Schüz, Manami Inoue, Tomohiro Matsuda

Faculty, Staff and Student Publications

This paper outlines the process undertaken by Asian National Cancer Centers Alliance (ANCCA) members in working towards an Asian Code Against Cancer (ACAC). The process involves: (i) identification of the criteria for selecting the existing set of national recommendations for ACAC (ii) compilation of existing national codes or recommendations on cancer prevention (iii) reviewing the scientific evidence on cancer risk factors in Asia and (iv) establishment of one or more ACAC under the World Code Against Cancer Framework. A matrix of national codes or key recommendations against cancer in ANCCA member countries is presented. These include taking actions to prevent …

Efficacy And Safety Of Endoscopic Submucosal Dissection For Colorectal Dysplasia In Patients With Inflammatory Bowel Disease: A Systematic Review And Meta-Analysis, Talia F Malik, Vaishnavi Sabesan, Babu P Mohan, Asad Ur Rahman, Mohamed O Othman, Peter V Draganov, Gursimran S Kochhar

Faculty, Staff and Students Publications

BACKGROUND/AIMS: In this meta-analysis, we studied the safety and efficacy of endoscopic submucosal dissection (ESD) for colorectal dysplasia in patients with inflammatory bowel disease (IBD).

METHODS: Multiple databases were searched, and studies were retrieved based on pre-specified criteria until October 2022. The outcomes assessed were resection rates, procedural complications, local recurrence, metachronous tumors, and the need for surgery after ESD in IBD. Standard meta-analysis methods were followed using the random-effects model, and I2% was used to assess heterogeneity.

RESULTS: Twelve studies comprising 291 dysplastic lesions in 274 patients were included with a median follow-up of 25 months. The pooled en-bloc …

Tenapanor As Therapy For Hyperphosphatemia In Maintenance Dialysis Patients: Results From The Optimize Study, Stuart M Sprague, Daniel E Weiner, David P Tietjen, Pablo E Pergola, Steven Fishbane, Geoffrey A Block, Arnold L Silva, Stephen Z Fadem, Robert I Lynn, George Fadda, Lynae Pagliaro, Suling Zhao, Susan Edelstein, David M Spiegel, David P Rosenbaum

Faculty, Staff and Students Publications

KEY POINTS: Tenapanor, a first-in-class local inhibitor of sodium/hydrogen exchanger isoform 3, acts as a phosphate absorption inhibitor by decreasing paracellular phosphate absorption. Tenapanor alone or with phosphate binders achieved

BACKGROUND: OPTIMIZE was a randomized, open-label study evaluating different tenapanor initiation methods. OPTIMIZE evaluated tenapanor alone and in combination with phosphate binders (PBs) to achieve target serum phosphate (P) ≤5.5 mg/dl.

METHODS: Patients with inadequately controlled P receiving maintenance dialysis from 42 US locations who were taking PBs with baseline

RESULTS: By part A end point, 34.4% (

CONCLUSIONS: Tenapanor as monotherapy or in combination with PBs effectively lowered P …

Association Of Cardiovascular Health With Subclinical Coronary Atherosclerosis Progression Among Five Racial And Ethnic Groups: The Masala And Mesa Studies, Vardhmaan Jain, Mahmoud Al Rifai, Alka M Kanaya, Nilay S Shah, Sameera A Talegawkar, Salim S Virani, Erin D Michos, Roger S Blumenthal, Jaideep Patel

Faculty, Staff and Students Publications

Background and aims: South Asian adults (SA) are at higher risk for atherosclerotic cardiovascular disease (ASCVD) compared with other racial/ethnic groups. Life's Simple 7 (LS7) is a guideline-recommended, cardiovascular health (CVH) construct to guide optimization of cardiovascular risk factors. We sought to assess if the LS7 metrics predict coronary artery calcium (CAC) incidence and progression in asymptomatic SA compared with four other racial/ethnic groups.

Methods: We assessed the distribution of CVH metrics (inadequate: score 0-8, average: 9-10, optimal: 11-14, and per 1-unit higher score) and its association with incidence and progression of CAC among South Asians in the Mediators of …

Rare Case Of Open Comminuted Scaphoid Fracture Dislocation: Treatment With Free Bone Graft And Locking Plate, Makoto Fukuda, Masahiro Miyashita, Masataka Yasuda

Children’s Nutrition Research Center Staff Publications

To the best of our knowledge, there are no reports in the literature of an open comminuted scaphoid fracture dislocation. We present such a rare case. The case report illustrates the case of a 58-year-old right-handed press operator who injured his left wrist when his hand got caught in a press machine. He received initial treatment at another hospital and was subsequently referred to our hospital. Eight days after the injury, surgery was performed under the brachial plexus block. Successful bone fusion was achieved through volar locking plate fixation, primary free bone grafting from the radius, and Kirschner wire fixation. …

Prevalence Of Distal Symmetrical Polyneuropathy By Diabetes Prevention Program Treatment Group, Diabetes Status, Duration Of Diabetes, And Cumulative Glycemic Exposure, Christine G Lee, Adam Ciarleglio, Sharon L Edelstein, Jill P Crandall, Dana Dabelea, Ronald B Goldberg, Steven E Kahn, William C Knowler, Maxwell T Ma, Neil H White, William H Herman, Diabetes Prevention Program Research Group

Children’s Nutrition Research Center Staff Publications

Objective: To assess associations between distal symmetric polyneuropathy (DSPN) and Diabetes Prevention Program (DPP) treatment groups, diabetes status or duration, and cumulative glycemic exposure approximately 21 years after DPP randomization.

Research design and methods: In the DPP, 3,234 adults ≥25 years old at high risk for diabetes were randomized to an intensive lifestyle (ILS), metformin, or placebo intervention to prevent diabetes. After the DPP ended, 2,779 joined the Diabetes Prevention Program Outcomes Study (DPPOS). Open-label metformin was continued, placebo was discontinued, ILS was provided in the form of semiannual group-based classes, and all participants were offered quarterly lifestyle classes. Symptoms …

Impact Of Sustained Calorie Restriction And Weight Cycling On Body Composition In High-Fat Diet-Fed Male And Female C57bl/6j Mice, Daniel L Smith, Yongbin Yang, Luis M Mestre, Beate Henschel, Erik Parker, Stephanie Dickinson, Amit Patki, David B Allison, Tim R Nagy

Children’s Nutrition Research Center Staff Publications

Objective: The objective of this study was to investigate body composition changes with weight cycling (WC) among adult C57BL/6J mice with diet-induced obesity.

Methods: A total of 555 single-housed mice were fed a high-fat diet ad libitum (AL) from 8 to 43 weeks of age. The 200 heaviest mice of each sex were randomized to the following four groups: ever obese (EO, continued AL feeding); obese weight loser (OWL, calorie-restricted); obese weight loser moderate (OWLM, body weight halfway between EO and OWL); and WC (diet restricted to OWL followed by AL refeeding cycles). Body weight and composition data were collected. …

Relationship Between Food Security, Nutrition Security, And Diabetes: The Role Of Supplemental Nutrition Assistance Program Participation, Maha Almohamad, Jayna M Dave, Eric E Calloway, Ruosha Li, Shreela Sharma

Faculty, Staff and Student Publications

BACKGROUND: Inadequate nutrition and poor diet quality are associated with a heightened risk of diabetes. The connection between food insecurity measures and diabetes has been established, with evidence indicating that Supplemental Nutrition Assistance Program (SNAP) participation contributes to reductions in food insecurity. Recently developed nutrition security measures, defined as the ability to acquire healthful foods to prevent diseases, and their association with diabetes and SNAP participation are not yet understood.

OBJECTIVES: This study aimed to assess the relationship between food security and nutrition security in relation to diabetes overall and by SNAP participation and nutrition security as potential modifiers.

METHODS: …

Physical Activity Policies At National And Subnational Levels: A Study In Colombia, Costa Rica, Ecuador, And Mexico, Juliana Mejía Grueso, Michael Pratt, Eugen Resendiz, Deborah Salvo, Gloria Isabel Niño Cruz, Nubia Yaneth Ruiz Gómez, Rafael Alexander Leandro Gómez, Inés Revuelta Sánchez, Gerardo Alonso Araya Vargas, Angélica María Ochoa Avilés, Raúl Francisco Pérez Tasigchana, Alejandra Jáuregui, Pedro C Hallal, Andrea Ramírez Varela

Faculty, Staff and Student Publications

Background: National physical activity (PA) policy processes are only beginning to be studied in Latin America, and little attention has focused at the subnational level. This study examined national-subnational relations in the policy process (agenda setting, policy formulation, adoption, implementation, and evaluation) in selected Latin American countries.

Methods: The Global Observatory for Physical Activity's (GoPA!) INTEGRATE-PA-Pol tool was applied in Colombia, Costa Rica, Ecuador, and Mexico. Data were collected in matched pairs of the capital plus one noncapital city among national and subnational policymakers (n = 27), previously identified by the GoPA! Country Contacts. PA policy development and implementation were …

Investigating The Role Of The Gut Microbiota On Immune Checkpoint Inhibitor-Mediated Colitis, Taylor Halsey, Robert Jenq

Dissertations and Theses (Open Access)

Immune checkpoint inhibitors (ICIs) have been revolutionary in the fight against cancer by recruiting the host immune system as an agent for attack on malignant cells. Unfortunately, immune-related adverse events (irAEs), including ICI-mediated colitis (IMC), are common side effects that result from immune cell mediated damage on healthy tissues. Recent studies have highlighted a role for the gut microbiota in modulating ICI-mediated anti-tumor responses, but less is known regarding how the gut microbiota may impact on irAEs. Considering that the gastrointestinal tract harbors thousands of unique microbial species, many of which are known to modulate the immune system, microbes and …

Mapping The Neural Circuits That Underlie Metabolic Vs. Emotional Regulation Of Food-Seeking Behavior, Xu Zhang

Dissertations and Theses (Open Access)

Flexibly adjusting food-seeking behaviors based on metabolic needs and environmental threats is crucial for animal survival. In humans, maladaptive food-seeking behaviors that contravene energy homeostasis, which is often driven by food-associated cues with hedonic reward values, lead to obesity and eating disorders. However, the neural mechanisms underlying the modulation of cued food-seeking behaviors by distinct metabolic and threat states remain elusive. Using an approach-food vs. avoid-predator threat conflict test in rats, we identified a subpopulation of neurons in the anterior portion of the paraventricular thalamic nucleus (aPVT) which express corticotrophin-releasing factor (CRF) and are preferentially recruited to respond to food …

Syntaxin-3 Mediates Baseline And Stimulated Mucin Secretion, Brianne Wharton

Dissertations and Theses (Open Access)

There are two rates at which airway epithelial cells secrete mucin. The low baseline rate accounts for ciliary clearance, and the high stimulated rate obstructs airways in protection from helminths or in obstructive pulmonary diseases. The exocytosis of mucins occurs via the four-helix SNARE complex. The SNARE proteins contributing helices are the vesicle-SNARE VAMP, and the target-SNAREs SNAP and Syntaxin. Coiling of the complex fuses the granule and plasma membranes to release mucins into the extracellular space. The VAMP and SNAP isoforms mediating baseline and stimulated secretion are known, but the Syntaxin (Stx) isoform remains unknown.

Three candidate exocytic Stx, …

Genomic Signatures Of Strawberry Domestication And Diversification, Zhen Fan, Vance M Whitaker

Faculty, Staff and Student Publications

Cultivated strawberry (Fragaria × ananassa) has a brief history of less than 300 yr, beginning with the hybridization of octoploids Fragaria chiloensis and Fragaria virginiana. Here we explored the genomic signatures of early domestication and subsequent diversification for different climates using whole-genome sequences of 289 wild, heirloom, and modern varieties from two major breeding programs in the United States. Four nonadmixed wild octoploid populations were identified, with recurrent introgression among the sympatric populations. The proportion of F. virginiana ancestry increased by 20% in modern varieties over initial hybrids, and the proportion of F. chiloensis subsp. pacifica rose from 0% to …

Intermittent Fasting And Its Impact On Toxicities, Symptoms And Quality Of Life In Patients On Active Cancer Treatment, Robert Li Sucholeiki, Casey L Propst, David S Hong, Goldy C George

Faculty, Staff and Student Publications

Intermittent fasting is a dietary intervention that is increasingly being tested for positive outcomes in patients receiving cancer treatment. In this review, we examine the impact of intermittent fasting on symptoms, toxicities, and quality of life in patients undergoing cancer therapy and highlight unmet investigative areas to prompt future research. While current evidence is preliminary and conclusions mixed, some promising clinical studies suggest that intermittent fasting interventions may improve fatigue and reduce gastrointestinal toxicities in certain patients with cancer. Emerging clinical evidence also demonstrates that intermittent fasting may reduce off-target DNA damage, and induce favorable cellular-level immune remodeling. Furthermore, intermittent …

Genomic Landscape Of Lynch Syndrome Colorectal Neoplasia Identifies Shared Mutated Neoantigens For Immunoprevention, Ana M Bolivar, Fahriye Duzagac, Nan Deng, Laura Reyes-Uribe, Kyle Chang, Wenhui Wu, Charles M Bowen, Melissa W Taggart, Selvi Thirumurthi, Patrick M Lynch, Y Nancy You, Jesus Rodriguez-Pascual, Steven M Lipkin, Scott Kopetz, Paul Scheet, Gregory A Lizee, Alexandre Reuben, Krishna M Sinha, Eduardo Vilar

Faculty, Staff and Student Publications

Background & aims: Lynch syndrome (LS) carriers develop mismatch repair-deficient neoplasia with high neoantigen (neoAg) rates. No detailed information on targetable neoAgs from LS precancers exists, which is crucial for vaccine development and immune-interception strategies. We report a focused somatic mutation and frameshift-neoAg landscape of microsatellite loci from colorectal polyps without malignant potential (PWOMP), precancers, and early-stage cancers in LS carriers.

Methods: We generated paired whole-exome and transcriptomic sequencing data from 8 colorectal PWOMP, 41 precancers, 8 advanced precancers, and 12 early-stage cancers of 43 LS carriers. A computational pipeline was developed to predict, rank, and prioritize the top 100 …

Revisiting Feeding Tube Utilization In Oropharynx Cancer: 6-Year Prospective Registry Analysis, Brady J Anderson, Amy C Moreno, Yun Qing, J Jack Lee, Faye M Johnson, Miriam N Lango, Carly E A Barbon, Lavanya Tripuraneni, Ariana Sahli, Vicki Piper, Neil Gross, Clifton D Fuller, Stephen Y Lai, Jeffrey N Myers, Katherine A Hutcheson

Faculty, Staff and Student Publications

OBJECTIVE: Patients treated for oropharyngeal cancer (OPC) have historically demonstrated high feeding tube rates for decreased oral intake and malnutrition. We re-examined feeding tube practices in these patients.

STUDY DESIGN: Retrospective analysis of prospective cohort from 2015 to 2021.

SETTING: Single-institution NCI-Designated Comprehensive Cancer Center.

METHODS: With IRB approval, patients with new oropharyngeal squamous cell cancer or (unknown primary with neck metastasis) were enrolled. Baseline swallowing was assessed via videofluoroscopy and Performance Status Scale for Head and Neck Cancer (PSSHN). G-tubes or nasogastric tubes (NGT) were placed for weight loss before, during, or after treatment. Prophylactic NGT were placed during …

Hypertensive Disorders Of Pregnancy And Long-Term Maternal Cardiovascular And Metabolic Biomarkers, Ashley N Battarbee, Lisa Mele, Mark B Landon, Michael W Varner, Brian M Casey, Uma M Reddy, Ronald J Wapner, Dwight J Rouse, John M Thorp, Edward K Chien, George Saade, Alan M Peaceman, Sean C Blackwell

Faculty, Staff and Student Publications

Objective: This study aimed to measure the association between hypertensive disorders of pregnancy (HDP) and long-term maternal metabolic and cardiovascular biomarkers.

Study design: Follow-up study of patients who completed glucose tolerance testing 5 to 10 years after enrollment in a mild gestational diabetes mellitus (GDM) treatment trial or concurrent non-GDM cohort. Maternal serum insulin concentrations and cardiovascular markers VCAM-1, VEGF, CD40L, GDF-15, and ST-2 were measured, and insulinogenic index (IGI, pancreatic β-cell function) and 1/ homeostatic model assessment (insulin resistance) were calculated. Biomarkers were compared by presence of HDP (gestational hypertension or preeclampsia) during pregnancy. Multivariable linear regression estimated the …

Avoidant/Restrictive Food Intake Disorder Prevalence Is High In Children With Gastroparesis And Functional Dyspepsia, Isha Kaul, Helen Burton-Murray, Salma Musaad, Yiming Mirabile, Danita Czyzewski, Miranda A L Van Tilburg, Andrew C Sher, Bruno P Chumpitazi, Robert J Shulman

Children’s Nutrition Research Center Staff Publications

BACKGROUND: Avoidant/restrictive food intake disorder (ARFID) prevalence in children with gastroparesis (Gp) and/or functional dyspepsia (FD) is unknown. We aimed to identify ARFID prevalence and trajectory over 2 months in children with Gp, FD, and healthy children (HC) using two screening questionnaires. We also explored the frequency of a positive ARFID screen between those with/without delayed gastric emptying or abnormal fundic accommodation.

METHODS: In this prospective longitudinal study conducted at an urban tertiary care hospital, patients ages 10-17 years with Gp or FD and age- and gender-matched HC completed two validated ARFID screening tools at baseline and 2-month follow-up: the …

Impact Of Obesity And Age On Mouse Corneal Innervation At The Epithelial-Stromal Interface, Justin A Courson, Rolando E Rumbaut, Alan R Burns

Faculty, Staff and Students Publications

PURPOSE: The corneal epithelium is the most highly innervated structure in the body. Previously, we reported a novel event whereby stromal axons fuse with basal epithelial cells, limiting nerve penetration into the epithelium. Although corneal-epithelial nerves undergo changes in sensitivity and distribution throughout life and in response to an obesogenic diet, it is unknown if neuronal-epithelial cell fusion is altered. Here, we sought to determine if neuronal-epithelial cell fusion frequency correlates with obesogenic diet consumption and age.

METHODS: Corneas were collected from C57BL/6 mice and evaluated for neuronal-epithelial cell fusion frequency using serial block-face scanning electron microscopy. To assess the …

Immunotherapy Withdrawal By Step-Down To Mesalamine In Pediatric Patients With Ulcerative Colitis, Reka Szigeti, Richard Kellermayer

Faculty, Staff and Students Publications

OBJECTIVE: Parents and pediatric patients with ulcerative colitis (UC) who progressed to systemic immunotherapy are concerned about lifelong risks from such treatments. There is limited knowledge about withdrawal of such agents and step-down (SD) to enteral 5-aminosalicylic acid (mesalamine) before transitioning to adult care.

METHODS: We studied nine pediatric cases with moderate to severe UC who after a median of 2.18 years of clinical remission on systemic immunotherapy stepped down to oral mesalamine treatment.

RESULTS: Average follow-up time from SD was 3.49 years. Five patients (55.5%) had sustained remission (without any flare noted) after SD during follow-up. Sustained clinical remission …

Herbal And Dietary Supplement Induced Liver Injury Leading To Hepatitis-Associated Severe Aplastic Anemia: A Case Report, Rebecca Mercedes, Sanjiv Harpavat, Paula M Hertel, Ghadir Sasa, Susan Kirk, Kalyani Patel, Krupa R Mysore

Faculty, Staff and Students Publications

Herbal and dietary supplements (HDS) are a common etiology of drug induced liver injury and, specifically, Herbalife® supplements have been implicated. Hepatitis associated aplastic anemia (HAAA) is a rare and potentially fatal complication after acute hepatitis characterized by pancytopenia. While there have been rare cases of HDS leading to HAAA, no cases of Herbalife® induced liver injury leading to HAAA have been reported from this specific HDS. We report a unique case of severe aplastic anemia developing after sub-fulminant liver failure associated with chronic HDS use. This case illustrates the importance of warning the public about HDS as their use …

Exposure To 4,4′-Dde In Visceral Adipose Tissue And Weight Loss In Adolescents From The Teen-Labs Cohort, Bruna Rubbo, Zhenjiang Li, Phum Tachachartvanich, Brittney O Baumert, Hongxu Wang, Shudi Pan, Sarah Rock, Justin R Ryder, Todd Jenkins, Stephanie Sisley, Xiangping Lin, Scott Bartell, Thomas H Inge, Stavra Xanthakos, Brooklynn Mcneil, Anna R Robuck, Michele A La Merrill, Douglas I Walker, David V Conti, Rob Mcconnell, Sandrah P Eckel, Lida Chatzi

Faculty, Staff and Students Publications

Objective: Dichlorodiphenyldichloroethylene (DDE), an obesogen accumulating in adipose tissue, is released into circulation with weight loss, although its impact is underexplored among adolescents. We tested the association using an integrative translational approach of epidemiological analysis among adolescents with obesity and in vitro measures exploring the impact of DDE on adipogenesis via preadipocytes.

Methods: We included 63 participants from the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) cohort. We assessed 4,4'-DDE in visceral adipose tissue at surgery and BMI and waist circumference at surgery and 0.5, 1, 3, and 5 years after. We conducted longitudinal analysis to estimate the interaction on weight …

Stabilizing Histamine Release In Gut Mast Cells Mitigates Peripheral And Central Inflammation After Stroke, Tyler J Lefevre, Wenyuan Wei, Elizaveta Mukhaleva, Sai Pranathi Meda Venkata, Naincy R Chandan, Saji Abraham, Yong Li, Carmen W Dessauer, Nagarajan Vaidehi, Alan V Smrcka

Faculty, Staff and Student Publications

Highly homologous members of the Gαi family, Gαi1-3, have distinct tissue distributions and physiological functions, yet their biochemical and functional properties are very similar. We recently identified PDZ-RhoGEF (PRG) as a novel Gαi1 effector that is poorly activated by Gαi2. In a proteomic proximity labeling screen we observed a strong preference for Gαi1 relative to Gαi2 with respect to engagement of a broad range of potential targets. We investigated the mechanistic basis for this selectivity using PRG as a representative target. Substitution of either the helical domain (HD) from Gαi1 into Gαi2 or substitution of a single amino acid, A230 …

Prospects For Leveraging The Microbiota As Medicine For Hypertension, David J Durgan, Jasenka Zubcevic, Matam Vijay-Kumar, Tao Yang, Ishan Manandhar, Sachin Aryal, Rikeish R Muralitharan, Hong-Bao Li, Ying Li, Justine M Abais-Battad, Jennifer L Pluznick, Dominik N Muller, Francine Z Marques, Bina Joe

Faculty, Staff and Students Publications

No abstract provided.