Digital Commons Network^™

Development Of An Antioxidant-Rich Sugar-Free Plantain Candy And Assessment Of Its Shelf Life In A Flexible Laminate, Poulami Sarkar, Paramita Bhattacharjee, Bidhan Das

Faculty, Staff and Student Publications

RESEARCH BACKGROUND: Candy is a popular confection worldwide, and it would be beneficial to society if it were converted into a source of antioxidant molecules to eliminate its adverse health effects. The amount of antioxidants available even in fruit candies is questionable due to the high thermal processing losses they undergo and the presence of various food additives. Plantains (

EXPERIMENTAL APPROACH: To accomplish the first objective, lyophilized plantain powder, sorbitol and mannitol were used as base materials with minimal additives under minimal processing conditions to reduce processing loss. Sensory, proximate, physicochemical and phytochemical properties, including the antioxidant synergy among …

Trends In Shortages Of Lead Chelators From 2001 To 2022, James D Whitledge, Pelayia Soto, Kieran M Glowacki, Diane P Calello, Erin R Fox, Maryann Mazer-Amirshahi

Faculty, Staff and Student Publications

OBJECTIVE: The study aims to describe drug shortages affecting lead chelators in the United States from 2001 through 2022.

METHODS: Drug shortage data were retrieved from the University of Utah Drug Information Service from January 1, 2001, through December 31, 2022. Shortages of first- and second-line lead chelators were analyzed. Drug class, formulation, administration route, shortage reason, shortage duration, generic status, single-source status, and presence of temporally overlapping shortages were examined. Total shortage months, percentages of study period on shortage, and median shortage durations were calculated.

RESULTS: Thirteen lead chelator shortages were reported during the study period. Median duration was …

Loss Of Ovol2 In Triple-Negative Breast Cancer Promotes Fatty Acid Oxidation Fueling Stemness Characteristics, Ruipeng Lu, Jingjing Hong, Tong Fu, Yu Zhu, Ruiqi Tong, Di Ai, Shuai Wang, Qingsong Huang, Ceshi Chen, Zhiming Zhang, Rui Zhang, Huiling Guo, Boan Li

Faculty, Staff and Student Publications

Triple-negative breast cancer (TNBC), the most aggressive subtype of breast cancer, has a poor prognosis and lacks effective treatment strategies. Here, the study discovered that TNBC shows a decreased expression of epithelial transcription factor ovo-like 2 (OVOL2). The loss of OVOL2 promotes fatty acid oxidation (FAO), providing additional energy and NADPH to sustain stemness characteristics, including sphere-forming capacity and tumor initiation. Mechanistically, OVOL2 not only suppressed STAT3 phosphorylation by directly inhibiting JAK transcription but also recruited histone deacetylase 1 (HDAC1) to STAT3, thereby reducing the transcriptional activation of downstream genes carnitine palmitoyltransferase1 (CPT1A and CPT1B). PyVT-Ovol2 knockout mice develop a …

Prediction Accuracy Of Soil Chemical Parameters By Field- And Laboratory-Obtained Vis-Nir Spectra After External Parameter Orthogonalization, Konrad Metzger, Frank Liebisch, Juan M Herrera, Thomas Guillaume, Luca Bragazza

Faculty, Staff and Student Publications

One challenge in predicting soil parameters using in situ visible and near infrared spectroscopy is the distortion of the spectra due to soil moisture. External parameter orthogonalization (EPO) is a mathematical method to remove unwanted variability from spectra. We created two different EPO correction matrices based on the difference between spectra collected in situ and, respectively, spectra collected from the same soil samples after drying and sieving and after drying, sieving and finely grinding. Spectra from 134 soil samples recorded with two different spectrometers were split into calibration and validation sets and the two EPO corrections were applied. Clay, organic …

Two Genome-Wide Interaction Loci Modify The Association Of Nonsteroidal Anti-Inflammatory Drugs With Colorectal Cancer, David A Drew, Andre E Kim, Yi Lin, Conghui Qu, John Morrison, Juan Pablo Lewinger, Eric Kawaguchi, Jun Wang, Yubo Fu, Natalia Zemlianskaia, Virginia Díez-Obrero, Stephanie A Bien, Niki Dimou, Demetrius Albanes, James W Baurley, Anna H Wu, Daniel D Buchanan, John D Potter, Ross L Prentice, Sophia Harlid, Volker Arndt, Elizabeth L Barry, Sonja I Berndt, Emmanouil Bouras, Hermann Brenner, Arif Budiarto, Andrea Burnett-Hartman, Peter T Campbell, Robert Carreras-Torres, Graham Casey, Jenny Chang-Claude, David V Conti, Matthew A M Devall, Jane C Figueiredo, Stephen B Gruber, Andrea Gsur, Marc J Gunter, Tabitha A Harrison, Akihisa Hidaka, Michael Hoffmeister, Jeroen R Huyghe, Mark A Jenkins, Kristina M Jordahl, Anshul Kundaje, Loic Le Marchand, Li Li, Brigid M Lynch, Neil Murphy, Rami Nassir, Polly A Newcomb, Christina C Newton, Mireia Obón-Santacana, Shuji Ogino, Jennifer Ose, Rish K Pai, Julie R Palmer, Nikos Papadimitriou, Bens Pardamean, Andrew J Pellatt, Anita R Peoples, Elizabeth A Platz, Gad Rennert, Edward Ruiz-Narvaez, Lori C Sakoda, Peter C Scacheri, Stephanie L Schmit, Robert E Schoen, Mariana C Stern, Yu-Ru Su, Duncan C Thomas, Yu Tian, Konstantinos K Tsilidis, Cornelia M Ulrich, Caroline Y Um, Fränzel J B Van Duijnhoven, Bethany Van Guelpen, Emily White, Li Hsu, Victor Moreno, Ulrike Peters, Andrew T Chan, W James Gauderman

Faculty, Staff and Student Publications

Regular, long-term aspirin use may act synergistically with genetic variants, particularly those in mechanistically relevant pathways, to confer a protective effect on colorectal cancer (CRC) risk. We leveraged pooled data from 52 clinical trial, cohort, and case-control studies that included 30,806 CRC cases and 41,861 controls of European ancestry to conduct a genome-wide interaction scan between regular aspirin/nonsteroidal anti-inflammatory drug (NSAID) use and imputed genetic variants. After adjusting for multiple comparisons, we identified statistically significant interactions between regular aspirin/NSAID use and variants in 6q24.1 (top hit

Validation Of A Blood-Based Protein Biomarker Panel For A Risk Assessment Of Lethal Lung Cancer In The Physicians' Health Study, Lulu Song, Ehsan Irajizad, Andrew Rundle, Howard D Sesso, John Michael Gaziano, Jody V Vykoukal, Kim-Anh Do, Jennifer B Dennison, Edwin J Ostrin, Johannes F Fahrmann, Frederica Perera, Samir Hanash

Faculty, Staff and Student Publications

This study aimed to assess a four-marker protein panel (4MP)'s performance, including the precursor form of surfactant protein B, cancer antigen 125, carcinoembryonic antigen, and cytokeratin-19, for predicting lung cancer in a cohort enriched with never- and ever-smokers. Blinded pre-diagnostic plasma samples collected within 2 years prior to a lung cancer diagnosis from 25 cases and 100 sex-, age-, and smoking-matched controls were obtained from the Physicians' Health Study (PHS). The 4MP yielded AUC performance estimates of 0.76 (95% CI: 0.61-0.92) and 0.69 (95% CI: 0.56-0.82) for predicting lung cancer within one year and within two years of diagnosis, respectively. …

Metabolic Alterations And Cellular Responses To Β-Hydroxybutyrate Treatment In Breast Cancer Cells, Hadas Fulman-Levy, Raichel Cohen-Harazi, Bar Levi, Lital Argaev-Frenkel, Ifat Abramovich, Eyal Gottlieb, Sarah Hofmann, Igor Koman, Elimelech Nesher

Faculty, Staff and Student Publications

BACKGROUND: The ketogenic diet (KD), based on high fat (over 70% of daily calories), low carbohydrate, and adequate protein intake, has become popular due to its potential therapeutic benefits for several diseases including cancer. Under KD and starvation conditions, the lack of carbohydrates promotes the production of ketone bodies (KB) from fats by the liver as an alternative source of metabolic energy. KD and starvation may affect the metabolism in cancer cells, as well as tumor characteristics. The aim of this study is to evaluate the effect of KD conditions on a wide variety of aspects of breast cancer cells …

Nature Of The Evidence Base And Approaches To Guide Nutrition Interventions For Individuals: A Position Paper From The Academy Of Nutrition Sciences, Mary Hickson, Constantina Papoutsakis, Angela M Madden, Mary Anne Smith, Kevin Whelan

Faculty, Staff and Student Publications

This Position Paper from the Academy of Nutrition Sciences is the third in a series which describe the nature of the scientific evidence and frameworks that underpin nutrition recommendations for health. This paper focuses on evidence which guides the application of dietary recommendations for individuals. In some situations, modified nutrient intake becomes essential to prevent deficiency, optimise development and health, or manage symptoms and disease progression. Disease and its treatment can also affect taste, appetite and ability to access and prepare foods, with associated financial impacts. Therefore, the practice of nutrition and dietetics must integrate and apply the sciences of …

A Technology-Assisted Web Application For Consumer Access To A Nonprescription Statin Medication, Steven E Nissen, Howard G Hutchinson, Kathy Wolski, Karol Watson, Seth S Martin, Erin D Michos, William S Weintraub, Melanie Morris, Leslie Cho, Luke Laffin, Douglas Jacoby, Christie M Ballantyne, Jan Ekelund, Filip Birve, Venu Menon, Michelle Strzelecki, Paul M Ridker

Faculty, Staff and Students Publications

Background: Although statins reduce adverse cardiovascular outcomes, less than one-half of eligible patients receive treatment. A nonprescription statin has the potential to improve access to statins.

Objectives: This study sought to assess concordance between clinician and consumer assessment of eligibility for nonprescription statin treatment using a technology assisted self-selection Web application (Web App) and evaluate effect on low-density lipoprotein cholesterol (LDL-C) levels.

Methods: This study was a prospective actual use 6-month study to evaluate use of a Web App to qualify participants without a medical background for a moderate-intensity statin based on current guidelines. Participants entered demographic information, cholesterol values, …

Thbs1 Regulates Skeletal Muscle Mass In A Tgfβ-Smad2/3-Atf4-Dependent Manner, Davy Vanhoutte, Tobias G Schips, Rachel A Minerath, Jiuzhou Huo, Naga Swathi Sree Kavuri, Vikram Prasad, Suh-Chin Lin, Michael J Bround, Michelle A Sargent, Christopher M Adams, Jeffery D Molkentin

Faculty, Staff and Students Publications

Loss of muscle mass is a feature of chronic illness and aging. Here, we report that skeletal muscle-specific thrombospondin-1 transgenic mice (Thbs1 Tg) have profound muscle atrophy with age-dependent decreases in exercise capacity and premature lethality. Mechanistically, Thbs1 activates transforming growth factor β (TGFβ)-Smad2/3 signaling, which also induces activating transcription factor 4 (ATF4) expression that together modulates the autophagy-lysosomal pathway (ALP) and ubiquitin-proteasome system (UPS) to facilitate muscle atrophy. Indeed, myofiber-specific inhibition of TGFβ-receptor signaling represses the induction of ATF4, normalizes ALP and UPS, and partially restores muscle mass in Thbs1 Tg mice. Similarly, myofiber-specific deletion of Smad2 and Smad3 …

Therapeutic Strategies Against Metabolic Imbalance In A Male Mouse Model With 5-Ht2cr Loss-Of-Function, Hailan Liu, Zhaoxun Liu, Hueyxian Kelly Wong, Nathan Xu, Qingzhuo Liu, Yongxiang Li, Yao Liu, Hueyzhong Wong, Megan E Burt, Sanika V Jossy, Junying Han, Yang He

Faculty, Staff and Students Publications

The serotonin 2C receptor (5-HT2CR)-melanocortin pathway plays well-established roles in the regulation of feeding behavior and body weight homeostasis. Dysfunctions in this system, such as loss-of-function mutations in the Htr2c gene, can lead to hyperphagia and obesity. In this study, we aimed to investigate the potential therapeutic strategies for ameliorating hyperphagia, hyperglycemia, and obesity associated with a loss-of-function mutation in the Htr2c gene (Htr2cF327L/Y). We demonstrated that reexpressing functional 5-HT2CR solely in hypothalamic pro-opiomelanocortin (POMC) neurons is sufficient to reduce food intake and body weight in Htr2cF327L/Y mice subjected to a high-fat diet (HFD). In addition, 5-HT2CR expression restores the …

The Inform (International Framework For Rehabilitation Medics) Project To Strengthen The Medical Specialty, Man Hung, Himani Patel, Samantha Lee, Justin Nguyen, Amir Mohajeri

Faculty, Staff and Student Publications

(1) Background: This study examines vitamin D’s impact on dental caries to inform prevention strategies, given its critical role in bone and calcium regulation, vital for dental health. (2) Methods: Data from 18,683 participants of the National Health and Nutrition Examination Survey (NHANES) 2011–2016 were analyzed. NHANES collects U.S. population data through interviews, physical exams, and tests, including vitamin D levels and dental health assessed using both the decayed, missing, and filled teeth (DMFT) index and the presence of untreated dental caries. Vitamin D levels were measured according to serum 25(OH)D concentrations, and the analyses adjusted for confounders such as …

Selective Refueling Of Car T Cells Using Ada1 And Cd26 Boosts Antitumor Immunity, Yue Hu, Abhijit Sarkar, Kevin Song, Sara Michael, Magnus Hook, Ruoning Wang, Andras Heczey, Xiaotong Song

Faculty, Staff and Student Publications

Chimeric antigen receptor (CAR) T cell therapy is hindered in solid tumor treatment due to the immunosuppressive tumor microenvironment and suboptimal T cell persistence. Current strategies do not address nutrient competition in the microenvironment. Hence, we present a metabolic refueling approach using inosine as an alternative fuel. CAR T cells were engineered to express membrane-bound CD26 and cytoplasmic adenosine deaminase 1 (ADA1), converting adenosine to inosine. Autocrine secretion of ADA1 upon CD3/CD26 stimulation activates CAR T cells, improving migration and resistance to transforming growth factor β1 suppression. Fusion of ADA1 with anti-CD3 scFv further boosts inosine production and minimizes tumor …

Systemic Inflammatory Markers Of Persistent Cerebral Edema After Aneurysmal Subarachnoid Hemorrhage, Nadia Khan, Magdalena Kurnik-Łucka, Gniewomir Latacz, Krzysztof Gil

Faculty, Staff and Student Publications

In the first part of this article, the role of intestinal epithelial tight junctions (TJs), together with gastrointestinal dopaminergic and renin-angiotensin systems, are narratively reviewed to provide sufficient background. In the second part, the current experimental data on the interplay between gastrointestinal (GI) dopaminergic and renin-angiotensin systems in the regulation of intestinal epithelial permeability are reviewed in a systematic manner using the PRISMA methodology. Experimental data confirmed the copresence of DOPA decarboxylase (DDC) and angiotensin converting enzyme 2 (ACE2) in human and rodent enterocytes. The intestinal barrier structure and integrity can be altered by angiotensin (1-7) and dopamine (DA). Both …

Feasibility Of Fit24, A Digital Diabetes Prevention Program For Hispanic Adolescents: Qualitative Evaluation Study, Erica G Soltero, Salma M Musaad, Teresia M O'Connor, Debbe Thompson, Keith Norris, Bettina M Beech

Faculty, Staff and Students Publications

BACKGROUND: Digital health interventions are promising for reaching and engaging high-risk youth in disease prevention opportunities; however, few digital prevention interventions have been developed for Hispanic youth, limiting our knowledge of these strategies among this population.

OBJECTIVE: This study qualitatively assessed the feasibility and acceptability of Fit24, a 12-week goal-setting intervention that uses a Fitbit watch (Fitbit Inc) and theoretically grounded SMS text messages to promote physical activity and sleep among Hispanic adolescents (aged between 14 and 16 years) with obesity.

METHODS: After completing the intervention, a subsample of youth (N=15) participated in an in-depth interview. We categorized the themes …

The Long-Term Effects Of Blood Urea Nitrogen Levels On Cardiovascular Disease And All-Cause Mortality In Diabetes: A Prospective Cohort Study, Hongfang Liu, Xiaoqin Xin, Jinghui Gan, Jungao Huang

Faculty, Staff and Student Publications

BACKGROUND: The long-term effects of blood urea nitrogen(BUN) in patients with diabetes remain unknown. Current studies reporting the target BUN level in patients with diabetes are also limited. Hence, this prospective study aimed to explore the relationship of BUN with all-cause and cardiovascular mortalities in patients with diabetes.

METHODS: In total, 10,507 participants with diabetes from the National Health and Nutrition Examination Survey (1999-2018) were enrolled. The causes and numbers of deaths were determined based on the National Death Index mortality data from the date of NHANES interview until follow-up (December 31, 2019). Multivariate Cox proportional hazard regression models were …

Misstatements, Misperceptions, And Mistakes In Controlling For Covariates In Observational Research, Xiaoxin Yu, Roger S Zoh, David A Fluharty, Luis M Mestre, Danny Valdez, Carmen D Tekwe, Colby J Vorland, Yasaman Jamshidi-Naeini, Sy Han Chiou, Stella T Lartey, David B Allison

Children’s Nutrition Research Center Staff Publications

We discuss 12 misperceptions, misstatements, or mistakes concerning the use of covariates in observational or nonrandomized research. Additionally, we offer advice to help investigators, editors, reviewers, and readers make more informed decisions about conducting and interpreting research where the influence of covariates may be at issue. We primarily address misperceptions in the context of statistical management of the covariates through various forms of modeling, although we also emphasize design and model or variable selection. Other approaches to addressing the effects of covariates, including matching, have logical extensions from what we discuss here but are not dwelled upon heavily. The misperceptions, …

Disparate Outcomes In Hispanic Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease/Steatohepatitis And Type 2 Diabetes: Large Cohort Study, Joseph Matthew Gosnell, George Golovko, Esteban Arroyave, Akshata Moghe, Michael L Kueht, Omar Abdul Saldarriaga, Kevin H Mckinney, Heather L Stevenson, Monique R Ferguson

Faculty, Staff and Student Publications

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are a growing health burden across a significant portion of the global patient population. However, these conditions seem to have disparate rates and outcomes between different ethnic populations. The combination of MASLD/MASH and type 2 diabetes increases the risk of hepatocellular carcinoma (HCC), and Hispanic patients experience the greatest burden, particularly those in South Texas.

Aim: To compare outcomes between Hispanic and non-Hispanic patients in the United States, while further focusing on the Hispanic population within Southeast Texas to determine whether the documented disparity in outcomes is a …

Optical Coherence Tomography-Guided Brillouin Microscopy Highlights Regional Tissue Stiffness Differences During Anterior Neural Tube Closure In The Mthfd1l Murine Mutant, Yogeshwari S Ambekar, Carlo Donato Caiaffa, Bogdan J Wlodarczyk, Manmohan Singh, Alexander W Schill, John W Steele, Jitao Zhang, Salavat R Aglyamov, Giuliano Scarcelli, Richard H Finnell, Kirill V Larin

Faculty, Staff and Students Publications

Neurulation is a highly synchronized biomechanical process leading to the formation of the brain and spinal cord, and its failure leads to neural tube defects (NTDs). Although we are rapidly learning the genetic mechanisms underlying NTDs, the biomechanical aspects are largely unknown. To understand the correlation between NTDs and tissue stiffness during neural tube closure (NTC), we imaged an NTD murine model using optical coherence tomography (OCT), Brillouin microscopy and confocal fluorescence microscopy. Here, we associate structural information from OCT with local stiffness from the Brillouin signal of embryos undergoing neurulation. The stiffness of neuroepithelial tissues in Mthfd1l null embryos …

Optical Coherence Tomography-Guided Brillouin Microscopy Highlights Regional Tissue Stiffness Differences During Anterior Neural Tube Closure In The Mthfd1l Murine Mutant, Yogeshwari S Ambekar, Carlo Donato Caiaffa, Bogdan J Wlodarczyk, Manmohan Singh, Alexander W Schill, John W Steele, Jitao Zhang, Salavat R Aglyamov, Giuliano Scarcelli, Richard H Finnell, Kirill V Larin

Faculty, Staff and Students Publications

Neurulation is a highly synchronized biomechanical process leading to the formation of the brain and spinal cord, and its failure leads to neural tube defects (NTDs). Although we are rapidly learning the genetic mechanisms underlying NTDs, the biomechanical aspects are largely unknown. To understand the correlation between NTDs and tissue stiffness during neural tube closure (NTC), we imaged an NTD murine model using optical coherence tomography (OCT), Brillouin microscopy and confocal fluorescence microscopy. Here, we associate structural information from OCT with local stiffness from the Brillouin signal of embryos undergoing neurulation. The stiffness of neuroepithelial tissues in Mthfd1l null embryos …

Multiple Job Holding, Job Changes, And Associations With Gestational Diabetes And Pregnancy-Related Hypertension In The National Birth Defects Prevention Study, Amel Omari, Miriam R Siegel, Carissa M Rocheleau, Kaori Fujishiro, Kristen Van Buren, Dallas Shi, A J Agopian, Suzanne M Gilboa, Paul A Romitti

Faculty, Staff and Student Publications

We used National Birth Defects Prevention Study data to investigate associations between working patterns shortly before and during pregnancy and gestational diabetes and pregnancy-related hypertension. We analyzed working patterns (multiple-job holders, job changers, single-job holders) during the three months before and during pregnancy for 8140 participants who delivered a live-born child without a birth defect. "Multiple-job holders" worked more than one job simultaneously, "job changers" worked more than one job with no overlap, and "single-job holders" (referent) worked one job. We used multivariable logistic regression to estimate associations between working pattern and each outcome, adjusting for maternal age and educational …

Third-Party Fecal Microbiota Transplantation For High-Risk Treatment-Naïve Acute Gvhd Of The Lower Gi Tract, Zachariah Defilipp, Ashish V Damania, Haesook T Kim, Chia-Chi Chang, Areej El-Jawahri, Steven L Mcafee, Aj S Bottoms, Vesselina Toncheva, Melissa M Smith, Maria Dolaher, Lindsey Perry, Meghan White, Brittany Diana, Sheila Connolly, Bimalangshu R Dey, Matthew J Frigault, Richard A Newcomb, Paul V O'Donnell, Thomas R Spitzer, Michael K Mansour, Daniela Weber, Nadim J Ajami, Elizabeth Hohmann, Robert R Jenq, Yi-Bin Chen

Faculty, Staff and Student Publications

Disruption of the intestinal microbiome is observed with acute graft-versus-host disease (GVHD) of the lower gastrointestinal (LGI) tract, and fecal microbiota transplantation (FMT) has successfully cured steroid-refractory cases. In this open-label, single-arm, pilot study, third-party, single-donor FMT was administered in combination with systemic corticosteroids to participants with high-risk acute LGI GVHD, with a focus on treatment-naïve cases. Participants were scheduled to receive 1 induction dose (15 capsules per day for 2 consecutive days), followed by 3 weekly maintenance doses, consisting of 15 capsules per dose. The primary end point of the study was feasibility, which would be achieved if ≥80% …

Buprenorphine Use For Analgesia In Palliative Care, Leanne K Jackson, Ivy O Poon, Mary A Garcia, Syed Imam, Ursula K Braun

Center for Medical Ethics and Health Policy Staff Publications

Buprenorphine is a semi-synthetic long-acting partial µ-opioid receptor (MOR) agonist that can be used for chronic pain as a sublingual tablet, transdermal patch (Butrans®), or a buccal film (Belbuca®). Buprenorphine’s unique high receptor binding affinity and slow dissociation at the MOR allow for effective analgesia while offering less adverse effects compared to a full agonist opioid, in particular, less concern for respiratory depression and constipation. It is underused in chronic pain and palliative care due to misconceptions and stigma from its use in opioid use disorder (OUD). This case report discusses the unique pharmacology of buprenorphine, including its advantages, disadvantages, …

Recent Advances In The Prevention And Treatment Of Decompensated Cirrhosis And Acute-On-Chronic Liver Failure (Aclf) And The Role Of Biomarkers, Jonel Trebicka, Ruben Hernaez, Debbie Lindsay Shawcross, Alexander L Gerbes

Faculty, Staff and Students Publications

The progression of cirrhosis with clinically significant portal hypertension towards decompensated cirrhosis remains clinically challenging and the evolution towards acute-on-chronic liver failure (ACLF), with one or more extrahepatic organ failures, is associated with very high mortality. In the last decade, significant progress has been made in the understanding of the mechanisms leading to decompensation and ACLF. As portal hypertension advances, bacterial translocation across an impaired gut barrier culminates in endotoxaemia, systemic inflammation and cirrhosis-associated immune dysfunction (CAID). Gut-derived systemic inflammation and CAID have become the logical targets for innovative therapies that prevent hepatic decompensation episodes and the progression to ACLF.Furthermore, …

Mitochondria Regulate Proliferation In Adult Cardiac Myocytes, Gregory B Waypa, Kimberly A Smith, Paul T Mungai, Vincent J Dudley, Kathryn A Helmin, Benjamin D Singer, Clara Bien Peek, Joseph Bass, Lauren Nelson, Sanjiv J Shah, Gaston Ofman, J Andrew Wasserstrom, William A Muller, Alexander V Misharin, G R Scott Budinger, Hiam Abdala-Valencia, Navdeep S Chandel, Danijela Dokic, Elizabeth Bartom, Shuang Zhang, Yuki Tatekoshi, Amir Mahmoodzadeh, Hossein Ardehali, Edward B Thorp, Paul T Schumacker

Faculty, Staff and Student Publications

Newborn mammalian cardiomyocytes quickly transition from a fetal to an adult phenotype that utilizes mitochondrial oxidative phosphorylation but loses mitotic capacity. We tested whether forced reversal of adult cardiomyocytes back to a fetal glycolytic phenotype would restore proliferative capacity. We deleted Uqcrfs1 (mitochondrial Rieske iron-sulfur protein, RISP) in hearts of adult mice. As RISP protein decreased, heart mitochondrial function declined, and glucose utilization increased. Simultaneously, the hearts underwent hyperplastic remodeling during which cardiomyocyte number doubled without cellular hypertrophy. Cellular energy supply was preserved, AMPK activation was absent, and mTOR activation was evident. In ischemic hearts with RISP deletion, new cardiomyocytes …

Effect Of Methyl Jasmonate And Ga3 On Canola (Brassica Napus L) Growth, Antioxidants Activity, And Nutrient Concentration Cultivated In Salt-Affected Soils, Subhan Danish, Sundas Sana, Muhammad Baqir Hussain, Khadim Dawar, Hesham S Almoallim, Mohammad Javed Ansari, Misbah Hareem, Rahul Datta

Faculty, Staff and Student Publications

Salinity stress is a significant challenge in agricultural production. When soil contains high salts, it can adversely affect plant growth and productivity due to the high concentration of soluble salts in the soil water. To overcome this issue, foliar applications of methyl jasmonate (MJ) and gibberellic acid (GA3) can be productive amendments. Both can potentially improve the plant's growth attributes and flowering, which are imperative in improving growth and yield. However, limited literature is available on their combined use in canola to mitigate salinity stress. That's why the current study investigates the impact of different levels of MJ (at concentrations …

Exome Sequencing Implicates Ancestry-Related Mendelian Variation At Syne1 In Childhood-Onset Essential Hypertension, Ian Copeland, Edmond Wonkam-Tingang, Monesha Gupta-Malhotra, S Shahrukh Hashmi, Yixing Han, Aarti Jajoo, Nancy J Hall, Paula P Hernandez, Natasha Lie, Dan Liu, Jun Xu, Jill Rosenfeld, Aparna Haldipur, Zelene Desire, Zeynep H Coban-Akdemir, Daryl A Scott, Qing Li, Hsiao-Tuan Chao, Ana M Zaske, James R Lupski, Dianna M Milewicz, Sanjay Shete, Jennifer E Posey, Neil A Hanchard

Faculty, Staff and Student Publications

Childhood-onset essential hypertension (COEH) is an uncommon form of hypertension that manifests in childhood or adolescence and, in the United States, disproportionately affects children of African ancestry. The etiology of COEH is unknown, but its childhood onset, low prevalence, high heritability, and skewed ancestral demography suggest the potential to identify rare genetic variation segregating in a Mendelian manner among affected individuals and thereby implicate genes important to disease pathogenesis. However, no COEH genes have been reported to date. Here, we identify recessive segregation of rare and putatively damaging missense variation in the spectrin domain of spectrin repeat containing nuclear envelope …

Towards A Remote Patient Monitoring Platform For Comprehensive Risk Evaluations For People With Diabetic Foot Ulcers, Gozde Cay, M G Finco, Jason Garcia, Jill L Mcnitt-Gray, David G Armstrong, Bijan Najafi

Center on Aging Staff Publications

Diabetic foot ulcers (DFUs) significantly affect the lives of patients and increase the risk of hospital stays and amputation. We suggest a remote monitoring platform for better DFU care. This system uses digital health metrics (scaled from 0 to 10, where higher scores indicate a greater risk of slow healing) to provide a comprehensive overview through a visual interface. The platform features smart offloading devices that capture behavioral metrics such as offloading adherence, daily steps, and cadence. Coupled with remotely measurable frailty and phenotypic metrics, it offers an in-depth patient profile. Additional demographic data, characteristics of the wound, and clinical …

Determinants Of Mosaic Chromosomal Alteration Fitness, Yash Pershad, Taralynn Mack, Hannah Poisner, Yasminka A Jakubek, Adrienne M Stilp, Braxton D Mitchell, Joshua P Lewis, Eric Boerwinkle, Ruth J F Loos, Nathalie Chami, Zhe Wang, Kathleen Barnes, Nathan Pankratz, Myriam Fornage, Susan Redline, Bruce M Psaty, Joshua C Bis, Ali Shojaie, Edwin K Silverman, Michael H Cho, Jeong H Yun, Dawn Demeo, Daniel Levy, Andrew D Johnson, Rasika A Mathias, Margaret A Taub, Donna Arnett, Kari E North, Laura M Raffield, April P Carson, Margaret F Doyle, Stephen S Rich, Jerome I Rotter, Xiuqing Guo, Nancy J Cox, Dan M Roden, Nora Franceschini, Pinkal Desai, Alex P Reiner, Paul L Auer, Paul A Scheet, Siddhartha Jaiswal, Joshua S Weinstock, Alexander G Bick

Faculty, Staff and Student Publications

Clonal hematopoiesis (CH) is characterized by the acquisition of a somatic mutation in a hematopoietic stem cell that results in a clonal expansion. These driver mutations can be single nucleotide variants in cancer driver genes or larger structural rearrangements called mosaic chromosomal alterations (mCAs). The factors that influence the variations in mCA fitness and ultimately result in different clonal expansion rates are not well understood. We used the Passenger-Approximated Clonal Expansion Rate (PACER) method to estimate clonal expansion rate as PACER scores for 6,381 individuals in the NHLBI toPMed cohort with gain, loss, and copy-neutral loss of heterozygosity mCAs. Our …

Effects Of Improved Amino Acid Balance Diet On Lysine Mammary Utilization, Whole Body Protein Turnover And Muscle Protein Breakdown On Lactating Sows, Sai Zhang, Juan C Marini, Vengai Mavangira, Andrew Claude, Julie Moore, Mahmoud A Mohammad, Nathalie L Trottier

Children’s Nutrition Research Center Staff Publications

Background: The study objective was to test the hypothesis that low crude protein (CP) diet with crystalline amino acids (CAA) supplementation improves Lys utilization efficiency for milk production and reduces protein turnover and muscle protein breakdown. Eighteen lactating multiparous Yorkshire sows were allotted to 1 of 2 isocaloric diets (10.80 MJ/kg net energy): control (CON; 19.24% CP) and reduced CP with "optimal" AA profile (OPT; 14.00% CP). Sow body weight and backfat were recorded on d 1 and 21 of lactation and piglets were weighed on d 1, 14, 18, and 21 of lactation. Between d 14 and 18, a …