Digital Commons Network^™

A, B, C'S Of Trk Receptors And Their Ligands In Ocular Repair, Akash Gupta, Jeremias G Galletti, Zhiyuan Yu, Kevin Burgess, Cintia S De Paiva

Faculty, Staff and Students Publications

Neurotrophins are a family of closely related secreted proteins that promote differentiation, development, and survival of neurons, which include nerve growth factor (NGF), brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4. All neurotrophins signal through tropomyosin receptor kinases (TrkA, TrkB, and TrkC) which are more selective to NGF, brain-derived neurotrophic factor, and neurotrophin-3, respectively. NGF is the most studied neurotrophin in the ocular surface and a human recombinant NGF has reached clinics, having been approved to treat neurotrophic keratitis. Brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4 are less studied neurotrophins in the ocular surface, even though brain-derived neurotrophic factor is well characterized in …

Repeated Out-Of-Africa Expansions Of Helicobacter Pylori Driven By Replacement Of Deleterious Mutations, Harry A Thorpe, Elise Tourrette, Koji Yahara, Filipa F Vale, Siqi Liu, Mónica Oleastro, Teresa Alarcon, Tsachi-Tsadok Perets, Saeid Latifi-Navid, Yoshio Yamaoka, Beatriz Martinez-Gonzalez, Ioannis Karayiannis, Timokratis Karamitros, Dionyssios N Sgouras, Wael Elamin, Ben Pascoe, Samuel K Sheppard, Jukka Ronkainen, Pertti Aro, Lars Engstrand, Lars Agreus, Sebastian Suerbaum, Kaisa Thorell, Daniel Falush

Faculty, Staff and Students Publications

Helicobacter pylori lives in the human stomach and has a population structure resembling that of its host. However, H. pylori from Europe and the Middle East trace substantially more ancestry from modern African populations than the humans that carry them. Here, we use a collection of Afro-Eurasian H. pylori genomes to show that this African ancestry is due to at least three distinct admixture events. H. pylori from East Asia, which have undergone little admixture, have accumulated many more non-synonymous mutations than African strains. European and Middle Eastern bacteria have elevated African ancestry at the sites of these mutations, implying …

Erk Inhibitor Ulixertinib Inhibits High-Risk Neuroblastoma Growth In Vitro And In Vivo, Yang Yu, Yanling Zhao, Jongmin Choi, Zhongcheng Shi, Linjie Guo, John Elizarraras, Andy Gu, Feng Cheng, Yanxin Pei, Dai Lu, Muller Fabbri, Saurabh Agarwal, Chunchao Zhang, Sung Yun Jung, Jennifer H Foster, Jianhua Yang

Faculty, Staff and Students Publications

Neuroblastoma (NB) is a pediatric tumor of the peripheral nervous system. Approximately 80% of relapsed NB show RAS-MAPK pathway mutations that activate ERK, resulting in the promotion of cell proliferation and drug resistance. Ulixertinib, a first-in-class ERK-specific inhibitor, has shown promising antitumor activity in phase 1 clinical trials for advanced solid tumors. Here, we show that ulixertinib significantly and dose-dependently inhibits cell proliferation and colony formation in different NB cell lines, including PDX cells. Transcriptomic analysis revealed that ulixertinib extensively inhibits different oncogenic and neuronal developmental pathways, including EGFR, VEGF, WNT, MAPK, NGF, and NTRK1. The proteomic analysis further revealed …

Modified Messengers: Flatworm Stem Cells And Regeneration Are Guarded By Rna Methylation, Blair W Benham-Pyle

Faculty, Staff and Students Publications

The contribution of RNA modifications to whole-body regeneration remains unclear. In this issue, Dagan et al (2022) show that m6a mRNA pathway components are critically required for stem cell differentiation, survival, and tissue renewal in the planarian Schmidtea mediterranea.

Secreted Fas Decoys Enhance The Antitumor Activity Of Engineered And Bystander T Cells In Fas Ligand-Expressing Solid Tumors, Pradip Bajgain, Alejandro G Torres Chavez, Kishore Balasubramanian, Lindsey Fleckenstein, Premal Lulla, Helen E Heslop, Juan Vera, Ann M Leen

Faculty, Staff and Students Publications

T-cell immunotherapy has demonstrated remarkable clinical outcomes in certain hematologic malignancies. However, efficacy in solid tumors has been suboptimal, partially due to the hostile tumor microenvironment composed of immune-inhibitory molecules. One such suppressive agent abundantly expressed in solid tumors is Fas ligand (FasL), which can trigger apoptosis of Fas-expressing effector cells such as T cells and natural killer (NK) cells. To alleviate this FasL-induced suppression of tumor-specific immune cells in solid tumors, we describe here the development of a Fas decoy that is secreted by engineered cells upon activation and sequesters the ligand, preventing it from engaging with Fas on …

Opportunities And Challenges In Heart Rhythm Research: Rationale And Development Of An Electrophysiology Collaboratory, Duy T Nguyen, Kenneth C Bilchick, Sanjiv M Narayan, Mina K Chung, Kevin L Thomas, Kenneth R Laurita, Marmar Vaseghi, Roopinder Sandhu, Mihail G Chelu, Prince J Kannankeril, Douglas L Packer, David D Mcmanus, Atul Verma, Matthew Singleton, Khaldoun Tarakji, Sana M Al-Khatib, Jonathan R Kaltman, Ravi C Balijepalli, George F Van Hare, Jodie L Hurwitz, Andrea M Russo, Fred M Kusumoto, Christine M Albert

Faculty, Staff and Students Publications

There are many challenges in the current landscape of electrophysiology (EP) clinical and translational research, including increasing costs and complexity, competing demands, regulatory requirements, and challenges with study implementation. This review seeks to broadly discuss the state of EP research, including challenges and opportunities. Included here are results from a Heart Rhythm Society (HRS) Research Committee member survey detailing HRS members' perspectives regarding both barriers to clinical and translational research and opportunities to address these challenges. We also provide stakeholder perspectives on barriers and opportunities for future EP research, including input from representatives of the U.S. Food and Drug Administration, …

Combination Of Aibp, Apoa-I, And Aflibercept Overcomes Anti-Vegf Resistance In Neovascular Amd By Inhibiting Arteriolar Choroidal Neovascularization, Zhao Zhang, Megan M Shen, Yingbin Fu

Faculty, Staff and Students Publications

PURPOSE: Anti-VEGF resistance represents a major unmet clinical need in the management of choroidal neovascularization (CNV). We have previously reported that a combination of AIBP, apoA-I, and an anti-VEGF antibody overcomes anti-VEGF resistance in laser-induced CNV in old mice in prevention experiments. The purpose of this work is to conduct a more clinically relevant study to assess the efficacy of the combination of AIBP, apoA-I, and aflibercept in the treatment of anti-VEGF resistance of experimental CNV at different time points after laser photocoagulation.

METHODS: To understand the pathobiology of anti-VEGF resistance, we performed comprehensive examinations of the vascular morphology of …

Development Of A Novel Mouse Model Of Menopause-Associated Asthma, William P Pederson, Laurie M Ellerman, Estevan C Sandoval, Scott Boitano, Jennifer B Frye, Kristian P Doyle, Heddwen L Brooks, Francesca Polverino, Julie G Ledford

Faculty, Staff and Students Publications

No abstract provided.

Clearance Of Hiv-1 Or Siv Reservoirs By Promotion Of Apoptosis And Inhibition Of Autophagy: Targeting Intracellular Molecules In Cure-Directed Strategies, Min Chen, Min Li, Marietta M Budai, Andrew P Rice, Jason T Kimata, Mahesh Mohan, Jin Wang

Faculty, Staff and Students Publications

The reservoirs of the HIV display cellular properties resembling long-lived immune memory cells that could be exploited for viral clearance. Our interest in developing a cure for HIV stems from the studies of immunologic memory against infections. We and others have found that long-lived immune memory cells employ prosurvival autophagy and antiapoptotic mechanisms to protect their longevity. Here, we describe the rationale for the development of an approach to clear HIV-1 by selective elimination of host cells harboring replication-competent HIV (SECH). While reactivation of HIV-1 in the host cells with latency reversing agents (LRAs) induces viral gene expression leading to …

A Microtubule-Connexin-43 Regulatory Link Suppresses Arrhythmias And Cardiac Fibrosis In Duchenne Muscular Dystrophy Mice, Eric Himelman, Julie Nouet, Mauricio A Lillo, Alexander Chong, Delong Zhou, Xander H T Wehrens, George G Rodney, Lai-Hua Xie, Natalia Shirokova, Jorge E Contreras, Diego Fraidenraich

Faculty, Staff and Students Publications

Dilated cardiomyopathy is the leading cause of death in Duchenne muscular dystrophy (DMD), an inherited degenerative disease of the cardiac and skeletal muscle caused by absence of the protein dystrophin. We showed one hallmark of DMD cardiomyopathy is the dysregulation of cardiac gap junction channel protein connexin-43 (Cx43). Proper Cx43 localization and function at the cardiac intercalated disc (ID) is regulated by post-translational phosphorylation of Cx43-carboxy-terminus residues S325/S328/S330 (pS-Cx43). Concurrently, Cx43 traffics along microtubules (MTs) for targeted delivery to the ID. In DMD hearts, absence of dystrophin results in a hyperdensified and disorganized MT cytoskeleton, yet the link with pS-Cx43 …

Aging-Associated Regγ Proteasome Decline Predisposes To Tauopathy, Jialu Tu, Haiyang Zhang, Ting Yang, Yun Liu, Solomon Kibreab, Yunpeng Zhang, Liangcai Gao, Robb E Moses, Bert W O'Malley, Jianru Xiao, Xiaotao Li

Faculty, Staff and Students Publications

The REGγ-20S proteasome is an ubiquitin- and ATP-independent degradation system, targeting selective substrates, possibly helping to regulate aging. The studies we report here demonstrate that aging-associated REGγ decline predisposes to decreasing tau turnover, as in a tauopathy. The REGγ proteasome promotes degradation of human and mouse tau, notably phosphorylated tau and toxic tau oligomers that shuttle between the cytoplasm and nuclei. REGγ-mediated proteasomal degradation of tau was validated in 3- to 12-month-old REGγ KO mice, REGγ KO;PS19 mice, and PS19 mice with forebrain conditional neuron-specific overexpression of REGγ (REGγ OE) and behavioral abnormalities. Coupled with tau accumulation, we found …

Histone-Stimulated Platelet Adhesion To Mouse Cremaster Venules In Vivo Is Dependent On Von Willebrand Factor, Justin A Courson, Fong W Lam, Kimberly W Langlois, Rolando E Rumbaut

Faculty, Staff and Students Publications

Objective: Extracellular histones are known mediators of platelet activation, inflammation, and thrombosis. Von Willebrand Factor (vWF) and Toll-like receptor 4 (TLR4) have been implicated in pro-inflammatory and prothrombotic histone responses. The objective of this study was to assess the role of vWF and TLR4 on histone-induced platelet adhesion in vivo.

Methods: Intravital microscopy of the mouse cremaster microcirculation, in the presence of extracellular histones or saline control, was conducted in wild-type, vWF-deficient, and TLR4-deficient mice to assess histone-mediated platelet adhesion. Platelet counts following extracellular histone exposure were conducted. Platelets were isolated from vWF-deficient mice and littermates to assess the role …

Looking On The Horizon; Potential And Unique Approaches To Developing Radiation Countermeasures For Deep Space Travel, Rihana S Bokhari, Afshin Beheshti, Sarah E Blutt, Dawn E Bowles, David Brenner, Robert Britton, Lawrence Bronk, Xu Cao, Anushree Chatterjee, Delisa E Clay, Colleen Courtney, Donald T Fox, M Waleed Gaber, Sharon Gerecht, Peter Grabham, David Grosshans, Fada Guan, Erin A Jezuit, David G Kirsch, Zhandong Liu, Mirjana Maletic-Savatic, Kyle M Miller, Ruth A Montague, Prashant Nagpal, Sivan Osenberg, Luke Parkitny, Niles A Pierce, Christopher Porada, Susan M Rosenberg, Paul Sargunas, Sadhana Sharma, Jamie Spangler, Daniel Naveed Tavakol, Dilip Thomas, Gordana Vunjak-Novakovic, Chunbo Wang, Luke Whitcomb, Damian W Young, Dorit Donoviel

Faculty, Staff and Students Publications

Future lunar missions and beyond will require new and innovative approaches to radiation countermeasures. The Translational Research Institute for Space Health (TRISH) is focused on identifying and supporting unique approaches to reduce risks to human health and performance on future missions beyond low Earth orbit. This paper will describe three funded and complementary avenues for reducing the risk to humans from radiation exposure experienced in deep space. The first focus is on identifying new therapeutic targets to reduce the damaging effects of radiation by focusing on high throughput genetic screens in accessible, sometimes called lower, organism models. The second focus …

Triphenyl Phosphate Activates Estrogen Receptor Α/Nf-Κb/ Cyclin D1 Signaling To Stimulate Cell Cycle Progression In Human Ishikawa Endometrial Cancer Cells, Hyun Young Kwon, Seung Bin Park, Myoungseok Han, Jung-Woo Park, Yongmin Lee, Sang Jun Han, Youngmin Kwon, Yeon Jean Cho

Faculty, Staff and Students Publications

OBJECTIVE: Triphenyl phosphate (TPHP) is one of the most commonly used organophosphorus flame retardants that may accumulate in the environment. However, its effects on human reproductive organs have not been well studied. We aimed to investigate the in vitro effects of TPHP in human Ishikawa endometrial cancer cells to elucidate how TPHP exposure disrupts intracellular signaling and cell proliferation in reproductive tissues.

METHODS: Human Ishikawa endometrial cancer cells were exposed to TPHP.

RESULTS: Exposure to TPHP elevated the levels of estrogen receptor (ER) α and progesterone receptor-B and reduced ER β in human Ishikawa endometrial cancer cells. TPHP stimulated phosphoinositide …

Relationship Between Obstructive Sleep Apnea And Balance On Computerized Dynamic Posturography, Meha G Fox, Helen S Cohen, Haleh Sangi-Haghpeykar, Masayoshi Takashima

Faculty, Staff and Students Publications

BACKGROUND: Obstructive sleep apnea (OSA) leads to chronic sleep deprivation. The relationship between OSA and balance is poorly understood.

AIM/OBJECTIVE: This study aimed to determine if OSA adversely affects standing balance.

MATERIAL AND METHODS: Adults with a clinically indicated polysomnogram (PSG) diagnostic of OSA, who were not on therapy, were recruited from an academic tertiary care referral clinic. Subjects completed the Epworth Sleepiness Scale (ESS), the Stanford Sleepiness Scale (SSS), and the STOP-BANG questionnaire (SBQ). Their balance was tested with the Sensory Organization Test (SOT) of computerized dynamic posturography (CDP).

RESULTS: Sixteen subjects participated in the study, including three with …

Steroid Receptor Coactivator-3 Inhibition Generates Breast Cancer Antitumor Immune Microenvironment, Sang Jun Han, Nuri Sung, Jin Wang, Bert W O'Malley, David M Lonard

Faculty, Staff and Students Publications

BACKGROUND: The tumor immune microenvironment (TIME) generated by cancer-infiltrating immune cells has a crucial role in promoting or suppressing breast cancer progression. However, whether the steroid receptor coactivator-3 (SRC-3) modulates TIME to progress breast cancer is unclear. Therefore, the present study evaluates whether SRC-3 generates a tumor-promoting TIME in breast tumors using a syngeneic immune-intact mouse model of breast cancer.

METHODS: We employed E0771 and 4T1 breast cancer in immune-intact syngeneic female C57BL/6 and BALB/c mice, respectively. SI-2, a specific small-molecule inhibitor of SRC-3, was administered daily (2.5 mg/kg) to E0771 and 4T1 breast tumor-bearing immune-intact mice. In addition, SRC-3 …

A Cop1-Gata2 Axis Suppresses Ar Signaling And Prostate Cancer, Tao Shen, Bingning Dong, Yanling Meng, David D Moore, Feng Yang

Faculty, Staff and Students Publications

Androgen receptor (AR) signaling is crucial for driving prostate cancer (PCa), the most diagnosed and the second leading cause of death in male patients with cancer in the United States. Androgen deprivation therapy is initially effective in most instances of AR-positive advanced or metastatic PCa. However, patients inevitably develop lethal castration-resistant PCa (CRPC), which is also resistant to the next-generation AR signaling inhibitors. Most CRPCs maintain AR expression, and blocking AR signaling remains a main therapeutic approach. GATA2 is a pioneer transcription factor emerging as a key therapeutic target for PCa because it promotes AR expression and activation. While directly …

Loss Of Non-Motor Kinesin Kif26a Causes Congenital Brain Malformations Via Dysregulated Neuronal Migration And Axonal Growth As Well As Apoptosis, Xuyu Qian, Ellen M Degennaro, Maya Talukdar, Shyam K Akula, Abbe Lai, Diane D Shao, Dilenny Gonzalez, Jack H Marciano, Richard S Smith, Norma K Hylton, Edward Yang, J Fernando Bazan, Lee Barrett, Rebecca C Yeh, R Sean Hill, Samantha G Beck, Aoi Otani, Jolly Angad, Tadahiro Mitani, Jennifer E Posey, Davut Pehlivan, Daniel Calame, Hatip Aydin, Osman Yesilbas, Kendall C Parks, Emanuela Argilli, Eleina England, Kiho Im, Ajay Taranath, Hamish S Scott, Christopher P Barnett, Peer Arts, Elliott H Sherr, James R Lupski, Christopher A Walsh

Faculty, Staff and Students Publications

Kinesins are canonical molecular motors but can also function as modulators of intracellular signaling. KIF26A, an unconventional kinesin that lacks motor activity, inhibits growth-factor-receptor-bound protein 2 (GRB2)- and focal adhesion kinase (FAK)-dependent signal transduction, but its functions in the brain have not been characterized. We report a patient cohort with biallelic loss-of-function variants in KIF26A, exhibiting a spectrum of congenital brain malformations. In the developing brain, KIF26A is preferentially expressed during early- and mid-gestation in excitatory neurons. Combining mice and human iPSC-derived organoid models, we discovered that loss of KIF26A causes excitatory neuron-specific defects in radial migration, localization, dendritic and …

Cgas-Sting Activation Contributes To Podocyte Injury In Diabetic Kidney Disease, Nan Zang, Chen Cui, Xinghong Guo, Jia Song, Huiqing Hu, Mengmeng Yang, Mingyue Xu, Lingshu Wang, Xinguo Hou, Qin He, Zheng Sun, Chuan Wang, Li Chen

Faculty, Staff and Students Publications

Diabetic kidney disease (DKD) is the leading cause of end-stage renal diseases. DKD does not have efficacious treatment. The cGAS-STING pathway is activated in podocytes at the early stage of kidney dysfunction, which is associated with the activation of STING downstream effectors TBK1 and NF-κB but not IRF3. Lipotoxicity induces mitochondrial damage and mtDNA leakage to the cytosol through Bcl-2 associated X protein (BAX) in podocytes. BAX-mediated mtDNA cytosolic leakage can activate the cGAS-STING pathway in the absence of lipotoxicity and is sufficient to cause podocyte injury. Depletion of cytosolic mtDNA, genetic STING knockdown, or pharmacological inhibition of STING or …

Genetic Inhibition Of Nuclear Factor Of Activated T-Cell C2 Prevents Atrial Fibrillation In Crem Transgenic Mice, Li Ni, Satadru K Lahiri, Jiali Nie, Xiaolu Pan, Issam Abu-Taha, Julia O Reynolds, Hannah M Campbell, Haihao Wang, Markus Kamler, Wilhelm Schmitz, Frank Ulrich Müller, Na Li, Xiang Wei, Dao Wen Wang, Dobromir Dobrev, Xander H T Wehrens

Faculty, Staff and Students Publications

AIMS: Abnormal intracellular calcium (Ca2+) handling contributes to the progressive nature of atrial fibrillation (AF), the most common sustained cardiac arrhythmia. Evidence in mouse models suggests that activation of the nuclear factor of activated T-cell (NFAT) signalling pathway contributes to atrial remodelling. Our aim was to determine the role of NFATc2 in AF in humans and mouse models.

METHODS AND RESULTS: Expression levels of NFATc1-c4 isoforms were assessed by quantitative reverse transcription-polymerase chain reaction in right atrial appendages from patients with chronic AF (cAF). NFATc1 and NFATc2 mRNA levels were elevated in cAF patients compared with those in normal sinus …

Control Of Ribosomal Rna Synthesis By Hematopoietic Transcription Factors, Charles Antony, Subin S George, Justin Blum, Patrick Somers, Chelsea L Thorsheim, Dexter J Wu-Corts, Yuxi Ai, Long Gao, Kaosheng Lv, Michel G Tremblay, Tom Moss, Kai Tan, Jeremy E Wilusz, Austen R D Ganley, Maxim Pimkin, Vikram R Paralkar

Faculty, Staff and Students Publications

Ribosomal RNAs (rRNAs) are the most abundant cellular RNAs, and their synthesis from rDNA repeats by RNA polymerase I accounts for the bulk of all transcription. Despite substantial variation in rRNA transcription rates across cell types, little is known about cell-type-specific factors that bind rDNA and regulate rRNA transcription to meet tissue-specific needs. Using hematopoiesis as a model system, we mapped about 2,200 ChIP-seq datasets for 250 transcription factors (TFs) and chromatin proteins to human and mouse rDNA and identified robust binding of multiple TF families to canonical TF motifs on rDNA. Using a 47S-FISH-Flow assay developed for nascent rRNA …

Loss Of Activity-Induced Mitochondrial Atp Production Underlies The Synaptic Defects In A Drosophila Model Of Als, Nicholas E Karagas, Richa Gupta, Elham Rastegari, Kai Li Tan, Ho Hang Leung, Hugo J Bellen, Kartik Venkatachalam, Ching-On Wong

Faculty, Staff and Students Publications

Mutations in the gene encoding vesicle-associated membrane protein B (VAPB) cause a familial form of amyotrophic lateral sclerosis (ALS). Expression of an ALS-related variant of vapb (vapb^P58S) in Drosophila motor neurons results in morphologic changes at the larval neuromuscular junction (NMJ) characterized by the appearance of fewer, but larger, presynaptic boutons. Although diminished microtubule stability is known to underlie these morphologic changes, a mechanism for the loss of presynaptic microtubules has been lacking. By studying flies of both sexes, we demonstrate the suppression of vapb^P58S-induced changes in NMJ morphology by either a loss of endoplasmic …

Maternal Gut Microbiota Mediate Intergenerational Effects Of High-Fat Diet On Descendant Social Behavior, Claudia M Di Gesù, Lisa M Matz, Ian J Bolding, Robert Fultz, Kristi L Hoffman, Antonella Marino Gammazza, Joseph F Petrosino, Shelly A Buffington

Faculty, Staff and Students Publications

Dysbiosis of the maternal gut microbiome during pregnancy is associated with adverse neurodevelopmental outcomes. We previously showed that maternal high-fat diet (MHFD) in mice induces gut dysbiosis, social dysfunction, and underlying synaptic plasticity deficits in male offspring (F1). Here, we reason that, if HFD-mediated changes in maternal gut microbiota drive offspring social deficits, then MHFD-induced dysbiosis in F1 female MHFD offspring would likewise impair F2 social behavior. Metataxonomic sequencing reveals reduced microbial richness among female F1 MHFD offspring. Despite recovery of microbial richness among MHFD-descendant F2 mice, they display social dysfunction. Post-weaning Limosilactobacillus reuteri treatment increases the abundance of short-chain …

Ez Clear For Simple, Rapid, And Robust Mouse Whole Organ Clearing, Chih-Wei Hsu, Juan Cerda, Jason M Kirk, Williamson D Turner, Tara L Rasmussen, Carlos P Flores Suarez, Mary E Dickinson, Joshua D Wythe

Faculty, Staff and Students Publications

Tissue clearing for whole organ cell profiling has revolutionized biology and imaging for exploration of organs in three-dimensional space without compromising tissue architecture. But complicated, laborious procedures, or expensive equipment, as well as the use of hazardous, organic solvents prevent the widespread adoption of these methods. Here, we report a simple and rapid tissue clearing method, EZ Clear, that can clear whole adult mouse organs in 48 hr in just three simple steps. Samples stay at room temperature and remain hydrated throughout the clearing process, preserving endogenous and synthetic fluorescence, without altering sample size. After wholemount clearing and imaging, samples …

Infant Behavioral State And Stool Microbiome In Infants Receiving Lactocaseibacillus Rhamnosus Gg In Formula: Randomized Controlled Trial, Robert J Shulman, Maciej Chichlowski, Fabiola Gutierrez Orozco, Cheryl L Harris, Jennifer L Wampler, Nicholas A Bokulich, Carol Lynn Berseth

Faculty, Staff and Students Publications

BACKGROUND: Our aim was to evaluate infant behavioral state, stool microbiome profile and calprotectin in infants with infantile colic receiving a partially hydrolyzed protein formula with or without added Lacticaseibacillus (formerly Lactobacillus) rhamnosus GG (LGG).

METHODS: In this single-center, double-blind, controlled, parallel, prospective study, term infants (14-28 days of age) identified with colic (using modified Wessel's criteria: cried and/or fussed ≥ 3 h/day for ≥ 3 days/week, in a one-week period) were randomized to receive one of two formulas over a three-week feeding period: marketed partially hydrolyzed cow's milk-based infant formula (PHF, n = 35) or a similar formula with …

Diabetes Duration And Subclinical Myocardial Injury: The Atherosclerosis Risk In Communities Study (Aric), Carine E Hamo, Justin B Echouffo-Tcheugui, Sui Zhang, Roberta Florido, James S Pankow, Erin D Michos, Ronald Goldberg, Vijay Nambi, Gary Gerstenblith, Wendy S Post, Roger S Blumenthal, Christie Ballantyne, Elizabeth Selvin, Josef Coresh, Chiadi E Ndumele

Faculty, Staff and Students Publications

Background: Diabetes exerts adverse effects on the heart, and a longer diabetes duration is associated with greater heart failure risk. We studied diabetes duration and subclinical myocardial injury, as reflected by high-sensitivity cardiac troponin (hs-cTnT).

Methods: We analyzed 9052 participants without heart failure or coronary heart disease (mean age 63 years, 58% female, 21% Black, 15% with diabetes) at The Atherosclerosis Risk in Communities Study (ARIC) Visit 4 (1996 to 1998). Diabetes duration was calculated based on diabetes status at Visits 1 (1987 to 1989) through 4, or using self-reported age of diabetes diagnosis prior to Visit 1. We used …

Tryptophan Oxidation In Young Children With Environmental Enteric Dysfunction Classified By The Lactulose Rhamnose Ratio, Nirupama Shivakumar, Jean W Hsu, Sindhu Kashyap, Tinku Thomas, Anura V Kurpad, Farook Jahoor

Faculty, Staff and Students Publications

BACKGROUND: In young children, associations between linear growth faltering, environmental enteric dysfunction (EED), and the plasma kynurenine (Kyn)/tryptophan (Trp) ratio (KTR) have led to the proposal that higher Trp catabolism in response to intestinal/systemic inflammation limits Trp availability for protein synthesis, resulting in impaired growth.

OBJECTIVES: We sought to estimate the Trp oxidation rate and the Trp conversion rate to Kyn in young children with and without EED.

METHODS: Children aged 18-24 mo, from urban slums, were assigned to EED (n = 19) or no-EED (n = 26) groups on the basis of a urinary lactulose/rhamnose ratio (LRR) cutoff based …

Association Between Mnsod Activity And Cognitive Impairment In Unmedicated First-Episode Schizophrenia: Regulated By Mnsod Ala-9val Gene Polymorphism, Dong Mei Wang, Rong Rong Zhu, Yang Tian, Kadir Uludag, Jia Jing Chen, Hui Xia Zhou, Li Wang, Thomas R Kosten, Xiang Yang Zhang

Faculty, Staff and Students Publications

The imbalance between pro-oxidants and antioxidants is thought to be responsible for aging and cognitive impairment in many degenerative diseases, including schizophrenia (SZ). As the first antioxidant enzyme to detoxify superoxide radicals in mitochondria, manganese superoxide dismutase (MnSOD) activity and its functional polymorphism of Ala-9Val have been found to be associated with SZ. In this study, we explored the association between MnSOD activity, MnSOD Ala-9Val polymorphism and cognitive dysfunction in unmedicated first-episode (UMFE) SZ patients, which has not been examined. We recruited 234 UMFE SZ patients and 232 healthy controls (HC) and evaluated them with Repeated Battery for the Assessment …

Covid-19 Pandemic And Infant Neurodevelopmental Impairment: A Systematic Review And Meta-Analysis, Kamran Hessami, Amir Hossein Norooznezhad, Sonia Monteiro, Enrico R Barrozo, Abolfazl Shirdel Abdolmaleki, Sara E Arian, Nikan Zargarzadeh, Lara S Shekerdemian, Kjersti M Aagaard, Alireza A Shamshirsaz

Faculty, Staff and Students Publications

IMPORTANCE: Primary studies proposed that aberrant maternal antiviral immunity and/or giving birth in quarantine, such as during the ongoing COVID-19 pandemic, may be associated with the risk of neurodevelopmental impairment (NDI) in offspring.

OBJECTIVES: To evaluate the associations of birth and being raised during the COVID-19 pandemic with risk of NDI among infants and to assess the association of gestational exposure to SARS-CoV-2 with risk of NDI.

DATA SOURCES: PubMed, Web of Science, Scopus, Embase, and preprint servers were systematically searched from inception to March 25, 2022.

STUDY SELECTION: Studies evaluating the neurodevelopment of infants born during the SARS-CoV-2 pandemic …

Dietary Interventions For Gastroparesis: A Systematic Review, Debra Eseonu, Tanya Su, Keya Lee, Bruno P Chumpitazi, Robert J Shulman, Ruben Hernaez

Faculty, Staff and Students Publications

Gastroparesis (Gp) is a delay in gastric emptying in the absence of a mechanical obstruction and has the capacity to cause symptoms that significantly impact a patient's quality of life. Dietary interventions are the first-line treatment in Gp, but the efficacy of different diets is unclear. This systematic review seeks to determine the effectiveness of dietary interventions on clinical outcomes in Gp. A literature search of MEDLINE Ovid from 1 March 2008 to 1 October 2021 was conducted to identify randomized controlled trials, cohort studies, and cross-sectional studies that reported dietary interventions in Gp. From the initial search, 2789 studies …