Digital Commons Network^™

Siglec15, Negatively Correlated With Pd-L1 In Hcc, Could Induce Cd8+ T Cell Apoptosis To Promote Immune Evasion, Zheng Chen, Mincheng Yu, Bo Zhang, Lei Jin, Qiang Yu, Shuang Liu, Binghai Zhou, Jiuliang Yan, Wentao Zhang, Xiaoqiang Li, Yongfeng Xu, Yongsheng Xiao, Jian Zhou, Jia Fan, Mien-Chie Hung, Qinghai Ye, Hui Li, Lei Guo

Faculty, Staff and Student Publications

Functional roles of SIGLEC15 in hepatocellular carcinoma (HCC) were not clear, which was recently found to be an immune inhibitor with similar structure of inhibitory B7 family members. SIGLEC15 expression in HCC was explored in public databases and further examined by PCR analysis. SIGLEC15 and PD-L1 expression patterns were examined in HCC samples through immunohistochemistry. SIGLEC15 expression was knocked-down or over-expressed in HCC cell lines, and CCK8 tests were used to examine cell proliferative ability in vitro. Influences of SIGLEC15 expression on tumor growth were examined in immune deficient and immunocompetent mice respectively. Co-culture system of HCC cell lines and …

Campylobacter Colonization And Undernutrition In Infants In Rural Eastern Ethiopia — A Longitudinal Community-Based Birth Cohort Study, Dehao Chen, Nurmohammad Shaik, Mark J Manary, Et Al.

2020-Current year OA Pubs

BACKGROUND:

METHODS: We followed a birth cohort of 106 infants in rural smallholder households in eastern Ethiopia up to 13 months of age. We measured anthropometry, surveyed sociodemographic determinants, and collected stool and urine samples. A short survey was conducted during monthly visits, infant stool samples were collected, and

RESULTS: The

CONCLUSION: This study found that most determinants associated with increased

From Sabers To Spikes: A Newfangled Reconstruction Of The Ancient, Giant, Sexually Dimorphic Pacific Salmon, †Oncorhynchus Rastrosus (Salmoninae: Salmonini)., Kerin M. Claeson, Brian L Sidlauskas, Ray Troll, Zabrina M Prescott, Edward B Davis

PCOM Scholarly Works

The impressive †Oncorhynchus rastrosus of the Pacific Northwest's Miocene and Pliocene eras was the largest salmonid ever to live. It sported a hypertrophied premaxilla with a pair of enlarged teeth which the original describers reconstructed as projecting ventrally into the mouth, leading them to assign the species to "Smilodonichthys," a genus now in synonymy. Through CT reconstruction of the holotype and newly collected specimens, we demonstrate that the famed teeth projected laterally like tusks, not ventrally like sabers or fangs. We also expand the original description to characterize sexual dimorphism in mature, breeding individuals. Male and female †Oncorhynchus rastrosus differ …

Select Gut Microbiota Impede Rotavirus Vaccine Efficacy, Vu L Ngo, Yanling Wang, Yadong Wang, Zhenda Shi, Robert Britton, Jun Zou, Sasirekha Ramani, Baoming Jiang, Andrew T Gewirtz

Faculty, Staff and Students Publications

BACKGROUND & AIMS: The protection provided by rotavirus (RV) vaccines is highly heterogeneous among individuals. We hypothesized that microbiota composition might influence RV vaccine efficacy.

METHODS: First, we examined the potential of segmented filamentous bacteria (SFB) colonization to influence RV vaccine efficacy in mice. Next, we probed the influence of human microbiomes on RV vaccination via administering mice fecal microbial transplants (FMTs) from children with robust or minimal RV vaccine responsiveness. Post-FMT, mice were subjected to RV vaccination followed by RV challenge.

RESULTS: SFB colonization induced a phenotype that was reminiscent of RV vaccine failure (ie, failure to generate RV …

Ginkgo Biloba For Tardive Dyskinesia And Plasma Mnsod Activity: Association With Mnsod Ala-9val Variant: A Randomized, Double-Blind Trial, Dongmei Wang, Yang Tian, Jiajing Chen, Rongrong Zhu, Jiaxin Li, Huixia Zhou, Dachun Chen, Li Wang, Thomas R Kosten, Xiang-Yang Zhang

Faculty, Staff and Students Publications

Background: Excessive free radicals are implicated in the pathophysiology of tardive dyskinesia (TD), and Ginkgo biloba extract (EGb761) scavenges free radicals, thereby enhancing antioxidant enzymes such as mitochondrial manganese superoxide dismutase (MnSOD). This study examined whether EGb761 treatment would improve TD symptoms and increase MnSOD activity, particularly in TD patients with specific MnSOD Val-9Ala genotype.

Methods: An EGb761 (240 mg/day) 12-week double-blind clinical trial with 157 TD patients was randomized. The severity of TD was measured by the Abnormal Involuntary Movement Scale (AIMS) and plasma MnSOD activity was assayed before and after 12 weeks of treatment. Further, in an expanded …

Non-Invasive Auricular Vagus Nerve Stimulation For Subarachnoid Hemorrhage (Navsah): Protocol For A Prospective, Triple-Blinded, Randomized Controlled Trial, Anna Huguenard, Gansheng Tan, Gabrielle Johnson, Markus Adamek, Andrew Coxon, Terrance Kummer, Joshua Osbun, Ananth Vellimana, David Limbrick, Gregory Zipfel, Peter Brunner, Eric Leuthardt

2020-Current year OA Pubs

BACKGROUND: Inflammation has been implicated in driving the morbidity associated with subarachnoid hemorrhage (SAH). Despite understanding the important role of inflammation in morbidity following SAH, there is no current effective way to modulate this deleterious response. There is a critical need for a novel approach to immunomodulation that can be safely, rapidly, and effectively deployed in SAH patients. Vagus nerve stimulation (VNS) provides a non-pharmacologic approach to immunomodulation, with prior studies demonstrating VNS can reduce systemic inflammatory markers, and VNS has had early success treating inflammatory conditions such as arthritis, sepsis, and inflammatory bowel diseases. The aim of the Non-invasive …

Neurosteroids Mediate And Modulate The Effects Of Pro-Inflammatory Stimulation And Toll-Like Receptors On Hippocampal Plasticity And Learning, Yukitoshi Izumi, Kazuko A. O'Dell, Anil G. Cashikar, Steven M. Paul, Douglas F. Covey, Steven J. Mennerick, Charles F. Zorumski

2020-Current year OA Pubs

Pro-inflammatory changes contribute to multiple neuropsychiatric illnesses. Understanding how these changes are involved in illnesses and identifying strategies to alter inflammatory responses offer paths to potentially novel treatments. We previously found that acute pro-inflammatory stimulation with high (μg/ml) lipopolysaccharide (LPS) for 10-15 min dampens long-term potentiation (LTP) in the hippocampus and impairs learning. Effects of LPS involved non-canonical inflammasome signaling but were independent of toll-like receptor 4 (TLR4), a known LPS receptor. Low (ng/ml) LPS also inhibits LTP when administered for 2-4 h, and here we report that this LPS exposure requires TLR4. We also found that effects of low …

Dsm-5 Conduct Disorder And Symptoms In Youths At High Risk Of Psychosis In Kenya With Dsm-5 Mental Disorders And Substance Use: Towards Integrated Management, David M Ndetei, Victoria Mutiso, Christine Musyimi, Reinpeter Momanyi, Pascalyne Nyamai, Peter Tyrer, Daniel Mamah

2020-Current year OA Pubs

Little is known about the prevalence of Conduct Disorder (CD) and symptoms of CD in high risk psychosis persons at both clinical and community populations in LMICs and in particular Kenya. This study aimed to document (1) the prevalence of CD diagnosis and symptoms in youth who screened positive for psychosis and (2) the associated mental disorders and substance use in the same cohort in LMIC. The sample size was 536 students who had screened positive on the Washington Early Recognition Center Affectivity and Psychosis (WERCAP) from a population of 9,742 high school, college and university students, but had not …

Nucleus Accumbens Core Single Cell Ensembles Bidirectionally Respond To Experienced Versus Observed Aversive Events, Oyku Dinckol, Noah Harris Wenger, Jennifer E Zachry, Munir Gunes Kutlu

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Fear learning is a critical feature of survival skills among mammals. In rodents, fear learning manifests itself through direct experience of the aversive event or social transmission of aversive stimuli such as observing and acting on conspecifics' distress. The neuronal network underlying the social transmission of information largely overlaps with the brain regions that mediate behavioral responses to aversive and rewarding stimuli. In this study, we recorded single cell activity patterns of nucleus accumbens (NAc) core neurons using in vivo optical imaging of calcium transients via miniature scopes. This cutting-edge imaging methodology not only allows us to record activity patterns …

On The Benefits Of The Tryptophan Metabolite 3-Hydroxyanthranilic Acid In Caenorhabditis Elegans And Mouse Aging., Hope Dang, Raul Castro-Portuguez, Luis Espejo, Grant Backer, Samuel Freitas, Erica Spence, Jeremy Meyers, Karissa Shuck, Emily A Gardea, Leah M Chang, Jonah Balsa, Niall Thorns, Caroline Corban, Teresa Liu, Shannon Bean, Susan Sheehan, Ron Korstanje, George L Sutphin

Faculty Research 2023

Tryptophan metabolism through the kynurenine pathway influences molecular processes critical to healthy aging including immune signaling, redox homeostasis, and energy production. Aberrant kynurenine metabolism occurs during normal aging and is implicated in many age-associated pathologies including chronic inflammation, atherosclerosis, neurodegeneration, and cancer. We and others previously identified three kynurenine pathway genes-tdo-2, kynu-1, and acsd-1-for which decreasing expression extends lifespan in invertebrates. Here we report that knockdown of haao-1, a fourth gene encoding the enzyme 3-hydroxyanthranilic acid (3HAA) dioxygenase (HAAO), extends lifespan by ~30% and delays age-associated health decline in Caenorhabditis elegans. Lifespan extension is mediated by increased physiological levels of …

Monitoring Glucocorticoid Receptor In Plasma-Derived Extracellular Vesicles As A Marker Of Resistance To Androgen Receptor Signaling Inhibition In Prostate Cancer, Emanuela Gentile, Andrew W Hahn, Jian H Song, Anh Hoang, Peter D A Shepherd, Sumankalai Ramachandran, Nora M Navone, Eleni Efstathiou, Mark Titus, Paul G Corn, Sue-Hwa Lin, Christopher J Logothetis, Theocharis Panaretakis

Faculty, Staff and Student Publications

Disease progression following androgen ablation was shown to be associated with upregulation of the glucocorticoid receptor (GR). Longitudinal monitoring of GR expression in circulating extracellular vesicles (EV) may reflect changes in the tumor cell and facilitates detection of acquired resistance. We utilized LNCaP, LREX cells and a patient-derived xenograft, MDA PDX 322-2-6a, for in vitro and in vivo experiments. Plasma-derived EVs were isolated from patients with localized high-risk prostate cancer undergoing androgen ablation. The mRNA levels of GR in EVs and their responsive genes were detected by transcriptome analysis, qRT-PCR and the protein levels by Western blot analysis. We detected …

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 …

Design And Structural Validation Of Peptide-Drug Conjugate Ligands Of The Kappa-Opioid Receptor, Edin Muratspahić, Jianming Han, Balazs R Varga, Kevin Appourchaux, Susruta Majumdar, Tao Che, Et Al.

2020-Current year OA Pubs

Despite the increasing number of GPCR structures and recent advances in peptide design, the development of efficient technologies allowing rational design of high-affinity peptide ligands for single GPCRs remains an unmet challenge. Here, we develop a computational approach for designing conjugates of lariat-shaped macrocyclized peptides and a small molecule opioid ligand. We demonstrate its feasibility by discovering chemical scaffolds for the kappa-opioid receptor (KOR) with desired pharmacological activities. The designed De Novo Cyclic Peptide (DNCP)-β-naloxamine (NalA) exhibit in vitro potent mixed KOR agonism/mu-opioid receptor (MOR) antagonism, nanomolar binding affinity, selectivity, and efficacy bias at KOR. Proof-of-concept in vivo efficacy studies …

Salivary Duct Carcinoma Arising In A Warthin Tumor Of The Parotid Gland: A Rare Case Report With Review Of Literature And Pd-L1 Expression, Kaitlyn J. Nielson, Gamaliel Lorenzo, Shweta Agarwal

Pathology Research and Scholarship

Warthin's tumor is the second most common neoplasm of the parotid gland and consists of 2 components, including lymphoid stroma and glandular epithelium. Malignant transformation in this tumor is mostly seen in the lymphoid component; however, the carcinomatous transformation of the epithelial component is extremely rare. Cases of latter reported in the literature include squamous cell carcinoma, adenocarcinoma, mucoepidermoid carcinoma, oncocytic carcinoma, Merkel cell carcinoma, and undifferentiated carcinoma. We describe an extremely rare case of salivary duct carcinoma arising in a Warthin tumor in a 64-year-old male. Patient presented with an enlarging left parotid mass, biopsy of which showed salivary …

Early-Life Stress Perturbs The Epigenetics Of Cd36 Concurrent With Adult Onset Of Nafld In Mice., Qi Fu, Jenna M. Frick, Maura F. O'Neil, Olivia C. Eller, E Matthew Morris, John P. Thyfault, Julie A. Christianson, Robert H. Lane

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases in the U.S. and worldwide. The roles of early postnatal life stress (EPLS) and the fatty acid translocase (CD36) on the pathogenesis of adult-onset NAFLD remain unknown. We hypothesized that EPLS, in the form of neonatal maternal separation (NMS), would predispose mice towards developing adult NAFLD, increase hepatic CD36 expression, and differentially methylate Cd36 promoter concurrently.

METHODS: NMS was performed on mice from postnatal day 1 to 21 and a high-fat/high-sucrose (HFS) diet was started at 4 weeks of age to generate four experimental groups: Naive-control …

The Effect Of Nitroglycerin In Testicular Histopathology, Reproductive Hormones And Testicular Oxidative Stress In Adolescent Rats, Volkan Koşal, Çağlar Okulmuş, Yılmaz Koçak, Ömer Faruk Keleş, Nesrin Ceylan, Yıldıray Başbuğan

Mansoura Veterinary Medical Journal

Background: Nitroglycerin (NTG) exerts a vasodilation effect by acting on vascular smooth muscles. The exact impact of vasodilation on the testes is not fully understood. Objectives: This study aimed to investigate the effects of NTG on the testes before the onset of spermatogenesis and reproductive activity in adolescent rats. Methods: An Average of 45 days male Albino Wistar rats were used. Two groups were formed: an adolescent control group and an adolescent NTG group (10 mg/kg, 5 d). Results: At the end of the study, testicular oxidative stress (malondialdehyde /MDA, catalase/ CAT, advanced oxidation protein products /AOPP, and nitric oxide/ …

Estradiol Mediates Colonic Epithelial Protection In Aged Mice After Stroke And Is Associated With Shifts In The Gut Microbiome, Juneyoung Lee, Pedram Peesh, Victoria Quaicoe, Chunfeng Tan, Anik Banerjee, Patrick Mooz, Bhanu P Ganesh, Joseph Petrosino, Robert M Bryan, Louise D Mccullough, Venugopal Reddy Venna

Faculty, Staff and Student Publications

The gut is a major source of bacteria and antigens that contribute to neuroinflammation after brain injury. Colonic epithelial cells (ECs) are responsible for secreting major cellular components of the innate defense system, including antimicrobial proteins (AMP) and mucins. These cells serve as a critical regulator of gut barrier function and maintain host-microbe homeostasis. In this study, we determined post-stroke host defense responses at the colonic epithelial surface in mice. We then tested if the enhancement of these epithelial protective mechanisms is beneficial in young and aged mice after stroke. AMPs were significantly increased in the colonic ECs of young …

Nonsense Variant Prdm16-Q187x Causes Impaired Myocardial Development And Tgf-Β Signaling Resulting In Noncompaction Cardiomyopathy In Humans And Mice, Bo Sun, Omid M T Rouzbehani, Ryan J Kramer, Rajeshwary Ghosh, Robin M Perelli, Sage Atkins, Amir Nima Fatahian, Kathryn Davis, Marta W Szulik, Michael A Goodman, Marissa A Hathaway, Ellenor Chi, Tarah A Word, Hari Tunuguntla, Susan W Denfield, Xander H T Wehrens, Kevin J Whitehead, Hala Y Abdelnasser, Junco S Warren, Mingfu Wu, Sarah Franklin, Sihem Boudina, Andrew P Landstrom

Faculty, Staff and Students Publications

BACKGROUND: PRDM16 plays a role in myocardial development through TGF-β (transforming growth factor-beta) signaling. Recent evidence suggests that loss of PRDM16 expression is associated with cardiomyopathy development in mice, although its role in human cardiomyopathy development is unclear. This study aims to determine the impact of PRDM16 loss-of-function variants on cardiomyopathy in humans.

METHODS: Individuals with PRDM16 variants were identified and consented. Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) were generated from a proband hosting a Q187X nonsense variant as an in vitro model and underwent proliferative and transcriptional analyses. CRISPR-mediated knock-in mouse model hosting the Prdm16Q187X allele was generated …

Exposure To Agent Orange And Hepatocellular Carcinoma Among Us Military Personnel, Jihane N Benhammou, Mei Leng, Shailja C Shah, George Cholankeril, Tien S Dong, Arpan A Patel, Myron J Tong

Faculty, Staff and Students Publications

IMPORTANCE: Hepatocellular carcinoma (HCC) and its mortality are on the rise. Viral hepatitis and alcohol are leading risk factors; however, other risk factors among veterans are less defined, including Agent Orange (AO), an herbicide linked to several cancers.

OBJECTIVE: To assess the association of AO exposure and HCC in a national cohort of Vietnam veterans.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included Vietnam veterans who served between 1966 and 1975, were male, were older than 18 years at the time of deployment, and had established follow-up in the Veterans Affairs (VA) between 2000 and 2019. Veterans with AO …

Nutrition Assessment And Mash Severity In Children Using The Healthy Eating Index, Ajay Kumar Jain, Paula Buchannan, Katherine P Yates, Patricia Belt, Jeffrey B Schwimmer, Philip Rosenthal, Karen F Murray, Jean P Molleston, Ann Scheimann, Stavra A Xanthakos, Cynthia A Behling, Paula Hertel, Jamie Nilson, Brent A Neuschwander-Tetri, James Tonascia, Miriam B Vos, Nonalcoholic Steatohepatitis Clinical Research Network (Nash Crn)

Faculty, Staff and Students Publications

BACKGROUND: Pediatric metabolic-associated fatty liver disease (MAFLD) is a global health problem, with lifestyle modification as its major therapeutic strategy. Rigorous characterization of dietary content on MAFLD in children is lacking. We hypothesized an objectively measured healthier diet would positively modulate MAFLD.

METHODS: Diet was assessed using the Nutrition Data System for Research in children enrolled from 10 tertiary clinical centers to determine the Healthy Eating Index (HEI, 0-100) and individual food components.

RESULTS: In all, 119 children were included (13.3 ± 2.7 y), 80 (67%) male, 67 (18%) White, and 90 (76%) Hispanic, with an average body mass index …

Enlarged Perivascular Spaces In Infancy And Autism Diagnosis, Cerebrospinal Fluid Volume, And Later Sleep Problems, Dea Garic, Robert C Mckinstry, Kelly N Botteron, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Perivascular spaces (PVS) and cerebrospinal fluid (CSF) are essential components of the glymphatic system, regulating brain homeostasis and clearing neural waste throughout the lifespan. Enlarged PVS have been implicated in neurological disorders and sleep problems in adults, and excessive CSF volume has been reported in infants who develop autism. Enlarged PVS have not been sufficiently studied longitudinally in infancy or in relation to autism outcomes or CSF volume.

OBJECTIVE: To examine whether enlarged PVS are more prevalent in infants who develop autism compared with controls and whether they are associated with trajectories of extra-axial CSF volume (EA-CSF) and sleep …

Recombinant Human Perlecan Dv And Its Lg3 Subdomain Are Neuroprotective And Acutely Functionally Restorative In Severe Experimental Ischemic Stroke, Ifechukwude Joachim Biose, Ibolya Rutkai, Bryan Clossen, Gary Gage, Kenneth Schechtman, H Davis Adkisson 4th, Gregory J Bix

2020-Current year OA Pubs

Despite recent therapeutic advancements, ischemic stroke remains a major cause of death and disability. It has been previously demonstrated that  ~ 85-kDa recombinant human perlecan domain V (rhPDV) binds to upregulated integrin receptors (α2β1 and α5β1) associated with neuroprotective and functional improvements in various animal models of acute ischemic stroke. Recombinant human perlecan laminin-like globular domain 3 (rhPDV

Glial Cell Adhesion Molecule (Glialcam) Determines Proliferative Versus Invasive Cell States In Glioblastoma, Arpan De, John M Lattier, John E Morales, Jack R Kelly, Xiaofeng Zheng, Zhihua Chen, Sumod Sebastian, Zahra Nassiri Toosi, Jason T Huse, Frederick F Lang, Joseph H Mccarty

Faculty, Staff and Student Publications

The malignant brain cancer glioblastoma (GBM) contains groups of highly invasive cells that drive tumor progression as well as recurrence after surgery and chemotherapy. The molecular mechanisms that enable these GBM cells to exit the primary mass and disperse throughout the brain remain largely unknown. Here we report using human tumor specimens and primary spheroids from male and female patients that glial cell adhesion molecule (GlialCAM), which has normal roles in brain astrocytes and is mutated in the developmental brain disorder megalencephalic leukoencephalopathy with subcortical cysts (MLC), is differentially expressed in subpopulations of GBM cells. High levels of GlialCAM promote …

Molecular Basis Of Retinal Remodeling In A Zebrafish Model Of Retinitis Pigmentosa, Abirami Santhanam, Eyad Shihabeddin, Haichao Wei, Jiaqian Wu, John O'Brien

Faculty, Staff and Student Publications

A hallmark of inherited retinal degenerative diseases such as retinitis pigmentosa (RP) is progressive structural and functional remodeling of the remaining retinal cells as photoreceptors degenerate. Extensive remodeling of the retina stands as a barrier for the successful implementation of strategies to restore vision. To understand the molecular basis of remodeling, we performed analyses of single-cell transcriptome data from adult zebrafish retina of wild type AB strain (WT) and a P23H mutant rhodopsin transgenic model of RP with continuous degeneration and regeneration. Retinas from both female and male fish were pooled to generate each library, combining data from both sexes. …

Targeting The Αvβ3/Ngr2 Pathway In Neuroendocrine Prostate Cancer, Anna Testa, Fabio Quaglia, Nicole M. Naranjo, Cecilia E. Verrillo, Christopher D. Shields, Stephen Lin, Maxwell W. Pickles, Drini F. Hamza, Tami Von Schalscha, David A. Cheresh, Benjamin E Leiby, Qin Liu, Jianyi Ding, William K. Kelly, D. Craig Hooper, Eva Corey, Edward F. Plow, Dario C. Altieri, Lucia R. Languino

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Highly aggressive, metastatic, neuroendocrine prostate cancer, which typically develops from prostate cancer cells acquiring resistance to androgen deprivation therapy, is associated with limited treatment options and hence poor prognosis. We have previously demonstrated that the αVβ3 integrin is over-expressed in neuroendocrine prostate cancer. We now show that LM609, a monoclonal antibody that specifically targets the human αVβ3 integrin, hinders the growth of neuroendocrine prostate cancer patient-derived xenografts in vivo. Our group has recently identified a novel αVβ3 integrin binding partner, NgR2, responsible for regulating the expression of neuroendocrine markers and for inducing neuroendocrine differentiation in prostate cancer cells. Through in …

Quantification Of Observable Behaviors Following Oral Administration Of Oxycodone And Nalfurafine In Male Rhesus Monkeys, Sally L. Huskinson, Donna M. Platt, Zachary R. Smith, William S. Doyle, C. Austin Zamarripa, Kristen Dunaway, Thomas E. Prisinzano, Kevin B. Freeman

Pharmaceutical Sciences Faculty Publications

BACKGROUND: Recent preclinical studies have investigated the atypical kappa-opioid receptor (KOR) agonist, nalfurafine, as a co-formulary with mu-opioid receptor (MOR) agonists as a potential deterrent for misuse. However, no study has investigated effects of nalfurafine combined with a MOR agonist using an oral route of administration. The objective of the current study was to measure behavioral effects of orally administered oxycodone and nalfurafine, alone and combined, in rhesus monkeys using a quantitative behavioral observation procedure.

METHODS: Adult male rhesus monkeys (N=5) were orally administered vehicle, oxycodone (0.56-1.8mg/kg), nalfurafine (0.001-0.0056mg/kg), or mixtures (1.0mg/kg oxycodone/0.001-0.0056mg/kg nalfurafine) in a Jell-O vehicle at multiple …

Multimodal Analysis Of Secondary Cerebellar Alterations After Pediatric Traumatic Brain Injury, Finian Keleher, Hannah M Lindsey, Rebecca Kerestes, Houshang Amiri, Robert F Asarnow, Talin Babikian, Brenda Bartnik-Olson, Erin D Bigler, Karen Caeyenberghs, Carrie Esopenko, Linda Ewing-Cobbs, Christopher C Giza, Naomi J Goodrich-Hunsaker, Cooper B Hodges, Kristen R Hoskinson, Andrei Irimia, Marsh Königs, Jeffrey E Max, Mary R Newsome, Alexander Olsen, Nicholas P Ryan, Adam T Schmidt, Dan J Stein, Stacy J Suskauer, Ashley L Ware, Anne L Wheeler, Brandon A Zielinski, Paul M Thompson, Ian H Harding, David F Tate, Elisabeth A Wilde, Emily L Dennis

Faculty, Staff and Student Publications

Importance: Traumatic brain injury (TBI) is known to cause widespread neural disruption in the cerebrum. However, less is known about the association of TBI with cerebellar structure and how such changes may alter executive functioning.

Objective: To investigate alterations in subregional cerebellum volume and cerebral white matter microstructure after pediatric TBI and examine subsequent changes in executive function.

Design, setting, and participants: This retrospective cohort study combined 12 data sets (collected between 2006 and 2020) from 9 sites in the Enhancing Neuroimaging Genetics Through Meta-Analysis Consortium Pediatric TBI working group in a mega-analysis of cerebellar structure. Participants with TBI or …

Epidemiology Of Giardiasis And Assemblages A And B And Effects On Diarrhea And Growth Trajectories During The First 8 Years Of Life: Analysis Of A Birth Cohort In A Rural District In Tropical Ecuador, Tannya Sandoval-Ramírez, Victor Seco-Hidalgo, Evelyn Calderon-Espinosa, Diana Garcia-Ramon, Andrea Lopez, Manuel Calvopiña, Irene Guadalupe, Martha Chico, Rojelio Mejia, Irina Chis Ster, Philip J Cooper

Faculty, Staff and Students Publications

BACKGROUND: There are limited longitudinal data on the acquisition of Giardia lamblia infections in childhood using molecular assays to detect and type assemblages, and measure effects of infections on diarrhea risk and childhood growth.

METHODS: We analysed stool samples from a surveillance sample within a birth cohort in a rural district in tropical Ecuador. The cohort was followed to 8 years of age for the presence of G. lamblia in stools by quantitative PCR and A and B assemblages by Taqman assay or Sanger sequencing. We explored risk factors associated with infection using generalized estimating equations applied to longitudinal binary …

Alterations In Salivary Biochemical Composition And Redox State Disruption Induced By The Anticonvulsant Valproic Acid In Male Rat Salivary Glands, Rayara Nogueira De Freitas, Lucas Guilherme Leite Da Silva, Gabriela Alice Fiais, Douglas Sandrac De Biagi Ferreira, Allice Santos Cruz Veras, Giovana Rampazzo Teixeira, Sandra Helena Penha Oliveira, Rita Cássia Menegati Dornelles, Ana Cláudia De Melo Stevanato Nakamune, Walid D Fakhouri, Antonio Hernandes Chaves-Neto

Faculty, Staff and Student Publications

Objective: To investigate the effects of the anticonvulsant valproic acid (VPA) on salivary glands in male rat using biochemical, functional, histomorphometric, and redox state parameters.

Materials and methods: Twenty-four male Wistar rats were randomly distributed into three groups (n = 8 per group): Control (0.9% saline solution), VPA100 (100 mg/kg), and VPA400 (400 mg/kg). After 21 consecutive days of treatment with by intragastric gavage. Pilocarpine-induced saliva was collected to determine salivary flow rate, pH, buffering capacity, and biochemical composition. Analyses of histomorphometric parameters and redox balance markers were performed on the parotid and submandibular glands.

Results: Salivary flow rate, pH, …

Clonal Hematopoiesis Of Indeterminate Potential (Chip) And Incident Type 2 Diabetes Risk, Deirdre K Tobias, Alisa K Manning, Jennifer Wessel, Sridharan Raghavan, Kenneth E Westerman, Alexander G Bick, Daniel Dicorpo, Eric A Whitsel, Jason Collins, Adolfo Correa, L Adrienne Cupples, Josée Dupuis, Mark O Goodarzi, Xiuqing Guo, Barbara Howard, Leslie A Lange, Simin Liu, Laura M Raffield, Alex P Reiner, Stephen S Rich, Kent D Taylor, Lesley Tinker, James G Wilson, Peitao Wu, April P Carson, Ramachandran S Vasan, Myriam Fornage, Bruce M Psaty, Charles Kooperberg, Jerome I Rotter, James Meigs, Joann E Manson

Faculty, Staff and Student Publications

OBJECTIVE: Clonal hematopoiesis of indeterminate potential (CHIP) is an aging-related accumulation of somatic mutations in hematopoietic stem cells, leading to clonal expansion. CHIP presence has been implicated in atherosclerotic coronary heart disease (CHD) and all-cause mortality, but its association with incident type 2 diabetes (T2D) is unknown. We hypothesized that CHIP is associated with elevated risk of T2D.

RESEARCH DESIGN AND METHODS: CHIP was derived from whole-genome sequencing of blood DNA in the National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine (TOPMed) prospective cohorts. We performed analysis for 17,637 participants from six cohorts, without prior T2D, cardiovascular disease, …