Digital Commons Network^™

The Dose-Response Effect Of Aerobic Exercise On Inflammation In Colon Cancer Survivors, Justin C. Brown, Stephanie L.E. Compton, Jeffrey A. Meyerhardt, Guillaume Spielmann, Shengping Yang

School of Medicine Faculty Publications

Background; Physical activity after surgical resection for colon cancer is associated with significantly longer disease-free survival. Inflammation is hypothesized to mediate the association between physical activity and disease-free survival in colon cancer. Methods; In this exploratory analysis of a randomized dose-response trial, 39 colon cancer survivors who completed standard therapy were stratified by cancer stage and randomized in a 1;1;1 ratio to one of three treatment groups for 24 weeks of usual-care control, 150 min/wk of moderate-intensity aerobic exercise (low-dose), or 300 min/wk of moderate-intensity aerobic exercise (high-dose). Inflammation outcomes included high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL6), and soluble tumor …

Oncogenic Kras Drives Lipofibrogenesis To Promote Angiogenesis And Colon Cancer Progression, Wen-Hao Hsu, Kyle A Labella, Yiyun Lin, Ping Xu, Rumi Lee, Cheng-En Hsieh, Lei Yang, Ashley Zhou, Jonathan M Blecher, Chang-Jiun Wu, Kangyu Lin, Xiaoying Shang, Shan Jiang, Denise J Spring, Yan Xia, Peiwen Chen, John Paul Shen, Scott Kopetz, Ronald A Depinho

Faculty, Staff and Student Publications

Oncogenic KRAS (KRAS*) contributes to many cancer hallmarks. In colorectal cancer, KRAS* suppresses antitumor immunity to promote tumor invasion and metastasis. Here, we uncovered that KRAS* transforms the phenotype of carcinoma-associated fibroblasts (CAF) into lipid-laden CAFs, promoting angiogenesis and tumor progression. Mechanistically, KRAS* activates the transcription factor CP2 (TFCP2) that upregulates the expression of the proadipogenic factors BMP4 and WNT5B, triggering the transformation of CAFs into lipid-rich CAFs. These lipid-rich CAFs, in turn, produce VEGFA to spur angiogenesis. In KRAS*-driven colorectal cancer mouse models, genetic or pharmacologic neutralization of TFCP2 reduced lipid-rich CAFs, lessened tumor angiogenesis, and improved overall survival. …

Formate Supplementation Enhances Antitumor Cd8+ T-Cell Fitness And Efficacy Of Pd-1 Blockade, Jared H Rowe, Ilaria Elia, Osmaan Shahid, Emily F Gaudiano, Natalia E Sifnugel, Sheila Johnson, Amy G Reynolds, Megan E Fung, Shakchhi Joshi, Martin W Lafleur, Joon Seok Park, Kristen E Pauken, Joshua D Rabinowitz, Gordon J Freeman, Marcia C Haigis, Arlene H Sharpe

Faculty, Staff and Student Publications

UNLABELLED: The tumor microenvironment (TME) restricts antitumor CD8+ T-cell function and immunotherapy responses. Cancer cells compromise the metabolic fitness of CD8+ T cells within the TME, but the mechanisms are largely unknown. Here we demonstrate that one-carbon (1C) metabolism is enhanced in T cells in an antigen-specific manner. Therapeutic supplementation of 1C metabolism using formate enhances CD8+ T-cell fitness and antitumor efficacy of PD-1 blockade in B16-OVA tumors. Formate supplementation drives transcriptional alterations in CD8+ T-cell metabolism and increases gene signatures for cellular proliferation and activation. Combined formate and anti-PD-1 therapy increases tumor-infiltrating CD8+ T cells, which are essential for …

Circulating Senescent Myeloid Cells Infiltrate The Brain And Cause Neurodegeneration In Histiocytic Disorders, C Matthias Wilk, Flurin Cathomas, Orsolya Török, Jessica Le Berichel, Matthew D Park, Camille Bigenwald, George R Heaton, Pauline Hamon, Leanna Troncoso, Brooks P Scull, Diana Dangoor, Aymeric Silvin, Ryan Fleischmann, Meriem Belabed, Howard Lin, Elias Merad Taouli, Steffen Boettcher, Long Li, Antonio Aubry, Markus G Manz, Julia K Kofler, Zhenyu Yue, Sergio A Lira, Florent Ginhoux, John F Crary, Kenneth L Mcclain, Jennifer L Picarsic, Scott J Russo, Carl E Allen, Miriam Merad

Faculty, Staff and Students Publications

Neurodegenerative diseases (ND) are characterized by progressive loss of neuronal function. Mechanisms of ND pathogenesis are incompletely understood, hampering the development of effective therapies. Langerhans cell histiocytosis (LCH) is an inflammatory neoplastic disorder caused by hematopoietic progenitors expressing mitogen-activated protein kinase (MAPK)-activating mutations that differentiate into senescent myeloid cells that drive lesion formation. Some individuals with LCH subsequently develop progressive and incurable neurodegeneration (LCH-ND). Here, we showed that LCH-ND was caused by myeloid cells that were clonal with peripheral LCH cells. Circulating BRAFV600E

Nitric Oxide Is Required For Lung Alveolarization Revealed By Deficiency Of Argininosuccinate Lyase, Zixue Jin, Ming-Ming Jiang, Brendan Lee

Faculty, Staff and Students Publications

Inhaled nitric oxide (NO) therapy has been reported to improve lung growth in premature newborns. However, the underlying mechanisms by which NO regulates lung development remain largely unclear. NO is enzymatically produced by three isoforms of nitric oxide synthase (NOS) enzymes. NOS knockout mice are useful tools to investigate NO function in the lung. Each single NOS knockout mouse does not show obvious lung alveolar phenotype, likely due to compensatory mechanisms. While mice lacking all three NOS isoforms display impaired lung alveolarization, implicating NO plays a pivotal role in lung alveolarization. Argininosuccinate lyase (ASL) is the only mammalian enzyme capable …

Allelic Strengths Of Encephalopathy-Associated Uba5 Variants Correlate Between In Vivo And In Vitro Assays, Xueyang Pan, Albert N Alvarez, Mengqi Ma, Shenzhao Lu, Michael W Crawford, Lauren C Briere, Oguz Kanca, Shinya Yamamoto, David A Sweetser, Jenny L Wilson, Ruth J Napier, Jonathan N Pruneda, Hugo J Bellen

Faculty, Staff and Students Publications

Protein UFMylation downstream of the E1 enzyme UBA5 plays essential roles in development and endoplasmic reticulum stress. Variants in the UBA5 gene are associated with developmental and epileptic encephalopathy 44 (DEE44), an autosomal recessive disorder characterized by early-onset encephalopathy, movement abnormalities, global developmental delay, intellectual disability, and seizures. DEE44 is caused by at least 12 different missense variants described as loss of function (LoF), but the relationships between genotypes and molecular or clinical phenotypes remain to be established. We developed a humanized UBA5 fly model and biochemical activity assays in order to describe in vivo and in vitro genotype–phenotype relationships …

Metformin: A Potential Treatment For Acne, Hidradenitis Suppurativa And Rosacea, Minah Cho, Yu Ri Woo, Sang Hyun Cho, Jeong Deuk Lee, Hei Sung Kim

Faculty, Staff and Student Publications

Metformin is a widely used drug for treatment of diabetes mellitus, due to its safety and efficacy. In addition to its role as an antidiabetic drug, numerous beneficial effects of metformin have enabled its use in various diseases. Considering the anti-androgenic, anti-angiogenic, anti-fibrotic and antioxidant properties of metformin, it may have the potential to improve chronic inflammatory skin diseases. However, further evidence is needed to confirm the efficacy of metformin in dermatological conditions, This review focuses on exploring the therapeutic targets of metformin in acne vulgaris, hidradenitis suppurativa and rosacea, by studying their pathogeneses.

Microstructural Alterations Of Major Thalamic Nuclei In The Chronic Pediatric Spinal Cord Injured Population, K. Kang, K. Fleming, A. Sathe, J. Muller, J. Harrop, D. Middleton, J. Heller, A. Sharan, F. Mohamed, L. Krisa, M. Alizadeh

Department of Radiology Faculty Papers

BACKGROUND: The brain undergoes reorganization following spinal cord injury (SCI), but little is known about how the thalamus is affected in pediatric SCIs.

PURPOSE: To characterize microstructural alterations in the thalamus after SCI with diffusion tensor imaging (DTI) metrics.

METHODS: 18 pediatric participants with chronic SCI (8-20 years) were stratified using the American Spinal Injury Association Impairment Scale (AIS) into groups: A, B, and C/D. DTI of the brain used a 3 T Siemens Verio MRI using the parameters: 20 directions, number of averages = 3, b = 1000 s/mm

DATA ANALYSIS: DTI metrics were acquired by superimposing the AAL3 …

Detection Of Prions In The Urine Of Patients Affected By Sporadic Creutzfeldt-Jakob Disease, M Talke

Faculty, Staff and Student Publications

Objective

Currently, it is unknown whether infectious prions are present in peripheral tissues and biological fluids of patients affected by sporadic Creutzfeldt–Jakob disease (sCJD), the most common prion disorder in humans. This represents a potential risk for inter‐individual prion infection. The main goal of this study was to evaluate the presence of prions in urine of patients suffering from the major subtypes of sCJD.

Methods

Urine samples from sCJD patients spanning the six major subtypes were tested. As controls, we used urine samples from people affected by other neurological or neurodegenerative diseases as well as healthy controls. These samples were …

Diet And Nutrition In Inflammatory Bowel Disease: A Review Of The Literature, Scott Manski, Nicholas Noverati, Tatiana Policarpo, Emily Rubin, Raina Shivashankar

Division of Gastroenterology and Hepatology Faculty Papers

Diet is thought to contribute to the development of inflammatory bowel disease (IBD) and may act as a mediator of inflammation in patients with IBD. Patients commonly associate their diet with symptoms and inquire about dietary modifications to manage their IBD. Without clinical guidelines and well-established nutritional data, healthcare providers managing patients with IBD may find it difficult to provide recommendations. Strong evidence for enteral nutrition, particularly in the pediatric population, has been established in Crohn's disease (CD) as a therapeutic option. Enteral nutrition may also serve as an adjunct to an exclusion diet. Recent studies such as the randomized …

Sirtuin 6 Activation Rescues The Age-Related Decline In Dna Damage Repair In Primary Human Chondrocytes, Michaela E. Copp, Jacqueline Shine, Hannon L. Brown, Kirti R. Nimmala, Oliver B. Hansen, Susan Chubinskaya, John A. Collins, Richard F. Loeser, Brian O. Diekman

Department of Orthopaedic Surgery Faculty Papers

While advanced age is widely recognized as the greatest risk factor for osteoarthritis (OA), the biological mechanisms behind this connection remain unclear. Previous work has demonstrated that chondrocytes from older cadaveric donors have elevated levels of DNA damage as compared to chondrocytes from younger donors. The purpose of this study was to determine whether a decline in DNA repair efficiency is one explanation for the accumulation of DNA damage with age, and to quantify the improvement in repair with activation of Sirtuin 6 (SIRT6). After acute damage with irradiation, DNA repair was shown to be more efficient in chondrocytes from …

The Dna Glycosylase Neil2 Is Protective During Sars-Cov-2 Infection, Nisha Tapryal, Anirban Chakraborty, Kaushik Saha, Azharul Islam, Lang Pan, Koa Hosoki, Ibrahim M Sayed, Jason M Duran, Joshua Alcantara, Vanessa Castillo, Courtney Tindle, Altaf H Sarker, Maki Wakamiya, Victor J Cardenas, Gulshan Sharma, Laura E Crotty Alexander, Sanjiv Sur, Debashis Sahoo, Gourisankar Ghosh, Soumita Das, Pradipta Ghosh, Istvan Boldogh, Tapas K Hazra

Faculty, Staff and Students Publications

SARS-CoV-2 infection-induced aggravation of host innate immune response not only causes tissue damage and multiorgan failure in COVID-19 patients but also induces host genome damage and activates DNA damage response pathways. To test whether the compromised DNA repair capacity of individuals modulates the severity of COVID-19 infection, we analyze DNA repair gene expression in publicly available patient datasets and observe a lower level of the DNA glycosylase NEIL2 in the lungs of severely infected COVID-19 patients. This observation of lower NEIL2 levels is further validated in infected patients, hamsters and ACE2 receptor-expressing human A549 (A549-ACE2) cells. Furthermore, delivery of recombinant …

The Defined Tlr3 Agonist, Nexavant, Exhibits Anti-Cancer Efficacy And Potentiates Anti-Pd-1 Antibody Therapy By Enhancing Immune Cell Infiltration, Seung-Hwan Lee, Young-Ho Choi, Soon Myung Kang, Min-Gyu Lee, Arnaud Debin, Eric Perouzel, Seung-Beom Hong, Dong-Ho Kim

Faculty, Staff and Student Publications

Nexavant was reported as an alternative to the TLR3 agonist of Poly(I:C) and its derivatives. The physicochemical properties, signaling pathways, anti-cancer effects, and mechanisms of Nexavant were investigated. The distinctive characteristics of Nexavant compared to that of Poly(I:C) were demonstrated by precise quantification, enhanced thermostability, and increased resistance to RNase A. Unlike Poly(I:C), which activates TLR3, RIG-I, and MDA5, Nexavant stimulates signaling through TLR3 and RIG-I but not through MDA5. Compared to Poly(I:C), an intratumoral Nexavant treatment led to a unique immune response, immune cell infiltration, and suppression of tumor growth in various animal cancer models. Nexavant therapy outperformed anti-PD-1 …

Ewsr1::Atf1 Orchestrates The Clear Cell Sarcoma Transcriptome In Human Tumors And A Mouse Genetic Model, Benjamin B Ozenberger, Li Li, Emily R Wilson, Alexander J Lazar, Jared J Barrott, Kevin B Jones

Faculty, Staff and Student Publications

Clear cell sarcoma (CCS) is a rare, aggressive malignancy that most frequently arises in the soft tissues of the extremities. It is defined and driven by expression of one member of a family of related translocation-generated fusion oncogenes, the most common of which is EWSR1::ATF1. The EWSR1::ATF1 fusion oncoprotein reprograms transcription. However, the binding distribution of EWSR1::ATF1 across the genome and its target genes remain unclear. Here, we interrogated the genomic distribution of V5-tagged EWSR1::ATF1 in tumors it had induced upon expression in mice that also recapitulated the transcriptome of human CCS. ChIP-sequencing of V5-EWSR1::ATF1 identified previously unreported motifs …

Therapeutic Effect Of Echinococcus Granulosus Cyst Fluid On Bacterial Sepsis In Mice, Shuying Wang, Donghui Jiang, Feifei Huang, Yayun Qian, Meitao Qi, Huihui Li, Xiaoli Wang, Zhi Wang, Kaigui Wang, Yin Wang, Pengfei Du, Bin Zhan, Rui Zhou, Liang Chu, Xiaodi Yang

Faculty, Staff and Students Publications

BACKGROUND: The primary pathophysiological process of sepsis is to stimulate a massive release of inflammatory mediators to trigger systemic inflammatory response syndrome (SIRS), the major cause of multi-organ dysfunction and death. Like other helminths, Echinococcus granulosus induces host immunomodulation. We sought to determine whether E. granulosus cyst fluid (EgCF) displays a therapeutic effect on sepsis-induced inflammation and tissue damage in a mouse model.

METHODS: The anti-inflammatory effects of EgCF were determined by in vitro culture with bone marrow-derived macrophages (BMDMs) and in vivo treatment of BALB/C mice with cecal ligation and puncture (CLP)-induced sepsis. The macrophage phenotypes were determined by …

Nicotinic Acetylcholine Receptor Signaling Maintains Epithelial Barrier Integrity, Nadja S Katheder, Kristen C Browder, Diana Chang, Ann De Maziere, Pekka Kujala, Suzanne Van Dijk, Judith Klumperman, Tzu-Chiao Lu, Hongjie Li, Zijuan Lai, Dewakar Sangaraju, Heinrich Jasper

Faculty, Staff and Students Publications

Disruption of epithelial barriers is a common disease manifestation in chronic degenerative diseases of the airways, lung, and intestine. Extensive human genetic studies have identified risk loci in such diseases, including in chronic obstructive pulmonary disease (COPD) and inflammatory bowel diseases. The genes associated with these loci have not fully been determined, and functional characterization of such genes requires extensive studies in model organisms. Here, we report the results of a screen in

Aged And Induced-Premature Ovarian Failure Mouse Models Affect Diestrus Profile And Ovarian Features, Ana Carolina Zucon Bacelar, Nataira Regina Momesso, Felipe Haddad Martim Pederro, Alaíde Gonçalves, Edilson Ervolino, Antonio Hernandes Chaves-Neto, Cláudia Cristina Biguetti, Mariza Akemi Matsumoto

School of Podiatric Medicine Publications

Sex hormones exert a wide influence on several systems of the human body, especially in women, who undergo intense changes in the trans and postmenopausal periods. Different experimental models are used to mimic these conditions; however, the impact on hormonal profile may be different. This study aimed to analyze and compare vaginal cytology of different post-estropausal mice models, along with their microscopical ovarian features. Forty-six C57BL/6J female mice with the ages of 4, 6 and 18 months at the beginning of the experiment, weighing about 25–28 grams, constituted five groups: NC–(negative control) animals with no treatment, OVX-SHAM—sham ovariectomized, OVX–ovariectomized, VCD–medicated …

Novel Insights Into The Pathogenesis Of Human Post-Primary Tuberculosis From Archival Material Of The Pre-Antibiotic Era, 1931-1947, Syeda Mariam Riaz, Kurt Hanevik, Lars Helgeland, Lisbet Sviland, Robert L Hunter, Tehmina Mustafa

Faculty, Staff and Student Publications

OBJECTIVES: Primary and post-primary tuberculosis (TB) are distinct entities. The aim of this study was to study the histopathology of primary and post-primary TB by using the unique human autopsy material from the pre-antibiotic era, 1931-1947.

MATERIAL AND METHODS: Autopsy data were collected from the autopsy journals, and the human tissue was collected from the pathology archives at the Department of Pathology, the Gades Institute.

RESULTS: Histological presentations of TB lesions showed great diversity within a single lung. Post-primary TB starts as a pneumonia forming early lesions, characterized by the infiltration of foamy macrophages containing mycobacterial antigens within alveoli, and …

Whole Genome Analysis Of Snv And Indel Polymorphism In Common Marmosets (Callithrix Jacchus), R Alan Harris, Muthuswamy Raveendran, Wes Warren, Hillier W Ladeana, Chad Tomlinson, Tina Graves-Lindsay, Richard E Green, Jenna K Schmidt, Julia C Colwell, Allison T Makulec, Shelley A Cole, Ian H Cheeseman, Corinna N Ross, Saverio Capuano, Evan E Eichler, Jon E Levine, Jeffrey Rogers

Faculty, Staff and Students Publications

The common marmoset (Callithrix jacchus) is one of the most widely used nonhuman primate models of human disease. Owing to limitations in sequencing technology, early genome assemblies of this species using short-read sequencing suffered from gaps. In addition, the genetic diversity of the species has not yet been adequately explored. Using long-read genome sequencing and expert annotation, we generated a high-quality genome resource creating a 2.898 Gb marmoset genome in which most of the euchromatin portion is assembled contiguously (contig N50 = 25.23 Mbp, scaffold N50 = 98.2 Mbp). We then performed whole genome sequencing on 84 marmosets …

Do We Still Need Aspirin In Coronary Artery Disease?, Muhammad Haisum Maqsood, Glenn N Levine, Neal D Kleiman, David Hasdai, Barry F Uretsky, Yochai Birnbaum

Faculty, Staff and Students Publications

Aspirin has for some time been used as a first-line treatment for acute coronary syndromes, including ST-elevation myocardial infarction, for secondary prevention of established coronary disease, and for primary prevention in patients at risk of coronary artery disease. Although aspirin has been in use for decades, the available evidence for its efficacy largely predates the introduction of other drugs, such as statins and P2Y12 inhibitors. Based on recent trials, the recommendation for aspirin use as primary prevention has been downgraded. In addition, P2Y12 inhibitors given as a single antiplatelet therapy have been associated with a lower incidence of bleeding than …

Inhibition Of Neurogenic Inflammatory Pathways Associated With The Reduction In Discogenic Back Pain, Jose A. Canseco, Hannah A. Levy, Brian A. Karamian, Olivia Blaber, Michael Chang, Neil Patel, John G. Curran, Alan S. Hilibrand, Gregory D. Schroeder, Alex R. Vaccaro, Dessislava Z. Markova, David E. Surrey, Christopher K. Kepler

Rothman Institute Papers

STUDY DESIGN: Retrospective cohort study.

PURPOSE: This study aimed to determine whether the initiation of anti-calcitonin gene-related peptide (CGRP inhibitor) medication therapy for migraines was also associated with improvements in back/neck pain, mobility, and function in a patient population with comorbid degenerative spinal disease and migraine.

OVERVIEW OF LITERATURE: CGRP upregulates pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-6, brain-derived neurotrophic factor, and nerve growth factor in spinal spondylotic disease, which results in disc degeneration and sensitization of nociceptive neurons. Although CGRP inhibitors can quell neurogenic inflammation in migraines, their off-site efficacy as a therapeutic target for discogenic back/neck pain …

Chromosome 10q2432 Variants Associate With Brain Arterial Diameters In Diverse Populations: A Genome-Wide Association Study, Minghua Liu, Farid Khasiyev, Sanjeev Sariya, Antonio Spagnolo-Allende, Danurys L Sanchez, Howard Andrews, Qiong Yang, Alexa Beiser, Ye Qiao, Emy A Thomas, Jose Rafael Romero, Tatjana Rundek, Adam M Brickman, Jennifer J Manly, Mitchell Sv Elkind, Sudha Seshadri, Christopher Chen, Saima Hilal, Bruce A Wasserman, Giuseppe Tosto, Myriam Fornage, Jose Gutierrez

Faculty, Staff and Student Publications

Background: Brain arterial diameters (BADs) are novel imaging biomarkers of cerebrovascular disease, cognitive decline, and dementia. Traditional vascular risk factors have been associated with BADs, but whether there may be genetic determinants of BADs is unknown.

Methods and results: The authors studied 4150 participants from 6 geographically diverse population-based cohorts (40% European, 14% African, 22% Hispanic, 24% Asian ancestries). Brain arterial diameters for 13 segments were measured and averaged to obtain a global measure of BADs as well as the posterior and anterior circulations. A genome-wide association study revealed 14 variants at one locus associated with global BAD at genome-wide …

Antiseizure Effects Of Peganum Harmala L. And Lavandula Angustifolia, Zahra Rahimian, Seyedhassan Sadrian, Mina Shahisavandi, Hadi Aligholi, Mohammad M. Zarshenas, Alireza Abyar, Zahra Zeraatpisheh, Ali A. Asadi-Pooya

Department of Neurology Faculty Papers

Peganum harmala L. and Lavandula angustifolia are two traditional herbs with probable antiseizure effects. This study evaluated the effects of these two herbal extracts on pentylenetetrazol- (PTZ-) induced seizures in mice. We prepared hydroalcoholic extracts using P. harmala seeds and the aerial parts of L. angustifolia and then randomly divided 190 mice into 19 groups. Normal saline (10 mg/kg), diazepam (2 mg/kg), P. harmala (2.5, 5, 10, 15, 30, 45, and 60 mg/kg), and L. angustifolia (200, 400, 600, and 800 mg/kg) were intraperitoneally (IP) administrated 30 min before an IP administration of PTZ (90 mg/kg). Animals were observed for …

Acss2 Gene Variants Determine Kidney Disease Risk By Controlling De Novo Lipogenesis In Kidney Tubules, Dhanunjay Mukhi, Lingzhi Li, Hongbo Liu, Tomohito Doke, Lakshmi P Kolligundla, Eunji Ha, Konstantin Kloetzer, Amin Abedini, Sarmistha Mukherjee, Junnan Wu, Poonam Dhillon, Hailong Hu, Dongyin Guan, Katsuhiko Funai, Kahealani Uehara, Paul M Titchenell, Joseph A Baur, Kathryn E Wellen, Katalin Susztak

Faculty, Staff and Students Publications

Worldwide, over 800 million people are affected by kidney disease, yet its pathogenesis remains elusive, hindering the development of novel therapeutics. In this study, we used kidney-specific expression of quantitative traits and single-nucleus open chromatin analysis to show that genetic variants linked to kidney dysfunction on chromosome 20 target the acyl-CoA synthetase short-chain family 2 (ACSS2). By generating ACSS2-KO mice, we demonstrated their protection from kidney fibrosis in multiple disease models. Our analysis of primary tubular cells revealed that ACSS2 regulated de novo lipogenesis (DNL), causing NADPH depletion and increasing ROS levels, ultimately leading to NLRP3-dependent pyroptosis. Additionally, we discovered …

Wellness Review 2023, Part 1, Brian A. Ferguson, Martin Huecker

Journal of Wellness

Introduction: The 2023 Part 1 summary reviews research on wellness in healthcare professionals published outside of JWellness from January 1, 2023 to June 30, 2023.

Methods: Editors conducted a Boolean search of titles and abstracts in PubMed utilizing keyword identifiers pairing healthcare personnel (providers, nurses, and other staff) with a well-being metric. Of 416 relevant articles, an intriguing and innovative 30 were selected for inclusion, with two additional articles manually curated.

Literature in Review: This sample of the recent literature into healthcare professional wellness included multiple targeted interventions and studies of resilience. Main themes that emerged include: positive systematic healthcare …

Hnf4Α Isoforms Regulate The Circadian Balance Between Carbohydrate And Lipid Metabolism In The Liver, Jonathan R Deans, Poonamjot Deol, Nina Titova, Sarah H Radi, Linh M Vuong, Jane R Evans, Songqin Pan, Johannes Fahrmann, Jun Yang, Bruce D Hammock, Oliver Fiehn, Baharan Fekry, Kristin Eckel-Mahan, Frances M Sladek

Faculty, Staff and Student Publications

Hepatocyte Nuclear Factor 4α (HNF4α), a master regulator of hepatocyte differentiation, is regulated by two promoters (P1 and P2) which drive the expression of different isoforms. P1-HNF4α is the major isoform in the adult liver while P2-HNF4α is thought to be expressed only in fetal liver and liver cancer. Here, we show that P2-HNF4α is indeed expressed in the normal adult liver at Zeitgeber time (ZT)9 and ZT21. Using exon swap mice that express only P2-HNF4α we show that this isoform orchestrates a distinct transcriptome and metabolome via unique chromatin and protein-protein interactions, including with different clock proteins at different …

Plasma Exchange Reduces Aβ Levels In Plasma And Decreases Amyloid Plaques In The Brain In A Mouse Model Of Alzheimer's Disease, Santiago Ramirez, Suelyn Koerich, Natalia Astudillo, Nicole De Gregorio, Rabab Al-Lahham, Tyler Allison, Natalia Pessoa Rocha, Fei Wang, Claudio Soto

Faculty, Staff and Student Publications

Alzheimer's disease (AD) is the most common type of dementia, characterized by the abnormal accumulation of protein aggregates in the brain, known as neurofibrillary tangles and amyloid-β (Aβ) plaques. It is believed that an imbalance between cerebral and peripheral pools of Aβ may play a relevant role in the deposition of Aβ aggregates. Therefore, in this study, we aimed to evaluate the effect of the removal of Aβ from blood plasma on the accumulation of amyloid plaques in the brain. We performed monthly plasma exchange with a 5% mouse albumin solution in the APP/PS1 mouse model from 3 to 7 …

Examining The Potential Of Vitamin C Supplementation In Tissue-Engineered Equine Superficial Digital Flexor Tendon Constructs, Michael J Mienaltowski, Mitchell Callahan, Nicole L Gonzales, Angelique Wong

Faculty, Staff and Student Publications

Because equine tendinopathies are slow to heal and often recur, therapeutic strategies are being considered that aid tendon repair. Given the success of utilizing vitamin C to promote tenogenesis in other species, we hypothesized that vitamin C supplementation would produce dose-dependent improvements in the tenogenic properties of tendon proper (TP) and peritenon (PERI) cells of the equine superficial digital flexor tendon (SDFT). Equine TP- and PERI-progenitor-cell-seeded fibrin three-dimensional constructs were supplemented with four concentrations of vitamin C. The gene expression profiles of the constructs were assessed with 3'-Tag-Seq and real-time quantitative polymerase chain reaction (RT-qPCR); collagen content and fibril ultrastructure …

Written Communication From Pharmacy Benefit Managers: Is It Helpful?, Lily G. Cessna, Lynne J. Goebel

Internal Medicine

Introduction: Physicians are experiencing greater burnout due to excessive time spent on paperwork. Pharmacy benefit managers (PBMs) are adding to this problem by sending excessive mail to physicians. This study examined these mailed communications to determine their frequency and if the physician acted upon them. We hypothesized that few of these mailings would be helpful to the physician.

Methods: From July 2021 to May 2023, we collected all written communications from PBMs to a single geriatrics outpatient physician. We sorted this information by specific PBM, by communication category, if it resulted in an intervention, and if communications were repeated.

Results: …

Perioperative Chest X-Ray Interpretation For Anesthesia Providers, Kaitlyn Brown, Jessica Parsons

Doctoral Projects

Currently, a knowledge gap exists among anesthesia providers regarding perioperative chest x-ray (CXR) appropriateness and interpretation (Collins, 2022). The Council on Accreditation (COA) requires that students graduating from a nurse anesthesia program (NAP) interpret a minimum of five CXRs before program completion (Council on Accreditation [COA], 2020). This DNP project aimed to address the knowledge gap by offering an easily accessible online forum that guides anesthesia providers on CXR indications in surgical patients, and in identifying pathologies and invasive line and tube placement using CXR.

The authors created four learning modules regarding perioperative CXRs using Microsoft PowerPoint presentations with animation …